Sample records for vaccine clinical research

  1. Conceptual framework for behavioral and social science in HIV vaccine clinical research

    PubMed Central

    Lau, Chuen-Yen; Swann, Edith M.; Singh, Sagri; Kafaar, Zuhayr; Meissner, Helen I.; Stansbury, James P.

    2011-01-01

    HIV vaccine clinical research occurs within a context where biomedical science and social issues are interlinked. Previous HIV vaccine research has considered behavioral and social issues, but often treated them as independent of clinical research processes. Systematic attention to the intersection of behavioral and social issues within a defined clinical research framework is needed to address gaps, such as those related to participation in trials, completion of trials, and the overall research experience. Rigorous attention to these issues at project inception can inform trial design and conduct by matching research approaches to the context in which trials are to be conducted. Conducting behavioral and social sciences research concurrent with vaccine clinical research is important because it can help identify potential barriers to trial implementation, as well as ultimate acceptance and dissemination of trial results. We therefore propose a conceptual framework for behavioral and social science in HIV vaccine clinical research and use examples from the behavioral and social science literature to demonstrate how the model can facilitate identification of significant areas meriting additional exploration. Standardized use of the conceptual framework could improve HIV vaccine clinical research efficiency and relevance. PMID:21821083

  2. Conceptual framework for behavioral and social science in HIV vaccine clinical research.

    PubMed

    Lau, Chuen-Yen; Swann, Edith M; Singh, Sagri; Kafaar, Zuhayr; Meissner, Helen I; Stansbury, James P

    2011-10-13

    HIV vaccine clinical research occurs within a context where biomedical science and social issues are interlinked. Previous HIV vaccine research has considered behavioral and social issues, but often treated them as independent of clinical research processes. Systematic attention to the intersection of behavioral and social issues within a defined clinical research framework is needed to address gaps, such as those related to participation in trials, completion of trials, and the overall research experience. Rigorous attention to these issues at project inception can inform trial design and conduct by matching research approaches to the context in which trials are to be conducted. Conducting behavioral and social sciences research concurrent with vaccine clinical research is important because it can help identify potential barriers to trial implementation, as well as ultimate acceptance and dissemination of trial results. We therefore propose a conceptual framework for behavioral and social science in HIV vaccine clinical research and use examples from the behavioral and social science literature to demonstrate how the model can facilitate identification of significant areas meriting additional exploration. Standardized use of the conceptual framework could improve HIV vaccine clinical research efficiency and relevance. Published by Elsevier Ltd.

  3. Clinical development of Ebola vaccines

    PubMed Central

    Sridhar, Saranya

    2015-01-01

    The ongoing outbreak of Ebola virus disease in West Africa highlighted the lack of a licensed drug or vaccine to combat the disease and has renewed the urgency to develop a pipeline of Ebola vaccines. A number of different vaccine platforms are being developed by assessing preclinical efficacy in animal models and expediting clinical development. Over 15 different vaccines are in preclinical development and 8 vaccines are now in different stages of clinical evaluation. These vaccines include DNA vaccines, virus-like particles and viral vectors such as live replicating vesicular stomatitis virus (rVSV), human and chimpanzee adenovirus, and vaccinia virus. Recently, in preliminary results reported from the first phase III trial of an Ebola vaccine, the rVSV-vectored vaccine showed promising efficacy. This review charts this rapidly advancing area of research focusing on vaccines in clinical development and discusses the future opportunities and challenges faced in the licensure and deployment of Ebola vaccines. PMID:26668751

  4. Malaria vaccine clinical trials: what’s on the horizon

    PubMed Central

    Moreno, Alberto; Joyner, Chester

    2015-01-01

    Significant progress towards a malaria vaccine, specifically for Plasmodium falciparum, has been made in the past few years with the completion of numerous clinical trials. Each trial has utilized a unique combination of antigens, delivery platforms, and adjuvants, and the data that has been obtained provides critical information that has poises the research community for the development of next generation malaria vaccines. Despite the progress towards a P. falciparum vaccine, P. vivax vaccine research requires more momentum and additional investigations to identify novel vaccine candidates. In this review, recently completed and ongoing malaria vaccine clinical trials as well as vaccine candidates that are in the development pipeline are reviewed. Perspectives for future research using post-genomic mining, nonhuman primate models, and systems biology are also discussed. PMID:26172291

  5. [Overview of the Ebola vaccines in pre-clinical and clinical development].

    PubMed

    Buchy, P

    2016-10-01

    The Ebola epidemic that occurred in West Africa between 2013-2016 significantly accelerated the research and development of Ebola vaccines. Few dozens of clinical trials have been recently conducted leading to opportunities to test several new vaccine candidates. Other vaccines are still in early development phases (table 1). This paper provides an overview of the new developments in that area.

  6. European Union vaccine research--an overview.

    PubMed

    Sautter, Jürgen; Olesen, Ole F; Bray, Jeremy; Draghia-Akli, Ruxandra

    2011-09-09

    Recent developments in vaccine research provide new momentum for an important area in health innovation. Particularly interesting are novel DNA vaccine approaches, many of which are already under clinical investigation. The Framework Programmes of the European Union play an important role in supporting collaborative efforts in vaccine research to develop new and better vaccines and bring them to the market. With a timely strategic reorientation towards a sustainable investment in innovation, the current seventh Framework Programme will help to bring large industry and small and medium-sized enterprises (SME) on board and foster partnership between stakeholders. As the first human DNA vaccines progresses through the development pipeline, more and more questions revolve around licensing and regulation and appropriate guidelines are being developed. Copyright © 2011. Published by Elsevier Ltd.

  7. An Interview with AIDS Vaccine Researcher Chris Parks

    ERIC Educational Resources Information Center

    Sullivan, Megan

    2010-01-01

    The search for an AIDS (acquired immune deficiency syndrome) vaccine is truly a global effort, with university laboratories, biotech firms, pharmaceutical companies, nonprofit research organizations, hospitals, and clinics all working together to develop an effective vaccine as quickly as possible. The International AIDS Vaccine Initiative (IAVI)…

  8. Now that you want to take your HIV/AIDS vaccine/biological product research concept into the clinic: what are the "cGMP"?

    PubMed

    Sheets, Rebecca L; Rangavajhula, Vijaya; Pullen, Jeffrey K; Butler, Chris; Mehra, Vijay; Shapiro, Stuart; Pensiero, Michael

    2015-04-08

    The Division of AIDS Vaccine Research Program funds the discovery and development of HIV/AIDS vaccine candidates. Basic researchers, having discovered a potential vaccine in the laboratory, next want to take that candidate into the clinic to test the concept in humans, to see if it translates. Many of them have heard of "cGMP" and know that they are supposed to make a "GMP product" to take into the clinic, but often they are not very familiar with what "cGMP" means and why these good practices are so important. As members of the Vaccine Translational Research Branch, we frequently get asked "can't we use the material we made in the lab in the clinic?" or "aren't Phase 1 studies exempt from cGMP?" Over the years, we have had many experiences where researchers or their selected contract manufacturing organizations have not applied an appropriate degree of compliance with cGMP suitable for the clinical phase of development. We share some of these experiences and the lessons learned, along with explaining the importance of cGMP, just what cGMP means, and what they can assure, in an effort to de-mystify this subject and facilitate the rapid and safe translational development of HIV vaccines. Published by Elsevier Ltd.

  9. 42 CFR 70.9 - Vaccination clinics.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Vaccination clinics. 70.9 Section 70.9 Public... INTERSTATE QUARANTINE § 70.9 Vaccination clinics. (a) The Director may establish vaccination clinics, through contract or otherwise, authorized to administer vaccines and/or other prophylaxis. (b) A vaccination fee...

  10. 42 CFR 70.9 - Vaccination clinics.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Vaccination clinics. 70.9 Section 70.9 Public... INTERSTATE QUARANTINE § 70.9 Vaccination clinics. (a) The Director may establish vaccination clinics, through contract or otherwise, authorized to administer vaccines and/or other prophylaxis. (b) A vaccination fee...

  11. Design of clinical trials for therapeutic cancer vaccines development.

    PubMed

    Mackiewicz, Jacek; Mackiewicz, Andrzej

    2009-12-25

    Advances in molecular and cellular biology as well as biotechnology led to definition of a group of drugs referred to as medicinal products of advanced technologies. It includes gene therapy products, somatic cell therapeutics and tissue engineering. Therapeutic cancer vaccines including whole cell tumor cells vaccines or gene modified whole cells belong to somatic therapeutics and/or gene therapy products category. The drug development is a multistep complex process. It comprises of two phases: preclinical and clinical. Guidelines on preclinical testing of cell based immunotherapy medicinal products have been defined by regulatory agencies and are available. However, clinical testing of therapeutic cancer vaccines is still under debate. It presents a serious problem since recently clinical efficacy of the number of cancer vaccines has been demonstrated that focused a lot of public attention. In general clinical testing in the current form is very expensive, time consuming and poorly designed what may lead to overlooking of products clinically beneficial for patients. Accordingly regulatory authorities and researches including Cancer Vaccine Clinical Trial Working Group proposed three regulatory solutions to facilitate clinical development of cancer vaccines: cost-recovery program, conditional marketing authorization, and a new development paradigm. Paradigm includes a model in which cancer vaccines are investigated in two types of clinical trials: proof-of-principle and efficacy. The proof-of-principle trial objectives are: safety; dose selection and schedule of vaccination; and demonstration of proof-of-principle. Efficacy trials are randomized clinical trials with objectives of demonstrating clinical benefit either directly or through a surrogate. The clinical end points are still under debate.

  12. Now That You Want to Take Your HIV/AIDS Vaccine/Biological Product Research Concept into the Clinic: What are “cGMP”?

    PubMed Central

    Sheets, Rebecca L.; Rangavajhula, Vijaya; Pullen, Jeffrey K.; Butler, Chris; Mehra, Vijay; Shapiro, Stuart

    2015-01-01

    The Division of AIDS Vaccine Research Program funds the discovery and development of HIV/AIDS vaccine candidates. Basic researchers, having discovered a potential vaccine in the laboratory, next want to take that candidate into the clinic to test the concept in humans, to see if it translates. Many of them have heard of “cGMP” and know that they are supposed to make a “GMP product” to take into the clinic, but often they are not very familiar with what “cGMP” means and why these good practices are so important. As members of the Vaccine Translational Research Branch, we frequently get asked “can’t we use the material we made in the lab in the clinic?” or “aren’t Phase 1 studies exempt from cGMP?” Over the years, we have had many experiences where researchers or their selected contract manufacturing organizations have not applied an appropriate degree of compliance with cGMP suitable for the clinical phase of development. We share some of these experiences and the lessons learned, along with explaining the importance of cGMP, just what cGMP means, and what they can assure, in an effort to de-mystify this subject and facilitate the rapid and safe translational development of HIV vaccines. PMID:25698494

  13. Tuberculosis vaccines in clinical trials

    PubMed Central

    Rowland, Rosalind; McShane, Helen

    2011-01-01

    Effective prophylactic and/or therapeutic vaccination is a key strategy for controlling the global TB epidemic. The partial effectiveness of the existing TB vaccine, bacille Calmette–Guérin (BCG), suggests effective vaccination is possible and highlights the need for an improved vaccination strategy. Clinical trials are evaluating both modifications to the existing BCG immunization methods and also novel TB vaccines, designed to replace or boost BCG. Candidate vaccines in clinical development include live mycobacterial vaccines designed to replace BCG, subunit vaccines designed to boost BCG and therapeutic vaccines designed as an adjunct to chemotherapy. There is a great need for validated animal models, identification of immunological biomarkers of protection and field sites with the capacity for large-scale efficacy testing in order to develop and license a novel TB vaccine or regimen. PMID:21604985

  14. Status of vaccine research and development of vaccines for herpes simplex virus.

    PubMed

    Johnston, Christine; Gottlieb, Sami L; Wald, Anna

    2016-06-03

    Herpes simplex virus type-1 (HSV-1) and -2 (HSV-2) are highly prevalent global pathogens which commonly cause recurrent oral and genital ulcerations. Less common but more serious complications include meningitis, encephalitis, neonatal infection, and keratitis. HSV-2 infection is a significant driver of the HIV epidemic, increasing the risk of HIV acquisition 3 fold. As current control strategies for genital HSV-2 infection, including antiviral therapy and condom use, are only partially effective, vaccines will be required to reduce infection. Both preventive and therapeutic vaccines for HSV-2 are being pursued and are in various stages of development. We will provide an overview of efforts to develop HSV-2 vaccines, including a discussion of the clinical need for an HSV vaccine, and status of research and development with an emphasis on recent insights from trials of vaccine candidates in clinical testing. In addition, we will touch upon aspects of HSV vaccine development relevant to low and middle income countries. Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

  15. From research to phase III: preclinical, industrial and clinical development of the Sanofi Pasteur tetravalent dengue vaccine.

    PubMed

    Guy, Bruno; Barrere, Beatrice; Malinowski, Claire; Saville, Melanie; Teyssou, Remy; Lang, Jean

    2011-09-23

    Dengue vaccine development has reached a major milestone with the initiation, in 2010, of the first phase III clinical trial to investigate the Sanofi Pasteur CYD tetravalent dengue vaccine (TDV). The CYD TDV candidate is composed of four recombinant, live, attenuated vaccines (CYD-1-4) based on a yellow fever vaccine 17D (YFV 17D) backbone, each expressing the pre-membrane and envelope genes of one of the four dengue virus serotypes. The vaccine is genetically and phenotypically stable, non-hepatotropic, less neurovirulent than YFV 17D, and does not infect mosquitoes by the oral route. In vitro and in vivo preclinical studies showed that CYD TDV induces controlled stimulation of human dendritic cells, and significant immune responses in monkeys. Scale up and industrialization are being conducted in parallel with preclinical and clinical development to fulfill the needs of phase II/III trials, and to anticipate and facilitate supply and access to vaccine in the countries where the dengue disease burden makes it an urgent public health priority. The vaccine has now been administered to more than 6000 children and adults from dengue endemic and non-endemic areas and no safety concerns have arisen in any of the completed or ongoing trials. A three-dose vaccination regimen induces an immune response against all four serotypes in the large majority of vaccinees. Preexisting flavivirus immunity favors quicker and higher immune responses to CYD TDV, without adversely effecting clinical safety or increasing vaccine viremia. The observed level and nature of the cellular immune responses in humans are consistent with the good safety and immunogenicity profile of the vaccine. Preliminary results of an ongoing, proof-of-concept efficacy and large scale safety study in Thai children are expected by the end of 2012. Here we discuss the different steps and challenges of developing CYD TDV, from research to industrialization, and summarize some of the challenges to the successful

  16. Vaccination uptake by vaccine-hesitant parents attending a specialist immunization clinic in Australia.

    PubMed

    Forbes, Thomas A; McMinn, Alissa; Crawford, Nigel; Leask, Julie; Danchin, Margie

    2015-01-01

    Vaccine hesitancy (VH) is an issue of global concern. The quality of communication between healthcare providers and parents can influence parental immunization acceptance. We aimed to describe immunization uptake following specialist immunization clinic (SIC) consultation for Australian children of VH parents as a cohort, and according to pre-clinic parental position on immunization. At a single tertiary pediatric SIC (RCH, Melbourne) a retrospective descriptive study classified VH families according to 3 proposed parental positions on immunization at initial clinic attendance. Immunization status at follow up was ascertained via the Australian Children's Immunization Register and National HPV Program Register and compared between groups. Of the VH cohort, 13/38 (34%) families were classified as hesitant, 21 (55%) as late/selective vaccinators and 4 (11%) as vaccine refusers. Mean follow up post-SIC attendance was 14.5 months. For the overall VH cohort, the majority chose selective immunization (42%) following SIC consultation. When analyzed by pre-clinic parental position on immunization, there was a trend for hesitant families to proceed with full immunization, selective families to continue selective immunization and refusing families to remain unimmunised (p < 0.0001). The most commonly omitted vaccines were hepatitis B (66%) and Haemophilus influenzae type B (55%), followed by the meningococcal C conjugate vaccine (53%) and measles, mumps and rubella vaccine (53%). Immunization outcome appears to correlate with pre-clinic parental position on immunization for the majority of families attending a SIC in Australia, with selective immunization the most common outcome. Tailored communication approaches based on parental position on immunization may optimise clinic resources and engagement of families, but require prospective research evaluation.

  17. Vaccination uptake by vaccine-hesitant parents attending a specialist immunization clinic in Australia

    PubMed Central

    Forbes, Thomas A; McMinn, Alissa; Crawford, Nigel; Leask, Julie; Danchin, Margie

    2015-01-01

    Vaccine hesitancy (VH) is an issue of global concern. The quality of communication between healthcare providers and parents can influence parental immunization acceptance. We aimed to describe immunization uptake following specialist immunization clinic (SIC) consultation for Australian children of VH parents as a cohort, and according to pre-clinic parental position on immunization. At a single tertiary pediatric SIC (RCH, Melbourne) a retrospective descriptive study classified VH families according to 3 proposed parental positions on immunization at initial clinic attendance. Immunization status at follow up was ascertained via the Australian Children's Immunization Register and National HPV Program Register and compared between groups. Of the VH cohort, 13/38 (34%) families were classified as hesitant, 21 (55%) as late/selective vaccinators and 4 (11%) as vaccine refusers. Mean follow up post-SIC attendance was 14.5 months. For the overall VH cohort, the majority chose selective immunization (42%) following SIC consultation. When analyzed by pre-clinic parental position on immunization, there was a trend for hesitant families to proceed with full immunization, selective families to continue selective immunization and refusing families to remain unimmunised (p < 0.0001). The most commonly omitted vaccines were hepatitis B (66%) and Haemophilus influenzae type B (55%), followed by the meningococcal C conjugate vaccine (53%) and measles, mumps and rubella vaccine (53%). Immunization outcome appears to correlate with pre-clinic parental position on immunization for the majority of families attending a SIC in Australia, with selective immunization the most common outcome. Tailored communication approaches based on parental position on immunization may optimise clinic resources and engagement of families, but require prospective research evaluation. PMID:26366978

  18. 42 CFR 70.9 - Vaccination clinics.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Vaccination clinics. 70.9 Section 70.9 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES QUARANTINE, INSPECTION, LICENSING INTERSTATE QUARANTINE § 70.9 Vaccination clinics. (a) The Director may establish vaccination clinics, through...

  19. 42 CFR 70.9 - Vaccination clinics.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Vaccination clinics. 70.9 Section 70.9 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES QUARANTINE, INSPECTION, LICENSING INTERSTATE QUARANTINE § 70.9 Vaccination clinics. (a) The Director may establish vaccination clinics, through...

  20. 42 CFR 70.9 - Vaccination clinics.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false Vaccination clinics. 70.9 Section 70.9 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES QUARANTINE, INSPECTION, LICENSING INTERSTATE QUARANTINE § 70.9 Vaccination clinics. (a) The Director may establish vaccination clinics, through...

  1. Volunteer motivators for participating in HIV vaccine clinical trials in Nairobi, Kenya.

    PubMed

    Nyaoke, Borna A; Mutua, Gaudensia N; Sajabi, Rose; Nyasani, Delvin; Mureithi, Marianne W; Anzala, Omu A

    2017-01-01

    1.5 million Kenyans are living with HIV/AIDS as per 2015 estimates. Though there is a notable decline in new HIV infections, continued effort is still needed to develop an efficacious, accessible and affordable HIV vaccine. HIV vaccine clinical trials bear risks, hence a need to understand volunteer motivators for enrolment, retention and follow-up. Understanding the factors that motivate volunteers to participate in a clinical trial can help to strategize, refine targeting and thus increase enrolment of volunteers in future HIV vaccine clinical trials. The health belief model classifies motivators into social benefits such as 'advancing research' and collaboration with science, and personal benefits such as health benefits and financial interests. A thematic analysis was carried out on data obtained from four HIV clinical trials conducted at KAVI-Institute of Clinical Research in Nairobi Kenya from 2009 to 2015. Responses were obtained from a Questionnaire administered to the volunteers during their screening visit at the research site. Of the 281 healthy, HIV-uninfected volunteers participating in this study; 38% were motivated by personal benefits including, 31% motivated by health benefits and 7% motivated by possible financial gains. In addition, 62% of the volunteers were motivated by social benefits with 20% of who were seeking to help their family/society/world while 42% were interested in advancing research. The majority of volunteers in the HIV vaccine trials at our site were motivated by social benefits, suggesting that altruism can be a major contributor to participation in HIV vaccine studies. Personal benefits were a secondary motivator for the volunteers. The motivators to volunteer in HIV clinical trials were similar across ages, education level and gender. Education on what is needed (including volunteer participation) to develop an efficacious vaccine could be the key to greater volunteer motivation to participate in HIV vaccine clinical trials.

  2. Current status of registry of vaccine clinical trials conducted by Korean investigators in ClinicalTrials.gov, database of US National Institutes of Health.

    PubMed

    Cho, Jahyang; Kim, Bo Bae; Bae, Chong-Woo; Cha, Sung-Ho

    2013-01-01

    PubMed is not only includes international medical journals but also has a registration site for the ongoing clinical trials, such as ClinicalTrials.gov, under the supervision of US National Institutes of Health. We analyzed current status of vaccine clinical trials conducted by Korean investigators in database of ClinicalTrial.gov. As of October 2012, there are total of 72 trials found on registry of vaccine clinical trials conducted by Korean investigators in database of ClinicalTrial.gov. These trials were analyzed and classified by conditions of vaccine clinical trials, biologicals or drugs used in vaccine clinical trials, status of proceeding research, and list of sponsor and collaborators. Total 72 trials of vaccine clinical trials conducted by Korean investigators are classified by groups of infection (64 trials), cancer (4 trials), and others (4 trials). Infections group shown are as follows: poliomyelitis, pertussis, diphtheria, tetanus, and Haemophilus influenzae type b (10), influenza (9), human papillomavirus infection (8), pneumococcal vaccine (6), herpes zoster (4), smallpox (4), hepatitis B (4), etc. One trial of each in lung cancer, breast cancer, prostate cancer, and colorectal cancer are shown in cancer group. One trial of each in Crohn's disease, ulcerative colitis, renal failure, and rheumatoid arthritis are shown in other group. Vaccine clinical trials conducted by Korean investigators in ClinicalTrial.gov reflects the current status of Korean research on vaccine clinical trials at the international level and can indicate research progress. It is hoped that this aids the development of future vaccine clinical trials in Korea.

  3. Volunteer motivators for participating in HIV vaccine clinical trials in Nairobi, Kenya

    PubMed Central

    Mutua, Gaudensia N.; Sajabi, Rose; Nyasani, Delvin; Mureithi, Marianne W.; Anzala, Omu A.

    2017-01-01

    Background 1.5 million Kenyans are living with HIV/AIDS as per 2015 estimates. Though there is a notable decline in new HIV infections, continued effort is still needed to develop an efficacious, accessible and affordable HIV vaccine. HIV vaccine clinical trials bear risks, hence a need to understand volunteer motivators for enrolment, retention and follow-up. Understanding the factors that motivate volunteers to participate in a clinical trial can help to strategize, refine targeting and thus increase enrolment of volunteers in future HIV vaccine clinical trials. The health belief model classifies motivators into social benefits such as ‘advancing research’ and collaboration with science, and personal benefits such as health benefits and financial interests. Method A thematic analysis was carried out on data obtained from four HIV clinical trials conducted at KAVI-Institute of Clinical Research in Nairobi Kenya from 2009 to 2015. Responses were obtained from a Questionnaire administered to the volunteers during their screening visit at the research site. Results Of the 281 healthy, HIV-uninfected volunteers participating in this study; 38% were motivated by personal benefits including, 31% motivated by health benefits and 7% motivated by possible financial gains. In addition, 62% of the volunteers were motivated by social benefits with 20% of who were seeking to help their family/society/world while 42% were interested in advancing research. Conclusion The majority of volunteers in the HIV vaccine trials at our site were motivated by social benefits, suggesting that altruism can be a major contributor to participation in HIV vaccine studies. Personal benefits were a secondary motivator for the volunteers. The motivators to volunteer in HIV clinical trials were similar across ages, education level and gender. Education on what is needed (including volunteer participation) to develop an efficacious vaccine could be the key to greater volunteer motivation to

  4. Experience and challenges from clinical trials with malaria vaccines in Africa

    PubMed Central

    2013-01-01

    Malaria vaccines are considered amongst the most important modalities for potential elimination of malaria disease and transmission. Research and development in this field has been an area of intense effort by many groups over the last few decades. Despite this, there is currently no licensed malaria vaccine. Researchers, clinical trialists and vaccine developers have been working on many approached to make malaria vaccine available. African research institutions have developed and demonstrated a great capacity to undertake clinical trials in accordance to the International Conference on Harmonization-Good Clinical Practice (ICH-GCP) standards in the last decade; particularly in the field of malaria vaccines and anti-malarial drugs. This capacity is a result of networking among African scientists in collaboration with other partners; this has traversed both clinical trials and malaria control programmes as part of the Global Malaria Action Plan (GMAP). GMAP outlined and support global strategies toward the elimination and eradication of malaria in many areas, translating in reduction in public health burden, especially for African children. In the sub-Saharan region the capacity to undertake more clinical trials remains small in comparison to the actual need. However, sustainability of the already developed capacity is essential and crucial for the evaluation of different interventions and diagnostic tools/strategies for other diseases like TB, HIV, neglected tropical diseases and non-communicable diseases. There is urgent need for innovative mechanisms for the sustainability and expansion of the capacity in clinical trials in sub-Saharan Africa as the catalyst for health improvement and maintained. PMID:23496910

  5. Experience and challenges from clinical trials with malaria vaccines in Africa.

    PubMed

    Mwangoka, Grace; Ogutu, Bernhards; Msambichaka, Beverly; Mzee, Tutu; Salim, Nahya; Kafuruki, Shubis; Mpina, Maxmillian; Shekalaghe, Seif; Tanner, Marcel; Abdulla, Salim

    2013-03-04

    Malaria vaccines are considered amongst the most important modalities for potential elimination of malaria disease and transmission. Research and development in this field has been an area of intense effort by many groups over the last few decades. Despite this, there is currently no licensed malaria vaccine. Researchers, clinical trialists and vaccine developers have been working on many approached to make malaria vaccine available.African research institutions have developed and demonstrated a great capacity to undertake clinical trials in accordance to the International Conference on Harmonization-Good Clinical Practice (ICH-GCP) standards in the last decade; particularly in the field of malaria vaccines and anti-malarial drugs. This capacity is a result of networking among African scientists in collaboration with other partners; this has traversed both clinical trials and malaria control programmes as part of the Global Malaria Action Plan (GMAP). GMAP outlined and support global strategies toward the elimination and eradication of malaria in many areas, translating in reduction in public health burden, especially for African children. In the sub-Saharan region the capacity to undertake more clinical trials remains small in comparison to the actual need.However, sustainability of the already developed capacity is essential and crucial for the evaluation of different interventions and diagnostic tools/strategies for other diseases like TB, HIV, neglected tropical diseases and non-communicable diseases. There is urgent need for innovative mechanisms for the sustainability and expansion of the capacity in clinical trials in sub-Saharan Africa as the catalyst for health improvement and maintained.

  6. New clinical trial tests prime-and-boost vaccine delivery for advanced solid tumors | Center for Cancer Research

    Cancer.gov

    Researchers are testing a prime-and-boost approach to safely direct the immune system to kill tumor cells that express brachyury, a protein expressed in high levels in some cancers. A new clinical trial is testing an experimental vaccine in patients whose cancers have not responded to standard treatments.

  7. Clinical development of placental malaria vaccines and immunoassays harmonization: a workshop report.

    PubMed

    Chêne, Arnaud; Houard, Sophie; Nielsen, Morten A; Hundt, Sophia; D'Alessio, Flavia; Sirima, Sodiomon B; Luty, Adrian J F; Duffy, Patrick; Leroy, Odile; Gamain, Benoit; Viebig, Nicola K

    2016-09-17

    Placental malaria caused by Plasmodium falciparum infection constitutes a major health problem manifesting as severe disease and anaemia in the mother, impaired fetal development, low birth weight or spontaneous abortion. Prevention of placental malaria currently relies on two key strategies that are losing efficacy due to spread of resistance: long-lasting insecticide-treated nets and intermittent preventive treatment during pregnancy. A placental malaria vaccine would be an attractive, cost-effective complement to the existing control tools. Two placental malaria vaccine candidates are currently in Phase Ia/b clinical trials. During two workshops hosted by the European Vaccine Initiative, one in Paris in April 2014 and the other in Brussels in November 2014, the main actors in placental malaria vaccine research discussed the harmonization of clinical development plans and of the immunoassays with a goal to define standards that will allow comparative assessment of different placental malaria vaccine candidates. The recommendations of these workshops should guide researchers and clinicians in the further development of placental malaria vaccines.

  8. Vaccines 2.0 | Center for Cancer Research

    Cancer.gov

    In 1974, Jay A. Berzofsky, M.D., Ph.D., now Chief of CCR’s Vaccine Branch, came to NIH to study protein folding. His curious mind and collaborative spirit quickly led him into the intertwined fields of immunology and vaccine development. With close to 500 publications to his name, Berzofsky has pioneered the characterization of B- and T-cell epitopes and their modification to make vaccines directed against cancer and chronic infectious diseases. He has also characterized and taken advantage of the cellular and molecular regulators of immune responses in order to enhance tumor immunity and vaccine efficacy. In the last several years, he has translated many of these strategies into promising clinical trials. From the microcosm of his laboratory, he brings the same spirit of cross-fertilizing, bench-to-bedside research to leading the Vaccine Branch as a whole.

  9. The future of HIV vaccine research and the role of the Global HIV Vaccine Enterprise.

    PubMed

    Voronin, Yegor; Manrique, Amapola; Bernstein, Alan

    2010-09-01

    This review covers the role of the Global HIV Vaccine Enterprise (the Enterprise), an alliance of independent organizations committed to development of a safe and effective HIV vaccine. It discusses the history, impact on the field, and future directions and initiatives of the alliance in the context of recent progress in HIV vaccine research and development. Significant progress has been made in the field since the release of the 2005 Scientific Strategic Plan (the Plan) of the Enterprise. Over the last year, the Enterprise embarked on an impact assessment of the 2005 Plan and the development of the 2010 Plan. Enterprise Working Groups identified key priorities in the field, several of which are discussed in this review, including changing the nature, purpose and process of clinical trials, increasing and facilitating data sharing, and optimizing existing and mobilizing new resources. This time is an important moment in HIV vaccine research. New clinical trial and laboratory results have created new opportunities to advance the search for an HIV vaccine and reinvigorated the field. The Enterprise will publish its 2010 Plan this year, providing a framework for setting new priorities and directions and encouraging new and existing partners to embark on a shared scientific agenda.

  10. DNA vaccination for prostate cancer, from preclinical to clinical trials - where we stand?

    PubMed Central

    2012-01-01

    Development of various vaccines for prostate cancer (PCa) is becoming an active research area. PCa vaccines are perceived to have less toxicity compared with the available cytotoxic agents. While various immune-based strategies can elicit anti-tumour responses, DNA vaccines present increased efficacy, inducing both humoural and cellular immunity. This immune activation has been proven effective in animal models and initial clinical trials are encouraging. However, to validate the role of DNA vaccination in currently available PCa management paradigms, strong clinical evidence is still lacking. This article provides an overview of the basic principles of DNA vaccines and aims to provide a summary of preclinical and clinical trials outlining the benefits of this immunotherapy in the management of PCa. PMID:23046944

  11. Resolving legal, ethical, and human rights challenges in HIV vaccine research.

    PubMed

    Patterson, D

    2000-01-01

    In the absence of a cure for AIDS, attention has turned to the possibility of developing a preventive vaccine for HIV infection. Yet many scientific, ethical, legal, and economic obstacles remain. At the current rate, the development and production of an effective vaccine could take 15 to 20 years or longer. If tens of millions more HIV infections and deaths are to be avoided in the coming decades, vaccine research needs to be greatly expedited. Furthermore, it must be undertaken ethically, and the products of this research must benefit people in developing countries. This article, an edited and updated version of a paper presented at "Putting Third First," addresses challenges arising in HIV preventive vaccine research in developing countries. It does not address clinical research in developing countries relating to treatments or therapeutic vaccines. Nor does it address legal and ethical issues relating to HIV vaccine research in industrialized countries, although similar issues arise in both contexts. The article concludes that while ethical codes are silent on the obligation to undertake research and development, international law provides strong legal obligations--particularly with regard to industrialized states--that should be invoked to accelerate HIV vaccine development, and distribution.

  12. Heterologous Prime-Boost HIV-1 Vaccination Regimens in Pre-Clinical and Clinical Trials

    PubMed Central

    Brown, Scott A.; Surman, Sherri L.; Sealy, Robert; Jones, Bart G.; Slobod, Karen S.; Branum, Kristen; Lockey, Timothy D.; Howlett, Nanna; Freiden, Pamela; Flynn, Patricia; Hurwitz, Julia L.

    2010-01-01

    Currently, there are more than 30 million people infected with HIV-1 and thousands more are infected each day. Vaccination is the single most effective mechanism for prevention of viral disease, and after more than 25 years of research, one vaccine has shown somewhat encouraging results in an advanced clinical efficacy trial. A modified intent-to-treat analysis of trial results showed that infection was approximately 30% lower in the vaccine group compared to the placebo group. The vaccine was administered using a heterologous prime-boost regimen in which both target antigens and delivery vehicles were changed during the course of inoculations. Here we examine the complexity of heterologous prime-boost immunizations. We show that the use of different delivery vehicles in prime and boost inoculations can help to avert the inhibitory effects caused by vector-specific immune responses. We also show that the introduction of new antigens into boost inoculations can be advantageous, demonstrating that the effect of ‘original antigenic sin’ is not absolute. Pre-clinical and clinical studies are reviewed, including our own work with a three-vector vaccination regimen using recombinant DNA, virus (Sendai virus or vaccinia virus) and protein. Promising preliminary results suggest that the heterologous prime-boost strategy may possibly provide a foundation for the future prevention of HIV-1 infections in humans. PMID:20407589

  13. Conflicts of interest in vaccine safety research.

    PubMed

    DeLong, Gayle

    2012-01-01

    Conflicts of interest (COIs) cloud vaccine safety research. Sponsors of research have competing interests that may impede the objective study of vaccine side effects. Vaccine manufacturers, health officials, and medical journals may have financial and bureaucratic reasons for not wanting to acknowledge the risks of vaccines. Conversely, some advocacy groups may have legislative and financial reasons to sponsor research that finds risks in vaccines. Using the vaccine-autism debate as an illustration, this article details the conflicts of interest each of these groups faces, outlines the current state of vaccine safety research, and suggests remedies to address COIs. Minimizing COIs in vaccine safety research could reduce research bias and restore greater trust in the vaccine program.

  14. Animal Models for Salmonellosis: Applications in Vaccine Research

    PubMed Central

    Higginson, Ellen E.; Simon, Raphael

    2016-01-01

    Salmonellosis remains an important cause of human disease worldwide. While there are several licensed vaccines for Salmonella enterica serovar Typhi, these vaccines are generally ineffective against other Salmonella serovars. Vaccines that target paratyphoid and nontyphoidal Salmonella serovars are very much in need. Preclinical evaluation of candidate vaccines is highly dependent on the availability of appropriate scientific tools, particularly animal models. Many different animal models exist for various Salmonella serovars, from whole-animal models to smaller models, such as those recently established in insects. Here, we discuss various mouse, rat, rabbit, calf, primate, and insect models for Salmonella infection, all of which have their place in research. However, choosing the right model is imperative in selecting the best vaccine candidates for further clinical testing. In this minireview, we summarize the various animal models that are used to assess salmonellosis, highlight some of the advantages and disadvantages of each, and discuss their value in vaccine development. PMID:27413068

  15. The Future of HIV Vaccine Research and the Role of the Global HIV Vaccine Enterprise

    PubMed Central

    Voronin, Yegor; Manrique, Amapola; Bernstein, Alan

    2010-01-01

    Purpose of review This review covers the role of the Global HIV Vaccine Enterprise (the Enterprise), an alliance of independent organizations committed to development of a safe and effective HIV vaccine. It discussesthe history, impact on the field and future directions and initiatives of the alliance, in the context of recent progress in HIV vaccine research and development. Recent Findings Significant progress has been made in the field since the release of the 2005 Scientific Strategic Plan (The Plan) of the Enterprise. Over the last year, the Enterprise embarked on an impact assessment of the 2005 Planand the development of the 2010 Plan. Enterprise Working Groups identified key priorities in the field, several of which are discussed in this review, including: changing the nature, purpose and process of clinical trials; increasing and facilitating data sharing; and optimizing existing and attracting new resources. Summary This isan important moment in HIV vaccine research. New clinical trial and laboratory results have created new opportunities to advance the search for an HIV vaccineand reinvigorated the field. The Enterprise will publish its 2010 Scientific Strategic Planthis year, providinga framework for setting new priorities and directions, and encouraging new and existing partners to embark on a shared scientific agenda. PMID:20978383

  16. Current status of Zika vaccine development: Zika vaccines advance into clinical evaluation.

    PubMed

    Barrett, Alan D T

    2018-01-01

    Zika virus (ZIKV), a mosquito-borne flavivirus, was first identified in the 1940s in Uganda in Africa and emerged in the Americas in Brazil in May 2015. In the 30 months since ZIKV emerged as a major public health problem, spectacular progress has been made with vaccine development cumulating with the publication of three reports of phase 1 clinical trials in the 4th quarter of 2017. Clinical trials involving candidate DNA and purified inactivated virus vaccines showed all were safe and well-tolerated in the small number of volunteers and all induced neutralizing antibodies, although these varied by vaccine candidate and dosing regimen. These results suggest that a Zika vaccine can be developed and that phase 2 clinical trials are warranted. However, it is difficult to compare the results from the different phase 1 studies or with neutralizing antibodies induced by licensed flavivirus vaccines (Japanese encephalitis, tick-borne encephalitis, and yellow fever) as neutralizing antibody assays vary and, unfortunately, there are no standards for Zika virus neutralizing antibodies. In addition to clinical studies, substantial progress continues to be made in nonclinical development, particularly in terms of the ability of candidate vaccines to protect reproductive tissues, and the potential use of monoclonal antibodies for passive prophylaxis.

  17. Examining dog owners' beliefs regarding rabies vaccination during government-funded vaccine clinics in Grenada to improve vaccine coverage rates.

    PubMed

    Thomas, D; Delgado, A; Louison, B; Lefrancois, T; Shaw, J

    2013-07-01

    Vaccination of domestic pets is an important component of rabies control and prevention in countries where the disease is maintained in a wildlife reservoir. In Grenada, vaccine coverage rates were low, despite extensive public education and advertising of government-sponsored vaccine clinics where rabies vaccine is administered to animals at no cost to animal owners. Information was needed on reasons for decreased dog owner participation in government-funded rabies vaccination clinics. A total of 120 dog owners from 6 different parishes were asked to complete a questionnaire assessing their currently held beliefs about rabies vaccination and perception of the risk posed by rabies. Over 70% of respondents believed that problems in the organization and management of clinic sites could allow for fighting between dogs or disease spread among dogs, while 35% of owners did not believe that they had the ability or adequate help to bring their dogs to the clinic sites. Recommendations for improving vaccine coverage rates included: improved scheduling of clinic sites and dates; increased biosecurity at clinic locations; focused advertising on the availability of home visits, particularly for aggressive dogs or dogs with visible skin-related diseases such as mange; and the recruitment of community volunteers to assist with bringing dogs to the clinic sites. Copyright © 2013. Published by Elsevier B.V.

  18. Physician Attitudes Regarding School-Located Vaccination Clinics

    ERIC Educational Resources Information Center

    Fiala, Steven C.; Cieslak, Paul R.; DeBess, Emilio E.; Young, Collette M.; Winthrop, Kevin L.; Stevenson, Ellen B.

    2013-01-01

    Background: School-located vaccination clinics offer an opportunity to target children for vaccination programs during communicable disease outbreaks. However, children in the United States are primarily vaccinated in the pediatrician's or family physician's office, and the concept of school-located vaccinations may be unfamiliar to some parents…

  19. Status of vaccine research and development of vaccines for leishmaniasis.

    PubMed

    Gillespie, Portia M; Beaumier, Coreen M; Strych, Ulrich; Hayward, Tara; Hotez, Peter J; Bottazzi, Maria Elena

    2016-06-03

    A number of leishmaniasis vaccine candidates are at various stages of pre-clinical and clinical development. Leishmaniasis is a vector-borne neglected tropical disease (NTD) caused by a protozoan parasite of the genus Leishmania and transmitted to humans by the bite of a sand fly. Visceral leishmaniasis (VL, kala-azar) is a high mortality NTD found mostly in South Asia and East Africa, while cutaneous leishmaniasis (CL) is a disfiguring NTD highly endemic in the Middle East, Central Asia, North Africa, and the Americas. Estimates attribute 50,000 annual deaths and 3.3 million disability-adjusted life years to leishmaniasis. There are only a few approved drug treatments, no prophylactic drug and no vaccine. Ideally, an effective vaccine against leishmaniasis will elicit long-lasting immunity and protect broadly against VL and CL. Vaccines such as Leish-F1, F2 and F3, developed at IDRI and designed based on selected Leishmania antigen epitopes, have been in clinical trials. Other groups, including the Sabin Vaccine Institute in collaboration with the National Institutes of Health are investigating recombinant Leishmania antigens in combination with selected sand fly salivary gland antigens in order to augment host immunity. To date, both VL and CL vaccines have been shown to be cost-effective in economic modeling studies. Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

  20. Establishment of a research pharmacy to support Ebola clinical research in Liberia.

    PubMed

    Pierson, Jerome F; Kirchoff, Matthew Carl; Tyee, Rev Tijli; Montello, Michael J; Rhie, Julie K

    This article describes the establishment of a research pharmacy to support the Partnership for Research on Ebola Vaccines in Liberia (PREVAIL) vaccine study for Ebola virus disease. This article describes the establishment of the pharmacy element to support the overall research program during an Ebola outbreak in Monrovia, Liberia, in 2014 and 2015. The need for the rapid establishment of infrastructure to support the Liberia-United States joint clinical research partnership in response to the emerging Ebola virus disease provided the opportunity for collaboration among Liberian and U.S. pharmacists. Resource austere and research naïve. Research pharmacy prepared and randomized 1500 vaccinations in support of PREVAIL. Experiences of the Liberian and U.S. pharmacists involved in the program are described. The partnership was successful in the conduct of the study. More importantly, the capacity for Liberian pharmacists to support clinical research was established. In addition, the U.S. team learned several important lessons that will help prepare them for responding to research needs in future infectious disease outbreaks. Published by Elsevier Inc.

  1. TBVAC2020: Advancing Tuberculosis Vaccines from Discovery to Clinical Development.

    PubMed

    Kaufmann, Stefan H E; Dockrell, Hazel M; Drager, Nick; Ho, Mei Mei; McShane, Helen; Neyrolles, Olivier; Ottenhoff, Tom H M; Patel, Brij; Roordink, Danielle; Spertini, François; Stenger, Steffen; Thole, Jelle; Verreck, Frank A W; Williams, Ann

    2017-01-01

    TBVAC2020 is a research project supported by the Horizon 2020 program of the European Commission (EC). It aims at the discovery and development of novel tuberculosis (TB) vaccines from preclinical research projects to early clinical assessment. The project builds on previous collaborations from 1998 onwards funded through the EC framework programs FP5, FP6, and FP7. It has succeeded in attracting new partners from outstanding laboratories from all over the world, now totaling 40 institutions. Next to the development of novel vaccines, TB biomarker development is also considered an important asset to facilitate rational vaccine selection and development. In addition, TBVAC2020 offers portfolio management that provides selection criteria for entry, gating, and priority settings of novel vaccines at an early developmental stage. The TBVAC2020 consortium coordinated by TBVI facilitates collaboration and early data sharing between partners with the common aim of working toward the development of an effective TB vaccine. Close links with funders and other consortia with shared interests further contribute to this goal.

  2. TBVAC2020: Advancing Tuberculosis Vaccines from Discovery to Clinical Development

    PubMed Central

    Kaufmann, Stefan H. E.; Dockrell, Hazel M.; Drager, Nick; Ho, Mei Mei; McShane, Helen; Neyrolles, Olivier; Ottenhoff, Tom H. M.; Patel, Brij; Roordink, Danielle; Spertini, François; Stenger, Steffen; Thole, Jelle; Verreck, Frank A. W.; Williams, Ann; Britton, Warwick

    2017-01-01

    TBVAC2020 is a research project supported by the Horizon 2020 program of the European Commission (EC). It aims at the discovery and development of novel tuberculosis (TB) vaccines from preclinical research projects to early clinical assessment. The project builds on previous collaborations from 1998 onwards funded through the EC framework programs FP5, FP6, and FP7. It has succeeded in attracting new partners from outstanding laboratories from all over the world, now totaling 40 institutions. Next to the development of novel vaccines, TB biomarker development is also considered an important asset to facilitate rational vaccine selection and development. In addition, TBVAC2020 offers portfolio management that provides selection criteria for entry, gating, and priority settings of novel vaccines at an early developmental stage. The TBVAC2020 consortium coordinated by TBVI facilitates collaboration and early data sharing between partners with the common aim of working toward the development of an effective TB vaccine. Close links with funders and other consortia with shared interests further contribute to this goal. PMID:29046674

  3. Malaria vaccine research and development: the role of the WHO MALVAC committee

    PubMed Central

    2013-01-01

    The WHO Malaria Vaccine Advisory Committee (MALVAC) provides advice to WHO on strategic priorities, activities and technical issues related to global efforts to develop vaccines against malaria. MALVAC convened a series of meetings to obtain expert, impartial consensus views on the priorities and best practice for vaccine-related research and development strategies. The technical areas covered during these consultations included: guidance on clinical trial design for candidate sporozoite and asexual blood stage vaccines; measures of efficacy of malaria vaccines in Phase IIb and Phase III trials; standardization of immunoassays; the challenges of developing assays and designing trials for interventions against malaria transmission; modelling impact of anti-malarial interventions; whole organism malaria vaccines, and Plasmodium vivax vaccine-related research and evaluation. These informed discussions and opinions are summarized here to provide guidance on harmonization of strategies to help ensure high standards of practice and comparability between centres and the outcome of vaccine trials. PMID:24112689

  4. The growth of retail clinics in vaccination delivery in the U.S.

    PubMed

    Uscher-Pines, Lori; Harris, Katherine M; Burns, Rachel M; Mehrotra, Ateev

    2012-07-01

    Retail clinics are a promising venue in which to promote and administer vaccinations; however, little is known about who receives vaccinations at a retail clinic. The aim of this paper was to describe the use of retail clinics in the delivery of recommended vaccinations. The three largest retail clinic operators in the U.S.--MinuteClinic, TakeCare, and LittleClinic--provided de-identified clinic data for 2007-2009. Descriptive statistics were generated in 2011 on visit type, type of vaccination, patient age, and payment method. From 2007 to 2009, there were 8.9 million retail clinic visits across the three largest clinic operators. In 2009, vaccinations were administered at 1,952,610 visits, up from 469,330 visits in 2007. Visits in which vaccinations were administered accounted for 39.9%, 36.4%, and 42.0% of total visits in 2007, 2008, and 2009, respectively. In 2009, 1.8 million influenza vaccinations (including seasonal and H1N1 vaccinations) were administered by the two largest retail clinic operators (94% of all vaccination visits). Pneumococcal vaccination was administered at 59,849 visits (3% of all vaccination visits). In 2009, vaccinations were also administered in 0.8% of acute care visits (n=18,807); 0.8% of chronic care visits (n=261); and 1.3% of general medical exams (n=2497). Results suggest that retail clinics play a growing role in vaccination delivery, and vaccinations constitute a substantial share of the business conducted by retail clinics. As such, retail clinics have the potential to play an important role in vaccination delivery in the U.S. Retail clinics potentially could deliver more vaccinations if they reviewed vaccination histories and counseled patients regarding the benefits of vaccination during acute care visits. Copyright © 2012 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  5. Clinical safety issues of measles, mumps and rubella vaccines.

    PubMed Central

    Afzal, M. A.; Minor, P. D.; Schild, G. C.

    2000-01-01

    The clinical safety of measles and measles-mumps-rubella vaccines has been questioned in recent reports that propose a possible link between measles virus or measles vaccines and the occurrence of juvenile Crohn disease and autism. This article reviews the outcomes of several laboratory investigations which were carried out independently to identify the presence or absence of measles virus in the intestinal tissues derived from cases of inflammatory bowel disease. One research group reported the presence of measles virus particles and genomic RNA in inflammatory bowel disease tissues, but this could not be confirmed by other groups, despite use of techniques that are highly specific and sensitive for the detection of measles virus nucleic acid in clinical specimens down to the molecular level. Based on the published data reviewed here, it can be concluded that there is no direct association between measles virus or measles vaccines and the development of Crohn disease, a conclusion which is supported by most epidemiological findings. PMID:10743285

  6. Tularemia vaccine: Safety, reactogenicity, "Take" skin reactions, and antibody responses following vaccination with a new lot of the Francisella tularensis live vaccine strain - A phase 2 randomized clinical Trial.

    PubMed

    Mulligan, Mark J; Stapleton, Jack T; Keitel, Wendy A; Frey, Sharon E; Chen, Wilbur H; Rouphael, Nadine; Edupuganti, Srilatha; Beck, Allison; Winokur, Patricia L; El Sahly, Hana M; Patel, Shital M; Atmar, Robert L; Graham, Irene; Anderson, Edwin; El-Kamary, Samer S; Pasetti, Marcela F; Sztein, Marcelo B; Hill, Heather; Goll, Johannes B

    2017-08-24

    Tularemia is caused by Francisella tularensis, a gram-negative bacterium that has been weaponized as an aerosol. For protection of personnel conducting biodefense research, the United States Army required clinical evaluation of a new lot of tularemia live vaccine strain manufactured in accordance with Current Good Manufacturing Practices. A phase 2 randomized clinical trial compared the new lot (DVC-LVS) to the existing vaccine that has been in use for decades (USAMRIID-LVS). The vaccines were delivered by scarification to 228 participants. Safety, reactogenicity, take and/or antibody levels were assessed on days 0, 1, 2, 8, 14, 28, 56, and 180. Both vaccines were safe and had acceptable reactogenicity profiles during six months of follow-up. There were no serious or grade 3 and 4 laboratory adverse events. Moderate systemic reactogenicity (mostly headache or feeling tired) was reported by ∼23% of participants receiving either vaccine. Injection site reactogenicity was mostly mild itchiness and pain. The frequencies of vaccine take skin reactions were 73% (95% CI, 64, 81) for DVC-LVS and 80% (95% CI, 71, 87) for USAMRIID-LVS. The 90% CI for the difference in proportions was -6.9% (-16.4, 2.6). The rates of seroconversion measured by microagglutination assay on days 28 or 56 were 94% (95% CI, 88, 98; n=98/104) for DVC-LVS and 94% (95% CI, 87, 97; n=103/110) for USAMRIID-LVS (p=1.00). Day 14 sera revealed more rapid seroconversion for DVC-LVS relative to USAMRIID-LVS: 82% (95% CI, 73, 89) versus 55% (95% CI, 45, 65), respectively (p<0.0001). The DVC-LVS vaccine had similar safety, reactogenicity, take and antibody responses compared to the older USAMRIID vaccine, and was superior for early (day 14) antibody production. Vaccination take was not a sensitive surrogate for seroconversion in a multi-center study where personnel at five research clinics performed assessments. ClinicalTrials.gov identifier NCT01150695. Copyright © 2017 The Authors. Published by Elsevier

  7. Size of clinical trials and Introductory prices of prophylactic vaccine series

    PubMed Central

    Weinberg, Steven H.; Butchart, Amy T.; Davis, Matthew M.

    2012-01-01

    Costs of completing the recommended immunization schedule have increased over the last decade. Access to prophylactic vaccines may become limited due to financing obstacles within current delivery systems. Vaccine prices reflect research and development expenses incurred by vaccine manufacturers, including costs associated with evaluating candidate vaccines in human subjects. If the number of subjects in clinical trials is increasing over time and associated with vaccine price, this may help explain increases in prices of vaccine series. We examined whether: (A) the initial public- and private-sector prices for recommended prophylactic vaccine series licensed and recommended in the US increased from 2000–2011, (B) the number of human subjects per licensed vaccine increased during the time period, and (C) the number of human subjects was associated with the initial public–and private–sector prices of the vaccine series. In regression analyses of 13 vaccines, approval year was not significantly associated with the number of human subjects, initial public-sector prices, or initial private-sector prices. While the number of phase II subjects was not significantly associated with prices, the numbers of phase III and combined late phase (phases II + III) subjects were significantly associated with initial public- and private-sector series prices (p < 0.05). The association between number of subjects and initial prices demonstrated diminishing marginal increases in price with increasing numbers of subjects. These findings may help guide the number of subjects required by the FDA in clinical trials, in order to reduce expenses for manufacturers and thereby help mitigate increases in initial vaccine series prices. PMID:22854668

  8. Size of clinical trials and Introductory prices of prophylactic vaccine series.

    PubMed

    Weinberg, Steven H; Butchart, Amy T; Davis, Matthew M

    2012-08-01

    Costs of completing the recommended immunization schedule have increased over the last decade. Access to prophylactic vaccines may become limited due to financing obstacles within current delivery systems. Vaccine prices reflect research and development expenses incurred by vaccine manufacturers, including costs associated with evaluating candidate vaccines in human subjects. If the number of subjects in clinical trials is increasing over time and associated with vaccine price, this may help explain increases in prices of vaccine series. We examined whether: (A) the initial public- and private-sector prices for recommended prophylactic vaccine series licensed and recommended in the US increased from 2000-2011, (B) the number of human subjects per licensed vaccine increased during the time period, and (C) the number of human subjects was associated with the initial public-and private-sector prices of the vaccine series. In regression analyses of 13 vaccines, approval year was not significantly associated with the number of human subjects, initial public-sector prices, or initial private-sector prices. While the number of phase II subjects was not significantly associated with prices, the numbers of phase III and combined late phase (phases II + III) subjects were significantly associated with initial public- and private-sector series prices (p < 0.05). The association between number of subjects and initial prices demonstrated diminishing marginal increases in price with increasing numbers of subjects. These findings may help guide the number of subjects required by the FDA in clinical trials, in order to reduce expenses for manufacturers and thereby help mitigate increases in initial vaccine series prices.

  9. Status of vaccine research and development of vaccines for malaria.

    PubMed

    Birkett, Ashley J

    2016-06-03

    Despite recent progress in reducing deaths attributable to malaria, it continues to claim approximately 500,000 lives per year and is associated with approximately 200 million infections. New tools, including safe and effective vaccines, are needed to ensure that the gains of the last 15 years are leveraged toward achieving the ultimate goal of malaria parasite eradication. In 2015, the European Medicines Agency announced the adoption of a positive opinion for the malaria vaccine candidate most advanced in development, RTS,S/AS01, which provides modest protection against clinical malaria; in early 2016, WHO recommended large-scale pilot implementations of RTS,S in settings of moderate-to-high malaria transmission. In alignment with these advancements, the community goals and preferred product characteristics for next-generation vaccines have been updated to inform the development of vaccines that are highly efficacious in preventing clinical malaria, and those needed to accelerate parasite elimination. Next-generation vaccines, targeting all stages of the parasite lifecycle, are in early-stage development with the most advanced in Phase 2 trials. Importantly, progress is being made in the definition of feasible regulatory pathways to accelerate timelines, including for vaccines designed to interrupt transmission of parasites from humans to mosquitoes. The continued absence of financially lucrative, high-income markets to drive investment in malaria vaccine development points to continued heavy reliance on public and philanthropic funding. Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

  10. Status of vaccine research and development of vaccines for Staphylococcus aureus.

    PubMed

    Giersing, Birgitte K; Dastgheyb, Sana S; Modjarrad, Kayvon; Moorthy, Vasee

    2016-06-03

    Staphylococcus aureus is a highly versatile gram positive bacterium that is resident as an asymptomatic colonizer on the skin and in the nasopharynx of approximately 30% of individuals. Nasopharyngeal colonization is a risk for acquiring S. aureus infections, which can cause a range of clinical symptoms that are commonly associated with skin and soft-tissue infections. The emergence of S. aureus strains that are highly resistant to antimicrobials has recently become a major public health concern. In low-income countries the incidence of S. aureus disease is highest in neonates and children up to one year of age and mortality rates are estimated to be up to 50%. In the United States, S. aureus infection accounts for approximately 300,000 hospitalizations per year. A vaccine against multi-drug resistant S. aureus, therefore, is urgently needed. Two vaccine candidates have previously been evaluated in late-stage clinical trials but have not demonstrated efficacy. At present, one vaccine candidate and two monoclonal antibody are undergoing clinical evaluation in target groups at high risk for S. aureus infection. This review provides an overview of current vaccine development efforts and presents the major technical and regulatory challenges to developing a licensed S. aureus vaccine. Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

  11. Evaluation of vaccines against enteric infections: a clinical and public health research agenda for developing countries

    PubMed Central

    Clemens, John

    2011-01-01

    Enteric infections are a major cause of morbidity and mortality in developing countries. To date, vaccines have played a limited role in public health efforts to control enteric infections. Licensed vaccines exist for cholera and typhoid, but these vaccines are used primarily for travellers; and there are two internationally licensed vaccines for rotavirus, but they are mainly used in affluent countries. The reasons that enteric vaccines are little used in developing countries are multiple, and certainly include financial and political constraints. Also important is the need for more cogent evidence on the performance of enteric vaccines in developing country populations. A partial inventory of research questions would include: (i) does the vaccine perform well in the most relevant settings? (ii) does the vaccine perform well in all epidemiologically relevant age groups? (iii) is there adequate evidence of vaccine safety once the vaccines have been deployed in developing countries? (iv) how effective is the vaccine when given in conjunction with non-vaccine cointerventions? (v) what is the level of vaccine protection against all relevant outcomes? and (vi) what is the expected population level of vaccine protection, including both direct and herd vaccine protective effects? Provision of evidence addressing these questions will help expand the use of enteric vaccines in developing countries. PMID:21893543

  12. Testing vaccines in pediatric research subjects.

    PubMed

    Jacobson, Robert M; Ovsyannikova, Inna G; Poland, Gregory A

    2009-05-26

    Past difficulties encountered in pediatric vaccine research have positively influenced the development of modern regulations of human subjects' research. These regulations permit pediatric research but impose special restrictions on the types of studies to which children may participate, and these restrictions have important implications for modern vaccine trials. These ethical issues pose real but surmountable concerns. Considerations also include the use of placebos, critical for trial design but an impediment to parental permission. Recent pediatric vaccine studies illustrate practical alternatives to placebos that preserve allocation concealment and blinding yet obtain parental support. Vaccine researchers must consider the role parents play, not just in giving formal permission for their children's participation, but also for their roles in active recruitment, successful retention, and data acquisition. Studies of parents' attitudes do identify consistencies among motivating forces that drive parents to participate or refuse their children's participation. These studies should influence how we design and execute pediatric vaccine trials. Finally, ethical considerations and current regulations raise certain issues concerning the remuneration of the research volunteer when that volunteer is a child. The published literature illustrates wide variation in practice. Better understanding of the restrictions in pediatric research, the use of placebos, the attitude of parents, and the concerns with remuneration can better equip the vaccine researcher in pursuing successful studies in children.

  13. Cancer vaccine characterization: from bench to clinic.

    PubMed

    de la Luz-Hernández, K; Rabasa, Y; Montesinos, R; Fuentes, D; Santo-Tomás, J F; Morales, O; Aguilar, Y; Pacheco, B; Castillo, A

    2014-05-19

    The development of safe, effective, and affordable vaccines has become a global effort due to its vast impact on overall world health conditions. A brief overview of vaccine characterization techniques, especially in the area of high-resolution mass spectrometry, is presented. It is highly conceivable that the proper use of advanced technologies such as high-resolution mass spectrometry, along with the appropriate chemical and physical property evaluations, will yield tremendous in-depth scientific understanding for the characterization of vaccines in various stages of vaccine development. This work presents the physicochemical and biological characterization of cancer vaccine Racotumomab/alumina, a murine anti-idiotypic antibody that mimics N-glycolyl-GM3 gangliosides. This antibody has been tested as an anti-idiotypic cancer vaccine, adjuvated in Al(OH)3, in several clinical trials for melanoma, breast, and lung cancer. Racotumomab was obtained from ascites fluid, transferred to fermentation in stirred tank at 10 L and followed to a scale up to 41 L. The mass spectrometry was used for the determination of intact molecule, light and heavy chains masses; amino acids sequence analysis, N- and C-terminal, glycosylation and posttranslational modifications. Also we used the DLS for the size distribution and zeta potential analysis. The biological analyses were performed in mice and chickens. We observed differences in glycosylation pattern, charge heterogeneity and structural stability between in vivo-produced and bioreactor-obtained Racotumomab products. Interestingly, these modifications had no significant impact on the immune responses elicited in two different animal models. We are demonstrated that this approach could potentially be more efficient and effective for supporting vaccine research and development. Copyright © 2014. Published by Elsevier Ltd.

  14. Fact and fiction in tuberculosis vaccine research: 10 years later.

    PubMed

    Kaufmann, Stefan H E

    2011-08-01

    Tuberculosis is one of the most deadly infectious diseases. The situation is worsening because of co-infection with HIV and increased occurrence of drug resistance. Although the BCG vaccine has been in use for 90 years, protection is insufficient; new vaccine candidates are therefore needed. 12 potential vaccines have gone into clinical trials. Ten are aimed at prevention of tuberculosis and, of these, seven are subunit vaccines either as adjuvanted or viral-vectored antigens. These vaccines would be boosters of BCG-prime vaccination. Three vaccines are recombinant BCG constructs-possible replacements for BCG. Additional vaccine candidates will enter clinical trials in the near future, including postexposure vaccines for individuals with latent infection. In the long term, vaccines that prevent or eradicate infection with Mycobacterium tuberculosis would be the best possible option. Improved knowledge of immunology, molecular microbiology, cell biology, biomics, and biotechnology has paved the way towards an effective and safe vaccine against tuberculosis. The pipeline of new vaccine candidates from preclinical to clinical testing could be accelerated by development of biomarkers that can predict the clinical outcome of tuberculosis. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Vaccines for Leprosy and Tuberculosis: Opportunities for Shared Research, Development, and Application

    PubMed Central

    Coppola, Mariateresa; van den Eeden, Susan J. F.; Robbins, Naoko; Wilson, Louis; Franken, Kees L. M. C.; Adams, Linda B.; Gillis, Tom P.; Ottenhoff, Tom H. M.; Geluk, Annemieke

    2018-01-01

    Tuberculosis (TB) and leprosy still represent significant public health challenges, especially in low- and lower middle-income countries. Both poverty-related mycobacterial diseases require better tools to improve disease control. For leprosy, there has been an increased emphasis on developing tools for improved detection of infection and early diagnosis of disease. For TB, there has been a similar emphasis on such diagnostic tests, while increased research efforts have also focused on the development of new vaccines. Bacille Calmette–Guérin (BCG), the only available TB vaccine, provides insufficient and inconsistent protection to pulmonary TB in adults. The impact of BCG on leprosy, however, is significant, and the introduction of new TB vaccines that might replace BCG could, therefore, have serious impact also on leprosy. Given the similarities in antigenic makeup between the pathogens Mycobacterium tuberculosis (Mtb) and M. leprae, it is well possible, however, that new TB vaccines could cross-protect against leprosy. New TB subunit vaccines currently evaluated in human phase I and II studies indeed often contain antigens with homologs in M. leprae. In this review, we discuss pre-clinical studies and clinical trials of subunit or whole mycobacterial vaccines for TB and leprosy and reflect on the development of vaccines that could provide protection against both diseases. Furthermore, we provide the first preclinical evidence of such cross-protection by Mtb antigen 85B (Ag85B)-early secretory antigenic target (ESAT6) fusion recombinant proteins in in vivo mouse models of Mtb and M. leprae infection. We propose that preclinical integration and harmonization of TB and leprosy research should be considered and included in global strategies with respect to cross-protective vaccine research and development. PMID:29535713

  16. Pre-clinical and clinical development of the first placental malaria vaccine.

    PubMed

    Pehrson, Caroline; Salanti, Ali; Theander, Thor G; Nielsen, Morten A

    2017-06-01

    Malaria during pregnancy is a massive health problem in endemic areas. Placental malaria infections caused by Plasmodium falciparum are responsible for up to one million babies being born with a low birth weight every year. Significant efforts have been invested into preventing the condition. Areas covered: Pub Med was searched using the broad terms 'malaria parasite placenta' to identify studies of interactions between parasite and host, 'prevention of placental malaria' to identify current strategies to prevent placental malaria, and 'placental malaria vaccine' to identify pre-clinical vaccine development. However, all papers from these searches were not systematically included. Expert commentary: The first phase I clinical trials of vaccines are well underway. Trials testing efficacy are more complicated to carry out as only women that are exposed to parasites during pregnancy will contribute to endpoint measurements, further it may require extensive follow-up to establish protection. Future second generation vaccines may overcome the inherent challenges in making an effective placental malaria vaccine.

  17. Development of the Vaccine Analytic Unit's research agenda for investigating potential adverse events associated with anthrax vaccine adsorbed.

    PubMed

    Payne, Daniel C; Franzke, Laura H; Stehr-Green, Paul A; Schwartz, Benjamin; McNeil, Michael M

    2007-01-01

    In 2002, the Centers for Disease Control and Prevention established the Vaccine Analytic Unit (VAU) in collaboration with the Department of Defense (DoD). The focus of this report is to describe the process by which the VAU's anthrax vaccine safety research plan was developed following a comprehensive review of these topics. Public health literature, surveillance data, and clinical sources were reviewed to create a list of adverse events hypothesized to be potentially related to anthrax vaccine adsorbed (AVA). From this list, a consensus process was used to select 11 important research topics. Adverse event background papers were written for each of these topics, addressing predetermined criteria. These were independently reviewed and ranked by a National Vaccine Advisory Committee (NVAC) workgroup. The adverse events included in the final priority list will be the subject of observational or other post marketing surveillance studies using the Defense Medical Surveillance System (DMSS) database. A review of various information sources identified over 100 potential adverse events. The review process recommended 11 topics as potentially warranting further study. The NVAC workgroup identified the following adverse event topics for study: arthritis, optic neuritis, and Stevens-Johnson syndrome/Toxic epidermal necrolysis. Two additional topics (systemic lupus erythematosus (SLE) and multiple, near-concurrent military vaccinations) were added in response to emerging public health and military concerns. The experience described, while specific for establishing the VAU's research agenda for the safety of the current anthrax vaccine, may be useful and adapted for research planning in other areas of public health research. Copyright (c) 2006 John Wiley & Sons, Ltd.

  18. [Clinical effectiveness and economical evaluation of preventive vaccination].

    PubMed

    Vaz Carneiro, António; Belo, Ana Isabel; Gouveia, Miguel; Costa, João; Borges, Margarida

    2011-01-01

    The value of mass vaccination as a preventive measure for infectious diseases is one of the most important advances of modern Medicine. The impact on incidence of several infectious diseases, until recently responsible for significant morbidity and mortality at world level, is well proved in a series of high quality epidemiological studies. In this scientific review we aimed firstly to briefly resume the history of mass vaccination and its scientists, responsible for synthesis and marketing of these drugs. In second place we present a group of a few disease preventable by vaccines as well as the Portuguese National Vaccination Plan and its benefits. In third place we identified groups of subjects in which a well structured vaccination plan is particularly important, as well as the correspondent diseases to be covered by vaccination. Fourthly, we discussed the ethical considerations of vaccination, and its tensions between subject autonomy and society advantages in com pulsive programs. Fifthly, we analyzed clinical effectiveness of vaccines through the concept of herd immunity, clinical evaluation of immune response to vaccines and some examples of systematic reviews on three relevant diseases (influenza, meningococcal and pneumococcal infections). In sixth place we discussed vaccine safety presenting monitoring methods of vaccination risks, as well as discussing the public myths concerning vaccines. Finally we present a economic analysis of preventive vaccination with a review of some published literature on specific diseases. We conclude that mass vaccination is a efficacious preventive measure, as well as a economic rational choice, and that this public health intervention should be a pillar of a modern preventive system.

  19. Ebola vaccines in clinical trial: The promising candidates

    PubMed Central

    Wang, Yuxiao; Li, Jingxin; Hu, Yuemei; Liang, Qi; Wei, Mingwei; Zhu, Fengcai

    2017-01-01

    ABSTRACT Ebola virus disease (EVD) has become a great threat to humans across the world in recent years. The 2014 Ebola epidemic in West Africa caused numerous deaths and attracted worldwide attentions. Since no specific drugs and treatments against EVD was available, vaccination was considered as the most promising and effective method of controlling this epidemic. So far, 7 vaccine candidates had been developed and evaluated through clinical trials. Among them, the recombinant vesicular stomatitis virus-based vaccine (rVSV-EBOV) is the most promising candidate, which demonstrated a significant protection against EVD in phase III clinical trial. However, several concerns were still associated with the Ebola vaccine candidates, including the safety profile in some particular populations, the immunization schedule for emergency vaccination, and the persistence of the protection. We retrospectively reviewed the current development of Ebola vaccines and discussed issues and challenges remaining to be investigated in the future. PMID:27764560

  20. Communicating vaccine safety during the development and introduction of vaccines.

    PubMed

    Kochhar, Sonali

    2015-01-01

    Vaccines are the best defense available against infectious diseases. Vaccine safety is of major focus for regulatory bodies, vaccine manufacturers, public health authorities, health care providers and the public as vaccines are often given to healthy children and adults as well as to pregnant woman. Safety assessment is critical at all stages of vaccine development. Effective, clear and consistent communication of the risks and benefits of vaccines and advocacy during all stages of clinical research (including the preparation, approvals, conduct of clinical trials through the post marketing phase) is critically important. This needs to be done for all major stakeholders (e.g. community members, Study Team, Health Care Providers, Ministry of Health, Regulators, Ethics Committee members, Public Health Authorities and Policy Makers). Improved stakeholder alignment would help to address some of the concerns that may affect the clinical research, licensing of vaccines and their wide-spread use in immunization programs around the world.

  1. Understanding Clinic Practices for Human Papilloma Virus Vaccination Series Completion in Clinics That Provide Primary Care: Survey of Clinic Managers in Iowa.

    PubMed

    Askelson, Natoshia M; Edmonds, Stephanie W; Momany, Elizabeth T; Tegegne, Mesay A

    2016-07-01

    Rates for human papilloma virus (HPV) vaccination are low across the United States. Evidence-based-practices to increase immunization coverage have been recommended by public health organizations, yet many primary care clinics do not follow these practices. The purpose of this study was to examine if primary care clinics use these best practices to promote completion of the HPV vaccine series for their adolescent patients. Understanding the prevalence of evidence-based immunization strategies is key to increasing vaccination coverage. We mailed 914 surveys to clinic managers of clinics that provide primary care in Iowa. The survey content was based on immunization strategies related to clinic practice and policies that have been proven effective to promote the completion of the HPV vaccination series. Survey responses from 127 clinics were used in the final analysis. Most clinics always used the state's immunization information system to record HPV vaccinations (89.4%). Over a quarter of clinics (27.6%) did not use any type of reminder or recall system to alert parents or providers that an HPV vaccine was due, and 35.0% did not give the vaccine at sick visits. Clinics need to focus more on the recommended logistics and processes to ensure that patients receive the entire HPV vaccination series. Survey results indicate that clinics are not consistently implementing the recommended best practices to ensure that vaccination series are completed.

  2. Frederick National Lab Supports Clinical Trials for Vaccine Against Mosquito-borne Chikungunya | Frederick National Laboratory for Cancer Research

    Cancer.gov

    An experimental vaccine for mosquito-borne chikungunya is being tested at sites in the Caribbean as part of a phase II clinical trial being managed by the Frederick National Lab. No vaccine or treatment currently exists for the viral disease, which c

  3. Exploring barriers and facilitators to participation of male-to-female transgender persons in preventive HIV vaccine clinical trials.

    PubMed

    Andrasik, Michele Peake; Yoon, Ro; Mooney, Jessica; Broder, Gail; Bolton, Marcus; Votto, Teress; Davis-Vogel, Annet

    2014-06-01

    Observed seroincidence and prevalence rates in male-to-female (MTF) transgender individuals highlight the need for effective targeted HIV prevention strategies for this community. In order to develop an effective vaccine that can be used by transgender women, researchers must understand and address existing structural issues that present barriers to this group's participation in HIV vaccine clinical trials. Overcoming barriers to participation is important for ensuring HIV vaccine acceptability and efficacy for the MTF transgender community. To explore barriers and facilitators to MTF transgender participation in preventive HIV vaccine clinical trials, the HIV Vaccine Trials Network conducted focus groups among transgender women in four urban areas (Atlanta, Boston, Philadelphia, and San Francisco). Barriers and facilitators to engagement of transgender women in preventive HIV vaccine clinical trials led to the following recommendations: (a) transgender cultural competency training, (b) creating trans-friendly environments, (c) true partnerships with local trans-friendly organizations and health care providers, (d) protocols that focus on transgender specific issues, and (e) data collection and tracking of transgender individuals. These results have implications for the conduct of HIV vaccine trials, as well as engagement of transgender women in research programs in general.

  4. A review of malaria vaccine clinical projects based on the WHO rainbow table

    PubMed Central

    2012-01-01

    Development and Phase 3 testing of the most advanced malaria vaccine, RTS,S/AS01, indicates that malaria vaccine R&D is moving into a new phase. Field trials of several research malaria vaccines have also confirmed that it is possible to impact the host-parasite relationship through vaccine-induced immune responses to multiple antigenic targets using different platforms. Other approaches have been appropriately tested but turned out to be disappointing after clinical evaluation. As the malaria community considers the potential role of a first-generation malaria vaccine in malaria control efforts, it is an apposite time to carefully document terminated and ongoing malaria vaccine research projects so that lessons learned can be applied to increase the chances of success for second-generation malaria vaccines over the next 10 years. The most comprehensive resource of malaria vaccine projects is a spreadsheet compiled by WHO thanks to the input from funding agencies, sponsors and investigators worldwide. This spreadsheet, available from WHO's website, is known as "the rainbow table". By summarizing the published and some unpublished information available for each project on the rainbow table, the most comprehensive review of malaria vaccine projects to be published in the last several years is provided below. PMID:22230255

  5. Enhancing diversity in the public health research workforce: the research and mentorship program for future HIV vaccine scientists.

    PubMed

    Sopher, Carrie J; Adamson, Blythe Jane S; Andrasik, Michele P; Flood, Danna M; Wakefield, Steven F; Stoff, David M; Cook, Ryan S; Kublin, James G; Fuchs, Jonathan D

    2015-04-01

    We developed and evaluated a novel National Institutes of Health-sponsored Research and Mentorship Program for African American and Hispanic medical students embedded within the international, multisite HIV Vaccine Trials Network, and explored its impact on scientific knowledge, acquired skills, and future career plans. Scholars conducted social, behavioral, clinical, or laboratory-based research projects with HIV Vaccine Trials Network investigators over 8 to 16 weeks (track 1) or 9 to 12 months (track 2). We conducted an in-depth, mixed-methods evaluation of the first 2 cohorts (2011-2013) to identify program strengths, areas for improvement, and influence on professional development. A pre-post program assessment demonstrated increases in self-reported knowledge, professional skills, and interest in future HIV vaccine research. During in-depth interviews, scholars reported that a supportive, centrally administered program; available funding; and highly involved mentors and staff were keys to the program's early success. A multicomponent, mentored research experience that engages medical students from underrepresented communities and is organized within a clinical trials network may expand the pool of diverse public health scientists. Efforts to sustain scholar interest over time and track career trajectories are warranted.

  6. Herpes Zoster Vaccination: Controversies and Common Clinical Questions.

    PubMed

    Van Epps, Puja; Schmader, Kenneth E; Canaday, David H

    2016-01-01

    Herpes zoster, clinically referred to as shingles, is an acute, cutaneous viral infection caused by reactivation of the varicella zoster virus, the same virus that causes chickenpox. The incidence of herpes zoster and its complications increase with decline in cell-mediated immunity, including age-associated decline. The most effective management strategy for herpes zoster is prevention of the disease through vaccination in those who are most vulnerable. Despite the demonstrated efficacy in reducing the incidence and severity of herpes zoster, the uptake of vaccine remains low. Here, we will discuss the controversies that surround the live herpes zoster vaccine and address the common clinical questions that arise. We will also discuss the new adjuvanted herpes zoster vaccine currently under investigation. © 2015 S. Karger AG, Basel.

  7. The Vaccination Model in Psychoneuroimmunology Research: A Review.

    PubMed

    Whittaker, Anna C

    2018-01-01

    This chapter explores the reasoning behind using the vaccination model to examine the influence of psychosocial factors on immunity. It then briefly discusses the mechanics of the vaccination response and the protocols used in psychoneuroimmunology vaccine research, before giving examples from the research literature of the studies examining relationships such as the association between stress and vaccination response. It also explores the ways the vaccination model can be used to answer key questions in psychoneuroimmunology, such as the following: "Does it matter when stressful life events occur relative to when the vaccine is received?" "What are the effects of prior exposure to the antigen?" "Do other psychosocial factors influence vaccine response besides stress?" Finally, it briefly considers the mechanisms underlying psychosocial factors and vaccination response associations and the future research needed to understand these better, and indeed to use current and future knowledge to improve and enhance vaccine responses in key at-risk populations.

  8. The use of transgenic parasites in malaria vaccine research.

    PubMed

    Othman, Ahmad Syibli; Marin-Mogollon, Catherin; Salman, Ahmed M; Franke-Fayard, Blandine M; Janse, Chris J; Khan, Shahid M

    2017-07-01

    Transgenic malaria parasites expressing foreign genes, for example fluorescent and luminescent proteins, are used extensively to interrogate parasite biology and host-parasite interactions associated with malaria pathology. Increasingly transgenic parasites are also exploited to advance malaria vaccine development. Areas covered: We review how transgenic malaria parasites are used, in vitro and in vivo, to determine protective efficacy of different antigens and vaccination strategies and to determine immunological correlates of protection. We describe how chimeric rodent parasites expressing P. falciparum or P. vivax antigens are being used to directly evaluate and rank order human malaria vaccines before their advancement to clinical testing. In addition, we describe how transgenic human and rodent parasites are used to develop and evaluate live (genetically) attenuated vaccines. Expert commentary: Transgenic rodent and human malaria parasites are being used to both identify vaccine candidate antigens and to evaluate both sub-unit and whole organism vaccines before they are advanced into clinical testing. Transgenic parasites combined with in vivo pre-clinical testing models (e.g. mice) are used to evaluate vaccine safety, potency and the durability of protection as well as to uncover critical protective immune responses and to refine vaccination strategies.

  9. Modified Vaccinia Virus Ankara: History, Value in Basic Research, and Current Perspectives for Vaccine Development.

    PubMed

    Volz, A; Sutter, G

    2017-01-01

    Safety tested Modified Vaccinia virus Ankara (MVA) is licensed as third-generation vaccine against smallpox and serves as a potent vector system for development of new candidate vaccines against infectious diseases and cancer. Historically, MVA was developed by serial tissue culture passage in primary chicken cells of vaccinia virus strain Ankara, and clinically used to avoid the undesirable side effects of conventional smallpox vaccination. Adapted to growth in avian cells MVA lost the ability to replicate in mammalian hosts and lacks many of the genes orthopoxviruses use to conquer their host (cell) environment. As a biologically well-characterized mutant virus, MVA facilitates fundamental research to elucidate the functions of poxvirus host-interaction factors. As extremely safe viral vectors MVA vaccines have been found immunogenic and protective in various preclinical infection models. Multiple recombinant MVA currently undergo clinical testing for vaccination against human immunodeficiency viruses, Mycobacterium tuberculosis or Plasmodium falciparum. The versatility of the MVA vector vaccine platform is readily demonstrated by the swift development of experimental vaccines for immunization against emerging infections such as the Middle East Respiratory Syndrome. Recent advances include promising results from the clinical testing of recombinant MVA-producing antigens of highly pathogenic avian influenza virus H5N1 or Ebola virus. This review summarizes our current knowledge about MVA as a unique strain of vaccinia virus, and discusses the prospects of exploiting this virus as research tool in poxvirus biology or as safe viral vector vaccine to challenge existing and future bottlenecks in vaccinology. © 2017 Elsevier Inc. All rights reserved.

  10. Universal fungal vaccines

    PubMed Central

    Hamad, Mawieh

    2012-01-01

    The complex nature of fungal pathogens, the intricate host-pathogen relationship and the health status of subjects in need of antifungal vaccination continue to hamper efforts to develop fungal vaccines for clinical use. That said, the rise of the universal vaccine concept is hoped to revive fungal vaccine research by expanding the pool of vaccine candidates worthy of clinical evaluation. It can do so through antigenic commonality-based screening for vaccine candidates from a wide range of pathogens and by reassessing the sizable collection of already available experimental and approved vaccines. Development of experimental vaccines protective against multiple fungal pathogens is evidence of the utility of this concept in fungal vaccine research. However, universal fungal vaccines are not without difficulties; for instance, development of vaccines with differential effectiveness is an issue that should be addressed. Additionally, rationalizing the development of universal fungal vaccines on health or economic basis could be contentious. Herein, universal fungal vaccines are discussed in terms of their potential usefulness and possible drawbacks. PMID:22922769

  11. Global Vaccine and Immunization Research Forum: Opportunities and challenges in vaccine discovery, development, and delivery.

    PubMed

    Ford, Andrew Q; Touchette, Nancy; Hall, B Fenton; Hwang, Angela; Hombach, Joachim

    2016-03-18

    The World Health Organization, the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, and the Bill & Melinda Gates Foundation convened the first Global Vaccine and Immunization Research Forum (GVIRF) in March 2014. This first GVIRF aimed to track recent progress of the Global Vaccine Action Plan research and development agenda, identify opportunities and challenges, promote partnerships in vaccine research, and facilitate the inclusion of all stakeholders in vaccine research and development. Leading scientists, vaccine developers, and public health officials from around the world discussed scientific and technical challenges in vaccine development, research to improve the impact of immunization, and regulatory issues. This report summarizes the discussions and conclusions from the forum participants. Copyright © 2016. Published by Elsevier Ltd.. All rights reserved.

  12. Chemistry, manufacturing and control (CMC) and clinical trial technical support for influenza vaccine manufacturers.

    PubMed

    Wahid, Rahnuma; Holt, Renee; Hjorth, Richard; Berlanda Scorza, Francesco

    2016-10-26

    With the support of the Biomedical Advanced Research and Development Authority (BARDA) of the US Department of Health and Human Services, PATH has contributed to the World Health Organization's (WHO's) Global Action Plan for Influenza Vaccines (GAP) by providing technical and clinical assistance to several developing country vaccine manufacturers (DCVMs). GAP builds regionally based independent and sustainable influenza vaccine production capacity to mitigate the overall global shortage of influenza vaccines. The program also ensures adequate influenza vaccine manufacturing capacity in the event of an influenza pandemic. Since 2009, PATH has worked closely with two DCVMs in Vietnam: the Institute of Vaccines and Medical Biologicals (IVAC) and VABIOTECH. Beginning in 2013, PATH also began working with Torlak Institute in Serbia; Instituto Butantan in Brazil; Serum Institute of India Private Ltd. in India; and Changchun BCHT Biotechnology Co. (BCHT) in China. The DCVMs supported under the GAP program all had existing influenza vaccine manufacturing capability and required technical support from PATH to improve vaccine yield, process efficiency, and product formulation. PATH has provided customized technical support for the manufacturing process to each DCVM based on their respective requirements. Additionally, PATH, working with BARDA and WHO, supported several DCVMs in the clinical development of influenza vaccine candidates progressing toward national licensure or WHO prequalification. As a result of the activities outlined in this review, several companies were able to make excellent progress in developing state-of-the-art manufacturing processes and completing early phase clinical trials. Licensure trials are currently ongoing or planned for several DCVMs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Reasons for Ineligibility in Phase 1 and 2A HIV Vaccine Clinical Trials at Kenya Aids Vaccine Initiative (KAVI), Kenya

    PubMed Central

    Omosa-Manyonyi, Gloria S.; Jaoko, Walter; Anzala, Omu; Ogutu, Hilda; Wakasiaka, Sabina; Malogo, Roselyn; Nyange, Jacqueline; Njuguna, Pamela; Ndinya-Achola, Jeckoniah; Bhatt, Kirana; Farah, Bashir; Oyaro, Micah; Schmidt, Claudia; Priddy, Frances; Fast, Patricia

    2011-01-01

    Background With the persistent challenges towards controlling the HIV epidemic, there is an ongoing need for research into HIV vaccines and drugs. Sub-Saharan African countries - worst affected by the HIV pandemic - have participated in the conduct of clinical trials for HIV vaccines. In Kenya, the Kenya AIDS Vaccine Initiative (KAVI) at the University of Nairobi has conducted HIV vaccine clinical trials since 2001. Methodology Participants were recruited after an extensive informed consent process followed by screening to determine eligibility. Screening included an assessment of risk behavior, medical history and physical examination, and if clinically healthy, laboratory testing. In the absence of locally derived laboratory reference ranges, the ranges used in these trials were derived from populations in the West. Principal findings Two hundred eighty-one participants were screened between 2003 and 2006 for two clinical trials. Of these, 167 (59.4%) met the inclusion/exclusion criteria. Overall, laboratory abnormalities based on the non-indigenous laboratory references used were the most frequent reasons (61.4%) for ineligibility. Medical abnormalities contributed 30.7% of the total reasons for ineligibility. Based on the laboratory reference intervals now developed from East and Southern Africa, those ineligible due to laboratory abnormalities would have been 46.3%. Of the eligible participants, 18.6% declined enrolment. Conclusions Participant recruitment for HIV vaccine clinical trials is a rigorous and time-consuming exercise. Over 61% of the screening exclusions in clinically healthy people were due to laboratory abnormalities. It is essential that laboratory reference ranges generated from local populations for laboratory values be used in the conduct of clinical trials to avoid unnecessary exclusion of willing participants and to avoid over-reporting of adverse events for enrolled participants. Trial registration Protocol IAVI VRC V001 [1]. Clinical

  14. Progress and pitfalls in Shigella vaccine research

    PubMed Central

    Barry, Eileen M.; Pasetti, Marcela F.; Sztein, Marcelo B.; Fasano, Alessio; Kotloff, Karen L.; Levine, Myron M.

    2013-01-01

    Renewed awareness of the significant morbidity and mortality that Shigella causes among young children in developing countries combined with technological innovations in vaccinology has led to the development of novel vaccine strategies in the past five years. Along with advancement of classical vaccines in clinical trials and new sophisticated measurements of immunological responses, much new data has been produced lending promise to the potential for production of safe and effective Shigella vaccines. Herein we review the recent progress in Shigella vaccine development within the framework of persistent obstacles. PMID:23419287

  15. Clinical Study of New Tetravalent (Type A, B, E, and F) Botulinum Toxoid Vaccine Derived from M Toxin in Japan.

    PubMed

    Torii, Yasushi; Sugimoto, Nakaba; Kohda, Tomoko; Kozaki, Shunji; Morokuma, Kazunori; Horikawa, Yoshikane; Ginnaga, Akihiro; Yamamoto, Akihiko; Takahashi, Motohide

    2017-07-24

    Botulinum toxin is the most poisonous substance known, and is believed to be a highly lethal as a biological weapon; researchers of the toxin are exposed to this hazard. Botulinum toxoid vaccines have been produced and used in Japan. However, since clinical studies involving these vaccines were conducted before establishment of the Ethical Guidelines for Clinical Research in Japan, their immunogenicity and safety were not systematically assessed. In this study, we produced a new tetravalent (type A, B, E, and F) botulinum toxoid vaccine, the first ever to be derived from M toxin, and conducted quality control tests with reference to the Minimum Requirements in Japan for adsorbed tetanus toxoid vaccine. Subsequently, a clinical study using the new vaccine in 48 healthy adult volunteers was conducted according to the guidelines in Japan. No clinically serious adverse event was noted. Neutralizing antibody titers for each type of toxin in the participants' sera, 1 month after the 4th injection were more than 0.25 IU/mL, indicating sufficient protection. This study demonstrated that the vaccine has marked immunogenicity and is safe for use in humans.

  16. Clinic accessibility and clinic-level predictors of the geographic variation in 2009 pandemic influenza vaccine coverage in Montreal, Canada

    PubMed Central

    Charland, Katia M; de Montigny, Luc; Brownstein, John S; Buckeridge, David L

    2014-01-01

    Background Nineteen mass vaccination clinics were established in Montreal, Canada, as part of the 2009 influenza A/H1N1p vaccination campaign. Although approximately 50% of the population was vaccinated, there was a considerable variation in clinic performance and community vaccine coverage. Objective To identify community- and clinic-level predictors of vaccine uptake, while accounting for the accessibility of clinics from the community of residence. Methods All records of influenza A/H1N1p vaccinations administered in Montreal were obtained from a vaccine registry. Multivariable regression models, specifically Bayesian gravity models, were used to assess the relationship between vaccination rates and clinic accessibility, clinic-level factors, and community-level factors. Results Relative risks compare the vaccination rates at the variable's upper quartile to the lower quartile. All else being equal, clinics in areas with high violent crime rates, high residential density, and high levels of material deprivation tended to perform poorly (adjusted relative risk [ARR]: 0·917, 95% CI [credible interval]: 0·915, 0·918; ARR: 0·663, 95% CI: 0·660, 0·666, ARR: 0·649, 95% CI: 0·645, 0·654, respectively). Even after controlling for accessibility and clinic-level predictors, communities with a greater proportion of new immigrants and families living below the poverty level tended to have lower rates (ARR: 0·936, 95% CI: 0·913, 0·959; ARR: 0·918, 95% CI: 0·893, 0·946, respectively), while communities with a higher proportion speaking English or French tended to have higher rates (ARR: 1·034, 95% CI: 1·012, 1·059). Conclusion In planning future mass vaccination campaigns, the gravity model could be used to compare expected vaccine uptake for different clinic location strategies. PMID:24382000

  17. Clinic accessibility and clinic-level predictors of the geographic variation in 2009 pandemic influenza vaccine coverage in Montreal, Canada.

    PubMed

    Charland, Katia M; de Montigny, Luc; Brownstein, John S; Buckeridge, David L

    2014-05-01

    Nineteen mass vaccination clinics were established in Montreal, Canada, as part of the 2009 influenza A/H1N1p vaccination campaign. Although approximately 50% of the population was vaccinated, there was a considerable variation in clinic performance and community vaccine coverage. To identify community- and clinic-level predictors of vaccine uptake, while accounting for the accessibility of clinics from the community of residence. All records of influenza A/H1N1p vaccinations administered in Montreal were obtained from a vaccine registry. Multivariable regression models, specifically Bayesian gravity models, were used to assess the relationship between vaccination rates and clinic accessibility, clinic-level factors, and community-level factors. Relative risks compare the vaccination rates at the variable's upper quartile to the lower quartile. All else being equal, clinics in areas with high violent crime rates, high residential density, and high levels of material deprivation tended to perform poorly (adjusted relative risk [ARR]: 0·917, 95% CI [credible interval]: 0·915, 0·918; ARR: 0·663, 95% CI: 0·660, 0·666, ARR: 0·649, 95% CI: 0·645, 0·654, respectively). Even after controlling for accessibility and clinic-level predictors, communities with a greater proportion of new immigrants and families living below the poverty level tended to have lower rates (ARR: 0·936, 95% CI: 0·913, 0·959; ARR: 0·918, 95% CI: 0·893, 0·946, respectively), while communities with a higher proportion speaking English or French tended to have higher rates (ARR: 1·034, 95% CI: 1·012, 1·059). In planning future mass vaccination campaigns, the gravity model could be used to compare expected vaccine uptake for different clinic location strategies. © 2014 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

  18. The clinical development process for a novel preventive vaccine: An overview.

    PubMed

    Singh, K; Mehta, S

    2016-01-01

    Each novel vaccine candidate needs to be evaluated for safety, immunogenicity, and protective efficacy in humans before it is licensed for use. After initial safety evaluation in healthy adults, each vaccine candidate follows a unique development path. This article on clinical development gives an overview on the development path based on the expectations of various guidelines issued by the World Health Organization (WHO), the European Medicines Agency (EMA), and the United States Food and Drug Administration (USFDA). The manuscript describes the objectives, study populations, study designs, study site, and outcome(s) of each phase (Phase I-III) of a clinical trial. Examples from the clinical development of a malaria vaccine candidate, a rotavirus vaccine, and two vaccines approved for human papillomavirus (HPV) have also been discussed. The article also tabulates relevant guidelines, which can be referred to while drafting the development path of a novel vaccine candidate.

  19. The development and clinical evaluation of second-generation leishmaniasis vaccines.

    PubMed

    Duthie, Malcolm S; Raman, Vanitha S; Piazza, Franco M; Reed, Steven G

    2012-01-05

    Infection with Leishmania parasites results in a range of clinical manifestations and outcomes. Control of Leishmania parasite transmission is extremely difficult due to the large number of vectors and potential reservoirs, and none of the current treatments are ideal. Vaccination could be an effective strategy to provide sustained control. In this review, the current global situation with regard to leishmaniasis, the immunology of Leishmania infection and various efforts to identify second generation vaccine candidates are briefly discussed. The variety of clinical trials conducted using the only current second generation vaccine approved for clinical use, LEISH-F1+MPL-SE, are described. Given that epidemiological evidence suggests that reducing the canine reservoir also positively impacts human incidence, efforts at providing a vaccine for leishmaniasis in dogs are highlighted. Finally, potential refinements and surrogate markers that could expedite the introduction of a vaccine that can limit the severity and incidence of leishmaniasis are discussed. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. The Development and Clinical Evaluation of Second-Generation Leishmaniasis Vaccines

    PubMed Central

    Duthie, Malcolm S.; Raman, Vanitha S.; Piazza, Franco M.; Reed, Steven G.

    2011-01-01

    Infection with Leishmania parasites results in a range of clinical manifestations and outcomes. Control of Leishmania parasite transmission is extremely difficult due to the large number of vectors and potential reservoirs, and none of the current treatments are ideal. Vaccination could be an effective strategy to provide sustained control. In this review, the current global situation with regard to leishmaniasis, the immunology of Leishmania infection and various efforts to identify second generation vaccine candidates are briefly discussed. The variety of clinical trials conducted using the only current second generation vaccine approved for clinical use, LEISH-F1 + MPL-SE, are described. Given that epidemiological evidence suggests that reducing the canine reservoir also positively impacts human incidence, efforts at providing a vaccine for leishmaniasis in dogs are highlighted. Finally, potential refinements and surrogate markers that could expedite the introduction of a vaccine that can limit the severity and incidence of leishmaniasis are discussed. PMID:22085553

  1. Health Education through Analogies: Preparation of a Community for Clinical Trials of a Vaccine against Hookworm in an Endemic Area of Brazil

    PubMed Central

    Gazzinelli, Maria Flavia; Lobato, Lucas; Matoso, Leonardo; Avila, Renato; de Cassia Marques, Rita; Shah Brown, Ami; Correa-Oliveira, Rodrigo; Bethony, Jeffrey M.; Diemert, David J.

    2010-01-01

    Background Obtaining informed consent for clinical trials is especially challenging when working in rural, resource-limited areas, where there are often high levels of illiteracy and lack of experience with clinical research. Such an area, a remote field site in the northeastern part of the state of Minas Gerais, Brazil, is currently being prepared for clinical trials of experimental hookworm vaccines. This study was conducted to assess whether special educational tools can be developed to increase the knowledge and comprehension of potential clinical trial participants and thereby enable them to make truly informed decisions to participate in such research. Methodology/Principal Findings An informational video was produced to explain the work of the research team and the first planned hookworm vaccine trial, using a pedagogical method based on analogies. Seventy-two adults living in a rural community of Minas Gerais were administered a structured questionnaire that assessed their knowledge of hookworm, of research and of the planned hookworm vaccine trial, as well as their attitudes and perceptions about the researchers and participation in future vaccine trials. The questionnaire was administered before being shown the educational video and two months after and the results compared. After viewing the video, significant improvements in knowledge related to hookworm infection and its health impact were observed: using a composite score combining related questions for which correct answers were assigned a value of 1 and incorrect answers a value of 0, participants had a mean score of 0.76 post-video compared to 0.68 pre-video (p = 0.0001). Similar improvements were seen in understanding the purpose of vaccination and the possible adverse effects of an experimental vaccine. Although 100% of participants expressed a positive opinion of the researchers even before viewing the film and over 90% said that they would participate in a hookworm vaccine trial, an

  2. Electronic patient registration and tracking at mass vaccination clinics: a clinical study.

    PubMed

    Billittier, Anthony J; Lupiani, Patrick; Masterson, Gary; Masterson, Tim; Zak, Christopher

    2003-01-01

    To protect the citizens of the United States from the use of dangerous biological agents, the Center for Disease Control and Prevention (CDC) has been actively preparing to deal with the consequences of such an attack. Their plans include the deployment of mass immunization clinics to handle postevent vaccinations. As part of the planning efforts by the Western New York Public Health Alliance, a Web-based electronic patient registration and tracking system was developed and tested at a recent trial smallpox vaccination clinic. Initial goals were to determine what the pitfalls and benefits of using such a system might be in comparison to other methods of data collection. This exercise proved that use of an electronic system capable of scanning two-dimensional bar codes was superior to both paper-based and optical character recognition (OCR) methods of data collection and management. Major improvements in speed and/or accuracy were evident in all areas of the clinic, especially in patient registration, vaccine tracking and postclinic data analysis.

  3. [Update on vaccine research. Proceedings of the 15th annual conference on vaccine research organized by the National Foundation for Infectious Diseases].

    PubMed

    Aubert, M; Beytout, J; Callamand, P; Cheymol, J; Combadière, B; Dahlab, A; Denis, F; Dodet, B; Dommergues, M-A; Gagneur, A; Gaillat, J; Gavazzi, G; Gras-le-Guen, C; Haas, H; Hau-Rainsard, I; Malvy, D; de Monléon, J-V; Picherot, G; Pinquier, D; Pretet, J-L; Pulcini, C; Rabaud, C; Regnier, F; Rogeaux, O; Savagner, C; Soubeyrand, B; Valdiguié, M; Weil-Olivier, C

    2013-04-01

    Every year, the National Foundation for Infectious Diseases brings together more than 300 participants to review progress in vaccine research and development and identify the most promising avenues of research. These conferences are among the most important scientific meetings entirely dedicated to vaccine research for both humans and animals, and provide a mix of plenary sessions with invited presentations by acknowledged international experts, parallel sessions, poster sessions, and informal exchanges between experts and young researchers. During the Fifteenth Conference that took place in Baltimore in May 2012, various topics were addressed, including the scientific basis for vaccinology; exploration of the immune response; novel vaccine design; new adjuvants; evaluation of the impact of newly introduced vaccines (such as rotavirus, HPV vaccines); vaccine safety; and immunization strategies. The new techniques of systems biology allow for a more comprehensive approach to the study of immune responses in order to identify correlates of protection and to design novel vaccines against chronic diseases such as AIDS or malaria, against which natural immunity is incomplete. Copyright © 2013. Published by Elsevier SAS.

  4. Regulatory considerations for clinical development of cancer vaccines.

    PubMed

    Heelan, Bridget Theresa

    2014-01-01

    Cancer vaccines are aimed at stimulating an immune response to tumor tissue. There is a high level of clinical activity in this rapidly advancing field with over 1,400 trials registered on Clincaltrials.gov. The recent approval of Sipuleucel-T which is the first cancer vaccine approved in the US and EU has encouraged developers in this field. In contrast to more established approaches for treating cancer such as chemotherapy, regulatory guidelines have been developed relatively recently for cancer vaccines. These guidelines advise on general clinical requirements. As there is an increase in innovative strategies with novel products, a 2-way dialog with regulators is recommended on a case-by-case basis to justify the clinical development plan, taking into account specific quality issues related to the product(s) in development. It is important that the rationale, background and justification for the planned development is convincing when interacting with the regulatory authorities, to enable drug developers and regulators to reach agreement.

  5. Vaccines licensed and in clinical trials for the prevention of dengue.

    PubMed

    Torresi, J; Ebert, G; Pellegrini, M

    2017-05-04

    Dengue has become a major global public health threat with almost half of the world's population living in at-risk areas. Vaccination would likely represent an effective strategy for the management of dengue disease in endemic regions, however to date there is only one licensed preventative vaccine for dengue infection. The development of a vaccine against dengue virus (DENV) has been hampered by an incomplete understanding of protective immune responses against DENV. The most clinically advanced dengue vaccine is the chimeric yellow fever-dengue vaccine (CYD) that employs the yellow fever virus 17D strain as the replication backbone (Chimerivax-DEN; CYD-TDV). This vaccine had an overall pooled protective efficacy of 65.6% but was substantially more effective against severe dengue and dengue hemorrhagic fever. Several other vaccine approaches have been developed including live attenuated chimeric dengue vaccines (DENVax and LAV Delta 30), DEN protein subunit V180 vaccine (DEN1-80E) and DENV DNA vaccines. These vaccines have been shown to be immunogenic in animals and also safe and immunogenic in humans. However, these vaccines are yet to progress to phase III trials to determine their protective efficacy against dengue. This review will summarize the details of vaccines that have progressed to clinical trials in humans.

  6. Vaccines licensed and in clinical trials for the prevention of dengue

    PubMed Central

    Torresi, J.; Ebert, G.; Pellegrini, M.

    2017-01-01

    ABSTRACT Dengue has become a major global public health threat with almost half of the world's population living in at-risk areas. Vaccination would likely represent an effective strategy for the management of dengue disease in endemic regions, however to date there is only one licensed preventative vaccine for dengue infection. The development of a vaccine against dengue virus (DENV) has been hampered by an incomplete understanding of protective immune responses against DENV. The most clinically advanced dengue vaccine is the chimeric yellow fever-dengue vaccine (CYD) that employs the yellow fever virus 17D strain as the replication backbone (Chimerivax-DEN; CYD-TDV). This vaccine had an overall pooled protective efficacy of 65.6% but was substantially more effective against severe dengue and dengue hemorrhagic fever. Several other vaccine approaches have been developed including live attenuated chimeric dengue vaccines (DENVax and LAV Delta 30), DEN protein subunit V180 vaccine (DEN1–80E) and DENV DNA vaccines. These vaccines have been shown to be immunogenic in animals and also safe and immunogenic in humans. However, these vaccines are yet to progress to phase III trials to determine their protective efficacy against dengue. This review will summarize the details of vaccines that have progressed to clinical trials in humans. PMID:28281864

  7. Inclusion of adolescents in preventive HIV vaccine trials: public health policy and research design at a crossroads.

    PubMed

    Jaspan, Heather B; Cunningham, Coleen K; Tucker, Tim J P; Wright, Peter F; Self, Steve G; Sheets, Rebecca L; Rogers, Audrey S; Bekker, Linda-Gail; Wilson, Craig M; Duerr, Ann; Wasserheit, Judith N

    2008-01-01

    The search for a safe effective HIV vaccine has been a centerpiece of HIV research for almost 2 decades. More than 60 clinical HIV vaccine trials have been conducted to date. Several promising candidate HIV vaccines are in advanced clinical development. To date, however, no trial has included adolescents, one of the most important target groups for any preventive HIV vaccine. To license a vaccine for use in this age group, efficacy data or, at a minimum, bridging safety and immunogenicity data in this population are needed. To accomplish this, several critical issues and special challenges in the development and implementation of HIV vaccine trials in adolescents must be addressed, including regulatory considerations, potential differentials in safety and immunogenicity, alternative trial design strategies, recruitment and retention challenges, community involvement models, and approaches to informed consent/assent. This article examines these issues and proposes specific next steps to facilitate the routine inclusion of this high-priority population in preventive HIV vaccine trials as early and seamlessly as possible.

  8. Cost analysis of public health influenza vaccine clinics in Ontario.

    PubMed

    Mercer, Nicola J

    2009-01-01

    Public health in Ontario delivers, promotes and provides each fall the universal influenza immunization program. This paper addresses the question of whether Ontario public health agencies are able to provide the influenza immunization program within the Ministry of Health fiscal funding envelope of $5 per dose. Actual program delivery data from the 2006 influenza season of Wellington-Dufferin-Guelph Public Health (WDGPH) were used to create a model template for influenza clinics capturing all variable costs. Promotional and administrative costs were separated from clinic costs. Maximum staff workloads were estimated. Vaccine clinics were delivered by public health staff in accordance with standard vaccine administration practices. The most significant economic variables for influenza clinics are labour costs and number of vaccines given per nurse per hour. The cost of facility rental was the only other significant cost driver. The ability of influenza clinics to break even depended on the ability to manage these cost drivers. At WDGPH, weekday flu clinics required the number of vaccines per nurse per hour to exceed 15, and for weekend flu clinics this number was greater than 21. We estimate that 20 vaccines per hour is at the limit of a safe workload over several hours. Managing cost then depends on minimizing hourly labour costs. The results of this analysis suggest that by managing the labour costs along with planning the volume of patients and avoiding expensive facilities, flu clinics can just break even. However, any increased costs, including negotiated wage increases or the move to safety needles, with a fixed revenue of $5.00 per dose will negate this conclusion.

  9. New opportunity for vaccinating older people: well-child clinic visits.

    PubMed

    Arslan, Ismail; Beyazova, Ufuk; Aksakal, Nur; Polat, Selda; Camurdan, Aysu Duyan; Sahin, Figen

    2012-02-01

    Streptococcus pneumoniae causes considerable morbidity and mortality in the elderly. As aging of the population is making the health of the elderly a universal priority, preventive measures, such as vaccination, will become increasingly important. We designed a prospective interventional study to determine whether recommendations to vaccinate grandparents of children attending well-child clinics would increase the pneumococcal vaccination rate in the elderly. Children younger than 5 years of age, attending a university well-child clinic from 1 May to 31 September 2008 who had grandparents over 65 years of age were eligible. A survey including the questions about the demographic characteristics of children, their parents and grandparents over 65 was carried out by face-to-face interview with the parents. High-risk medical conditions and vaccination history of grandparents was also noted and the benefits and necessity of pneumococcal vaccination (23vPPV) for the elderly was emphasized. Four months later these families were contacted to determine whether this intervention had increased the pneumococcal vaccination rates of the elderly. Information was obtained from 938 grandparents of 545 children. Before the interview, among all grandparents, only 0.9% were vaccinated with 23vPPV. Four months after this intervention, immunization coverage increased to 19.1%. The sex of the grandchild (OR: 1.99) and previous hepatitis B or influenza immunization of the grandparents (OR: 2.73) were the significant parameters accounting for higher immunization rates. Reminding elderly grandparents about vaccines in well-child clinics could be an opportunity in this field. © 2011 The Authors. Pediatrics International © 2011 Japan Pediatric Society.

  10. Immunogenicity and clinical protection against equine influenza by gene-based DNA vaccination of ponies

    PubMed Central

    Ault, Alida; Zajac, Alyse M.; Kong, Wing-Pui; Gorres, J. Patrick; Royals, Michael; Wei, Chih-Jen; Bao, Saran; Yang, Zhi-yong; Reedy, Stephanie E.; Sturgill, Tracy L.; Page, Allen E.; Donofrio-Newman, Jennifer; Adams, Amanda A.; Balasuriya, Udeni B.R.; Horohov, David W.; Chambers, Thomas M.; Nabel, Gary J.; Rao, Srinivas S.

    2012-01-01

    Equine influenza A (H3N8) virus is a leading cause of infectious respiratory disease in horses causing widespread morbidity and economic losses. As with influenza in other species, equine influenza strains continuously mutate, requiring constant re-evaluation of current vaccines and development of new vaccines. Current inactivated (killed) vaccines, while efficacious, only offer limited protection against multiple strains and require frequent boosts. Ongoing research into new vaccine technologies, including gene-based vaccines, aims to increase the neutralization potency, breadth, and duration of protective immunity of new or existing vaccines. In these hypothesis-generating experiments, we demonstrate that a DNA vaccine expressing the hemagglutinin protein of equine H3N8 influenza virus generates homologous and heterologous immune responses, and protects against clinical disease and viral replication following homologous H3N8 infection in horses. Furthermore, we demonstrate that a needle-free delivery device is as efficient and effective as conventional parenteral injection using a needle and syringe. The observed trends in this study drive the hypothesis that DNA vaccines offer a safe, effective, and promising alternative approach for veterinary vaccines against influenza, and applicable to combat equine influenza. PMID:22449425

  11. Pneumococcal Conjugate Vaccines and Otitis Media: An Appraisal of the Clinical Trials

    PubMed Central

    Fletcher, Mark A.; Fritzell, Bernard

    2012-01-01

    Streptococcus pneumoniae is the predominant otitis media pathogen and its prevention through effective vaccination could diminish childhood illness and antibiotic use. This paper reviews 5 pneumococcal conjugate vaccine (PCV) trials that used otitis media as an endpoint: Northern California Kaiser Permanente (NCKP; vaccine, 7-valent PCV [PCV7]-CRM); Finnish Otitis Media (FinOM; vaccines, PCV7-CRM or PCV7-OMPC); Native American Trial (vaccine, PCV7-CRM); Pneumococcal Otitis Efficacy Trial (POET; vaccine, 11-valent PCV [PCV11]-PD). For the microbiological endpoint, vaccine efficacy against vaccine-serotype pneumococcal otitis media was about 60% across trials. Against the clinical endpoint of all episodes, vaccine efficacy was 7% (PCV7-CRM/NCKP), 6% (PCV7-CRM/FinOM), −1% (PCV7-OMPC/FinOM), and −0.4% (PCV7-CRM/Native American Trial); 34% against first episodes of ear, nose, and throat specialist-referral cases (PCV11-PD/POET). Both follow-up through 2 years of age, for the 5 trials, and long-term follow-up, for PCV7-CRM/NCKP and PCV7-CRM/FinOM, demonstrated greater vaccine efficacy against recurrent AOM and tympanostomy-tube placement, suggesting that vaccination against early episodes of AOM may prevent subsequent episodes of complicated otitis media. Although study designs varied by primary endpoint measured, age at follow-up, source of middle-ear fluid for culture, case ascertainment, and type of randomization, each clinical trial demonstrated vaccine efficacy against microbiological and/or clinical otitis media. PMID:22701486

  12. NIH Research Leads to Cervical Cancer Vaccine

    MedlinePlus

    ... Transmitted Diseases NIH Research Leads to Cervical Cancer Vaccine Past Issues / Fall 2008 Table of Contents For ... Douglas Lowy (left) and John Schiller developed the vaccine to prevent HPV infection in women, the cause ...

  13. Clinical trials with canine distemper vaccines in exotic carnivores.

    PubMed

    Montali, R J; Bartz, C R; Teare, J A; Allen, J T; Appel, M J; Bush, M

    1983-12-01

    Two types of killed canine distemper virus (CDV) vaccine and a modified-live CDV vaccine were clinically evaluated in four species of exotic carnivores. In 16 trials in which 13 red pandas (Ailurus fulgens) were given the killed vaccine, only 1 animal had a virus-neutralization titer that exceeded 1:100. A red panda given modified-live CDV vaccine deemed safe for gray foxes and ferrets died of bacterial pneumonia 16 days later. There was no pathologic evidence of canine distemper in that panda. The same modified-live vaccine proved to be immunogenic and safe in 12 bush dogs (Speothos venaticus), 5 maned wolves (Chrysocyon brachyurus), and 3 fennec foxes (Fennecus zerda) in which virus-neutralization titers often exceeded 1:512 and persisted for several months after vaccination.

  14. 76 FR 68768 - Guidance for Industry: Clinical Considerations for Therapeutic Cancer Vaccines; Availability

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-07

    ... provides recommendations for the design of clinical trials for cancer vaccines conducted under an IND to... in this notice finalizes the draft guidance of the same title dated September 2009. DATES: Submit...), Center for Biologics Evaluation and Research (CBER), Food and Drug Administration, 1401 Rockville Pike...

  15. Feasibility and impact of providing feedback to vaccinating medical clinics: evaluating a public health intervention.

    PubMed

    Brousseau, Nicholas; Sauvageau, Chantal; Ouakki, Manale; Audet, Diane; Kiely, Marilou; Couture, Colette; Paré, Alain; Deceuninck, Geneviève

    2010-12-03

    Vaccine coverage (VC) at a given age is a widely-used indicator for measuring the performance of vaccination programs. However, there is increasing data suggesting that measuring delays in administering vaccines complements the measure of VC. Providing feedback to vaccinators is recognized as an effective strategy for improving vaccine coverage, but its implementation has not been widely documented in Canada. The objective of this study was to evaluate the feasibility of providing personalized feedback to vaccinators and its impact on vaccination delays (VD). In April and May 2008, a one-hour personalized feedback session was provided to health professionals in vaccinating medical clinics in the Quebec City region. VD for vaccines administered at two and twelve months of age were presented. Data from the regional vaccination registry were analysed for participating clinics. Two 12-month periods before and after the intervention were compared, namely from April 1st, 2007 to March 31st, 2008 and from June 1st, 2008 to May 31st, 2009. Ten medical clinics out of the twelve approached (83%), representing more than 2500 vaccinated children, participated in the project. Preparing and conducting the feedback involved 20 hours of work and expenses of $1000 per clinic. Based on a delay of one month, 94% of first doses of DTaP-Polio-Hib and 77% of meningococcal vaccine doses respected the vaccination schedule both before and after the intervention. Following the feedback, respect of the vaccination schedule increased for vaccines planned at 12 months for the four clinics that had modified their vaccination practices related to multiple injections (depending on the clinic, VD decreased by 24.4%, 32.0%, 40.2% and 44.6% respectively, p < 0.001 for all comparisons). The present study shows that it is feasible to provide personalized feedback to vaccinating clinics. While it may have encouraged positive changes in practice concerning multiple injections, this intervention on its

  16. Sm-p80-Based Schistosomiasis Vaccine: Preparation for Human Clinical Trials.

    PubMed

    Siddiqui, Afzal A; Siddiqui, Sabrina Z

    2017-03-01

    Mass antiparasitic drug administration programs and other control strategies have made important contributions in reducing the global prevalence of helminths. Schistosomiasis, however, continues to spread to new geographic areas. The advent of a viable vaccine and its deployment, coupled with existing control efforts, is expected to make significant headway towards sustained schistosomiasis control. In 2016, Science ranked the schistosomiasis vaccine as one of the top 10 vaccines that needs to be urgently developed. A vaccine that is effective against geographically distinct forms of intestinal/hepatic and urinary disease is essential to make a meaningful impact in global reduction of the disease burden. In this opinion article, we focus on salient features of schistosomiasis vaccines in different phases of the clinical development pipeline and highlight the Sm-p80-based vaccine which is now being prepared for human clinical trials. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Clinical, serological and echocardiographic examination of healthy field dogs before and after vaccination with a commercial tetravalent leptospirosis vaccine.

    PubMed

    Spiri, Andrea M; Rodriguez-Campos, Sabrina; Matos, José M; Glaus, Tony M; Riond, Barbara; Reusch, Claudia E; Hofmann-Lehmann, Regina; Willi, Barbara

    2017-05-25

    Leptospirosis is a re-emerging bacterial zoonosis caused by spirochetes of the genus Leptospira. Severe disease has been reported in dogs in Europe despite vaccination with bivalent Leptospira vaccines. Recently, a tetravalent canine Leptospira vaccine (Nobivac® L4) was licenced in Europe. The goal of this study was to investigate clinical signs, microscopic agglutination test (MAT) titres, haematology, blood biochemistry, cardiac (c) Troponin I levels and echocardiography before and after vaccination with this tetravalent vaccine. Forty-eight healthy dogs were prospectively enrolled and vaccinated twice, 3-4 weeks apart (T0 and T1). Before vaccination (T0) and 16-31 days after the second vaccination (T2), MAT (n = 48), haematology (n = 48), blood biochemistry (n = 36) and cTroponin I measurements (n = 29) were performed, and MAT was repeated 347-413 days after the second vaccination (T3, n = 44). Echocardiography was performed before the first and second vaccination (T0 and T1, n = 24). Mild and transient clinical signs within 5 days following the first and second vaccination occurred in 23% and 10% of the dogs, respectively. Before the first vaccination (T0), all dogs showed negative MAT titres for the tested serovars except for Canicola (50% with titres 100-400). At T2, positive MAT titres to the serovars Canicola (100%), Australis (89%), Grippotyphosa (86%), Bratislava (60%), Autumnalis (58%), Copenhageni (42%), Pomona (12%), Pyrogenes (8%) and Icterohaemorrhagiae (2%) were found. Median to high titres (≥ 400) were most common to the serovar Canicola (92%) and less common to the serovars Australis (41%), Grippotyphosa (21%), Bratislava (12%), Autumnalis (4%), Pyrogenes (4%) and Pomona (2%). At T3, positive MAT titres (titre range: 100-400) were found in 2-18% of the dogs to serovars of the vaccine serogroups and in 2-18% of the dogs to the non-vaccine serovars Pomona, Autumnalis, Pyrogenes and Ballum. Haematology, blood biochemistry, c

  18. Status of vaccine research and development of vaccines for GBS.

    PubMed

    Heath, Paul T

    2016-06-03

    Streptococcus agalactiae (group B streptococcus (GBS)) is the leading cause of neonatal sepsis and meningitis in many countries. Intrapartum antibiotic strategies have reduced the incidence of early-onset neonatal GBS in a number of countries but have had no impact on late onset GBS infection (LOD). In low/middle income settings, the disease burden remains uncertain although in several countries of Southern Africa appears comparable to or higher than that of high-income countries. As disease may be rapidly fulminating cases can be missed before appropriate samples are obtained and this may lead to underestimation of the true burden. Given the rapid onset and progression within hours of birth as well as the deficiencies in IAP strategies and absence of a solution for preventing LOD, it is clear that administration of a suitable vaccine in pregnancy could provide a better solution in all settings; it should also be cost effective. The current leading vaccine candidates are CPS-protein conjugate vaccines but protein-based vaccines are also in development and one has recently commenced clinical trials. Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

  19. A Research Agenda for Malaria Eradication: Vaccines

    PubMed Central

    2011-01-01

    Vaccines could be a crucial component of efforts to eradicate malaria. Current attempts to develop malaria vaccines are primarily focused on Plasmodium falciparum and are directed towards reducing morbidity and mortality. Continued support for these efforts is essential, but if malaria vaccines are to be used as part of a repertoire of tools for elimination or eradication of malaria, they will need to have an impact on malaria transmission. We introduce the concept of “vaccines that interrupt malaria transmission” (VIMT), which includes not only “classical” transmission-blocking vaccines that target the sexual and mosquito stages but also pre-erythrocytic and asexual stage vaccines that have an effect on transmission. VIMT may also include vaccines that target the vector to disrupt parasite development in the mosquito. Importantly, if eradication is to be achieved, malaria vaccine development efforts will need to target other malaria parasite species, especially Plasmodium vivax, where novel therapeutic vaccines against hypnozoites or preventive vaccines with effect against multiple stages could have enormous impact. A target product profile (TPP) for VIMT is proposed and a research agenda to address current knowledge gaps and develop tools necessary for design and development of VIMT is presented. PMID:21311586

  20. A research agenda for malaria eradication: vaccines.

    PubMed

    2011-01-25

    Vaccines could be a crucial component of efforts to eradicate malaria. Current attempts to develop malaria vaccines are primarily focused on Plasmodium falciparum and are directed towards reducing morbidity and mortality. Continued support for these efforts is essential, but if malaria vaccines are to be used as part of a repertoire of tools for elimination or eradication of malaria, they will need to have an impact on malaria transmission. We introduce the concept of "vaccines that interrupt malaria transmission" (VIMT), which includes not only "classical" transmission-blocking vaccines that target the sexual and mosquito stages but also pre-erythrocytic and asexual stage vaccines that have an effect on transmission. VIMT may also include vaccines that target the vector to disrupt parasite development in the mosquito. Importantly, if eradication is to be achieved, malaria vaccine development efforts will need to target other malaria parasite species, especially Plasmodium vivax, where novel therapeutic vaccines against hypnozoites or preventive vaccines with effect against multiple stages could have enormous impact. A target product profile (TPP) for VIMT is proposed and a research agenda to address current knowledge gaps and develop tools necessary for design and development of VIMT is presented.

  1. Comparable Antigenicity and Immunogenicity of Oligomeric Forms of a Novel, Acute HIV-1 Subtype C gp145 Envelope for Use in Preclinical and Clinical Vaccine Research.

    PubMed

    Wieczorek, Lindsay; Krebs, Shelly J; Kalyanaraman, Vaniambadi; Whitney, Stephen; Tovanabutra, Sodsai; Moscoso, Carlos G; Sanders-Buell, Eric; Williams, Constance; Slike, Bonnie; Molnar, Sebastian; Dussupt, Vincent; Alam, S Munir; Chenine, Agnes-Laurence; Tong, Tina; Hill, Edgar L; Liao, Hua-Xin; Hoelscher, Michael; Maboko, Leonard; Zolla-Pazner, Susan; Haynes, Barton F; Pensiero, Michael; McCutchan, Francine; Malek-Salehi, Shawyon; Cheng, R Holland; Robb, Merlin L; VanCott, Thomas; Michael, Nelson L; Marovich, Mary A; Alving, Carl R; Matyas, Gary R; Rao, Mangala; Polonis, Victoria R

    2015-08-01

    Eliciting broadly reactive functional antibodies remains a challenge in human immunodeficiency virus type 1 (HIV-1) vaccine development that is complicated by variations in envelope (Env) subtype and structure. The majority of new global HIV-1 infections are subtype C, and novel antigenic properties have been described for subtype C Env proteins. Thus, an HIV-1 subtype C Env protein (CO6980v0c22) from an infected person in the acute phase (Fiebig stage I/II) was developed as a research reagent and candidate immunogen. The gp145 envelope is a novel immunogen with a fully intact membrane-proximal external region (MPER), extended by a polylysine tail. Soluble gp145 was enriched for trimers that yielded the expected "fan blade" motifs when visualized by cryoelectron microscopy. CO6980v0c22 gp145 reacts with the 4E10, PG9, PG16, and VRC01 HIV-1 neutralizing monoclonal antibodies (MAbs), as well as the V1/V2-specific PGT121, 697, 2158, and 2297 MAbs. Different gp145 oligomers were tested for immunogenicity in rabbits, and purified dimers, trimers, and larger multimers elicited similar levels of cross-subtype binding and neutralizing antibodies to tier 1 and some tier 2 viruses. Immunized rabbit sera did not neutralize the highly resistant CO6980v0c22 pseudovirus but did inhibit the homologous infectious molecular clone in a peripheral blood mononuclear cell (PBMC) assay. This Env is currently in good manufacturing practice (GMP) production to be made available for use as a clinical research tool and further evaluation as a candidate vaccine. At present, the product pipeline for HIV vaccines is insufficient and is limited by inadequate capacity to produce large quantities of vaccine to standards required for human clinical trials. Such products are required to evaluate critical questions of vaccine formulation, route, dosing, and schedule, as well as to establish vaccine efficacy. The gp145 Env protein presented in this study forms physical trimers, binds to many of the

  2. Business Models, Vaccination Services, and Public Health Relationships of Retail Clinics: A Qualitative Study.

    PubMed

    Arthur, Bayo C; Fisher, Allison Kennedy; Shoemaker, Sarah J; Pozniak, Alyssa; Stokley, Shannon

    2015-01-01

    Despite the rapid growth of retail clinics (RCs), literature is limited in terms of how these facilities offer preventive services, particularly vaccination services. The purpose of this study was to obtain an in-depth understanding of the RC business model pertaining to vaccine offerings, profitability, and decision making. From March to June 2009, we conducted 15 interviews with key individuals from three types of organizations: 12 representatives of RC corporations, 2 representatives of retail hosts (i.e., stores in which the RCs are located), and 1 representative of an industry association. We analyzed interview transcripts qualitatively. Our results indicate that consumer demand and profitability were the main drivers in offering vaccinations. RCs in this sample primarily offered vaccinations to adults and adolescents, and they were not well integrated with local public health and immunization registries. Our findings demonstrate the potential for stronger linkages with public health in these settings. The findings also may help inform future research to increase patient access to vaccination services at RCs.

  3. Clinical trials for vaccine development in registry of Korea Food and Drug Administration.

    PubMed

    Kang, Seog-Youn

    2013-01-01

    Based on the action plan "Ensuring a stable supply of National Immunization Program vaccines and sovereignty of biopharmaceutical products," Korea Food and Drug Administration (KFDA) has made efforts to develop vaccines in the context of self reliance and to protect public health. Along with the recognized infrastructures for clinical trials, clinical trials for vaccines have also gradually been conducted at multinational sites as well as at local sites. KFDA will support to expand six to eleven kinds of vaccines by 2017. In accordance with integrated regulatory system, KFDA has promoted clinical trials, established national lot release procedure, and strengthened good manufacturing practices inspection and post marketing surveillance. Against this backdrop, KFDA will support the vaccine development and promote excellent public health protection.

  4. Clinical trials for vaccine development in registry of Korea Food and Drug Administration

    PubMed Central

    2013-01-01

    Based on the action plan "Ensuring a stable supply of National Immunization Program vaccines and sovereignty of biopharmaceutical products," Korea Food and Drug Administration (KFDA) has made efforts to develop vaccines in the context of self reliance and to protect public health. Along with the recognized infrastructures for clinical trials, clinical trials for vaccines have also gradually been conducted at multinational sites as well as at local sites. KFDA will support to expand six to eleven kinds of vaccines by 2017. In accordance with integrated regulatory system, KFDA has promoted clinical trials, established national lot release procedure, and strengthened good manufacturing practices inspection and post marketing surveillance. Against this backdrop, KFDA will support the vaccine development and promote excellent public health protection. PMID:23596594

  5. Throughput times for adults and children during two drive-through influenza vaccination clinics.

    PubMed

    Banks, Laura L; Crandall, Cameron; Esquibel, Luke

    2013-04-01

    Successful planning for public health emergencies requires knowledge of effective methods for mass distribution of medication and supplies to the public. We measured the time required for the key components of 2 drive-through vaccination clinics and summarized the results as they applied to providing medical countermeasures to large populations of children and adults. We hypothesized that vaccinating children in addition to adults would affect throughput time. Using 2 separate drive-through vaccination clinics, we measured elapsed time for vehicle flow and vaccination procedures. We calculated the median length of stay and the time to administer vaccinations based on the number of individual vaccinations given per vehicle, and compared the vehicles in which children (aged 9-18 years) were vaccinated to those in which only adults were vaccinated. A total of 2174 vaccinations and 1275 vehicles were timed during the 2 clinics. The number of vaccinations and vehicles per hour varied during the course of the day; the maximums were 200 and 361 per hour, respectively. The median throughput time was 5 minutes, and the median vaccination time was 48 seconds. Flow over time varied by the hour, and the optimum number of vaccinations per vehicle to maximize efficiency was between 3 and 4. Our findings showed that the presence of children raised the total number of vaccinations given per vehicle and, therefore, the total vaccination processing time per vehicle. However, the median individual procedure time in the vehicles with children was not significantly increased, indicating no need to calculate increased times for processing children 9 years of age or older during emergency planning. Drive-through clinics can provide a large number of seasonal influenza vaccinations in a relatively efficient manner; provide needed experience for students and practitioners in techniques for mass administration of medical countermeasures; and assist public health and emergency management

  6. Provider Communication, Prompts, and Feedback to Improve HPV Vaccination Rates in Resident Clinics.

    PubMed

    Rand, Cynthia M; Schaffer, Stanley J; Dhepyasuwan, Nui; Blumkin, Aaron; Albertin, Christina; Serwint, Janet R; Darden, Paul M; Humiston, Sharon G; Mann, Keith J; Stratbucker, William; Szilagyi, Peter G

    2018-04-01

    Human papillomavirus (HPV) vaccination rates lag behind vaccination rates for other adolescent vaccines; a bundled intervention may improve HPV vaccination rates. Our objective is to evaluate the impact of quality improvement (QI) training plus a bundled practice-based intervention (provider prompts plus communication skills training plus performance feedback) on improving HPV vaccinations in pediatric resident continuity clinics. Staff and providers in 8 resident clinics participated in a 12-month QI study. The intervention included training to strengthen provider communication about the HPV vaccine. Clinics also implemented provider prompts, received monthly performance feedback, and participated in learning collaborative calls. The primary outcome measure was eligible visits with vaccination divided by vaccine-eligible visits (captured HPV vaccination opportunities). Practices performed chart audits that were fed into monthly performance feedback on captured HPV vaccination opportunities. We used conditional logistic regression (conditioning on practice) to assess captured vaccination opportunities, with the time period of the study (before and after the QI intervention) as the independent variable. Overall, captured opportunities for HPV vaccination increased by 16.4 percentage points, from 46.9% to 63.3%. Special cause was demonstrated by centerline shift, with 8 consecutive points above the preintervention mean. On adjusted analyses, patients were more likely to receive a vaccine during, versus before, the intervention (odds ratio: 1.87; 95% confidence interval: 1.54-2.28). Captured HPV vaccination rates improved at both well-child and other visits (by 11.7 and 13.0 percentage points, respectively). A bundled intervention of provider prompts and training in communication skills plus performance feedback increased captured opportunities for HPV vaccination. Copyright © 2018 by the American Academy of Pediatrics.

  7. Future vaccination strategies against tuberculosis: thinking outside the box.

    PubMed

    Kaufmann, Stefan H E

    2010-10-29

    With almost a dozen vaccine candidates in clinical trials, tuberculosis (TB) research and development is finally reaping the first fruits of its labors. Vaccine candidates in clinical trials may prevent TB disease reactivation by efficiently containing the pathogen Mycobacterium tuberculosis (Mtb). Future research should target vaccines that achieve sterile eradication of Mtb or even prevent stable infection. These are ambitious goals that can be reached only by highly cooperative engagement of basic immunologists, vaccinologists, and clinical researchers--or in other words, by translation from basic immunology to vaccine research and development, as well as reverse translation of insights from clinical trials back to hypothesis-driven research in the basic laboratory. Here, we review current and future strategies toward the rational design of novel vaccines against TB, as well as the progress made thus far, and the hurdles that need to be overcome in the near and distant future. Copyright © 2010 Elsevier Inc. All rights reserved.

  8. Socioecological Influences on Community Involvement in HIV Vaccine Research

    PubMed Central

    Frew, Paula M.; Archibald, Matthew; Hixson, Brooke; del Rio, Carlos

    2011-01-01

    Objective This study investigated socioecological factors influencing HIV vaccine research participation among communities living in geographic areas with high HIV prevalence and high poverty rates. Methods We surveyed a sample of 453 adults ≥ 18 years from areas of high poverty and high HIV prevalence in metro Atlanta and differentiated the effects of individual-, social/organizational-, and community-level characteristics on participation in HIV vaccine research via multilevel modeling techniques that incorporated questionnaire, program, and census data. Results Models that adjusted for both individual-level covariates (such as race, gender, attitudes, and beliefs concerning HIV research), social/organizational- and community-level factors such as local HIV prevalence rates, revealed that the extent of HIV prevention-related programs and services in census tracts contributed to individuals’ likelihood of participation in an HIV vaccine study. Additionally, neighborhood-based organizations offering HIV medical and treatment programs, support groups, and services (e.g., food, shelter, and clothing) encourage greater HIV vaccine research participation. Conclusions The findings support the hypothesis that community-level factors facilitate participation in HIV vaccine research independent of both individual- and social/organizational-level factors. PMID:21722689

  9. Regulatory considerations in the clinical development of vaccines indicated for use during pregnancy.

    PubMed

    Roberts, Jeffrey N; Gruber, Marion F

    2015-02-18

    Despite supportive public health policies (e.g., ACIP recommendations), the potential for providing clinical benefit through maternal immunization has yet to be fully realized. For vaccines already licensed and approved for use in adults, specific FDA approval for use during pregnancy to prevent disease in the mother and/or infant may have a significant impact on uptake and usage in pregnant women. In addition, for either a licensed vaccine or a novel vaccine, FDA approval for use during pregnancy would result in labeling that would serve as a resource for practitioners and would facilitate the safe and effective use of the vaccine during pregnancy. In the U.S., while many vaccines are approved for use in adults and most are not contraindicated for use in pregnant women, no vaccine is licensed for use specifically during pregnancy. Among the perceived obstacles hindering the clinical development of vaccines for use in pregnancy, regulatory issues are frequently cited. One aim of this article is to address the perceived regulatory obstacles. General concepts and regulatory considerations for clinical safety and effectiveness evaluations for vaccines indicated for use during pregnancy will be discussed. This discussion is not intended to establish data requirements or to articulate agency policy or guidance regarding specific vaccine products. Published by Elsevier Ltd.

  10. A Multidisciplinary Research Agenda for Understanding Vaccine-Related Decisions

    PubMed Central

    Larson, Heidi; Leask, Julie; Aggett, Sian; Sevdalis, Nick; Thomson, Angus

    2013-01-01

    There is increasingly broad global recognition of the need to better understand determinants of vaccine acceptance. Fifteen social science, communication, health, and medical professionals (the “Motors of Trust in Vaccination” (MOTIV) think tank) explored factors relating to vaccination decision-making as a step to building a multidisciplinary research agenda. One hundred and forty seven factors impacting decisions made by consumers, professionals, and policy makers on vaccine acceptance, delay, or refusal were identified and grouped into three major categories: cognition and decision-making; groups and social norms; and communication and engagement. These factors should help frame a multidisciplinary research agenda to build an evidence base on the determinants of vaccine acceptance to inform the development of interventions and vaccination policies. PMID:26344114

  11. Health economic research on vaccinations and immunisation practices--an introductory primer.

    PubMed

    Szucs, Thomas D

    2005-03-18

    future is to conduct further health economic research on immunisation. Specific areas for such study include: effectiveness under field conditions (i.e., not under the conditions of a randomised controlled trial); the real value of economic production losses; the conditions for implementing novel immunization programmes; cost estimates for more ambitious immunization programmes; the economic benefits of combination vaccines. From this research, it will be important to disseminate the data and to adapt the findings to other countries. Nevertheless, the source of funding for research and its application in clinical trials programmes represent some of the practical problems faced by medical economics today within academia and the industry.

  12. DNA Vaccination Against Metastatic Breast Cancer

    DTIC Science & Technology

    2001-07-01

    cells. Although DNA vaccines have shown effectiveness in clinical trials , it is essential to demonstrate pre- clinical effectiveness for anti-tumor... clinical trials for infectious diseases (4), it is essential to (5-7)demonstrate pre- clinical effectiveness for anti-tumor vaccines before clinical testing...Program Clinical Translational Research (CTR) award to perform a Phase I clinical trial of ELVIS2-neu. Our preliminary application was selected for

  13. Hepatitis B Vaccine Antibody Response and the Risk of Clinical AIDS or Death

    PubMed Central

    Landrum, Michael L.; Hullsiek, Katherine Huppler; O'Connell, Robert J.; Chun, Helen M.; Ganesan, Anuradha; Okulicz, Jason F.; Lalani, Tahaniyat; Weintrob, Amy C.; Crum-Cianflone, Nancy F.; Agan, Brian K.

    2012-01-01

    Background Whether seroresponse to a vaccine such as hepatitis B virus (HBV) vaccine can provide a measure of the functional immune status of HIV-infected persons is unknown.This study evaluated the relationship between HBV vaccine seroresponses and progression to clinical AIDS or death. Methods and Findings From a large HIV cohort, we evaluated those who received HBV vaccine only after HIV diagnosis and had anti-HBs determination 1–12 months after the last vaccine dose. Non-response and positive response were defined as anti-HBs <10 and ≥10 IU/L, respectively. Participants were followed from date of last vaccination to clinical AIDS, death, or last visit. Univariate and multivariable risk of progression to clinical AIDS or death were evaluated with Cox regression models. A total of 795 participants vaccinated from 1986–2010 were included, of which 41% were responders. During 3,872 person-years of observation, 122 AIDS or death events occurred (53% after 1995). Twenty-two percent of non-responders experienced clinical AIDS or death compared with 5% of responders (p<0.001). Non-response to HBV vaccine was associated with a greater than 2-fold increased risk of clinical AIDS or death (HR 2.47; 95% CI, 1.38–4.43) compared with a positive response, after adjusting for CD4 count, HIV viral load, HAART use, and delayed type hypersensitivity skin test responses (an in vivo marker of cell-mediated immunity). This association remained evident among those with CD4 count ≥500 cells/mm3 (HR 3.40; 95% CI, 1.39–8.32). Conclusions HBV vaccine responses may have utility in assessing functional immune status and risk stratificating HIV-infected individuals, including those with CD4 count ≥500 cells/mm3. PMID:22457767

  14. Vaccine development: From concept to early clinical testing.

    PubMed

    Cunningham, Anthony L; Garçon, Nathalie; Leo, Oberdan; Friedland, Leonard R; Strugnell, Richard; Laupèze, Béatrice; Doherty, Mark; Stern, Peter

    2016-12-20

    & clinical testing. The candidate vaccine must be tested for immunogenicity, safety and efficacy in preclinical and appropriately designed clinical trials. This review considers these processes using examples of differing pathogenic challenges, including human papillomavirus, malaria, and ebola. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. TRANSVAC research infrastructure - Results and lessons learned from the European network of vaccine research and development.

    PubMed

    Geels, Mark J; Thøgersen, Regitze L; Guzman, Carlos A; Ho, Mei Mei; Verreck, Frank; Collin, Nicolas; Robertson, James S; McConkey, Samuel J; Kaufmann, Stefan H E; Leroy, Odile

    2015-10-05

    TRANSVAC was a collaborative infrastructure project aimed at enhancing European translational vaccine research and training. The objective of this four year project (2009-2013), funded under the European Commission's (EC) seventh framework programme (FP7), was to support European collaboration in the vaccine field, principally through the provision of transnational access (TNA) to critical vaccine research and development (R&D) infrastructures, as well as by improving and harmonising the services provided by these infrastructures through joint research activities (JRA). The project successfully provided all available services to advance 29 projects and, through engaging all vaccine stakeholders, successfully laid down the blueprint for the implementation of a permanent research infrastructure for early vaccine R&D in Europe. Copyright © 2015. Published by Elsevier Ltd.

  16. Smallpox: a review of clinical disease and vaccination.

    PubMed

    Lofquist, Jennifer M; Weimert, Nicole A; Hayney, Mary S

    2003-04-15

    The clinical course of smallpox infection and the current and future roles of vaccination and strategies for controlling smallpox outbreaks are reviewed. Close personal contact is required for transmission of variola, the DNA virus that causes smallpox. Following an incubation period, infected persons have prodromal symptoms that include high fever, back pain, malaise, and prostration. The eruptive stage is characterized by maculopapular rash that progresses to papules, then vesicles, and then pustules and scab lesions. The mortality rate for smallpox is approximately 30%. Patients having a fever and rash may be confused with having chickenpox. The most effective method for preventing smallpox epidemic progression is vaccination. Until recently, only 15 million doses of smallpox vaccine--manufactured 20 years ago--were available in the United States. The vaccine is a live vaccinia virus preparation administered by scarification with a bifurcated needle. The immune response is protective against orthopoxviruses, including variola. Vaccination is associated with moderate to severe complications, such as generalized vaccinia, eczema vaccinatum, progressive vaccinia, and postvaccinial encephalitis. Efforts for vaccine production are now focused on a live cell-culture-derived vaccinia virus vaccine. Although smallpox was eradicated in 1980, it remains a potential agent for bioterrorism. As a category A biological weapon, its potential to devastate populations causes concern among those in the public health community who have been actively developing plants to deal with smallpox and other potential agents of biological warfare. The only proven effective strategy against smallpox is vaccination.

  17. Impact of a clinical interventions bundle on uptake of HPV vaccine at an OB/GYN clinic.

    PubMed

    Deshmukh, Uma; Oliveira, Carlos R; Griggs, Susan; Coleman, Emily; Avni-Singer, Lital; Pathy, Shefali; Shapiro, Eugene D; Sheth, Sangini S

    2018-06-14

    HPV vaccine uptake is lowest among young adults. Little is known about the most effective way to decrease missed opportunities (MO) and increase uptake of the vaccine in this vulnerable population. To determine the impact of a clinical intervention bundle on the rate of MO and uptake of the vaccine among young adult women. From 2/2014 to 7/2015, an intervention bundle (designating physician and nurse champions, pre-screening patients' charts, empowering nurses to recommend immunization, providing no-cost vaccinations, placing prompts in clinic note templates, eliminating requirement for pre-vaccination pregnancy test) was implemented at an urban, hospital-based OB/GYN clinic. Medical records were reviewed for all vaccine-eligible (non-pregnant, 11-26 years) women seen between 2/2013 and 9/2016. Impact of the bundled interventions on the monthly rates of MO and vaccine uptake was estimated by analyzing immunization trends with an interrupted time-series model using counterfactual comparison groups in order to control for pre-existing trends. There were 6,463 vaccine-eligible visits during our study period. The prevalence of women who had both completed and initiated the series was significantly higher, 20.3% and 29.7% respectively, in the last month, compared to their counterfactuals (p < 0.01). In the last study month, the rate of MO was significantly lower than its counterfactual (19.73 per 100 encounters lower, p < 0.01). Hispanic women had attributable reductions in their rates of MO that were twice that of White women. Statistically significant attributable reductions were also seen among Spanish speakers, publicly insured, and uninsured women. Implementation of this intervention bundle effectively reduced the monthly rate of MO and increased the prevalence of women who had initiated and completed the HPV vaccine series. The reduction of MO was most drastic among Hispanic, publicly insured and uninsured women compared to White and privately insured

  18. Immunopathogenesis associated with formaldehyde-inactivated RSV vaccine in preclinical and clinical studies.

    PubMed

    Muralidharan, Abenaya; Li, Changgui; Wang, Lisheng; Li, Xuguang

    2017-04-01

    Respiratory syncytial virus (RSV) infection is responsible for one-third of deaths of acute lower respiratory infection in children less than one-year-old. The formaldehyde-inactivated RSV vaccine trial conducted in the 1960s predisposed the vaccinees to more serious RSV infection instead of protection. Better understanding of the underlying mechanism is of critical importance for better designing of safe and effective RSV vaccines. Areas covered: PubMed was searched to review immunopathology induced by RSV vaccines. We intend to dissect the differences in clinical and pathological manifestations of enhanced respiratory disease (ERD) in different animal models in comparison with humans. Formaldehyde-inactivated RSV vaccine causes ERD in both humans and animals, while RSV vaccine without formaldehyde treatment could also induce similar disease in animals, suggesting multiple pathways may be involved. Expert commentary: Identification of biomarkers pertinent to clinical evaluation should be further explored for safety assessment of RSV vaccines in human trials.

  19. Establishing Correlates of Protection for Vaccine Development: Considerations for the Respiratory Syncytial Virus Vaccine Field.

    PubMed

    Kulkarni, Prasad S; Hurwitz, Julia L; Simões, Eric A F; Piedra, Pedro A

    2018-03-01

    Correlates of protection (CoPs) can play a significant role in vaccine development by assisting the selection of vaccine candidates for clinical trials, supporting clinical trial design and implementation, and simplifying tests of vaccine modifications. Because of this important role in vaccine development, it is essential that CoPs be defined by well-designed immunogenicity and efficacy studies, with attention paid to benefits and limitations. The respiratory syncytial virus (RSV) field is unique in that a great deal of information about the humoral response is available from basic research and clinical studies. Polyclonal and monoclonal antibodies have been used routinely in the clinic to protect vulnerable infants from infection, providing a wealth of information about correlations between neutralizing antibodies and disease prevention. Considerations for the establishment of future CoPs to support RSV vaccine development in different populations are therefore discussed.

  20. Experimental Vaccine for Mosquito-Borne Chikungunya Virus Rates Well in Clinical Study | Frederick National Laboratory for Cancer Research

    Cancer.gov

    An experimental vaccine for mosquito-borne chikungunya virus, which spread to the U.S. this year, appears to be safe and well-tolerated while offering protection against the virus, according to the results of a first-in-human clinical trial. The vacc

  1. What can HIV vaccine trials teach us about future HIV vaccine dissemination?

    PubMed Central

    Newman, Peter A.; Duan, Naihua; Kakinami, Lisa; Roberts, Kathleen

    2008-01-01

    Summary This investigation explored commonalities and differences in barriers and motivators to HIV vaccine trial participation and acceptability of future U.S. Food and Drug Administration (FDA)-approved HIV vaccines in order to identify implications of clinical trials for future HIV vaccine dissemination. Fifteen focus groups were conducted with 157 predominately ethnic minority and low income participants recruited using venue-based sampling in Los Angeles. Data were analyzed using narrative thematic analysis. Barriers and motivators in common across willingness to participate (WTP) in HIV vaccine trials and future HIV vaccine acceptability (e.g., concerns about vaccine-induced infection, false-positives, side effects, efficacy, mistrust and stigma) suggest clinical trials present significant opportunities to develop and evaluate empirically based interventions to support future HIV vaccine dissemination. Barriers specific to HIV vaccine acceptability (e.g., concerns about duration of protection, cross-clade protection, cost and access) also indicate the need for formative research focused specifically on future dissemination. Protection motivation, common to WTP and acceptability, highlights the need to provide and evaluate prevention counseling and education in clinical trials, which may form the basis of evidence-informed preventive interventions to be launched in tandem with dissemination of partial efficacy HIV vaccines. PMID:18420313

  2. Clinical and economic impact of herpes zoster vaccination in elderly in Italy.

    PubMed

    Boccalini, Sara; Alicino, Cristiano; Martinelli, Domenico; Bechini, Angela; Tiscione, Emilia; Pellizzari, Barbara; Prato, Rosa; Icardi, Giancarlo; Iannazzo, Stefania; Bonanni, Paolo

    2017-02-01

    Herpes zoster (HZ) is a very relevant pathology among elderly people (≥ 60 years of age), with a considerable disease burden and loss of quality of life. In the last years a new vaccine against HZ became available in Italy. Therefore, the Italian decision makers are now confronted with the decision whether that vaccination should be implemented. Pharmaco-economic analyses represent useful tools to value the feasibility of new immunization programs and their sustainability. To this aim, an ad hoc population model was developed in order to value the clinical and economic impact of HZ vaccination program for the elderly in Italy. Particularly, different immunization scenarios were modeled: vaccination of 60 years-old subjects (single cohort strategy), simultaneous vaccination of people aged 60 and 65 years (double cohort strategy) and, lastly, immunization of people aged 60, 65 and 70 years (triple cohort strategy), thus leading to the vaccination of 5, 10 and 15 cohorts during the first 5 years of the program. The mathematical model valued the clinical impact of vaccination on the number of HZ, post-herpetic neuralgia (PHN) and ophthalmic HZ. The results of the analysis show that, in Italy, a cohort-based HZ vaccination program in elderly could have a relevant impact on the reduction of clinical cases and a favorable economic profile for the National Health Service (NHS), as already foreseen in other countries. In addition, further benefits could be obtained when extending the study period beyond the 5-year horizon of our analysis.

  3. Pneumococcal and influenza vaccination status of hospitalized adults with community acquired pneumonia and the effects of vaccination on clinical presentation.

    PubMed

    Demirdogen Cetinoglu, Ezgi; Uzaslan, Esra; Sayıner, Abdullah; Cilli, Aykut; Kılınc, Oguz; Sakar Coskun, Aysın; Hazar, Armağan; Kokturk, Nurdan; Filiz, Ayten; Polatli, Mehmet

    2017-09-02

    Previous reports have shown that vaccination rates of adult at-risk populations are low in Turkey. There are differing reports with regards to the effectiveness of the influenza and the pneumococcal polysaccharide vaccine (PPSV23) on the clinical outcomes of community acquired pneumonia (CAP). The purpose of this study was to analyze the influenza (FV) and pneumococcal vaccination (PV) status, the factors that influence the receipt of influenza/pneumococcal vaccine and the effects of prior vaccination on the clinical outcomes in adults hospitalized with CAP. Patients hospitalized with CAP between March 2009 and October 2013 and registered at the web-based Turkish Thoracic Society Pneumonia Database (TURCAP) were included in this multicentric, observational study. Of a total of 787 cases, data were analyzed for 466 patients for whom self-reported information on PV and FV was available. In this adult population with CAP, the vaccination rate with both the pneumococcal and influenza vaccines was found to be 6%. Prior FV was found to be the sole variable that was associated with the receipt of PV [OR 17.8, 95% CI (25-75:8.56-37.01), p < 0.001]. Conversely, being vaccinated with PPSV23 was the only predictor of receipt of FV [OR 18.1, 95% CI (25 - 75:8.75 - 37.83), p < 0.001]. Compared to the unvaccinated cases, the chest radiograms of the vaccinated patients revealed less consolidation. The latter also reported fatigue, muscle pain and gastrointestinal symptoms less frequently. Although there was a trend for lower 30-day mortality and for lower rates of intensive care unit (ICU) admission, these did not reach statistical significance. A pneumonia severity index (PSI) score ≥ 90, CURB-65 score ≥3 and multilobar involvement, but not the vaccination status, were identified as independent determinants of ICU admission. This study showed that, among patients hospitalized with CAP, the FV and/or PV rates are low. Prior vaccination does not appear to significantly affect

  4. Designing pediatric vaccine formularies and pricing pediatric combination vaccines using operations research models and algorithms.

    PubMed

    Jacobson, Sheldon H; Sewell, Edward C; Allwine, Daniel A; Medina, Enrique A; Weniger, Bruce G

    2003-02-01

    The National Immunization Program, housed within the Centers for Disease Control and Prevention in the USA, has identified several challenges that must be faced in childhood immunization programs to deliver and procure vaccines that immunize children from the plethora of childhood diseases. The biomedical issues cited include how drug manufacturers can combine and formulate vaccines, how such vaccines are scheduled and administered and how economically sound vaccine procurement can be achieved. This review discusses how operations research models can be used to address the economics of pediatric vaccine formulary design and pricing, as well as how such models can be used to address a new set of pediatric formulary problems that will surface with the introduction of pediatric combination vaccines into the US pediatric immunization market.

  5. Global Foot-and-Mouth Disease Research Update and Gap Analysis: 3 - Vaccines.

    PubMed

    Robinson, L; Knight-Jones, T J D; Charleston, B; Rodriguez, L L; Gay, C G; Sumption, K J; Vosloo, W

    2016-06-01

    This study assessed research knowledge gaps in the field of FMDV (foot-and-mouth disease virus) vaccines. The study took the form of a literature review (2011-15) combined with research updates collected in 2014 from 33 institutes from across the world. Findings were used to identify priority areas for future FMD vaccine research. Vaccines play a vital role in FMD control, used both to limit the spread of the virus during epidemics in FMD-free countries and as the mainstay of disease management in endemic regions, particularly where sanitary controls are difficult to apply. Improvements in the performance or cost-effectiveness of FMD vaccines will allow more widespread and efficient disease control. FMD vaccines have changed little in recent decades, typically produced by inactivation of whole virus, the quantity and stability of the intact viral capsids in the final preparation being key for immunogenicity. However, these are exciting times and several promising novel FMD vaccine candidates have recently been developed. This includes the first FMD vaccine licensed for manufacture and use in the USA; this adenovirus-vectored FMD vaccine causes in vivo expression of viral capsids in vaccinated animals. Another promising vaccine candidate comprises stabilized empty FMDV capsids produced in vitro in a baculovirus expression system. Recombinant technologies are also being developed to improve otherwise conventionally produced inactivated vaccines, for example, by creating a chimeric vaccine virus to increase capsid stability and by inserting sequences into the vaccine virus for desired antigen expression. Other important areas of ongoing research include enhanced adjuvants, vaccine quality control procedures and predicting vaccine protection from immune correlates, thus reducing dependency on animal challenge studies. Globally, the degree of independent vaccine evaluation is highly variable, and this is essential for vaccine quality. Previously neglected, the

  6. Vaccinations Administered During Off-Clinic Hours at a National Community Pharmacy: Implications for Increasing Patient Access and Convenience

    PubMed Central

    Goad, Jeffery A.; Taitel, Michael S.; Fensterheim, Leonard E.; Cannon, Adam E.

    2013-01-01

    PURPOSE Approximately 50,000 adults die annually from vaccine-preventable diseases in the United States. Most traditional vaccine providers (eg, physician offices) administer vaccinations during standard clinic hours, but community pharmacies offer expanded hours that allow patients to be vaccinated at convenient times. We analyzed the types of vaccines administered and patient populations vaccinated during off-clinic hours in a national community pharmacy, and their implications for vaccination access and convenience. METHODS We retrospectively reviewed data for all vaccinations given at the Walgreens pharmacy chain between August 2011 and July 2012. The time of vaccination was categorized as occurring during traditional hours (9:00 am–6:00 pm weekdays) or off-clinic hours, consisting of weekday evenings, weekends, and federal holidays. We compared demographic characteristics and types of vaccine. We used a logistic regression model to identify predictors of being vaccinated during off-clinic hours. RESULTS During the study period, pharmacists administered 6,250,402 vaccinations, of which 30.5% were provided during off-clinic hours: 17.4% were provided on weekends, 10.2% on evenings, and 2.9% on holidays. Patients had significantly higher odds of off-clinic vaccination if they were younger than 65 years of age, were male, resided in an urban area, and did not have any chronic conditions. CONCLUSIONS A large proportion of adults being vaccinated receive their vaccines during evening, weekend, and holiday hours at the pharmacy, when traditional vaccine providers are likely unavailable. Younger, working-aged, healthy adults, in particular, a variety of immunizations during off-clinic hours. With the low rates of adult and adolescent vaccination in the United States, community pharmacies are creating new opportunities for vaccination that expand access and convenience. PMID:24019274

  7. Plant-based vaccines for animals and humans: recent advances in technology and clinical trials

    PubMed Central

    Takeyama, Natsumi; Kiyono, Hiroshi; Yuki, Yoshikazu

    2015-01-01

    It has been about 30 years since the first plant engineering technology was established. Although the concept of plant-based pharmaceuticals or vaccines motivates us to develop practicable commercial products using plant engineering, there are some difficulties in reaching the final goal: to manufacture an approved product. At present, the only plant-made vaccine approved by the United States Department of Agriculture is a Newcastle disease vaccine for poultry that is produced in suspension-cultured tobacco cells. The progress toward commercialization of plant-based vaccines takes much effort and time, but several candidate vaccines for use in humans and animals are in clinical trials. This review discusses plant engineering technologies and regulations relevant to the development of plant-based vaccines and provides an overview of human and animal vaccines currently under clinical trials. PMID:26668752

  8. Reflections on clinical research in sub-Saharan Africa.

    PubMed

    Kuepfer, Irene; Burri, Christian

    2009-07-15

    The urgent need for new, safe and sustainable interventions against diseases that disproportionally affect the poor is finally receiving global attention and the funding landscape for development projects has significantly improved during the past decade. For the development of new drug and vaccine candidates, clinical trials have become the most important tool to assess their safety and efficacy. Recently, there has been a seismic shift in the number of clinical trials conducted in resource-limited settings. We discuss the current framework of clinical research in sub-Saharan Africa, from building product pipelines to the capacities needed for the conduct of trials according the harmonised Good Clinical Practice (GCP) ICH E6 guideline. We place emphasis on clinical research in neglected tropical diseases which still frequently has to be conducted with limited financial, logistical and human resources. Given those short-comings we recommend minimum standards needed at the local, national and sponsor levels to provide GCP-compliant clinical research.

  9. Association of School-Based Influenza Vaccination Clinics and School Absenteeism--Arkansas, 2012-2013.

    PubMed

    Gicquelais, Rachel E; Safi, Haytham; Butler, Sandra; Smith, Nathaniel; Haselow, Dirk T

    2016-04-01

    Influenza is a major cause of seasonal viral respiratory illness among school-aged children. Accordingly, the Arkansas Department of Health (ADH) coordinates >800 school-based influenza immunization clinics before each influenza season. We quantified the relationship between student influenza vaccination in Arkansas public schools and school absenteeism during the 2012-2013 influenza season. The relationship between the percent of students vaccinated in Arkansas public schools during ADH-facilitated clinics and the average daily percent of students absent from school during the 2012-2013 influenza season was quantified using linear regression modeling. The effect of increasing vaccination coverage among students on absentee days in the Arkansas public school system was estimated. For every 1% higher vaccination coverage, 0.027% fewer absenteeism days were predicted. Larger school size was associated with higher absenteeism and predicted decreases in absenteeism were larger in magnitude for larger schools compared with smaller schools. Extrapolation of the model showed that a 10% higher vaccination level was associated with a reduction of 16-163 student absentee days per school over a 12-week influenza season. Influenza vaccination is an effective tool to reduce school absenteeism. School-based clinics are a feasible way to target influenza vaccinations to school-aged children. © 2016, American School Health Association.

  10. Protein Crystallography in Vaccine Research and Development.

    PubMed

    Malito, Enrico; Carfi, Andrea; Bottomley, Matthew J

    2015-06-09

    The use of protein X-ray crystallography for structure-based design of small-molecule drugs is well-documented and includes several notable success stories. However, it is less well-known that structural biology has emerged as a major tool for the design of novel vaccine antigens. Here, we review the important contributions that protein crystallography has made so far to vaccine research and development. We discuss several examples of the crystallographic characterization of vaccine antigen structures, alone or in complexes with ligands or receptors. We cover the critical role of high-resolution epitope mapping by reviewing structures of complexes between antigens and their cognate neutralizing, or protective, antibody fragments. Most importantly, we provide recent examples where structural insights obtained via protein crystallography have been used to design novel optimized vaccine antigens. This review aims to illustrate the value of protein crystallography in the emerging discipline of structural vaccinology and its impact on the rational design of vaccines.

  11. Protein Crystallography in Vaccine Research and Development

    PubMed Central

    Malito, Enrico; Carfi, Andrea; Bottomley, Matthew J.

    2015-01-01

    The use of protein X-ray crystallography for structure-based design of small-molecule drugs is well-documented and includes several notable success stories. However, it is less well-known that structural biology has emerged as a major tool for the design of novel vaccine antigens. Here, we review the important contributions that protein crystallography has made so far to vaccine research and development. We discuss several examples of the crystallographic characterization of vaccine antigen structures, alone or in complexes with ligands or receptors. We cover the critical role of high-resolution epitope mapping by reviewing structures of complexes between antigens and their cognate neutralizing, or protective, antibody fragments. Most importantly, we provide recent examples where structural insights obtained via protein crystallography have been used to design novel optimized vaccine antigens. This review aims to illustrate the value of protein crystallography in the emerging discipline of structural vaccinology and its impact on the rational design of vaccines. PMID:26068237

  12. Human Papilloma Virus Vaccination Among Adolescents in a Community Clinic Before and After Intervention.

    PubMed

    Varman, M; Sharlin, C; Fernandez, C; Vasudevan, J; Wichman, C

    2018-06-01

    Human Papilloma Virus (HPV) is the most common sexually transmitted disease with over 14 million infections in 2008. Certain HPV types have been identified in up to 70% of cases of cervical and anal cancers. Despite being safe and effective, HPV vaccination rates remain low. Vaccination and demographic data was collected pre-and post-intervention. Among 13 thru 17-year-old cohort females were significantly more likely to be fully vaccinated. Assessment also found that patients insured by Medicaid were significantly more likely to be fully vaccinated than patients insured privately. Post-intervention vaccination rate is similar to baseline rates. There was non-significant improvement in HPV vaccination coverage after intervention. Male and privately insured patients of Creighton's Pediatric Clinic have lower HPV vaccination coverage than their counterparts. More direct efforts are needed in vaccination process and policy in the clinic to improve immunization against HPV among children and adolescents.

  13. Preclinical and clinical development of YFV 17D-based chimeric vaccines against dengue, West Nile and Japanese encephalitis viruses.

    PubMed

    Guy, Bruno; Guirakhoo, Farshad; Barban, Veronique; Higgs, Stephen; Monath, Thomas P; Lang, Jean

    2010-01-08

    Dengue viruses (DENV), West Nile virus (WNV) and Japanese encephalitis virus (JEV) are major global health and growing medical problems. While a live-attenuated vaccine exists since decades against the prototype flavivirus, yellow fever virus (YFV), there is an urgent need for vaccines against dengue or West Nile diseases, and for improved vaccines against Japanese encephalitis. Live-attenuated chimeric viruses were constructed by replacing the genes coding for Premembrane (prM) and Envelope (E) proteins from YFV 17D vaccine strain with those of heterologous flaviviruses (ChimeriVax technology). This technology has been used to produce vaccine candidates for humans, for construction of a horse vaccine for West Nile fever, and as diagnostic reagents for dengue, Japanese encephalitis, West Nile and St. Louis encephalitis infections. This review focuses on human vaccines and their characterization from the early stages of research through to clinical development. Phenotypic and genetic properties and stability were examined, preclinical evaluation through in vitro or animal models, and clinical testing were carried out. Theoretical environmental concerns linked to the live and genetically modified nature of these vaccines have been carefully addressed. Results of the extensive characterizations are in accordance with the immunogenicity and excellent safety profile of the ChimeriVax-based vaccine candidates, and support their development towards large-scale efficacy trials and registration.

  14. Cell-mediated immune response: a clinical review of the therapeutic potential of human papillomavirus vaccination.

    PubMed

    Meyer, Sonja Izquierdo; Fuglsang, Katrine; Blaakaer, Jan

    2014-12-01

    This clinical review aims to assess the efficacy of human papillomavirus 16/18 (HPV16/18) vaccination on the cell-mediated immune response in women with existing cervical intraepithelial neoplasia or cervical cancer induced by HPV16 or HPV18. A focused and thorough literature search conducted in five different databases found 996 publications. Six relevant articles were chosen for further review. In total, 154 patients (>18 years of age) were enrolled in prospective study trials with 3-15 months of follow up. The vaccine applications were administered two to four times. The vaccines contained different combinations of HPV16 and HPV18 and early proteins, E6 and E7. The primary outcome was the cell-mediated immune response. Correlation to clinical outcome (histopathology) and human leukocyte antigen genes were secondary endpoints. All vaccines triggered a detectable cell-mediated immune response, some of which were statistically significant. Correlations between immunological response and clinical outcome (histopathology) were not significant, so neoplasms may not be susceptible to vaccine-generated cytotoxic T cells (CD8(+)). Prophylactic HPV vaccines have been introduced to reduce the incidence of cervical cancer in young women. Women already infected with HPV could benefit from a therapeutic HPV vaccination. Hence, it is important to continue the development of therapeutic HPV vaccines to lower the rate of HPV-associated malignancies and crucial to evaluate vaccine efficacy clinically. This clinical review represents an attempt to elucidate the theories supporting the development of an HPV vaccine with a therapeutic effect on human papillomavirus-induced malignancies of the cervix. © 2014 Nordic Federation of Societies of Obstetrics and Gynecology.

  15. Meeting report: Global vaccine and immunization research forum.

    PubMed

    Ford, Andrew Q; Touchette, Nancy; Fenton Hall, B; Hwang, Angela; Hombach, Joachim

    2018-02-08

    Building on the success of the first Global Vaccine and Immunization Research Forum (GVIRF), the World Health Organization, the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health in the United States of America, and the Bill & Melinda Gates Foundation convened the second GVIRF in March 2016. Leading scientists, vaccine developers, and public health officials from around the world discussed scientific advances and innovative technologies to design and deliver vaccines as well as novel tools and approaches to increase the uptake of vaccines throughout the world. This report summarizes the discussions and conclusions from the forum participants. Copyright © 2018.

  16. The safety of influenza vaccine in clinically cured leprosy patients in China

    PubMed Central

    Zheng, Yi; Chen, Li; Zou, Jie; Zhu, Zheng-Gang; Zhu, Li; Wan, Jing; Hu, Quan

    2018-01-01

    ABSTRACT Background: Leprosy is an infectious disease caused by the bacterium Mycobacterium leprae. Influenza vaccine is an important influenza prevention strategy and the preparations used display good safety and tolerability profiles. But the safety of applying influenza vaccine on the clinical cured leprosy patients is unclear. Methods: We conducted an observational clinical study, in Wuhan between November 15, 2016 and March 1, 2017. Two groups of participants ≥50 years of age received a 0.5 ml dose of the inactivated split-virion trivalent influenza vaccine and a follow-up 28 days observation of any solicited and unsolicited adverse events. Results: A total of 134 subjects were included in the study. The total rate of reactogenicity was 5.4% [2/37] in leprosy group and 15.5% [15/ 97] in control group, the difference of reactogenicity between two groups was not significant (p = 0.1522). For solicited injection-sites adverse events (AEs), 12.4% [12/ 97] participants in the control group reported of itching, pain, erythema, swelling or induration, and no participants in leprosy group reported of any solicited injection-sites AEs. For solicited systemic AEs, 7.2% [7 / 97] participants in the control group reported of fever, malaise or headache, and 2.7% [1 / 37] participants in the leprosy group reported of fever, statistic result showed that the difference was not significant (p = 0.4438). Unsolicited AEs was reported by one male aged 76, 4 hours after vaccination administration, his plantar ulcer area began bleeding. All AEs were grade 1 or grade 2, and no recurrence of lepra reaction, AEs leading to early withdrawal from the study, or deaths were reported in this study. Conclusions: To our knowledge, the present study is the first clinical study to evaluate the safety of influenza vaccine in clinically cured leprosy patients. We concluded that clinically cured leprosy patients are relatively safe for influenza vaccine. More importantly, our study make a

  17. Priorities for CMV vaccine development

    PubMed Central

    Krause, Philip R.; Bialek, Stephanie R.; Boppana, Suresh B.; Griffiths, Paul D.; Laughlin, Catherine A.; Ljungman, Per; Mocarski, Edward S.; Pass, Robert F.; Read, Jennifer S.; Schleiss, Mark R.; Plotkin, Stanley A.

    2015-01-01

    A multidisciplinary meeting addressed priorities related to development of vaccines against cytomegalovirus (CMV), the cause of congenital CMV (cCMV) disease and of serious disease in the immunocompromised. Participants discussed optimal uses of a CMV vaccine, aspects of clinical study design, and the value of additional research. A universal childhood CMV vaccine could potentially rapidly reduce cCMV disease, as infected children are sources of viral transmission to seronegative and seropositive mothers. A vaccine administered to adolescents or adult women could also reduce cCMV disease by making them immune prior to pregnancy. Clinical trials of CMV vaccines in women should evaluate protection against cCMV infection, an essential precursor of cCMV disease, which is a more practical and acceptable endpoint for assessing vaccine effects on maternal-fetal transmission. Clinical trials of vaccines to evaluate prevention of CMV disease in stem cell transplant recipients could use CMV viremia at a level triggering preemptive antiviral therapy as an endpoint, because widespread use of preemptive and prophylactic antivirals has rendered CMV-induced disease too rare to be a practical endpoint for clinical trials. In solid organ transplant patients, CMV-associated disease is sufficiently common for use as a primary endpoint. Additional research to advance CMV vaccine development should include identifying factors that predict fetal loss due to CMV, determining age-specific incidence and transmission rates, defining the mechanism and relative contributions of maternal reactivation and re-infection to cCMV disease, developing assays that can distinguish between reactivation and re-infection in seropositive vaccinees, further defining predictors of sequelae from cCMV infection, and identifying clinically relevant immune response parameters to CMV (including developing validated assays that could assess CMV antibody avidity) that could lead to the establishment of immune

  18. Genome-derived vaccines.

    PubMed

    De Groot, Anne S; Rappuoli, Rino

    2004-02-01

    Vaccine research entered a new era when the complete genome of a pathogenic bacterium was published in 1995. Since then, more than 97 bacterial pathogens have been sequenced and at least 110 additional projects are now in progress. Genome sequencing has also dramatically accelerated: high-throughput facilities can draft the sequence of an entire microbe (two to four megabases) in 1 to 2 days. Vaccine developers are using microarrays, immunoinformatics, proteomics and high-throughput immunology assays to reduce the truly unmanageable volume of information available in genome databases to a manageable size. Vaccines composed by novel antigens discovered from genome mining are already in clinical trials. Within 5 years we can expect to see a novel class of vaccines composed by genome-predicted, assembled and engineered T- and Bcell epitopes. This article addresses the convergence of three forces--microbial genome sequencing, computational immunology and new vaccine technologies--that are shifting genome mining for vaccines onto the forefront of immunology research.

  19. The need for targeted implementation research to improve coverage of basic vaccines and introduction of new vaccines.

    PubMed

    Arora, Narendra K; Lal, Altaf A; Hombach, Joachim M; Santos, Jose I; Bhutta, Zulfiqar A; Sow, Samba O; Greenwood, Brian

    2013-04-18

    The Decade of Vaccines Collaboration (DoVC) Research and Development (R&D) Working Group identified implementation research as an important step toward achieving high vaccine coverage and the uptake of desirable new vaccines. The R&D Working Group noted that implementation research is highly complex and requires participation of stakeholders from diverse backgrounds to ensure effective planning, execution, interpretation, and adoption of research outcomes. Unlike other scientific disciplines, implementation research is highly contextual and depends on social, cultural, geographic, and economic factors to make the findings useful for local, national, and regional applications. This paper presents the broad framework for implementation research in support of immunization and sets out a series of research questions developed through a Delphi process (during a DoVC-supported workshop in Sitges, Spain) and a literature review. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Ensuring the optimal safety of licensed vaccines: a perspective of the vaccine research, development, and manufacturing companies.

    PubMed

    Kanesa-thasan, Niranjan; Shaw, Alan; Stoddard, Jeffrey J; Vernon, Thomas M

    2011-05-01

    Vaccine safety is increasingly a focus for the general public, health care providers, and vaccine manufacturers, because the efficacy of licensed vaccines is accepted as a given. Commitment to ensuring safety of all vaccines, including childhood vaccines, is addressed by the federal government, academia, and industry. Safety activities conducted by the vaccine research, development, and manufacturing companies occur at all stages of product development, from selection and formulation of candidate vaccines through postlicensure studies and surveillance of adverse-event reports. The contributions of multiple interacting functional groups are required to execute these tasks through the life cycle of a product. We describe here the safeguards used by vaccine manufacturers, including specific examples drawn from recent experience, and highlight some of the current challenges. Vaccine-risk communication becomes a critical area for partnership of vaccine companies with government, professional associations, and nonprofit advocacy groups to provide information on both benefits and risks of vaccines. The crucial role of the vaccine companies in ensuring the optimal vaccine-safety profile, often overlooked, will continue to grow with this dynamic arena.

  1. Parents who refuse or delay HPV vaccine: Differences in vaccination behavior, beliefs, and clinical communication preferences

    PubMed Central

    Gilkey, Melissa B.; Calo, William A.; Marciniak, Macary W.

    2017-01-01

    ABSTRACT Background: We sought to estimate the national prevalence of HPV vaccine refusal and delay in a nationally-representative sample of parents of adolescents. We also compared parents who refused versus delayed HPV vaccine in terms of their vaccination beliefs and clinical communication preferences. Methods: In 2014 to 2015, we conducted an online survey of 1,484 US parents who reported on an 11- to 17-year-old child in their household. We used weighted multinomial logistic regression to assess correlates of HPV vaccine refusal and delay. Results: Overall, 28% of parents reported that they had ever “refused or decided not to get” HPV vaccine for their child, and an additional 8% of parents reported that they had “delayed or put off getting” HPV vaccine. Compared to no refusal/delay, refusal was associated with lower confidence in adolescent vaccination (relative risk ratio [RRR] = 0.66, 95% confidence interval [CI], 0.48–0.91), lower perceived HPV vaccine effectiveness (RRR = 0.68, 95% CI, 0.50–0.91), and higher perceived harms (RRR = 3.49, 95% CI, 2.65–4.60). In contrast, delay was associated with needing more information (RRR = 1.76, 95% CI, 1.08–2.85). Most parents rated physicians and information sheets as helpful for making decisions about HPV vaccination, although parents who reported refusal endorsed these resources less often. Conclusions: Our findings suggest that HPV vaccine refusal is common among parents of adolescents and may have increased relative to previous estimates. Because the vaccination beliefs and communication preferences of parents who refuse appear to differ from those who delay, targeted communication strategies may be needed to effectively address HPV vaccine hesitancy. PMID:27763818

  2. Herpes Simplex Vaccines: Prospects of Live-attenuated HSV Vaccines to Combat Genital and Ocular infections

    PubMed Central

    Stanfield, Brent; Kousoulas, Konstantin Gus

    2015-01-01

    Herpes simplex virus type-1 (HSV-1) and its closely related type-2 (HSV-2) viruses cause important clinical manifestations in humans including acute ocular disease and genital infections. These viruses establish latency in the trigeminal ganglionic and dorsal root neurons, respectively. Both viruses are widespread among humans and can frequently reactivate from latency causing disease. Currently, there are no vaccines available against herpes simplex viral infections. However, a number of promising vaccine approaches are being explored in pre-clinical investigations with few progressing to early phase clinical trials. Consensus research findings suggest that robust humoral and cellular immune responses may partially control the frequency of reactivation episodes and reduce clinical symptoms. Live-attenuated viral vaccines have long been considered as a viable option for generating robust and protective immune responses against viral pathogens. Varicella zoster virus (VZV) belongs to the same alphaherpesvirus subfamily with herpes simplex viruses. A live-attenuated VZV vaccine has been extensively used in a prophylactic and therapeutic approach to combat primary and recurrent VZV infection indicating that a similar vaccine approach may be feasible for HSVs. In this review, we summarize pre-clinical approaches to HSV vaccine development and current efforts to test certain vaccine approaches in human clinical trials. Also, we discuss the potential advantages of using a safe, live-attenuated HSV-1 vaccine strain to protect against both HSV-1 and HSV-2 infections. PMID:27114893

  3. A Review of Clinical Trials of Human Papillomavirus Prophylactic Vaccines

    PubMed Central

    Schiller, John T.; Castellsagué, Xavier; Garland, Suzanne M.

    2015-01-01

    End of study analyses of the phase III trials of prophylactic human papillomavirus (HPV) virus-like particle (VLP) vaccines in young women are now largely completed. Two distinct vaccines were evaluated, Gardasil® (Merck & Co., Whitehouse Station, NJ USA) a quadrivalent vaccine containing VLPs of types 6, 11, 16 and 18 and Cervarix® (GlaxoSmithKline Biologicals, Rixensart, Belgium), a bivalent vaccine containing VLPs of types 16 and 18. Both vaccines exhibited excellent safety and immunogenicity profiles. The vaccines also demonstrated remarkably high and similar efficacy against the vaccine-targeted types for a range of cervical endpoints from persistent infection to cervical intraepithelial neoplasia grade 3 (CIN3) in women naïve to the corresponding type at the time of vaccination. However, protection from incident infection or disease from non-vaccine types was restricted, and the vaccines had no effect on prevalent infection or disease. Gardasil® also demonstrated strong protection against genital warts and vulvar/vaginal neoplasia associated with the vaccine types. In other trials, Gardasil® protected mid-adult women from incident infection and CIN caused by the vaccine types and protected men for incident infection, genital warts and anal intraepithelial neoplasia by the vaccine types. Cervarix® protected against vaccine-targeted anal infections in women in an end of study evaluation. For practical reasons, efficacy studies have not been conducted in the primary target populations of current vaccination programs, adolescent girls and boys. However, immunogenicity bridging studies demonstrating excellent safety and strong immune responses in adolescence, coupled with the documentation of durable antibody responses and protection in young adults, leads to an optimistic projection of the effectiveness of the vaccines in adolescent vaccination programs. Taken together, the excellent clinical trial results strongly support the potential of the vaccines as

  4. Recombinant Human Papillomavirus (HPV) Quadrivalent Vaccine

    Cancer.gov

    This page contains brief information about recombinant human papillomavirus (HPV) quadrivalent vaccine and a collection of links to more information about the use of this vaccine, research results, and ongoing clinical trials.

  5. Recombinant Human Papillomavirus (HPV) Nonavalent Vaccine

    Cancer.gov

    This page contains brief information about recombinant human papillomavirus (HPV) nonavalent vaccine and a collection of links to more information about the use of this vaccine, research results, and ongoing clinical trials.

  6. Recombinant Human Papillomavirus (HPV) Bivalent Vaccine

    Cancer.gov

    This page contains brief information about recombinant human papillomavirus (HPV) bivalent vaccine and a collection of links to more information about the use of this vaccine, research results, and ongoing clinical trials.

  7. "Living versus dead": The Pasteurian paradigm and imperial vaccine research.

    PubMed

    Chakrabarti, Pratik

    2010-01-01

    The Semple antirabies vaccine was developed by David Semple in India in 1911. Semple introduced a peculiarly British approach within the Pasteurian tradition by using carbolized dead virus. This article studies this unique phase of vaccine research between 1910 and 1935 to show that in the debates and laboratory experiments around the potency and safety of vaccines, categories like "living" and "dead" were often used as ideological and moral denominations. These abstract and ideological debates were crucial in defining the final configuration of the Semple vaccine, the most popular antirabies vaccine used globally, and also in shaping international vaccination policies.

  8. [Vaccinations in psychiatry].

    PubMed

    Dols, A; van den Brink, W; Eikelenboom, P

    2009-01-01

    Vaccination is a well-known strategy for preventing and treating infections. The purpose of vaccinations is to render antigens harmless by the production of antibodies. In psychiatry there are also situations where antigens that have been introduced from outside or that have developed during an illness constitute a threat to the patient's health. To explore the possible applications of vaccination in psychiatry. In this article we discuss the applications of vaccination in psychiatry on the basis of two examples. In addiction research, trials are being conducted with antibodies against substances such as cocaine and nicotine in order to prevent such addictive substances from crossing the blood-brain barrier and thereby initiating their rewarding effect. The first clinical results are very promising, but vaccines have not yet been applied clinically. With regard to Alzheimer's disease it has been shown by means of animal models that specific antibodies can prevent AlphaBeta aggregation and dissolve existing aggregates. On the basis of these findings various large-scale clinical trials have begun in order to study immunotherapy for Alzheimer's disease. The first clinical results showed little neurocognitive effects. A wellknown study had to be terminated because of side-effects of the therapy, in the form of neuro-encephalitis. Our tentative conclusion is that the clinical application of immunotherapy in psychiatry still has its limitations, but is indeed promising.

  9. A clinically applicable adjuvant for an atherosclerosis vaccine in mice.

    PubMed

    Kobiyama, Kouji; Vassallo, Melanie; Mitzi, Jessica; Winkels, Holger; Pei, Hong; Kimura, Takayuki; Miller, Jacqueline; Wolf, Dennis; Ley, Klaus

    2018-06-22

    Vaccination with MHC-II-restricted peptides from Apolipoprotein B (ApoB) with complete and incomplete Freund's adjuvant (CFA/IFA) is known to protect mice from atherosclerosis. This vaccination induces antigen-specific IgG1 and IgG2c antibody responses and a robust CD4 T cell response in lymph nodes. However, CFA/IFA cannot be used in humans. To find a clinically applicable adjuvant, we tested the effect of vaccinating Apoe-deficient mice with ApoB peptide P6 (TGAYSNASSTESASY). In a broad screening experiment, Addavax, a squalene oil similar to MF59, was the only adjuvant that showed similar efficacy as CFA/IFA. This was confirmed in a confirmation experiment for both the aortic arch and whole aorta analyzed by en face analysis after atherosclerotic lesion staining. Mechanistically, restimulated peritoneal cells from mice immunized with P6 in Addavax released significant amounts of IL-10. Unlike P6 in CFA/IFA, vaccination with P6 in Addavax did not induce any detectable IgG1 or IgG2c antibodies to P6. These data suggest that squalene-based adjuvants such as MF59 are good candidate adjuvants for developing a clinically effective atherosclerosis vaccine. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  10. Comparative Systems Analyses Reveal Molecular Signatures of Clinically tested Vaccine Adjuvants

    NASA Astrophysics Data System (ADS)

    Olafsdottir, Thorunn A.; Lindqvist, Madelene; Nookaew, Intawat; Andersen, Peter; Maertzdorf, Jeroen; Persson, Josefine; Christensen, Dennis; Zhang, Yuan; Anderson, Jenna; Khoomrung, Sakda; Sen, Partho; Agger, Else Marie; Coler, Rhea; Carter, Darrick; Meinke, Andreas; Rappuoli, Rino; Kaufmann, Stefan H. E.; Reed, Steven G.; Harandi, Ali M.

    2016-12-01

    A better understanding of the mechanisms of action of human adjuvants could inform a rational development of next generation vaccines for human use. Here, we exploited a genome wide transcriptomics analysis combined with a systems biology approach to determine the molecular signatures induced by four clinically tested vaccine adjuvants, namely CAF01, IC31, GLA-SE and Alum in mice. We report signature molecules, pathways, gene modules and networks, which are shared by or otherwise exclusive to these clinical-grade adjuvants in whole blood and draining lymph nodes of mice. Intriguingly, co-expression analysis revealed blood gene modules highly enriched for molecules with documented roles in T follicular helper (TFH) and germinal center (GC) responses. We could show that all adjuvants enhanced, although with different magnitude and kinetics, TFH and GC B cell responses in draining lymph nodes. These results represent, to our knowledge, the first comparative systems analysis of clinically tested vaccine adjuvants that may provide new insights into the mechanisms of action of human adjuvants.

  11. Challenges of assessing the clinical efficacy of asexual blood-stage Plasmodium falciparum malaria vaccines.

    PubMed

    Sheehy, Susanne H; Douglas, Alexander D; Draper, Simon J

    2013-09-01

    In the absence of any highly effective vaccine candidate against Plasmodium falciparum malaria, it remains imperative for the field to pursue all avenues that may lead to the successful development of such a formulation. The development of a subunit vaccine targeting the asexual blood-stage of Plasmodium falciparum malaria infection has proven particularly challenging with only limited success to date in clinical trials. However, only a fraction of potential blood-stage vaccine antigens have been evaluated as targets, and a number of new promising candidate antigen formulations and delivery platforms are approaching clinical development. It is therefore essential that reliable and sensitive methods of detecting, or ruling out, even modest efficacy of blood-stage vaccines in small clinical trials be established. In this article we evaluate the challenges facing blood-stage vaccine developers, assess the appropriateness and limitations of various in vivo approaches for efficacy assessment and suggest future directions for the field.

  12. Establishment of a Research Pharmacy to Support Ebola Clinical Research in Liberia

    PubMed Central

    Pierson, Jerome F.; Kirchoff, Matthew Carl; Tyee, Rev Tegli; Rhie, Julie K.; Montello, Michael J

    2017-01-01

    Objective This paper describes the establishment of a research pharmacy to support the PREVAIL vaccine study for Ebola Virus Disease. Setting This paper describes the establishment of the pharmacy element to support the overall research program during an Ebola outbreak in Monrovia, Liberia in 2014 and 2015. Practice Innovation The need to rapidly establish infrastructure to support the Liberian-US joint clinical research partnership in response to the emerging Ebola Virus Disease provided the opportunity for collaboration among Liberian and US pharmacists. Evaluation and Results Experiences of the Liberian and US pharmacists involved in the program are described. Conclusion The partnership was successful in the conduct of the study, but more importantly, capacity for Liberian pharmacists to support clinical research was established. Additionally, the US team learned several important lessons that will help prepare them for responding to research needs in future infectious disease outbreaks. PMID:28610940

  13. Evidence for single-dose protection by the bivalent HPV vaccine-Review of the Costa Rica HPV vaccine trial and future research studies.

    PubMed

    Kreimer, Aimée R; Herrero, Rolando; Sampson, Joshua N; Porras, Carolina; Lowy, Douglas R; Schiller, John T; Schiffman, Mark; Rodriguez, Ana Cecilia; Chanock, Stephen; Jimenez, Silvia; Schussler, John; Gail, Mitchell H; Safaeian, Mahboobeh; Kemp, Troy J; Cortes, Bernal; Pinto, Ligia A; Hildesheim, Allan; Gonzalez, Paula

    2018-01-20

    The Costa Rica Vaccine Trial (CVT), a phase III randomized clinical trial, provided the initial data that one dose of the HPV vaccine could provide durable protection against HPV infection. Although the study design was to administer all participants three doses of HPV or control vaccine, 20% of women did not receive the three-dose regimens, mostly due to involuntary reasons unrelated to vaccination. In 2011, we reported that a single dose of the bivalent HPV vaccine could be as efficacious as three doses of the vaccine using the endpoint of persistent HPV infection accumulated over the first four years of the trial; findings independently confirmed in the GSK-sponsored PATRICIA trial. Antibody levels after one dose, although lower than levels elicited by three doses, were 9-times higher than levels elicited by natural infection. Importantly, levels remained essentially constant over at least seven years, suggesting that the observed protection provided by a single dose might be durable. Much work has been done to assure these non-randomized findings are valid. Yet, the group of recipients who received one dose of the bivalent HPV vaccine in the CVT and PATRICIA trials was small and not randomly selected nor blinded to the number of doses received. The next phase of research is to conduct a formal randomized, controlled trial to evaluate the protection afforded by a single dose of HPV vaccine. Complementary studies are in progress to bridge our findings to other populations, and to further document the long-term durability of antibody response following a single dose. Published by Elsevier Ltd.

  14. Neutropenia as an Adverse Event following Vaccination: Results from Randomized Clinical Trials in Healthy Adults and Systematic Review

    PubMed Central

    Muturi-Kioi, Vincent; Lewis, David; Launay, Odile; Leroux-Roels, Geert; Anemona, Alessandra; Loulergue, Pierre; Bodinham, Caroline L.; Aerssens, Annelies; Groth, Nicola; Saul, Allan; Podda, Audino

    2016-01-01

    Background In the context of early vaccine trials aimed at evaluating the safety profile of novel vaccines, abnormal haematological values, such as neutropenia, are often reported. It is therefore important to evaluate how these trials should be planned not to miss potentially important safety signals, but also to understand the implications and the clinical relevance. Methodology We report and discuss the results from five clinical trials (two with a new Shigella vaccine in the early stage of clinical development and three with licensed vaccines) where the absolute neutrophil counts (ANC) were evaluated before and after vaccination. Additionally, we have performed a systematic review of the literature on cases of neutropenia reported during vaccine trials to discuss our results in a more general context. Principal Findings Both in our clinical trials and in the literature review, several cases of neutropenia have been reported, in the first two weeks after vaccination. However, neutropenia was generally transient and had a benign clinical outcome, after vaccination with either multiple novel candidates or well-known licensed vaccines. Additionally, the vaccine recipients with neutropenia frequently had lower baseline ANC than non-neutropenic vaccinees. In many instances neutropenia occurred in subjects of African descent, known to have lower ANC compared to western populations. Conclusions It is important to include ANC and other haematological tests in early vaccine trials to identify potential safety signals. Post-vaccination neutropenia is not uncommon, generally transient and clinically benign, but many vaccine trials do not have a sampling schedule that allows its detection. Given ethnic variability in the level of circulating neutrophils, normal ranges taking into account ethnicity should be used for determination of trial inclusion/exclusion criteria and classification of neutropenia related adverse events. Trial registration ClinicalTrials.gov NCT02017899

  15. An extended model of reasoned action to understand the influence of individual- and network-level factors on African Americans' participation in HIV vaccine research.

    PubMed

    Frew, Paula M; Archibald, Matthew; Diallo, Dazon Dixon; Hou, Su-I; Horton, Takeia; Chan, Kayshin; Mulligan, Mark J; del Rio, Carlos

    2010-06-01

    In the United States, the number and proportion of HIV/AIDS cases among black/African Americans continue to highlight the need for new biomedical prevention interventions, including an HIV vaccine, microbicide, or new antiretroviral (ARV) prevention strategies such as pre-exposure prophylaxis (PrEP) to complement existing condom usage, harm reduction methods, and behavioral change strategies to stem the HIV epidemic. Although black/African Americans are disproportionately impacted by HIV/AIDS, their participation in HIV clinical research continues to have unique challenges. We theorize that interaction among multilevel factors creates ideal alignment for minority participation in HIV clinical studies. Thus, we initially set out to test an extended model of reasoned action with 362 participants to understand the interplay of sociopsychological and network-level considerations influencing minority participation in HIV prevention research efforts. In this study, we linked the intrapersonal dimensions of attitudes, beliefs, and normative concerns to community-level components, appraisal of involvement with the clinical research organization, an entity which operates within a networked structure of community partner agencies, and identification with coalition advocacy aims. Various participatory outcomes were explored including involvement in future HIV vaccine community functions, participation in community promotion of HIV vaccine research, and community mobilization. Three-stage least squares estimates indicated similar findings across three models. Significant effects demonstrate the importance of positive attitudes toward HIV vaccine research, favorable health research beliefs, perceived social support for participation, HIV/AIDS issue engagement, and perceived relevance of the clinical research site's mission and values. Identification of these nuanced pathway effects provides implications for tailored community program development.

  16. [History of vaccination: from empiricism towards recombinant vaccines].

    PubMed

    Guérin, N

    2007-01-01

    Two hundreds years after the discovery of the smallpox vaccine, immunization remains one of the most powerful tools of preventive medicine. Immunization was born with Jenner, then Pasteur and expanded during the 19th and 20th century. It started with the empirical observation of cross-immunity between two diseases, cowpox and smallpox. It became a real science, with pathogen isolation, culture and attenuation or inactivation, to prepare a vaccine. Together with clinical and biological efficacy studies and adverse events assessments, it constructed the concept of "vaccinology". Protein conjugation of polyosidic vaccines has made possible early immunisation of infants. Nowadays, recombinant, reassortant, or virus-like particles technologies open the road for new vaccines. Ongoing research opens the way for the development of new vaccines that will help to control transmittable diseases for which we are lacking antimicrobial agents.

  17. Insights from clinical research completed during the west Africa Ebola virus disease epidemic

    PubMed Central

    Rojek, Amanda; Horby, Peter; Dunning, Jake

    2018-01-01

    The west Africa Ebola virus disease (EVD) epidemic was extraordinary in scale. Now that the epidemic has ended, it is a relevant time to examine published studies with direct relevance to clinical care and, more broadly, to examine the implications of the clinical research response mounted. Clinically relevant research includes literature detailing risk factors for and clinical manifestations of EVD, laboratory and other investigation findings in patients, experimental vaccine and therapeutic clinical trials, and analyses of survivor syndrome. In this Review, we discuss new insights from patient-oriented research completed during the west Africa epidemic, identify ongoing knowledge gaps, and suggest priorities for future research. PMID:28461209

  18. The impact of clinical research activities on communities in rural Africa: the development of the Clinical Research Unit of Nanoro (CRUN) in Burkina Faso.

    PubMed

    Tinto, Halidou; Valea, Innocent; Sorgho, Hermann; Tahita, Marc Christian; Traore, Maminata; Bihoun, Biébo; Guiraud, Issa; Kpoda, Hervé; Rouamba, Jérémi; Ouédraogo, Sayouba; Lompo, Palpouguini; Yara, Sandrine; Kabore, William; Ouédraogo, Jean-Bosco; Guiguemdé, Robert Tinga; Binka, Fred N; Ogutu, Bernhards

    2014-03-22

    The opportunities for developing new drugs and vaccines for malaria control look brighter now than ten years ago. However, there are few places in sub-Saharan Africa with the necessary infrastructure and expertise to support such research in compliance to international standards of clinical research (ICH-GCP). The Clinical Research Unit of Nanoro (CRUN) was founded in 2008 to provide a much-needed GCP-compliant clinical trial platform for an imminent large-scale Phase 3 malaria vaccine trial. A dynamic approach was used that entailed developing the required infrastructure and human resources, while engaging local communities in the process as key stakeholders. This provided a better understanding and ownership of the research activities by the local population. Within five years (2008-2013), the CRUN set up a fully and well-equipped GCP-compliant clinical trial research facility, which enabled to attract 25 grants. The research team grew from ten health workers prior to 2008 to 254 in 2013. A Health and Demographic Surveillance System (HDSS), which covers a total population of about 60,000 people in 24 villages was set up in the district. The local community contributed to the development of the facility through the leadership of the king and the mayor of Nanoro. As a result of their active advocacy, the government extended the national electrical grid to the new research center, and later to the entire village. This produced a positive impact on the community's quality of life. The quality of health care improved substantially, due to the creation of more elaborate clinical laboratory services and the acquisition of state-of-the-art equipment. Involving the community in the key steps of establishing the centre provided the foundation for what was to become the CRUN success story. This experience demonstrates that when clinical trials research sites are carefully developed and implemented, they can have a positive and powerful impact on local communities in

  19. Development of a rotavirus vaccine: clinical safety, immunogenicity, and efficacy of the pentavalent rotavirus vaccine, RotaTeq.

    PubMed

    Ciarlet, Max; Schödel, Florian

    2009-12-30

    Initial approaches for rotavirus vaccines were based on the classical "Jennerian" approach and utilized simian and bovine rotavirus strains, which provided cross-protection against human rotavirus strains but did not cause illness in infants and young children because of their species-specific tropism. The demonstrated efficacy of these vaccines was not consistent across studies. Thus, human-animal reassortants containing an animal rotavirus backbone with human rotavirus surface G and/or P proteins were developed, which demonstrated more consistent efficacy than that observed with the non-reassortant rotavirus strains. The pentavalent rotavirus vaccine, RotaTeq, contains 5 human-bovine reassortant rotaviruses consisting of a bovine (WC3) backbone with human rotavirus surface proteins representative of the most common G (G1, G2, G3, G4) or P (P1A[8]) types worldwide. The present review focuses on the development of the pentavalent rotavirus vaccine RotaTeq. Results of a large-scale Phase III clinical study showed that three doses of RotaTeq were immunogenic, efficacious, and well tolerated with no increased clinical risk of intussusception. RotaTeq was efficacious against rotavirus gastroenteritis of any severity (74%) and severe disease (98-100%), using a validated clinical scoring system. Reductions in rotavirus-associated hospitalizations and emergency department (ED) visits, for up to 2 years post-vaccination, were 95% in Europe, 97% in the United States, and 90% in the Latin American/Caribbean regions. RotaTeq was recently shown to be up to 100% effective in routine use in the US in reducing hospitalizations and ED visits and 96% effective in reducing physician visits. Additional studies in 8 different locations in the US have shown 85-95% reduction in rotavirus-associated hospitalizations and/or ED visits in the first 2-2.5 years of routine use.

  20. Transmission blocking malaria vaccines: Assays and candidates in clinical development.

    PubMed

    Sauerwein, R W; Bousema, T

    2015-12-22

    Stimulated by recent advances in malaria control and increased funding, the elimination of malaria is now considered to be an attainable goal for an increasing number of malaria-endemic regions. This has boosted the interest in transmission-reducing interventions including vaccines that target sexual, sporogenic, and/or mosquito-stage antigens to interrupt malaria transmission (SSM-VIMT). SSM-VIMT aim to prevent human malaria infection in vaccinated communities by inhibiting parasite development within the mosquito after a blood meal taken from a gametocyte carrier. Only a handful of target antigens are in clinical development and progress has been slow over the years. Major stumbling blocks include (i) the expression of appropriately folded target proteins and their downstream purification, (ii) insufficient induction of sustained functional blocking antibody titers by candidate vaccines in humans, and (iii) validation of a number of (bio)-assays as correlate for blocking activity in the field. Here we discuss clinical manufacturing and testing of current SSM-VIMT candidates and the latest bio-assay development for clinical evaluation. New testing strategies are discussed that may accelerate the evaluation and application of SSM-VIMT. Copyright © 2015. Published by Elsevier Ltd.

  1. Local health department 2009 H1N1 influenza vaccination clinics-CDC staffing model comparison and other best practices.

    PubMed

    Porter, Dayna; Hall, Mark; Hartl, Brian; Raevsky, Cathy; Peacock, Roberta; Kraker, David; Walls, Sandra; Brink, Gail

    2011-01-01

    Mass vaccination clinic staffing models, such as the Centers for Disease Control and Prevention Large-Scale Vaccination Clinic Output and Staff Estimates: An Example, provide guidance on appropriate roles and number of staff for successful mass vaccination clinics within local and state health departments. The Kent County Health Department used this model as a starting point for mass vaccination clinics in response to 2009 H1N1 influenza. In addition to discussion of successful modification of the Centers for Disease Control and Prevention model to maximize local health department mass vaccination clinic efficiency, additional best practices including use of the Incident Command System and a reservation system are provided. Use of the provided modified staffing model and additional best practices will increase the success of health department mass vaccination clinics, and should be considered not only for future public health emergencies, but also for seasonal influenza vaccination campaigns.

  2. Beyond empiricism: Informing vaccine development through innate immunity research

    PubMed Central

    Levitz, Stuart M.; Golenbock, Douglas T.

    2012-01-01

    Summary While a great public heath success, vaccines provide suboptimal protection in some patient populations and are not available to protect against many infectious diseases. Insights from innate immunity research have led to a better understanding of how existing vaccines work and informed vaccine development. New adjuvants and delivery systems are being designed based upon their capacity to stimulate innate immune sensors and target antigens to dendritic cells, the cells responsible for initiating adaptive immune responses. Incorporating these adjuvants and delivery systems in vaccines can beneficially alter the quantitative and qualitative nature of the adaptive immune response resulting in enhanced protection. PMID:22424235

  3. Blood-stage malaria vaccines: post-genome strategies for the identification of novel vaccine candidates.

    PubMed

    Ntege, Edward H; Takashima, Eizo; Morita, Masayuki; Nagaoka, Hikaru; Ishino, Tomoko; Tsuboi, Takafumi

    2017-08-01

    An efficacious malaria vaccine is necessary to advance the current control measures towards malaria elimination. To-date, only RTS,S/AS01, a leading pre-erythrocytic stage vaccine completed phase 3 trials, but with an efficacy of 28-36% in children, and 18-26% in infants, that waned over time. Blood-stage malaria vaccines protect against disease, and are considered effective targets for the logical design of next generation vaccines to improve the RTS,S field efficacy. Therefore, novel blood-stage vaccine candidate discovery efforts are critical, albeit with several challenges including, high polymorphisms in vaccine antigens, poor understanding of targets of naturally protective immunity, and difficulties in the expression of high AT-rich plasmodial proteins. Areas covered: PubMed ( www.ncbi.nlm.nih.gov/pubmed ) was searched to review the progress and future prospects of malaria vaccine research and development. We focused on post-genome vaccine candidate discovery, malaria vaccine development, sequence diversity, pre-clinical and clinical trials. Expert commentary: Post-genome high-throughput technologies using wheat germ cell-free protein synthesis technology and immuno-profiling with sera from malaria patients with clearly defined outcomes are highlighted to overcome current challenges of malaria vaccine candidate discovery.

  4. Capacity building among african american faith leaders to promote HIV prevention and vaccine research.

    PubMed

    Alio, Amina P; Lewis, Cindi A; Bunce, Catherine A; Wakefield, Steven; Thomas, Weldon G; Sanders, Edwin; Keefer, Michael C

    2014-01-01

    In light of the increasing rates of HIV infection in African Americans, it is essential that black faith leaders become more proactive in the fight against the epidemic. The study aim was to engage faith leaders in a sustainable partnership to increase community participation in preventive HIV vaccine clinical research while improving their access to and utilization of HIV/AIDS prevention services. Leadership Development Seminars were adapted for faith leaders in Rochester, NY, with topics ranging from the importance of preventive HIV vaccine research to social issues surrounding HIV/AIDs within a theological framework. Seminars were taught by field-specific experts from the black community and included the development of action plans to institute HIV preventive ministries. To assess the outcome of the Seminars, baseline and post-training surveys were administered and analyzed through paired sample t Tests and informal interviews. 19 faith leaders completed the intervention. In general, the majority of clergy felt that their understanding of HIV vaccine research and its goals had increased postintervention. A critical outcome was the subsequent formation of the Rochester Faith Collaborative by participating clergy seeking to sustain the collaborative and address the implementation of community action plans. Providing scientific HIV/AIDS knowledge within the context of clergy members' belief structure was an effective method for engaging black Church leaders in Rochester, NY. Collaborative efforts with various local institutions and community-based organizations were essential in building trust with the faith leaders, thereby building bridges for better understanding of HIV/AIDS prevention efforts, including HIV vaccine research.

  5. Measuring Adolescent Human Papillomavirus Vaccine Coverage: A Match of Sexually Transmitted Disease Clinic and Immunization Registry Data.

    PubMed

    Pathela, Preeti; Jamison, Kelly; Papadouka, Vikki; Kabir, Rezaul; Markowitz, Lauri E; Dunne, Eileen F; Schillinger, Julia A

    2016-12-01

    Human papillomavirus (HPV) vaccine is recommended for adolescents. By the end of 2013, 64% of female and 40% of male New York City residents aged 13-18 years had received ≥1 HPV vaccine dose. Adolescents attending sexually transmitted disease (STD) clinics are at high risk for HPV exposure and could benefit from vaccination. Our objective was to estimate HPV vaccination coverage for this population. We matched records of New York City's STD clinic patients aged 13-18 years during 2010-2013 with the Citywide Immunization Registry. We assessed HPV vaccine initiation (≥1 dose) and series completion (≥3 doses among those who initiated) as of clinic visit date and by patient demographics. We compared receipt of ≥1 dose for HPV, tetanus-diphtheria-acellular pertussis, and meningococcal conjugate vaccine. Eighty-two percent of clinic attendees (13,505/16,364) had records in the Citywide Immunization Registry. Receipt of ≥1 HPV dose increased during 2010-2013 (females: 57.6%-69.7%; males: 1.5%-36.3%). Among females, ≥1-dose coverage was lowest among whites (53.4%) and highest among Hispanics (73.3%); among males, ≥1-dose coverage was lowest among whites (6.9%) and highest among Asians (20.9%). Series completion averaged 57.7% (females) and 28.0% (males), with little variation by race/ethnicity or poverty level. Receipt of ≥1 dose was 59.7% for HPV, 82% for tetanus-diphtheria-acellular pertussis, and 76% for meningococcal conjugate vaccines. HPV vaccine initiation and completion were low among adolescent STD clinic patients; coverage was lower compared with other recommended vaccines. STD clinics may be good venues for delivering HPV vaccine, thereby enhancing efforts to improve HPV vaccination. Copyright © 2016 Society for Adolescent Health and Medicine. All rights reserved.

  6. Status of research and development of vaccines for Streptococcus pyogenes.

    PubMed

    Steer, Andrew C; Carapetis, Jonathan R; Dale, James B; Fraser, John D; Good, Michael F; Guilherme, Luiza; Moreland, Nicole J; Mulholland, E Kim; Schodel, Florian; Smeesters, Pierre R

    2016-06-03

    Streptococcus pyogenes is an important global pathogen, causing considerable morbidity and mortality, especially in low and middle income countries where rheumatic heart disease and invasive infections are common. There is a number of promising vaccine candidates, most notably those based on the M protein, the key virulence factor for the bacterium. Vaccines against Streptococcus pyogenes are considered as impeded vaccines because of a number of crucial barriers to development. Considerable effort is needed by key players to bring current vaccine candidates through phase III clinical trials and there is a clear need to develop a roadmap for future development of current and new candidates. Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

  7. Advocacy, partnership and political commitment for TB vaccine research.

    PubMed

    Olesen, Ole F; Chan, Sharon; Chappell, Janice; Guo, Yan; Leite, Luciana C C

    2016-08-01

    The 4th Global Forum on TB Vaccines, convened in Shanghai, China, from 21 - 24 April 2015, brought together a wide and diverse community involved in tuberculosis vaccine research and development to discuss the current status of, and future directions for this critical effort. This paper summarizes the sessions on Advancing the Pipeline: A Vision for the Next Decade, Engaging the BRICS: Basic Research to Manufacturing, and Regulatory and Access Issues for New TB Vaccines. Summaries of all sessions from the 4th Global Forum are compiled in a special supplement of Tuberculosis. [August 2016, Vol 99, Supp S1, S1-S30]. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  8. Travel and vaccination patterns: a report from a travel medicine clinic in northern Sweden.

    PubMed

    Angelin, Martin; Evengård, Birgitta; Palmgren, Helena

    2011-09-01

    The Travel Medicine Clinic in Umeå is one of Sweden's largest public providers of vaccination and counselling prior to international travel. During the study period it was the only travel medicine clinic in Umeå. This study describes the demography of the visitors to the clinic and travel destinations and durations, as well as vaccinations administered. This was a retrospective study for the period January 2005 to April 2008 based on pre-travel consultation questionnaires and on vaccine expenditure data. A 10% sample of 16,735 first visits prior to international travel was consecutively selected according to the chronology of the visits. Data on 1698 travellers were included in the study. Thailand was the most common destination among visitors, accounting for one third of all destinations. Medical problems affecting pre-travel health planning were rare. Four out of 5 visitors (79%) received only 1 vaccination, mainly for hepatitis A. Travellers to Thailand more often sought travel health advice compared to travellers to Turkey, despite the fact that the 2 destinations were almost equally distributed among travellers from Umeå. We found differences between men and women in money spent on vaccines and in particular in vaccination against Japanese encephalitis. To assess the optimal vaccination level at a travel medicine clinic is difficult. Decisions are affected by general recommendations and the risk perception of the travel medicine practitioner, as well as the risk perception of the traveller. The sex difference found in this study might be due to gender differences in risk perception and should be further investigated.

  9. Morality, responsibility and risk: the importance of alternative perspectives in vaccination research.

    PubMed

    Lyons, Antonia C

    2014-02-01

    The four papers presented in this special section together provide a striking example of the importance of eliciting people's understandings and meanings of vaccinations, from parents and children to health and medical professionals. This commentary reflects on the findings of the papers in this special section and considers them within a broader sociocultural view on vaccination research. The four papers in the special section were integrated with previous research and scholarship on public health and vaccinations. The studies demonstrate how both uptake of vaccinations and their meanings vary by cultural context, most notably across Eastern and Western Europe, and the fundamental role that political, economic and healthcare systems play. Nevertheless, there are many similarities across seemingly diverse contexts. Three specific tensions are apparent across the findings (and within other vaccination research). These tensions revolve around (1) responsible citizen versus responsible individual, (2) scientific knowledge versus lay understandings and (3) uncertainty and risk versus certainty and trust. Threaded through these tensions are discourses around citizenship, trust, morality, gender and power that are important to consider in research on vaccinations.

  10. HIV vaccine development: past, present and future.

    PubMed

    Robb, Merlin L

    2010-12-01

    The search for an HIV vaccine began following the discovery of the virus more than 25 years ago. Despite important progress, an effective vaccine remains an elusive goal that will likely require many more years of R&D to achieve. Following recent advances in research, however, there has been increased optimism that a prophylactic HIV vaccine is feasible. A consensus is forming among researchers to support a larger role for proof-of-concept efficacy clinical trials, conducted in parallel with invigorated basic research efforts and testing in animal models, to accelerate the discovery of key principles that will guide rational vaccine development.

  11. Frederick National Lab Rallies to Meet Demand for Zika Vaccine | FNLCR Staging

    Cancer.gov

    The Frederick National Laboratory for Cancer Research’s Vaccine Pilot Plant, part of the Vaccine Clinical Materials Program (VCMP), is helping researchers produce investigational Zika vaccines for a new round of clinical trials. The plant has been

  12. Next Generation Vaccine Biomarkers workshop October 30–31, 2014 – Ottawa, Canada

    PubMed Central

    Twine, Susan M; Fulton, Kelly M; Spika, John; Ouellette, Marc; Raven, Jennifer F; Conlan, J Wayne; Krishnan, Lakshmi; Barreto, Luis; Richards, James C

    2015-01-01

    Vaccine biomarkers are critical to many aspects of vaccine development and licensure, including bridging findings in pre-clinical studies to clinical studies, predicting potential adverse events, and predicting vaccine efficacy. Despite advances in our understanding of various biological pathways, and advances in systems analyses of the immune response, there remains much to learn about qualitative and quantitative aspects of the human host response to vaccination. To stimulate discussion and identify opportunities for collaborative ways to advance the field of vaccine biomarkers, A Next Generation Vaccine Biomarker workshop was held in Ottawa. The two day workshop, sponsored by the National Research Council Canada, Canadian Institutes of Health Research, Public Health Agency of Canada, Pfizer, and Medicago, brought together stakeholders from Canadian and international industry, government and academia. The workshop was grouped in themes, covering vaccine biomarker challenges in the pre-clinical and clinical spaces, veterinary vaccines, regulatory challenges, and development of biomarkers for adjuvants and cancer vaccines. The use of case studies allowed participants to identify the needs and gaps requiring innovation. The workshop concluded with a discussion on opportunities for vaccine biomarker discovery, the Canadian context, and approaches for moving forward. This article provides a synopsis of these discussions and identifies steps forward for advancing vaccine biomarker research in Canada. PMID:26383909

  13. The anti-vaccination movement and resistance to allergen-immunotherapy: a guide for clinical allergists.

    PubMed

    Behrmann, Jason

    2010-09-15

    Despite over a century of clinical use and a well-documented record of efficacy and safety, a growing minority in society questions the validity of vaccination and fear that this common public health intervention is the root-cause of severe health problems. This article questions whether growing public anti-vaccine sentiments might have the potential to spill-over into other therapies distinct from vaccination, namely allergen-immunotherapy. Allergen-immunotherapy shares certain medical vernacular with vaccination (e.g., allergy shots, allergy vaccines), and thus may become "guilty by association" due to these similarities. Indeed, this article demonstrates that anti-vaccine websites have begun unduly discrediting this allergy treatment regimen. Following an explanation of the anti-vaccine movement, the article aims to provide guidance on how clinicians can respond to patient fears towards allergen-immunotherapy in the clinical setting. This guide focuses on the provision of reliable information to patients in order to dispel misconceived associations between vaccination and allergen-immunotherapy, and the discussion of the risks and benefits of both therapies in order to assist patients in making autonomous decisions about their choice of allergy treatment.

  14. The anti-vaccination movement and resistance to allergen-immunotherapy: a guide for clinical allergists

    PubMed Central

    2010-01-01

    Despite over a century of clinical use and a well-documented record of efficacy and safety, a growing minority in society questions the validity of vaccination and fear that this common public health intervention is the root-cause of severe health problems. This article questions whether growing public anti-vaccine sentiments might have the potential to spill-over into other therapies distinct from vaccination, namely allergen-immunotherapy. Allergen-immunotherapy shares certain medical vernacular with vaccination (e.g., allergy shots, allergy vaccines), and thus may become "guilty by association" due to these similarities. Indeed, this article demonstrates that anti-vaccine websites have begun unduly discrediting this allergy treatment regimen. Following an explanation of the anti-vaccine movement, the article aims to provide guidance on how clinicians can respond to patient fears towards allergen-immunotherapy in the clinical setting. This guide focuses on the provision of reliable information to patients in order to dispel misconceived associations between vaccination and allergen-immunotherapy, and the discussion of the risks and benefits of both therapies in order to assist patients in making autonomous decisions about their choice of allergy treatment. PMID:20843332

  15. Tuberculosis vaccine development: recent progress.

    PubMed

    Orme, I M; McMurray, D N; Belisle, J T

    2001-03-01

    Recent years have seen a renewed effort to develop new vaccines against tuberculosis. As a result, several promising avenues of research have developed, including the production of recombinant vaccines, auxotrophic vaccines, DNA vaccines and subunit vaccines. In this article we briefly review this work, as well as consider the pros and cons of the animal models needed to test these new vaccines. Screening to date has been carried out in mouse and guinea pig models, which have been used to obtain basic information such as the effect of the vaccine on bacterial load, and whether the vaccine can prevent or reduce lung pathology. The results to date lead us to be optimistic that new candidate vaccines could soon be considered for evaluation in clinical trials.

  16. An Extended Model of Reasoned Action to Understand the Influence of Individual- and Network-Level Factors on African Americans’ Participation in HIV Vaccine Research

    PubMed Central

    Frew, Paula M.; Archibald, Matthew; Diallo, Dazon Dixon; Hou, Su-I; Horton, Takeia; Chan, Kayshin; Mulligan, Mark J.; del Rio, Carlos

    2010-01-01

    In the United States, the number and proportion of HIV/AIDS cases among black/African Americans continue to highlight the need for new biomedical prevention interventions, including an HIV vaccine, microbicide, or new antiretroviral (ARV) prevention strategies such as pre-exposure prophylaxis (PrEP) to complement existing condom usage, harm reduction methods, and behavioral change strategies to stem the HIV epidemic. Although black/African Americans are disproportionately impacted by HIV/AIDS, their participation in HIV clinical research continues to have unique challenges. We theorize that interaction among multilevel factors creates ideal alignment for minority participation in HIV clinical studies. Thus, we initially set out to test an extended model of reasoned action with 362 participants to understand the interplay of sociopsychological and network-level considerations influencing minority participation in HIV prevention research efforts. In this study, we linked the intrapersonal dimensions of attitudes, beliefs, and normative concerns to community-level components, appraisal of involvement with the clinical research organization, an entity which operates within a networked structure of community partner agencies, and identification with coalition advocacy aims. Various participatory outcomes were explored including involvement in future HIV vaccine community functions, participation in community promotion of HIV vaccine research, and community mobilization. Three-stage least squares estimates indicated similar findings across three models. Significant effects demonstrate the importance of positive attitudes toward HIV vaccine research, favorable health research beliefs, perceived social support for participation, HIV/AIDS issue engagement, and perceived relevance of the clinical research site’s mission and values. Identification of these nuanced pathway effects provides implications for tailored community program development. PMID:20012200

  17. Beyond empiricism: informing vaccine development through innate immunity research.

    PubMed

    Levitz, Stuart M; Golenbock, Douglas T

    2012-03-16

    Although a great public heath success, vaccines provide suboptimal protection in some patient populations and are not available to protect against many infectious diseases. Insights from innate immunity research have led to a better understanding of how existing vaccines work and have informed vaccine development. New adjuvants and delivery systems are being designed based upon their capacity to stimulate innate immune sensors and target antigens to dendritic cells, the cells responsible for initiating adaptive immune responses. Incorporating these adjuvants and delivery systems in vaccines can beneficially alter the quantitative and qualitative nature of the adaptive immune response, resulting in enhanced protection. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Towards a Rational Design of an Asymptomatic Clinical Herpes Vaccine: The Old, the New, and the Unknown

    PubMed Central

    Alami Chentoufi, Aziz; Kritzer, Elizabeth; Yu, David M.; Nesburn, Anthony B.; BenMohamed, Lbachir

    2012-01-01

    The best hope of controlling the herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2) pandemic is the development of an effective vaccine. However, in spite of several clinical trials, starting as early as 1920s, no vaccine has been proven sufficiently safe and efficient to warrant commercial development. In recent years, great strides in cellular and molecular immunology have stimulated creative efforts in controlling herpes infection and disease. However, before moving towards new vaccine strategy, it is necessary to answer two fundamental questions: (i) why past herpes vaccines have failed? (ii) Why the majority of HSV seropositive individuals (i.e., asymptomatic individuals) are naturally “protected” exhibiting few or no recurrent clinical disease, while other HSV seropositive individuals (i.e., symptomatic individuals) have frequent ocular, orofacial, and/or genital herpes clinical episodes? We recently discovered several discrete sets of HSV-1 symptomatic and asymptomatic epitopes recognized by CD4+ and CD8+ T cells from seropositive symptomatic versus asymptomatic individuals. These asymptomatic epitopes will provide a solid foundation for the development of novel herpes epitope-based vaccine strategy. Here we provide a brief overview of past clinical vaccine trials, outline current progress towards developing a new generation “asymptomatic” clinical herpes vaccines, and discuss future mucosal “asymptomatic” prime-boost vaccines that could optimize local protective immunity. PMID:22548113

  19. Multiple Vaccinations: Friend or Foe

    PubMed Central

    Church, Sarah E.; Jensen, Shawn M.; Twitty, Chris; Bahjat, Keith; Hu, Hong-Ming; Urba, Walter J.; Fox, Bernard A.

    2013-01-01

    Few immunotherapists would accept the concept of a single vaccination inducing a therapeutic anti-cancer immune response in a patient with advanced cancer. But what is the evidence to support the “more-is-better” approach of multiple vaccinations? Since we are unaware of trials comparing the effect of a single vaccine versus multiple vaccinations on patient outcome, we considered that an anti-cancer immune response might provide a surrogate measure of the effectiveness of vaccination strategies. Since few large trials include immunological monitoring, the majority of information is gleaned from smaller trials in which an evaluation of immune responses to vaccine or tumor, before and at one or more times following the first vaccine was performed. In some studies there is convincing evidence that repeated administration of a specific vaccine can augment the immune response to antigens contained in the vaccine. In other settings multiple vaccinations can significantly reduce the immune response to one or more targets. Results from three large adjuvant vaccine studies support the potential detrimental effect of multiple vaccinations as clinical outcomes in the control arms were significantly better than that for treatment groups. Recent research has provided insights into mechanisms that are likely responsible for the reduced responses in the studies noted above, but supporting evidence from clinical specimens is generally lacking. Interpretation of these results is further complicated by the possibility that the dominant immune response may evolve to recognize epitopes not present in the vaccine. Nonetheless, the FDA-approval of the first therapeutic cancer vaccine and recent developments from preclinical models and clinical trials provide a substantial basis for optimism and a critical evaluation of cancer vaccine strategies. PMID:21952289

  20. Novel vaccines for glioblastoma: clinical update and perspective

    PubMed Central

    Winograd, Evan K; Ciesielski, Michael J; Fenstermaker, Robert A

    2016-01-01

    Glioblastoma is the most common primary brain cancer. Aggressive treatment with surgery, radiation therapy and chemotherapy provides limited overall survival benefit. Glioblastomas have a formidable tumor microenvironment that is hostile to immunological effector cells and these cancers produce profound systemic immunosuppression. However, surgical resection of these tumors creates conditions that favor the use of immunotherapeutic strategies. Therefore, extensive surgical resection, when feasible, will remain part of the equation to provide an environment in which active specific immunotherapy has the greatest chance of working. Toward that end, a number of vaccination protocols are under investigation. Vaccines studied to date have produced cellular and humoral antitumor responses, but unequivocal clinical efficacy has yet to be demonstrated. In addition, focus is shifting toward the prospect of therapies involving vaccines in combination with immune checkpoint inhibitors and other immunomodulatory agents so that effector cells remain active against their targets systemically and within the tumor microenvironment. PMID:27993092

  1. Clinical development of a novel inactivated poliomyelitis vaccine based on attenuated Sabin poliovirus strains.

    PubMed

    Verdijk, Pauline; Rots, Nynke Y; Bakker, Wilfried A M

    2011-05-01

    Following achievement of polio eradication, the routine use of all live-attenuated oral poliovirus vaccines should be discontinued. However, the costs per vaccine dose for the alternative inactivated poliovirus vaccine (IPV) are significantly higher and the current production capacity is not sufficient for worldwide distribution of the vaccine. In order to achieve cost-prize reduction and improve affordability, IPV production processes and dose-sparing strategies should be developed to facilitate local manufacture at a relatively lower cost. The use of attenuated Sabin instead of wild-type polio strains will provide additional safety during vaccine production and permits production in low-cost settings. Sabin-IPV is under development by several manufacturers. This article gives an overview of results from clinical trials with Sabin-IPV and discusses the requirements and challenges in the clinical development of this novel IPV.

  2. Vaccines Against Malaria

    PubMed Central

    Ouattara, Amed; Laurens, Matthew B.

    2015-01-01

    Despite global efforts to control malaria, the illness remains a significant public health threat. Currently, there is no licensed vaccine against malaria, but an efficacious vaccine would represent an important public health tool for successful malaria elimination. Malaria vaccine development continues to be hindered by a poor understanding of antimalarial immunity, a lack of an immune correlate of protection, and the genetic diversity of malaria parasites. Current vaccine development efforts largely target Plasmodium falciparum parasites in the pre-erythrocytic and erythrocytic stages, with some research on transmission-blocking vaccines against asexual stages and vaccines against pregnancy-associated malaria. The leading pre-erythrocytic vaccine candidate is RTS,S, and early results of ongoing Phase 3 testing show overall efficacy of 46% against clinical malaria. The next steps for malaria vaccine development will focus on the design of a product that is efficacious against the highly diverse strains of malaria and the identification of a correlate of protection against disease. PMID:25452593

  3. Vaccines for Malaria: How Close Are We?

    PubMed Central

    Thera, Mahamadou A.; Plowe, Christopher V.

    2012-01-01

    Vaccines are the most powerful public health tools mankind has created, but malaria parasites are bigger, more complicated, and wilier than the viruses and bacteria that have been conquered or controlled with vaccines. Despite decades of research toward a vaccine for malaria, this goal has remained elusive. Nevertheless, recent advances justify optimism that a licensed malaria vaccine is within reach. A subunit recombinant protein vaccine that affords in the neighborhood of 50% protective efficacy against clinical malaria is in the late stages of clinical evaluation in Africa. Incremental improvements on this successful vaccine are possible and worth pursuing, but the best hope for a highly efficacious malaria vaccine that would improve prospects for malaria eradication may lie with the use of attenuated whole parasites and powerful immune-boosting adjuvants. PMID:22077719

  4. Vaccines for malaria: how close are we?

    PubMed

    Thera, Mahamadou A; Plowe, Christopher V

    2012-01-01

    Vaccines are the most powerful public health tools mankind has created, but malaria parasites are bigger, more complicated, and wilier than the viruses and bacteria that have been conquered or controlled with vaccines. Despite decades of research toward a vaccine for malaria, this goal has remained elusive. Nevertheless, recent advances justify optimism that a licensed malaria vaccine is within reach. A subunit recombinant protein vaccine that affords in the neighborhood of 50% protective efficacy against clinical malaria is in the late stages of clinical evaluation in Africa. Incremental improvements on this successful vaccine are possible and worth pursuing, but the best hope for a highly efficacious malaria vaccine that would improve prospects for malaria eradication may lie with the use of attenuated whole parasites and powerful immune-boosting adjuvants.

  5. Preclinical and clinical development of a YFV 17 D-based chimeric vaccine against West Nile virus.

    PubMed

    Dayan, Gustavo H; Pugachev, Konstantin; Bevilacqua, Joan; Lang, Jean; Monath, Thomas P

    2013-12-09

    Substantial success has been achieved in the development and implementation of West Nile (WN) vaccines for horses; however, no human WN vaccines are approved. This review focuses on the construction, pre-clinical and clinical characterization of ChimeriVax-WN02 for humans, a live chimeric vaccine composed of a yellow fever (YF) 17D virus in which the prM-E envelope protein genes are replaced with the corresponding genes of the WN NY99 virus. Pre-clinical studies demonstrated that ChimeriVax-WN02 was significantly less neurovirulent than YF 17D in mice and rhesus and cynomolgus monkeys. The vaccine elicited neutralizing antibody titers after inoculation in hamsters and monkeys and protected immunized animals from lethal challenge including intracerebral inoculation of high dose of WN NY99 virus. Safety, viremia and immunogenicity of ChimeriVax-WN02 were assessed in one phase I study and in two phase II clinical trials. No safety signals were detected in the three clinical trials with no remarkable differences in incidence of adverse events (AEs) between vaccine and placebo recipients. Viremia was transient and the mean viremia levels were low. The vaccine elicited strong and durable neutralizing antibody and cytotoxic T cell responses. WN epidemiology impedes a classical licensure pathway; therefore, innovative licensure strategies should be explored.

  6. Midwives at youth clinics attitude to HPV vaccination and their role in cervical cancer prevention.

    PubMed

    Oscarsson, Marie G; Dahlberg, Annica; Tydén, Tanja

    2011-11-01

    To explore youth clinic midwives role in cervical cancer prevention and their attitude to HPV vaccination. Individual interviews with 13 midwives working at youth clinics in Sweden. The interviews were recorded, transcribed, and analysed by qualitative content analysis. Three themes were identified in the qualitative content analysis: "Cervical cancer prevention not a prioritised area", "Ambivalence to the HPV vaccine", and "Gender and socioeconomic controversies". Few midwives talked spontaneously about cervical cancer prevention. The responsibility for providing information about HPV vaccination was considered as primarily that of school health nurses and parents. Midwives were positive about the HPV vaccination, but recognised certain risks, such as its potential negative impact on cervical cancer screening and increased sexual risk taking. The midwives expressed concerns with medical risks, such as side effects and unknown long-term effects of the HPV vaccine. The midwives in the study had ethical concerns that boys were not included in the program and not all families had the financial resources to vaccinate their children. Thus, weak socioeconomic groups might be excluded. The midwives considered cervical cancer prevention as important, but did not integrate information on the HPV vaccine into their routine work, mainly because young people visiting youth clinics had had their sexual debut and they were concerned about the medical risks and that the vaccine was too expensive. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. Clinical trial explores new glioblastoma treatment regimen | Center for Cancer Research

    Cancer.gov

    On average, a patient with glioblastoma lives for only about a year after diagnosis. In a new clinical trial, CCR researchers will test whether a combination of a vaccine made from the patient’s tumor with another immunotherapy treatment can increase survival rates. Read more...  

  8. Vaccines: an ongoing promise?

    PubMed

    Alsahli, M; Farrell, R J; Michetti, P

    2001-01-01

    Over the past decade, intensive research has focused on developing a vaccine therapy for Helicobacter pylori. Substantial unresolved questions cloud the current approach, and the development of a vaccine against this unique organism has proved very challenging. Many candidate vaccines have been tested in animal models. The immunogenicity and the safety of some vaccine formulations have been recently evaluated through clinical trials, and the efficacy of these vaccine therapies in humans will be determined in the near future. This article will provide an overview of the current knowledge of natural and vaccine-induced immune responses to H. pylori infection. It will also review past vaccine successes and failures in animal models and the limited experience to date in using vaccine therapy in humans. Several obstacles to H. pylori vaccine development efforts along with the future direction of these efforts will be discussed. Copyright 2001 S. Karger AG, Basel

  9. European Vaccine Initiative: lessons from developing malaria vaccines.

    PubMed

    Geels, Mark J; Imoukhuede, Egeruan B; Imbault, Nathalie; van Schooten, Harry; McWade, Terry; Troye-Blomberg, Marita; Dobbelaer, Roland; Craig, Alister G; Leroy, Odile

    2011-12-01

    For over 10 years, the European Vaccine Initiative (EVI; European Malaria Vaccine Initiative until 2009) has contributed to the development of 24 malaria candidate vaccine antigens with 13 vaccine candidates being advanced into Phase I clinical trials, two of which have been transitioned for further clinical development in sub-Saharan Africa. Since its inception the EVI organization has operated as a funding agency, but with a clear service-oriented strategy. The scientific successes and difficulties encountered during these years and how these efforts have led to standardization and harmonization in vaccine development through large-scale European consortia are discussed. In the future, the EVI will remain instrumental in the pharmaceutical and clinical development of vaccines against 'diseases of poverty' with a continued focus on malaria. EVI will continue to focus on funding and managing preclinical evaluation up to Phase I/II clinical trials and strengthening the vaccine-development infrastructure in Europe, albeit with a global orientation.

  10. A Virtual Clinic Improves Pneumococcal Vaccination for Asplenic Veterans at High Risk for Pneumococcal Disease

    PubMed Central

    Jump, Robin L.; Banks, Richard; Wilson, Brigid; Montpetite, Michelle M.; Carter, Rebecca; Phillips, Susan; Perez, Federico

    2015-01-01

    We developed a “virtual clinic” to improve pneumococcal vaccination among asplenic adults. Using an electronic medical record, we identified patients, assessed their vaccination status, entered orders, and notified patients and providers. Within 180 days, 38 of 76 patients (50%) received a pneumococcal vaccination. A virtual clinic may optimize vaccinations among high-risk patients. PMID:26668815

  11. Phage idiotype vaccination: first phase I/II clinical trial in patients with multiple myeloma

    PubMed Central

    2014-01-01

    Background Multiple myeloma is characterized by clonal expansion of B cells producing monoclonal immunoglobulins or fragments thereof, which can be detected in the serum and/or urine and are ideal target antigens for patient-specific immunotherapies. Methods Using phage particles as immunological carriers, we employed a novel chemically linked idiotype vaccine in a clinical phase I/II trial including 15 patients with advanced multiple myeloma. Vaccines composed of purified paraproteins linked to phage were manufactured successfully for each patient. Patients received six intradermal immunizations with phage idiotype vaccines in three different dose groups. Results Phage idiotype was well tolerated by all study participants. A subset of patients (80% in the middle dose group) displayed a clinical response indicated by decrease or stabilization of paraprotein levels. Patients exhibiting a clinical response to phage vaccines also raised idiotype-specific immunoglobulins. Induction of a cellular immune response was demonstrated by a cytotoxicity assay and delayed type hypersensitivity tests. Conclusion We present a simple, time- and cost-efficient phage idiotype vaccination strategy, which represents a safe and feasible patient-specific therapy for patients with advanced multiple myeloma and produced promising anti-tumor activity in a subset of patients. PMID:24885819

  12. WHO consultation on clinical evaluation of vaccines, 17-18 July 2014, WHO Headquarters, Geneva, Switzerland.

    PubMed

    Knezevic, Ivana; Moorthy, Vasee; Sheets, Rebecca

    2015-04-21

    A World Health Organization (WHO) consultation on guidelines for National Regulatory Authorities (NRAs) and vaccine manufacturers on clinical evaluation of vaccines was held from 17 to 18 July 2014, to review key scientific challenges that regulators have been facing since the establishment of the WHO Guidelines on Clinical Evaluation of Vaccines. The guidelines, adopted by the WHO Expert Committee on Biological Standardization (ECBS) in 2001, have served as the basis for setting or updating national requirements for the evaluation and licensing of a broad range of vaccines as well as for WHO vaccine prequalification. Regulators from Australia, Brazil, China, Canada, Germany, India, Republic of Korea, South Africa, United States of America and the United Kingdom were represented. The International Federation for Pharmaceutical Manufacturers' Association (IFPMA) and the Developing Country Vaccine Manufacturers' Network (DCVMN) provided industry representation. The consultation concluded that the guidelines should be revised to address issues that were raised in the context of vaccines that were the subject of clinical development in the past decade. Although the current guidelines have served well over time, it was recognized that an update would further increase their utility and would help regulators, manufacturers, vaccine developers and academia to respond to the challenging questions regarding the safety, immunogenicity, efficacy and effectiveness of vaccines intended for global use. A summary of the main outcomes of the consultation and proposals for the next steps regarding the guidelines and beyond are provided in this report. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. Infectious disease research investments: systematic analysis of immunology and vaccine research funding in the UK.

    PubMed

    Fitchett, Joseph R; Head, Michael G; Atun, Rifat

    2013-12-05

    Financing for global health is a critical element of research and development. Innovations in new vaccines are critically dependent on research funding given the large sums required, however estimates of global research investments are lacking. We evaluate infectious disease research investments, focusing on immunology and vaccine research by UK research funding organisations. In 1997-2010, £2.6 billion were spent by public and philanthropic organisations, with £590 million allocated to immunology and vaccine research. Preclinical studies received the largest funding amount £505 million accounting for 85.6% of total investment. In terms of specific infection, "the big three" infections dominated funding: HIV received £127 million (21.5% of total), malaria received £59 million (10.0% of total) and tuberculosis received £36 million (6.0% of total). We excluded industry funding from our analysis, as open-access data were unavailable. A global investment surveillance system is needed to map and monitor funding and guide allocation of scarce resources. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  14. Leidos Biomed Supports Clinical Trials for Vaccine Against Mosquito-borne Chikungunya | FNLCR Staging

    Cancer.gov

    An experimental vaccine for mosquito-borne chikungunya is being tested at sites in the Caribbean as part of a phase II clinical trial being managed by the Frederick National Lab. No vaccine or treatment currently exists for the viral disease, which c

  15. Accelerating the development of a safe and effective HIV vaccine: HIV vaccine case study for the Decade of Vaccines.

    PubMed

    Koff, Wayne C; Russell, Nina D; Walport, Mark; Feinberg, Mark B; Shiver, John W; Karim, Salim Abdool; Walker, Bruce D; McGlynn, Margaret G; Nweneka, Chidi Victor; Nabel, Gary J

    2013-04-18

    Human immunodeficiency virus (HIV), the etiologic agent that causes AIDS, is the fourth largest killer in the world today. Despite the remarkable achievements in development of anti-retroviral therapies against HIV, and the recent advances in new prevention technologies, the rate of new HIV infections continue to outpace efforts on HIV prevention and control. Thus, the development of a safe and effective vaccine for prevention and control of AIDS remains a global public health priority and the greatest opportunity to eventually end the AIDS pandemic. Currently, there is a renaissance in HIV vaccine development, due in large part to the first demonstration of vaccine induced protection, albeit modest, in human efficacy trials, a generation of improved vaccine candidates advancing in the clinical pipeline, and newly defined targets on HIV for broadly neutralizing antibodies. The main barriers to HIV vaccine development include the global variability of HIV, lack of a validated animal model, lack of correlates of protective immunity, lack of natural protective immune responses against HIV, and the reservoir of infected cells conferred by integration of HIV's genome into the host. Some of these barriers are not unique to HIV, but generic to other variable viral pathogens such as hepatitis C and pandemic influenza. Recommendations to overcome these barriers are presented in this document, including but not limited to expansion of efforts to design immunogens capable of eliciting broadly neutralizing antibodies against HIV, expansion of clinical research capabilities to assess multiple immunogens concurrently with comprehensive immune monitoring, increased support for translational vaccine research, and engaging industry as full partners in vaccine discovery and development. Copyright © 2012 Elsevier Ltd. All rights reserved.

  16. Impact of a new vaccine clinic on hepatitis B vaccine completion and immunological response rates in an HIV-positive cohort.

    PubMed

    Rock, Clare; de Barra, Eoghan; Sadlier, Corinna; Kelly, Sinead; Dowling, Catherine; McNally, Cora; Bergin, Colm

    2013-06-01

    Hepatitis B virus vaccination (HBVV) in the HIV-infected population has poor reported completion rates and immunological response rates. At our HIV clinic, we established a vaccine clinic to improve HBVV outcomes using interventions such as SMS text reminders and double-dose (DD) HBVV for standard-dose non-responders (SD NRs). A five-year (2003-2008) retrospective review of the completion rates and immunological response rates for HBVV after the establishment of the dedicated vaccine clinic was conducted. Statistical significance was assumed at p<0.05, and the analysis was performed using SPSS (v16). A total of 354 HIV-infected patients were included. Seventy-five percent (268/354) of patients completed the SD HBVV, an 84% (226/268) returned for the hepatitis B surface antibody evaluation. Only 47.3% (107/226) responded to standard-dose hepatitis B vaccination. Responders had higher absolute numbers (p=0.017) and percentages of CD4 cells (p<0.001) and were more likely to be receiving HAART (p=0.001). There was a 70% (48/69) response rate to DD HBVV among SD NRs. On-treatment analysis showed an 88% (155/176) overall immunological response to SD HBVV and DD HBVV, if required. High HBVV completion and response rates in this HIV cohort were enabled through the use of multiple interventions, including the use of SMS text message reminders and routine referral for DD vaccination. Copyright © 2012 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

  17. Learning from Successful School-based Vaccination Clinics during 2009 pH1N1

    ERIC Educational Resources Information Center

    Klaiman, Tamar; O'Connell, Katherine; Stoto, Michael A.

    2014-01-01

    Background: The 2009 H1N1 vaccination campaign was the largest in US history. State health departments received vaccines from the federal government and sent them to local health departments (LHDs) who were responsible for getting vaccines to the public. Many LHD's used school-based clinics to ensure children were the first to receive limited…

  18. The HPV Vaccine | Center for Cancer Research

    Cancer.gov

    Two researchers leveraged CCR’s unique environment of investigator-driven inquiry to pursue studies of two cancer-causing genes that eventually led to the development of a vaccine against two forms of human papillomavirus.

  19. Tuberculosis vaccine development: strength lies in tenacity.

    PubMed

    Kaufmann, Stefan H E

    2012-07-01

    The past decade has witnessed a tremendous increase in the development of novel vaccines against tuberculosis (TB). In mice, each of these vaccine candidates stimulates an immune response that reduces the bacillary load, reflecting control but not sterilization of infection. Yet, the immune mechanisms underlying vaccine efficacy are only partially understood. In parallel to clinical assessment of current candidates, the next generation of vaccine candidates still needs to be developed. This requires basic research on how to induce the most efficacious immune response. Equally important is the dissection of immune responses in patients, latently infected healthy individuals, and participants of clinical vaccine trials. Amalgamation of this information will foster the way towards more efficacious vaccination strategies that not only prevent disease, but prevent or abolish infection. Copyright © 2012 Elsevier Ltd. All rights reserved.

  20. African-American and Hispanic perceptions of HIV vaccine clinical research: a qualitative study.

    PubMed

    Toledo, Lauren; McLellan-Lemal, Eleanor; Arreola, Sonya; Campbell, Chadwick; Sutton, Madeline

    2014-01-01

    To examine perceptions of phase-I human immunodeficiency virus (HIV) vaccine trial participation among African-Americans and Hispanics in San Francisco, California. Qualitative, semistructured interviews. San Francisco Department of Health. Thirty-six African-American and Hispanic men and women, 18 to 50 years of age, residing in the San Francisco Bay Area. Purposive sampling using advertisements, community-based organization rosters, and snowball referrals. Thematic analysis of transcripts identified salient themes and patterns. Participants viewed participation in HIV research as important; however, they held that HIV was not a health priority given limited awareness about HIV research or beliefs that only infected or high-risk persons were eligible for participation. Altruism and personal gain, trustworthy trial staff, convenient schedules and facilities, and involvement of trusted community groups in recruitment were perceived to motivate participants. Concerns about the social consequences of participating in HIV research and product-related side effects were seen as discouraging participation. Limitations include the possibility that participants in interview research have more favorable views of biomedical research than those who refuse to participate. Historically, African-Americans and Hispanics in the United States have had limited participation in HIV trials. Understanding their perceptions of HIV biomedical research, identifying facilitators and barriers to participation, addressing misinformation about HIV, distorted risk perceptions, HIV stigma, and providing accessible opportunities to participate are imperative to ensure health equity and generalizability of findings.

  1. An immunologic model for rapid vaccine assessment -- a clinical trial in a test tube.

    PubMed

    Higbee, Russell G; Byers, Anthony M; Dhir, Vipra; Drake, Donald; Fahlenkamp, Heather G; Gangur, Jyoti; Kachurin, Anatoly; Kachurina, Olga; Leistritz, Del; Ma, Yifan; Mehta, Riyaz; Mishkin, Eric; Moser, Janice; Mosquera, Luis; Nguyen, Mike; Parkhill, Robert; Pawar, Santosh; Poisson, Louis; Sanchez-Schmitz, Guzman; Schanen, Brian; Singh, Inderpal; Song, Haifeng; Tapia, Tenekua; Warren, William; Wittman, Vaughan

    2009-09-01

    While the duration and size of human clinical trials may be difficult to reduce, there are several parameters in pre-clinical vaccine development that may be possible to further optimise. By increasing the accuracy of the models used for pre-clinical vaccine testing, it should be possible to increase the probability that any particular vaccine candidate will be successful in human trials. In addition, an improved model will allow the collection of increasingly more-informative data in pre-clinical tests, thus aiding the rational design and formulation of candidates entered into clinical evaluation. An acceleration and increase in sophistication of pre-clinical vaccine development will thus require the advent of more physiologically-accurate models of the human immune system, coupled with substantial advances in the mechanistic understanding of vaccine efficacy, achieved by using this model. We believe the best viable option available is to use human cells and/or tissues in a functional in vitro model of human physiology. Not only will this more accurately model human diseases, it will also eliminate any ethical, moral and scientific issues involved with use of live humans and animals. An in vitro model, termed "MIMIC" (Modular IMmune In vitro Construct), was designed and developed to reflect the human immune system in a well-based format. The MIMIC System is a laboratory-based methodology that replicates the human immune system response. It is highly automated, and can be used to simulate a clinical trial for a diverse population, without putting human subjects at risk. The MIMIC System uses the circulating immune cells of individual donors to recapitulate each individual human immune response by maintaining the autonomy of the donor. Thus, an in vitro test system has been created that is functionally equivalent to the donor's own immune system and is designed to respond in a similar manner to the in vivo response. 2009 FRAME.

  2. HIV-1 Immunogen: an overview of almost 30 years of clinical testing of a candidate therapeutic vaccine.

    PubMed

    Graziani, Gina M; Angel, Jonathan B

    2016-07-01

    Although current antiretroviral therapy (ART) has transformed HIV infection into a chronic, manageable disease, ART does not cure HIV infection. Furthermore, the majority of the world's infected individuals live in resource-limited countries in which access to ART is limited. Thus, the development of an effective therapeutic HIV vaccine would be an invaluable treatment alternative. Developed by the late Dr. Jonas Salk, HIV-1 Immunogen (Remune®) is a candidate therapeutic vaccine that has been studied in thousands of HIV-infected individuals in more than a dozen clinical trials during almost three decades. This Drug Evaluation, which summarizes the results of these trials that have shown the vaccine to be safe and immunogenic, also discusses the contradictory and controversial conclusions drawn from the phases 2, 2/3 and 3 trials that assessed the clinical efficacy of this vaccine. Given the lack of unequivocal clinical benefits of HIV-1 Immunogen despite almost 30 years of extensive testing, it does not appear, in our view, that this vaccine is a clinically effective immunotherapy. However, inclusion of this vaccine in the newly proposed 'Kick/Shock and Kill' strategy for HIV eradication, or use as a prophylactic vaccine, could be considered for future trials.

  3. CCR’s Douglas Lowy and John Schiller receive the 2017 Lasker~DeBakey Clinical Medical Research Award | Center for Cancer Research

    Cancer.gov

    Douglas Lowy, M.D., and John Schiller, Ph.D., of CCR’s Laboratory of Cellular Oncology have received the 2017 Lasker~DeBakey Clinical Medical Research Award for their groundbreaking research leading to the development of human papillomavirus (HPV) vaccines. The Lasker Awards are widely regarded as the country’s most prestigious biomedical research prizes.

  4. Report of a consultation on the optimization of clinical challenge trials for evaluation of candidate blood stage malaria vaccines, 18-19 March 2009, Bethesda, MD, USA.

    PubMed

    Moorthy, V S; Diggs, C; Ferro, S; Good, M F; Herrera, S; Hill, A V; Imoukhuede, E B; Kumar, S; Loucq, C; Marsh, K; Ockenhouse, C F; Richie, T L; Sauerwein, R W

    2009-09-25

    Development and optimization of first generation malaria vaccine candidates has been facilitated by the existence of a well-established Plasmodium falciparum clinical challenge model in which infectious sporozoites are administered to human subjects via mosquito bite. While ideal for testing pre-erythrocytic stage vaccines, some researchers believe that the sporozoite challenge model is less appropriate for testing blood stage vaccines. Here we report a consultation, co-sponsored by PATH MVI, USAID, EMVI and WHO, where scientists from all institutions globally that have conducted such clinical challenges in recent years and representatives from regulatory agencies and funding agencies met to discuss clinical malaria challenge models. Participants discussed strengthening and harmonizing the sporozoite challenge model and considered the pros and cons of further developing a blood stage challenge possibly better suited for evaluating the efficacy of blood stage vaccines. This report summarizes major findings and recommendations, including an update on the Plasmodium vivax clinical challenge model, the prospects for performing experimental challenge trials in malaria endemic countries and an update on clinical safety data. While the focus of the meeting was on the optimization of clinical challenge models for evaluation of blood stage candidate malaria vaccines, many of the considerations are relevant for the application of challenge trials to other purposes.

  5. The effect of exercise on vaccine-related pain, anxiety and fear during HPV vaccinations in adolescents.

    PubMed

    Lee, V Y; Booy, R; Skinner, R; Edwards, K M

    2018-05-31

    With increased school-based vaccinations for improved coverage rates and practicality, the World Health Organization (WHO) recently endorsed research to identify possible interventions to reduce vaccine-related pain in mass clinical and school-based settings. In particular, the lack of research in adolescents indicate a particular need in this population. Acute exercise has analgesic effects and has been used as a behavioural adjuvant to vaccination. Here, we examine the effect of exercise on vaccine-related pain, anxiety and fear in adolescents, during a school-based program for HPV vaccinations. 116 students (Female: 61, Male: 55) aged 11-13 years were randomly allocated to either an Exercise (n = 60) or Control (n = 56) group. All participants completed demographic and Trait-anxiety questionnaires prior to receiving the vaccine according to usual care. The Exercise group also performed upper body exercise for 15 min prior to receiving the vaccine. Immediately after the vaccine administration, all participants reported on pain, anxiety and fear at the time of receiving the vaccine. Female adolescents in the Exercise group reported significantly less pain (3.64; 95% CI, 2.98-4.30) than Controls (4.58; 95% CI, 3.96-5.19; p = 0.04). Further, females reported greater pain and anxiety than males in the Control group but not the Exercise group. This study supports the use of exercise prior to vaccine administration, especially in female adolescents who are particularly vulnerable to negative experiences during vaccination procedures. Furthermore, the ease of application, as well as the benefit of exercise, provides support for the use of simple exercise prior to vaccination in mass vaccination settings. Clinical trial registry: ANZCTR, ACTRN12614001185651. Copyright © 2018 Elsevier Ltd. All rights reserved.

  6. Ontology-supported research on vaccine efficacy, safety and integrative biological networks.

    PubMed

    He, Yongqun

    2014-07-01

    While vaccine efficacy and safety research has dramatically progressed with the methods of in silico prediction and data mining, many challenges still exist. A formal ontology is a human- and computer-interpretable set of terms and relations that represent entities in a specific domain and how these terms relate to each other. Several community-based ontologies (including Vaccine Ontology, Ontology of Adverse Events and Ontology of Vaccine Adverse Events) have been developed to support vaccine and adverse event representation, classification, data integration, literature mining of host-vaccine interaction networks, and analysis of vaccine adverse events. The author further proposes minimal vaccine information standards and their ontology representations, ontology-based linked open vaccine data and meta-analysis, an integrative One Network ('OneNet') Theory of Life, and ontology-based approaches to study and apply the OneNet theory. In the Big Data era, these proposed strategies provide a novel framework for advanced data integration and analysis of fundamental biological networks including vaccine immune mechanisms.

  7. Towards clinical development of a Pfs48/45-based transmission blocking malaria vaccine.

    PubMed

    Theisen, Michael; Jore, Matthijs M; Sauerwein, Robert

    2017-04-01

    Malaria is a devastating vector-borne disease caused by the Plasmodium parasite, resulting in almost 0.5 million casualties per year. The parasite has a complex life-cycle that includes asexual replication in human red blood cells, causing symptomatic malaria, and sexual stages which are essential for the transmission to the mosquito vector. A vaccine targeting the sexual stages of the parasite and thus blocking transmission will be instrumental for the eradication of malaria. One of the leading transmission blocking vaccine candidates is the sexual stage antigen Pfs48/45. Areas covered: PubMed was searched to review the progress and future prospects for clinical development of a Pfs48/45-based subunit vaccine. We will focus on biological function, naturally acquired immunity, functional activity of specific antibodies, sequence diversity, production of recombinant protein and preclinical studies. Expert commentary: Pfs48/45 is one of the lead-candidates for a transmission blocking vaccine and should be further explored in clinical trials.

  8. Vaccine Hesitancy.

    PubMed

    Jacobson, Robert M; St Sauver, Jennifer L; Finney Rutten, Lila J

    2015-11-01

    Vaccine refusal received a lot of press with the 2015 Disneyland measles outbreak, but vaccine refusal is only a fraction of a much larger problem of vaccine delay and hesitancy. Opposition to vaccination dates back to the 1800 s, Edward Jenner, and the first vaccine ever. It has never gone away despite the public's growing scientific sophistication. A variety of factors contribute to modern vaccine hesitancy, including the layperson's heuristic thinking when it comes to balancing risks and benefits as well as a number of other features of vaccination, including falling victim to its own success. Vaccine hesitancy is pervasive, affecting a quarter to a third of US parents. Clinicians report that they routinely receive requests to delay vaccines and that they routinely acquiesce. Vaccine rates vary by state and locale and by specific vaccine, and vaccine hesitancy results in personal risk and in the failure to achieve or sustain herd immunity to protect others who have contraindications to the vaccine or fail to generate immunity to the vaccine. Clinicians should adopt a variety of practices to combat vaccine hesitancy, including a variety of population health management approaches that go beyond the usual call to educate patients, clinicians, and the public. Strategies include using every visit to vaccinate, the creation of standing orders or nursing protocols to provide vaccination without clinical encounters, and adopting the practice of stating clear recommendations. Up-to-date, trusted resources exist to support clinicians' efforts in adopting these approaches to reduce vaccine hesitancy and its impact. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  9. Targeting immune response with therapeutic vaccines in premalignant lesions and cervical cancer: hope or reality from clinical studies

    PubMed Central

    Vici, P; Pizzuti, L; Mariani, L; Zampa, G; Santini, D; Di Lauro, L; Gamucci, T; Natoli, C; Marchetti, P; Barba, M; Maugeri-Saccà, M; Sergi, D; Tomao, F; Vizza, E; Di Filippo, S; Paolini, F; Curzio, G; Corrado, G; Michelotti, A; Sanguineti, G; Giordano, A; De Maria, R; Venuti, A

    2016-01-01

    ABSTRACT Human papillomavirus (HPV) is widely known as a cause of cervical cancer (CC) and cervical intraepithelial neoplasia (CIN). HPVs related to cancer express two main oncogenes, i.e. E6 and E7, considered as tumorigenic genes; their integration into the host genome results in the abnormal regulation of cell cycle control. Due to their peculiarities, these oncogenes represent an excellent target for cancer immunotherapy. In this work the authors highlight the potential use of therapeutic vaccines as safe and effective pharmacological tools in cervical disease, focusing on vaccines that have reached the clinical trial phase. Many therapeutic HPV vaccines have been tested in clinical trials with promising results. Adoptive T-cell therapy showed clinical activity in a phase II trial involving advanced CC patients. A phase II randomized trial showed clinical activity of a nucleic acid-based vaccine in HPV16 or HPV18 positive CIN. Several trials involving peptide-protein-based vaccines and live-vector based vaccines demonstrated that these approaches are effective in CIN as well as in advanced CC patients. HPV therapeutic vaccines must be regarded as a therapeutic option in cervical disease. The synergic combination of HPV therapeutic vaccines with radiotherapy, chemotherapy, immunomodulators or immune checkpoint inhibitors opens a new and interesting scenario in this disease. PMID:27063030

  10. Changing the Face of Veterinary Medicine: Research and Clinical Developments at AAVMC Institutions.

    PubMed

    Smith, Donald F; Hagstrom, Melena R

    2015-01-01

    This paper provides a 50-year overview of research and clinical advances in AAVMC member colleges in four representative fields of veterinary medicine: oncology, vaccine development, production medicine, and public health. Though emphasis is on the progress since the mid-1960s, the salient background and associated personnel in each field are also identified to the extent that their description informs more recent events. Advances in board certification and post-graduate clinical and research educational opportunities are also described.

  11. Student agreement regarding adequacy of didactic content and practical experiences of vaccination clinic business operations.

    PubMed

    George, David L; Johnson, Eric J; O'Neal, Katherine S; Smith, Michael J

    2018-04-01

    To report student perceived adequacy regarding didactic content and practical experiences of vaccination clinic business operations. Didactic content, a case study, and practical experiences regarding vaccination clinic business operations were implemented in related lectures of a Pharmacy Business and Entrepreneurship (PBE) elective and the college of pharmacy sponsored vaccination clinics. An online survey was used to evaluate student perceived adequacy of didactic content and practical experiences of vaccination clinic business operations. Mean scaled agreement was compared between students in the PBE elective versus those not in the elective. Student confidence in performing business operations was also assessed. Students in the PBE had higher mean confidence than non-elective students regarding staff management (3.23 vs. 2.73, p = 0.04). Success of the interventions may be attributed to students in the PBE elective that reported a higher mean perceived adequacy of content and practical experiences and confidence in performing nearly all business operations. Still, further evaluation of interventions is being considered to assess effectiveness of learning. Published by Elsevier Inc.

  12. A tool for the economic analysis of mass prophylaxis operations with an application to H1N1 influenza vaccination clinics.

    PubMed

    Cho, Bo-Hyun; Hicks, Katherine A; Honeycutt, Amanda A; Hupert, Nathaniel; Khavjou, Olga; Messonnier, Mark; Washington, Michael L

    2011-01-01

    This article uses the 2009 H1N1 influenza vaccination program experience to introduce a cost analysis approach that may be relevant for planning mass prophylaxis operations, such as vaccination clinics at public health centers, work sites, schools, or pharmacy-based clinics. These costs are important for planning mass influenza vaccination activities and are relevant for all public health emergency preparedness scenarios requiring countermeasure dispensing. We demonstrate how costs vary depending on accounting perspective, staffing composition, and other factors. We also describe a mass vaccination clinic budgeting tool that clinic managers may use to estimate clinic costs and to examine how costs vary depending on the availability of volunteers or donated supplies and on the number of patients vaccinated per hour. Results from pilot tests with school-based H1N1 influenza vaccination clinic managers are described. The tool can also contribute to planning efforts for universal seasonal influenza vaccination.

  13. Japanese encephalitis vaccines: current vaccines and future prospects.

    PubMed

    Monath, T P

    2002-01-01

    Vaccination against JE ideally should be practiced in all areas of Asia where the virus is responsible for human disease. The WHO has placed a high priority on the development of a new vaccine for prevention of JE. Some countries in Asia (Japan, South Korea, North Korea, Taiwan, Vietnam, Thailand, and the PRC) manufacture JE vaccines and practice childhood immunization, while other countries suffering endemic or epidemic disease (India, Nepal, Laos, Cambodia, Bangladesh, Myanmar, Malaysia, Indonesia and the Philippines) have no JE vaccine manufacturing or policy for use. With the exception of the PRC, all countries practicing JE vaccination use formalin inactivated mouse brain vaccines, which are relatively expensive and are associated with rare but clinically significant allergic and neurological adverse events. New inactivated JE vaccines manufactured in Vero cells are in advanced preclinical or early clinical development in Japan, South Korea, Taiwan, and the PRC. An empirically derived, live attenuated vaccine (SA14-14-2) is widely used in the PRC. Trials in the PRC have shown SA14-14-2 to be safe and effective when administered in a two-dose regimen, but regulatory concerns over manufacturing and control have restricted international distribution. The genetic basis of attenuation of SA14-14-2 has been partially defined. A new live attenuated vaccine (ChimeriVax-JE) that uses a reliable flavivirus vaccine--yellow fever 17D--as a live vector for the envelope genes of SA14-14-2 virus is in early clinical trials and appears to be well tolerated and immunogenic after a single dose. Vaccinia and avipox vectored vaccines have also been tested clinically, but are no longer being pursued due to restricted effectiveness mediated by anti-vector immunity. Other approaches to JE vaccines--including naked DNA, oral vaccination, and recombinant subunit vaccines--have been reviewed.

  14. Review of the Persistence of Herpes Zoster Vaccine Efficacy in Clinical Trials.

    PubMed

    Cook, Stephen J; Flaherty, Dennis K

    2015-11-01

    The live attenuated herpes zoster vaccine(*) was approved for the prevention of shingles in 2006. Initial Phase III clinical trials proved vaccine efficacy persisted during the study duration; however, assessment of long-term efficacy required additional studies. This article reviews efficacy data for the zoster vaccine that have been published since 2004. It focuses on studies assessing declining vaccine efficacy. MEDLINE, EMBASE, CENTRAL, and CINAHL databases were searched for zoster vaccine efficacy trials. Randomized controlled trials published from 2004 to 2015 were included in the review. Six studies were included in the review. The zoster vaccine reduced the risk of herpes zoster by 51.3% to 72.4% in 2 Phase III trials. Primary and other analyses showed the vaccine was effective at reducing the burden of illness (61.1%), postherpetic neuralgia (66.5%), disease interference on functional status (66.2%), and disease impact on health-related quality of life (55%) compared with placebo. Surveillance studies showed a decrease in vaccine efficacy for reducing the incidence of herpes zoster during follow-up years 3.3 to 7.8 (39.6% relative reduction) and 4.7 to 11.6 (21.1% relative reduction). Initial zoster vaccine efficacy is significant, but declines in post-vaccination years 3 to 11. This raises the question about the need for possible revaccination with the zoster vaccine. Clinicians should consider the declining efficacy when administering the zoster vaccine to patients. Future studies will need to address the impact of the varicella vaccine on the incidence of shingles and whether this impacts the efficacy of the zoster vaccine. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

  15. Bacille Calmette-Guérin (BCG) vaccination at birth and antibody responses to childhood vaccines. A randomised clinical trial.

    PubMed

    Nissen, Thomas Nørrelykke; Birk, Nina Marie; Smits, Gaby; Jeppesen, Dorthe Lisbeth; Stensballe, Lone Graff; Netea, Mihai G; van der Klis, Fiona; Benn, Christine Stabell; Pryds, Ole

    2017-04-11

    BCG vaccination has been associated with beneficial non-specific effects on child health. Some immunological studies have reported heterologous effects of vaccines on antibody responses to heterologous vaccines. Within a randomised clinical trial of Bacille Calmette-Guérin (BCG) vaccination at birth, The Danish Calmette Study, we investigated the effect of BCG at birth on the antibody response to the three routine vaccines against DiTeKiPol/Act-Hib and Prevenar 13 in a subgroup of participants. Within 7days after birth, children were randomised 1:1 to BCG vaccination or to the control group (no intervention). After three routine vaccinations given at age 3, 5 and 12months, antibodies against DiTeKiPol/Act-Hib and Prevenar 13 (Streptococcus pneumoniae serotype type 4, 6B, 9V, 14, 18C, 19F and 23F) were measured 4weeks after the third vaccine dose. Among the 300 included children (178 BCG; 122 controls), almost all children (>96%) had antibody responses above the protective levels. Overall BCG vaccination at birth did not affect the antibody level. When stratifying by 'age at randomisation' we found a possible inducing effect of BCG on antibodies against B. pertussis and all pneumococcal serotypes, when BCG was given after the first day of life. Girls had significantly higher antibody levels for Haemophilus influenza type b and pneumococcus than boys. Three routine vaccinations with DiTeKiPol/Act-Hib and Prevenar 13 induced sero-protective levels in almost all children. No overall effect of neonatal BCG vaccination was observed. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  16. African swine fever virus: current state and future perspectives in vaccine and antiviral research.

    PubMed

    Zakaryan, Hovakim; Revilla, Yolanda

    2016-03-15

    African swine fever (ASF) is among the most significant of swine diseases for which no effective vaccines and antivirals are available. The disease, which is endemic in Africa, was introduced to Trans-Caucasian countries and the Russian Federation in 2007, where it remains prevalent today among domestic pigs and wild boars. Although some measures were implemented, ASF continues to pose a global risk for all countries, and thereby highlighting the importance of vaccine and antiviral research. In this review, an overview of research efforts toward the development of effective vaccines during the past decades is presented. As an alternative to vaccine development, the current state in antiviral research against ASFV is also presented. Finally, future perspectives in vaccine and antiviral research giving emphasis on some strategies that may allow researchers to develop effective countermeasures against ASF are discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Pre-clinical toxicity and immunogenicity evaluation of a MUC1-MBP/BCG anti-tumor vaccine.

    PubMed

    Hu, Boqi; Wang, Juan; Guo, Yingying; Chen, Tanxiu; Ni, Weihua; Yuan, Hongyan; Zhang, Nannan; Xie, Fei; Tai, Guixiang

    2016-04-01

    Mucin 1 (MUC1), as an oncogene, plays a key role in the progression and tumorigenesis of many human adenocarcinomas and is an attractive target in tumor immunotherapy. Our previous study showed that the MUC1-MBP/BCG anti-tumor vaccine induced a MUC1-specific Th1-dominant immune response, simulated MUC1-specific cytotoxic T lymphocyte killing activity, and could significantly inhibit MUC1-expression B16 cells' growth in mice. To help move the vaccine into a Phase I clinical trial, in the current study, a pre-clinical toxicity and immunogenicity evaluation of the vaccine was conducted. The evaluation was comprised of a single-dose acute toxicity study in mice, repeat-dose chronic toxicity and immunogenicity studies in rats, and pilot toxicity and immunogenicity studies in cynomolgus monkeys. The results showed that treatment with the MUC1-MBP/BCG anti-tumor vaccine did not cause any organ toxicity, except for arthritis or local nodules induced by BCG in several rats. Furthermore, the vaccine significantly increased the levels of IFN-γ in rats, indicating that Th1 cells were activated. In addition, the results showed that the MUC1-MBP/BCG anti-tumor vaccine induced a MUC1-specific IgG antibody response both in rats and cynomolgus monkeys. Collectively, these data are beneficial to move the MUC1-MBP/BCG anti-tumor vaccine into a Phase I clinical trial. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Emerging human papillomavirus vaccines

    PubMed Central

    Ma, Barbara; Maraj, Bharat; Tran, Nam Phuong; Knoff, Jayne; Chen, Alexander; Alvarez, Ronald D; Hung, Chien-Fu; Wu, T.-C.

    2013-01-01

    Introduction Identification of human papillomavirus (HPV) as the etiologic factor of cervical, anogenital, and a subset of head and neck cancers has stimulated the development of preventive and therapeutic HPV vaccines to control HPV-associated malignancies. Excitement has been generated by the commercialization of two preventive L1-based vaccines, which use HPV virus-like particles (VLPs) to generate capsid-specific neutralizing antibodies. However, factors such as high cost and requirement for cold chain have prevented widespread implementation where they are needed most. Areas covered Next generation preventive HPV vaccine candidates have focused on cost-effective stable alternatives and generating broader protection via targeting multivalent L1 VLPs, L2 capsid protein, and chimeric L1/L2 VLPs. Therapeutic HPV vaccine candidates have focused on enhancing T cell-mediated killing of HPV-transformed tumor cells, which constitutively express HPV-encoded proteins, E6 and E7. Several therapeutic HPV vaccines are in clinical trials. Expert opinion Although progress is being made, cost remains an issue inhibiting the use of preventive HPV vaccines in countries that carry the majority of the cervical cancer burden. In addition, progression of therapeutic HPV vaccines through clinical trials may require combination strategies employing different therapeutic modalities. As research in the development of HPV vaccines continues, we may generate effective strategies to control HPV-associated malignancies. PMID:23163511

  19. Pre-clinical development of a hydrogen peroxide-inactivated West Nile virus vaccine.

    PubMed

    Poore, Elizabeth A; Slifka, Dawn K; Raué, Hans-Peter; Thomas, Archana; Hammarlund, Erika; Quintel, Benjamin K; Torrey, Lindsay L; Slifka, Ariel M; Richner, Justin M; Dubois, Melissa E; Johnson, Lawrence P; Diamond, Michael S; Slifka, Mark K; Amanna, Ian J

    2017-01-05

    West Nile virus (WNV) is a mosquito-transmitted pathogen with a wide geographical range that can lead to long-term disability and death in some cases. Despite the public health risk posed by WNV, including an estimated 3 million infections in the United States alone, no vaccine is available for use in humans. Here, we present a scaled manufacturing approach for production of a hydrogen peroxide-inactivated whole virion WNV vaccine, termed HydroVax-001WNV. Vaccination resulted in robust virus-specific neutralizing antibody responses and protection against WNV-associated mortality in mice or viremia in rhesus macaques (RM). A GLP-compliant toxicology study performed in rats demonstrated an excellent safety profile with clinical findings limited to minor and transient irritation at the injection site. An in vitro relative potency (IVRP) assay was developed and shown to correlate with in vivo responses following forced degradation studies. Long-term in vivo potency comparisons between the intended storage condition (2-8°C) and a thermally stressed condition (40±2°C) demonstrated no loss in vaccine efficacy or protective immunity over a 6-month span of time. Together, the positive pre-clinical findings regarding immunogenicity, safety, and stability indicate that HydroVax-001WNV is a promising vaccine candidate. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Ontology-supported Research on Vaccine Efficacy, Safety, and Integrative Biological Networks

    PubMed Central

    He, Yongqun

    2016-01-01

    Summary While vaccine efficacy and safety research has dramatically progressed with the methods of in silico prediction and data mining, many challenges still exist. A formal ontology is a human- and computer-interpretable set of terms and relations that represent entities in a specific domain and how these terms relate to each other. Several community-based ontologies (including the Vaccine Ontology, Ontology of Adverse Events, and Ontology of Vaccine Adverse Events) have been developed to support vaccine and adverse event representation, classification, data integration, literature mining of host-vaccine interaction networks, and analysis of vaccine adverse events. The author further proposes minimal vaccine information standards and their ontology representations, ontology-based linked open vaccine data and meta-analysis, an integrative One Network (“OneNet”) Theory of Life, and ontology-based approaches to study and apply the OneNet theory. In the Big Data era, these proposed strategies provide a novel framework for advanced data integration and analysis of fundamental biological networks including vaccine immune mechanisms. PMID:24909153

  1. Ebola Virus Disease Candidate Vaccines Under Evaluation in Clinical Trials

    PubMed Central

    Martins, Karen A.; Jahrling, Peter B.; Bavari, Sina; Kuhn, Jens H.

    2016-01-01

    Summary Filoviruses are the etiological agents of two human illnesses: Ebola virus disease and Marburg virus disease. Until 2013, medical countermeasure development against these afflictions was limited to only a few research institutes worldwide as both infections were considered exotic due to very low case numbers. Together with the high case-fatality rate of both diseases, evaluation of any candidate countermeasure in properly controlled clinical trials seemed impossible. However, in 2013, Ebola virus was identified as the etiological agent of a large disease outbreak in Western Africa including almost 30,000 infections and more than 11,000 deaths, including case exportations to Europe and North America. These large case numbers resulted in medical countermeasure development against Ebola virus disease becoming a global public-health priority. This review summarizes the status quo of candidate vaccines against Ebola virus disease, with a focus on those that are currently under evaluation in clinical trials. PMID:27160784

  2. A clinically parameterized mathematical model of Shigella immunity to inform vaccine design

    PubMed Central

    Wahid, Rezwanul; Toapanta, Franklin R.; Simon, Jakub K.; Sztein, Marcelo B.

    2018-01-01

    We refine and clinically parameterize a mathematical model of the humoral immune response against Shigella, a diarrheal bacteria that infects 80-165 million people and kills an estimated 600,000 people worldwide each year. Using Latin hypercube sampling and Monte Carlo simulations for parameter estimation, we fit our model to human immune data from two Shigella EcSf2a-2 vaccine trials and a rechallenge study in which antibody and B-cell responses against Shigella′s lipopolysaccharide (LPS) and O-membrane proteins (OMP) were recorded. The clinically grounded model is used to mathematically investigate which key immune mechanisms and bacterial targets confer immunity against Shigella and to predict which humoral immune components should be elicited to create a protective vaccine against Shigella. The model offers insight into why the EcSf2a-2 vaccine had low efficacy and demonstrates that at a group level a humoral immune response induced by EcSf2a-2 vaccine or wild-type challenge against Shigella′s LPS or OMP does not appear sufficient for protection. That is, the model predicts an uncontrolled infection of gut epithelial cells that is present across all best-fit model parameterizations when fit to EcSf2a-2 vaccine or wild-type challenge data. Using sensitivity analysis, we explore which model parameter values must be altered to prevent the destructive epithelial invasion by Shigella bacteria and identify four key parameter groups as potential vaccine targets or immune correlates: 1) the rate that Shigella migrates into the lamina propria or epithelium, 2) the rate that memory B cells (BM) differentiate into antibody-secreting cells (ASC), 3) the rate at which antibodies are produced by activated ASC, and 4) the Shigella-specific BM carrying capacity. This paper underscores the need for a multifaceted approach in ongoing efforts to design an effective Shigella vaccine. PMID:29304144

  3. A clinically parameterized mathematical model of Shigella immunity to inform vaccine design.

    PubMed

    Davis, Courtney L; Wahid, Rezwanul; Toapanta, Franklin R; Simon, Jakub K; Sztein, Marcelo B

    2018-01-01

    We refine and clinically parameterize a mathematical model of the humoral immune response against Shigella, a diarrheal bacteria that infects 80-165 million people and kills an estimated 600,000 people worldwide each year. Using Latin hypercube sampling and Monte Carlo simulations for parameter estimation, we fit our model to human immune data from two Shigella EcSf2a-2 vaccine trials and a rechallenge study in which antibody and B-cell responses against Shigella's lipopolysaccharide (LPS) and O-membrane proteins (OMP) were recorded. The clinically grounded model is used to mathematically investigate which key immune mechanisms and bacterial targets confer immunity against Shigella and to predict which humoral immune components should be elicited to create a protective vaccine against Shigella. The model offers insight into why the EcSf2a-2 vaccine had low efficacy and demonstrates that at a group level a humoral immune response induced by EcSf2a-2 vaccine or wild-type challenge against Shigella's LPS or OMP does not appear sufficient for protection. That is, the model predicts an uncontrolled infection of gut epithelial cells that is present across all best-fit model parameterizations when fit to EcSf2a-2 vaccine or wild-type challenge data. Using sensitivity analysis, we explore which model parameter values must be altered to prevent the destructive epithelial invasion by Shigella bacteria and identify four key parameter groups as potential vaccine targets or immune correlates: 1) the rate that Shigella migrates into the lamina propria or epithelium, 2) the rate that memory B cells (BM) differentiate into antibody-secreting cells (ASC), 3) the rate at which antibodies are produced by activated ASC, and 4) the Shigella-specific BM carrying capacity. This paper underscores the need for a multifaceted approach in ongoing efforts to design an effective Shigella vaccine.

  4. Effect of human papillomavirus (HPV) vaccination on clinical indicators of sexual behaviour among adolescent girls: the Ontario Grade 8 HPV Vaccine Cohort Study.

    PubMed

    Smith, Leah M; Kaufman, Jay S; Strumpf, Erin C; Lévesque, Linda E

    2015-02-03

    Suboptimal human papillomavirus (HPV) vaccine coverage in some jurisdictions is partly attributed to fears that vaccination may increase risky sexual behaviour. We assessed the effect of HPV vaccination on clinical indicators of sexual behaviour among adolescent girls in Ontario. Using Ontario's administrative health databases, we identified a population-based cohort of girls in grade 8 in the 2 years before (2005/06 and 2006/07) and after (2007/08 and 2008/09) implementation of Ontario's grade 8 HPV vaccination program. For each girl, we then obtained data on vaccine receipt in grades 8 and 9 and data on indicators of sexual behaviour (pregnancy and non-HPV-related sexually transmitted infections) in grades 10-12. Using a quasi-experimental method known as regression discontinuity, we estimated, for each outcome, the risk difference (RD) and relative risk (RR) attributable to vaccination and to program eligibility. The cohort comprised 260 493 girls, of whom 131 781 were ineligible for the program and 128 712 were eligible. We identified 15 441 (5.9%) cases of pregnancy and sexually transmitted infection and found no evidence that vaccination increased the risk of this composite outcome: RD per 1000 girls -0.61 (95% confidence interval [CI] -10.71 to 9.49) and RR 0.96 (95% CI 0.81 to 1.14). Similarly, we found no discernible effect of program eligibility: RD per 1000 girls -0.25 (95% CI -4.35 to 3.85) and RR 0.99 (95% CI 0.93 to 1.06). The findings were similar when outcomes were assessed separately. We present strong evidence that HPV vaccination does not have any significant effect on clinical indicators of sexual behaviour among adolescent girls. These results suggest that concerns over increased promiscuity following HPV vaccination are unwarranted and should not deter from vaccinating at a young age. © 2015 Canadian Medical Association or its licensors.

  5. Concurrent vaccinations against PCV2 and PRRSV: study on the specific immunity and clinical protection in naturally infected pigs.

    PubMed

    Martelli, Paolo; Ardigò, Paolo; Ferrari, Luca; Morganti, Marina; De Angelis, Elena; Bonilauri, Paolo; Luppi, Andrea; Guazzetti, Stefano; Caleffi, Antonio; Borghetti, Paolo

    2013-03-23

    The present study aims at evaluating the efficacy of the concurrent PCV2 and PRRS vaccinations in comparison with single vaccinations and placebo in pigs exposed to both natural viral infections. Four groups of pigs (200 animals each) at 4 weeks of age were considered. Pigs from group A were concurrently vaccinated with a modified live PRRSV-1-based vaccine and a genotype a-based PCV2 subunit (Cap) vaccine via the intramuscular route. Animals from groups B and C were vaccinated with PRRSV and PCV2 vaccines alone, respectively, and group D was inoculated with the adjuvant alone. Clinical score (morbidity), mortality and average daily weight gain (ADWG) were evaluated. Viraemia, virus-specific ELISA antibodies and cell-mediated immunity (CMI) as IFN-γ secreting cells by ELISpot were detected. The clinical signs associated with PRRSV infection lasted from 8 to 16 weeks while those related to PCV2 infection from 5 months of age. The results showed that the concurrent vaccinations reduced clinical signs and increased the preventive fraction (40.4%) and the ADWG. In concurrently vaccinated pigs, the probability of dying due to infection, especially in association with PCV2 viraemia was reduced 3-fold. PRRSV viraemia was not reduced by vaccination but lower and shorter PCV2 viral load was detected in both concurrently and single PCV2-vaccinated pigs. Despite the presence of maternally derived antibodies, animals showed a prompt seroconversion after vaccination and PCV2 natural infection. Moreover, maternal immunity did not interfere with the development of the specific cellular IFN-γ SC response in single and concurrently vaccinated animals. The study demonstrates that concurrent PRRSV+PCV2 vaccination has no interference with the development of the specific humoral and cell-mediated immunity and it is associated with clinical protection upon natural challenge. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. Key Components of a School-Located Vaccination Clinic: Lessons Learned from Fall 2009

    ERIC Educational Resources Information Center

    Herl Jenlink, Carolyn; Kuehnert, Paul; Mazyck, Donna

    2010-01-01

    The 2009 H1N1 influenza A virus vaccination campaign focused on use of school-located vaccination (SLV) clinics because of the ability of SLV to reach targeted populations. Large numbers of children are found in schools, and schools are conveniently located throughout communities. Communities are generally familiar with and trust schools, and…

  7. Peptide vaccination of patients with metastatic melanoma: improved clinical outcome in patients demonstrating effective immunization.

    PubMed

    Markovic, Svetomir N; Suman, Vera J; Ingle, James N; Kaur, Judith S; Pitot, Henry C; Loprinzi, Charles L; Rao, Ravi D; Creagan, Edward T; Pittelkow, Mark R; Allred, Jakob B; Nevala, Wendy K; Celis, Esteban

    2006-08-01

    Therapeutic peptide vaccines for melanoma continue to only demonstrate anecdotal success. We set out to evaluate the impact of low-dose GM-CSF emulsified in Montanide ISA-51 on the immunogenicity of HLA-A2 restricted melanoma differentiation antigen peptide vaccines (MART-1, gp100 and tyrosinase) administered in separate subcutaneous injections. We conducted a randomized phase II clinical trial of HLA-A2+ patients with metastatic melanoma that were immunized every 3 weeks with one of the following vaccine preparations: (A) peptides + Montanide ISA-51; (B) peptides + Montanide ISA-51 + GM-CSF (10 microg); (C) peptides + Montanide ISA-51 + GM-CSF (50 microg). Immunization efficacy was determined by quantification of vaccine specific tetramer positive cytotoxic T cells in peripheral blood. Global assessment of immune competence was ascertained using DTH testing to common recall antigens as well as peripheral blood immunophenotyping. Twenty-five eligible patients were equally distributed across all 3 treatment groups. Only 9 patients demonstrated evidence of immunization. Most commonly, immune response was achieved to the gp100 peptide. The addition of low-dose GM-CSF did not impact immunization efficacy. DTH reactivity to Candida appeared predictive of successful immunization. Successful immunization with the peptide vaccines was associated with improved clinical outcomes. The addition of low dose GM-CSF to peptide vaccines did not enhance immunogenicity. Higher doses of GM-CSF may be needed to achieve this effect and this is a testable hypothesis. Likewise, better patient selection based on immunologic status (DTH reactivity) may be helpful to better understand the clinical impact of therapeutic cancer vaccines.

  8. Vaccines against malaria.

    PubMed

    Ouattara, Amed; Laurens, Matthew B

    2015-03-15

    Despite global efforts to control malaria, the illness remains a significant public health threat. Currently, there is no licensed vaccine against malaria, but an efficacious vaccine would represent an important public health tool for successful malaria elimination. Malaria vaccine development continues to be hindered by a poor understanding of antimalarial immunity, a lack of an immune correlate of protection, and the genetic diversity of malaria parasites. Current vaccine development efforts largely target Plasmodium falciparum parasites in the pre-erythrocytic and erythrocytic stages, with some research on transmission-blocking vaccines against asexual stages and vaccines against pregnancy-associated malaria. The leading pre-erythrocytic vaccine candidate is RTS,S, and early results of ongoing Phase 3 testing show overall efficacy of 46% against clinical malaria. The next steps for malaria vaccine development will focus on the design of a product that is efficacious against the highly diverse strains of malaria and the identification of a correlate of protection against disease. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  9. Implementation of an Ebola virus disease vaccine clinical trial during the Ebola epidemic in Liberia: Design, procedures, and challenges.

    PubMed

    Kennedy, Stephen B; Neaton, James D; Lane, H Clifford; Kieh, Mark W S; Massaquoi, Moses B F; Touchette, Nancy A; Nason, Martha C; Follmann, Dean A; Boley, Fatorma K; Johnson, Melvin P; Larson, Gregg; Kateh, Francis N; Nyenswah, Tolbert G

    2016-02-01

    The index case of the Ebola virus disease epidemic in West Africa is believed to have originated in Guinea. By June 2014, Guinea, Liberia, and Sierra Leone were in the midst of a full-blown and complex global health emergency. The devastating effects of this Ebola epidemic in West Africa put the global health response in acute focus for urgent international interventions. Accordingly, in October 2014, a World Health Organization high-level meeting endorsed the concept of a phase 2/3 clinical trial in Liberia to study Ebola vaccines. As a follow-up to the global response, in November 2014, the Government of Liberia and the US Government signed an agreement to form a research partnership to investigate Ebola and to assess intervention strategies for treating, controlling, and preventing the disease in Liberia. This agreement led to the establishment of the Joint Liberia-US Partnership for Research on Ebola Virus in Liberia as the beginning of a long-term collaborative partnership in clinical research between the two countries. In this article, we discuss the methodology and related challenges associated with the implementation of the Ebola vaccines clinical trial, based on a double-blinded randomized controlled trial, in Liberia. © The Author(s) 2016.

  10. Comparing risk behaviours of human papillomavirus-vaccinated and non-vaccinated women.

    PubMed

    Sadler, Laura; Roberts, Stephen A; Hampal, Gail; McManus, Dona; Mandal, Debashis; Brabin, Loretta

    2015-10-01

    Since September 2008, a national vaccine programme in the UK has offered routine human papillomavirus (HPV) vaccination to young women aged 12-13 years. A catch-up programme also offered HPV vaccination to women born after 1 September 1990. To compare indicators of risk and preventive behaviours among young women attending genitourinary medicine (GUM) clinics who had, and had not, received at least one dose of HPV vaccine. Clinical histories and HPV vaccination status were obtained from 363 participants eligible for HPV vaccination (Cervarix(®)) in the UK vaccination programme (born after 1 September 1990) attending GUM clinics in the North West of England. Using logistic regression, markers of sexual and non-sexual risk behaviours were compared between vaccinated and unvaccinated women. At least one dose of HPV vaccine had been received by 63.6% (n=231) of participants. Unvaccinated women demonstrated higher levels of risky behaviour than those who had undergone HPV vaccination. Unvaccinated women were significantly more likely to have had three or more partners in the last 6 months, attended the clinic with symptoms, not used a condom at first sexual intercourse, had anal intercourse with their last sexual contact, to have tested positive for Chlamydia trachomatis diagnosis at the clinic visit and to be a current smoker. In the UK, where vaccine coverage is high, failure to initiate HPV vaccination amongst GUM attendees is a marker of high-risk behaviours. As a result, HPV vaccination status should be ascertained as part of an individual's clinical history by sexual health services to ensure advice and counselling is provided to those at greatest risk of HPV-associated disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  11. A Pilot Study to Evaluate the Safety and Clinical Outcomes of Vaccination with Recombinant CEA-MUC-1-TRICOM (PANVAC) Poxviral-based Vaccines in Patients with Metastatic Carcinoma

    PubMed Central

    Gulley, James L.; Arlen, Philip M.; Tsang, Kwong-Yok; Yokokawa, Junko; Palena, Claudia; Poole, Diane J.; Remondo, Cinzia; Cereda, Vittore; Jones, Jacquin L.; Pazdur, Mary P.; Higgins, Jack P.; Hodge, James W.; Steinberg, Seth M.; Kotz, Herbert; Dahut, William L.; Schlom, Jeffrey

    2009-01-01

    Purpose: Poxviral vectors have a proven safety record and can be used to incorporate multiple transgenes. Prior clinical trials with poxviral vaccines have shown that immunologic tolerance to self-antigens can be broken. Carcinoembryonic antigen (CEA) and MUC-1 are overexpressed in a substantial proportion of common solid carcinomas. The primary endpoint of this study was vaccine safety, with immunologic and clinical responses as secondary endpoints. Experimental Design: We report here a pilot study of 25 patients treated with a poxviral vaccine regimen consisting of the genes for CEA and MUC-1, along with a triad of costimulatory molecules (TRICOM, composed of B7.1, ICAM-1, and LFA-3) engineered into vaccinia (PANVAC-V) as a prime and fowlpox (PANVAC-F) as booster vaccinations. Results: The vaccine was well-tolerated. Apart from injection-site reaction, no grade II or greater toxicity was seen in more than 2% of the cycles. Immune responses to MUC-1 and/or CEA were seen following vaccine in 9 of 16 patients tested. A patient with clear cell ovarian cancer and symptomatic ascites had a durable (18-month) clinical response radiographically and biochemically, and one breast cancer patient had a confirmed decrease of > 20% in the size of large liver metastasis. Conclusions: This vaccine strategy appears to be safe, is associated with both CD8 and CD4 immune responses, and has shown evidence of clinical activity. Further trials with this agent, either alone or in combination with immunopotentiating and other therapeutic agents, are warranted. PMID:18483372

  12. The swine flu vaccine, public attitudes, and researcher interpretations: a systematic review of qualitative research.

    PubMed

    Carlsen, Benedicte; Glenton, Claire

    2016-06-24

    During pandemics, health authorities may be uncertain about the spread and severity of the disease and the effectiveness and safety of available interventions. This was the case during the swine flu (H1N1) pandemic of 2009-2010, and governments were forced to make decisions despite these uncertainties. While many countries chose to implement wide scale vaccination programmes, few accomplished their vaccination goals. Many research studies aiming to explore barriers and facilitators to vaccine uptake have been conducted in the aftermath of the pandemic, including several qualitative studies. 1. To explore public attitudes to the swine flu vaccine in different countries through a review of qualitative primary studies. 2. To describe and discuss the implications drawn by the primary study authors. Systematic review of qualitative research studies, using a broadly comparative cross case-study approach. Study quality was appraised using an adaptation of the Critical Appraisal Skills Programme (CASP) quality assessment tool. The review indicates that the public had varying opinions about disease risk and prevalence and had concerns about vaccine safety. Most primary study authors concluded that participants were uninformed, and that more information about the disease and the vaccine would have led to an increase in vaccine uptake. We find these conclusions problematic. We suggest instead that people's questions and concerns were legitimate given the uncertainties of the situation at the time and the fact that the authorities did not have the necessary information to convince the public. Our quality assessment of the included studies points to a lack of reflexivity and a lack of information about study context. We suggest that these study weaknesses are tied to primary study authors' lack of acknowledgement of the uncertainties surrounding the disease and the vaccine. While primary study authors suggest that authorities could increase vaccine uptake through increased

  13. Vaccination of school children with live mumps virus vaccine.

    PubMed

    Furesz, J; Nagler, F P

    1970-05-30

    Live, attenuated mumps virus vaccine (Mumpsvax) was administered to 146 school children 6 to 9 years of age. One child developed clinical mumps nine days after vaccination; epidemiological and serological data strongly suggest that this child had become infected before vaccination. Apart from this single instance there were no apparent clinical reactions that could be ascribed to the administration of the vaccine. Sixty-three of the 146 children with no clinical history of mumps had an initial serum neutralizing antibody titre of less than 1:2. Specific antibodies to mumps virus were detected in 93.5% of the sera of the susceptible children 28 days after vaccination, and the geometric mean antibody titre of these sera was low (1:6). Of the 80 initially seropositive children 21 (26.2%) showed a significant antibody response to the vaccine and this was influenced by the pre-existing antibody level. These data have further demonstrated the safety and efficacy of the live mumps vaccine in children.

  14. Vaccination of School Children With Live Mumps Virus Vaccine

    PubMed Central

    Furesz, J.; Nagler, F. P.

    1970-01-01

    Live, attenuated mumps virus vaccine (Mumpsvax) was administered to 146 school children 6 to 9 years of age. One child developed clinical mumps nine days after vaccination; epidemiological and serological data strongly suggest that this child had become infected before vaccination. Apart from this single instance there were no apparent clinical reactions that could be ascribed to the administration of the vaccine. Sixty-three of the 146 children with no clinical history of mumps had an initial serum neutralizing antibody titre of less than 1:2. Specific antibodies to mumps virus were detected in 93.5% of the sera of the susceptible children 28 days after vaccination, and the geometric mean antibody titre of these sera was low (1:6). Of the 80 initially seropositive children 21 (26.2%) showed a significant antibody response to the vaccine and this was influenced by the pre-existing antibody level. These data have further demonstrated the safety and efficacy of the live mumps vaccine in children. PMID:5420994

  15. How the research-based industry approaches vaccine development and establishes priorities.

    PubMed

    André, F E

    2002-01-01

    Over the past two decades, progress in immunology, molecular biology and genomics as well as some technological breakthroughs in computer science has opened the way to the development of prophylactic vaccines against most acute infectious diseases. Therapeutic vaccines against chronic infections, allergic conditions, auto-immune diseases and cancer have also come into the realm of possibility. It is estimated that wordwide there are about 400 vaccine projects in R&D laboratories of academic institutions, research institutes and vaccine manufacturers. Most of these projects will not yield a licensed vaccine for routine or even targeted immunisation. This is mostly not because of scientific barriers but due to financial and politicoeconomic obstades that make their development feasible only by the handful of major research-based vaccine manufacturers that nowadays all form part of large global pharmaceutical corporations. Such enterprises have to be profitable to survive and priority setting, when it comes to R&D projects, has to take into account potential return on all investments, particularly as it currently costs between 200 and 500 million US dollars to bring a new vaccine from the concept stage to market. Factors that influence the decision to embark upon an R&D project on a new vaccine include the medical need for the vaccine, gauged by the global burden of the targeted disease, potential and probable market size - judged on volume (number of doses required) and value (total sales) -, probability of success and expertise of the company in the field (both R&D and marketing) as well as the likelihood of competitors taking a large part of the market. Moral imperatives such as the urgent need for vaccines against HIV/AIDS, malaria and an improved vaccine against tuberculosis to save the several millions of lives claimed each year by these diseases also play a role. However, for such investments to be sustainable other sources of financing than the commercial

  16. Research toward Malaria Vaccines

    NASA Astrophysics Data System (ADS)

    Miller, Louis H.; Howard, Russell J.; Carter, Richard; Good, Michael F.; Nussenzweig, Victor; Nussenzweig, Ruth S.

    1986-12-01

    Malaria exacts a toll of disease to people in the Tropics that seems incomprehensible to those only familiar with medicine and human health in the developed world. The methods of molecular biology, immunology, and cell biology are now being used to develop an antimalarial vaccine. The Plasmodium parasites that cause malaria have many stages in their life cycle. Each stage is antigenically distinct and potentially could be interrupted by different vaccines. However, achieving complete protection by vaccination may require a better understanding of the complexities of B- and T-cell priming in natural infections and the development of an appropriate adjuvant for use in humans.

  17. Status of vaccine research and development of vaccines for tuberculosis.

    PubMed

    Evans, Thomas G; Schrager, Lew; Thole, Jelle

    2016-06-03

    TB is now the single pathogen that causes the greatest mortality in the world, at over 1.6 million deaths each year. The widely used the 90 year old BCG vaccine appears to have minimal impact on the worldwide incidence despite some efficacy in infants. Novel vaccine development has accelerated in the past 15 years, with 15 candidates entering human trials; two vaccines are now in large-scale efficacy studies. Modeling by three groups has consistently shown that mass vaccination that includes activity in the latently infected population, especially adolescents and young adults, will likely have the largest impact on new disease transmission. At present the field requires better validated animal models, better understanding of a correlate of immunity, new cost-effective approaches to Proof of Concept trials, and increased appreciation by the public health and scientific community for the size of the problem and the need for a vaccine. Such a vaccine is likely to also play a role in the era of increasing antibiotic resistance. Ongoing efforts and studies are working to implement these needs over the next 5 years, which will lead to an understanding that will increase the likelihood of a successful TB vaccine. Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

  18. Knowledge and attitudes regarding influenza vaccination among nurses: a research review.

    PubMed

    Zhang, Jing; While, Alison E; Norman, Ian J

    2010-10-18

    Influenza vaccination rates among nurses remain suboptimal despite health authority recommendations in many countries and several vaccination campaign programmes to encourage nurses to be vaccinated in many institutions. We reviewed published studies investigating nurses' knowledge and attitudes towards influenza vaccination to establish what is known about the determinants of nurses' influenza vaccination practices. Relevant articles published up to July 2010 were identified through multiple databases (CINAHL, MEDLINE, PubMed, EMBASE, BNI, HMIC, PsycINFO, CMAC, and CNJ) using predetermined search strategies. Review of the titles and abstracts revealed 182 of 254 references were not relevant. Of 45 full papers reviewed, 32 did not report nurse data separately and one was a duplicate report of a study. We included 12 research studies which had investigated the relationship between knowledge and attitudes towards influenza vaccination and nurses' vaccination practices published between 2003 and 2010. All the studies were descriptive and relied upon self-report data. The findings of this review indicate a relationship between knowledge, attitudes and vaccination practices of nurses. There were three main findings: first, there was a strong association between nurses' knowledge of influenza and vaccination and their vaccination status; second, the surveys showed a positive relationship between perceptions of influenza as a serious illness and vaccination as effective and safe and a positive vaccination status; and third, there was a relationship between nurses' vaccination status and their reported promotion of vaccination to their patients. This review indicates that higher knowledge and positive attitudes towards influenza vaccination have a significantly positive association with vaccination coverage among nurses. Further studies are needed to identify influences on nurses' attitudes and practices regarding influenza vaccination and the personal, organizational, and

  19. Assessing the impact of wastage on pediatric vaccine immunization formulary costs using a vaccine selection algorithm.

    PubMed

    Jacobson, Sheldon H; Karnani, Tamana; Sewell, Edward C

    2004-06-02

    Pediatric immunization is an important factor in providing protection against numerous common preventable diseases. The success of the pharmaceutical industry in developing new pediatric vaccines has resulted in a crowded recommended immunization schedule requiring several clinic visits over the first 12 years of life. Operations research models have been developed and used to make economically sound procurement choices from among a growing number of competing vaccine products. One factor that has not been incorporated into such models is the economic impact of wastage on such decisions. This paper reports results obtained from a vaccine selection algorithm that incorporates vaccine wastage data. The lowest overall cost formularies comparing no wastage costs with wastage costs are presented. A sensitivity analysis of the vaccine formulary with respect to the wastage rates associated with each available vaccine is provided. The maximum permissible wastage rate for each vaccine is determined for which the vaccine earns a place in the lowest overall cost formulary. This research provides health maintenance organizations and healthcare providers information that can be used to gain a better understanding of wastage and its impact on pediatric formulary costs.

  20. Atypical feline sporotrichosis resembling vaccine-induced sarcoma: clinical and histopathological aspects.

    PubMed

    dos Santos, Isabele Barbieri; Quintella, Leonardo Pereira; de Miranda, Luisa Helena Monteiro; de Sousa Trotte, Marcele Nogueira; Schubach, Tânia Maria Pacheco; Tortelly, Rogerio

    2013-06-01

    A 7-year-old Siamese cat presenting with three ulcerated cutaneous nodules in the lumbosacral region was seen at the Laboratory for Clinical Research on Dermatozoonoses in Domestic Animals in Rio de Janeiro, Brazil. Histopathological analysis showed that the lesions consisted of polyhedral and spindle-shaped voluminous mononuclear cells with loose chromatin and clearly visible nucleoli, few giant cells, and foci of coagulative and caseous necrosis -- findings suggestive of a vaccine-induced sarcoma. No significant mitotic rate, cytological atypias or asteroid bodies were observed. Special histopathological staining with periodic acid-Schiff and Grocott's silver stain demonstrated the presence of small yeast cells characterized by simple and narrow-base budding compatible with Sporothrix schenckii. Mycological culture grew S schenckii. Cytopathology was negative for yeast cells. These atypical clinical and histopathological signs support the importance of histopathological analysis with special staining techniques, in addition to mycological culture in the diagnosis of feline sporotrichosis.

  1. Influenza Vaccinations, Fall 2009: Model School-Located Vaccination Clinics

    ERIC Educational Resources Information Center

    Herl Jenlink, Carolyn; Kuehnert, Paul; Mazyck, Donna

    2010-01-01

    The 2009 H1N1 influenza virus presented a major challenge to health departments, schools, and other community partners to effectively vaccinate large numbers of Americans, primarily children. The use of school-located vaccination (SLV) programs to address this challenge led health departments and schools to become creative in developing models for…

  2. Balancing justice and autonomy in clinical research with healthy volunteers.

    PubMed

    Kass, N E; Myers, R; Fuchs, E J; Carson, K A; Flexner, C

    2007-08-01

    In clinical research, ethics review generally first examines whether study risks are reasonable in light of benefits provided. Through informed consent, then, prospective subjects consider whether the risk/benefit balance and procedures are reasonable for them. Unique ethics issues emerge in clinical research with healthy volunteers. Certain types of studies only recruit healthy volunteers as participants. Phase 1 studies, for example, including first time in human studies of investigational drugs and vaccines, generally are conducted in healthy volunteers. Although such research carries inherent and often unknown risks, healthy subjects provide the most efficient target population in which to conduct such research, as these volunteers generally are free of concurrent diseases or medications that could confound interpretation of toxicity. Other studies enrolling healthy volunteers often are simply looking for the most scientifically sound population for the study of normal human physiology.

  3. Estimating the clinical benefits of vaccinating boys and girls against HPV-related diseases in Europe

    PubMed Central

    2013-01-01

    Background HPV is related to a number of cancer types, causing a considerable burden in both genders in Europe. Female vaccination programs can substantially reduce the incidence of HPV-related diseases in women and, to some extent, men through herd immunity. The objective was to estimate the incremental benefit of vaccinating boys and girls using the quadrivalent HPV vaccine in Europe versus girls-only vaccination. Incremental benefits in terms of reduction in the incidence of HPV 6, 11, 16 and 18-related diseases (including cervical, vaginal, vulvar, anal, penile, and head and neck carcinomas and genital warts) were assessed. Methods The analysis was performed using a model constructed in Microsoft®Excel, based on a previously-published dynamic transmission model of HPV vaccination and published European epidemiological data on incidence of HPV-related diseases. The incremental benefits of vaccinating 12-year old girls and boys versus girls-only vaccination was assessed (70% vaccine coverage were assumed for both). Sensitivity analyses around vaccine coverage and duration of protection were performed. Results Compared with screening alone, girls-only vaccination led to 84% reduction in HPV 16/18-related carcinomas in females and a 61% reduction in males. Vaccination of girls and boys led to a 90% reduction in HPV 16/18-related carcinomas in females and 86% reduction in males versus screening alone. Relative to a girls-only program, vaccination of girls and boys led to a reduction in female and male HPV-related carcinomas of 40% and 65%, respectively and a reduction in the incidence of HPV 6/11-related genital warts of 58% for females and 71% for males versus girls-only vaccination. Conclusions In Europe, the vaccination of 12-year old boys and girls against HPV 6, 11, 16 and 18 would be associated with substantial additional clinical benefits in terms of reduced incidence of HPV-related genital warts and carcinomas versus girls-only vaccination. The incremental

  4. Estimating the clinical benefits of vaccinating boys and girls against HPV-related diseases in Europe.

    PubMed

    Marty, Rémi; Roze, Stéphane; Bresse, Xavier; Largeron, Nathalie; Smith-Palmer, Jayne

    2013-01-08

    HPV is related to a number of cancer types, causing a considerable burden in both genders in Europe. Female vaccination programs can substantially reduce the incidence of HPV-related diseases in women and, to some extent, men through herd immunity. The objective was to estimate the incremental benefit of vaccinating boys and girls using the quadrivalent HPV vaccine in Europe versus girls-only vaccination. Incremental benefits in terms of reduction in the incidence of HPV 6, 11, 16 and 18-related diseases (including cervical, vaginal, vulvar, anal, penile, and head and neck carcinomas and genital warts) were assessed. The analysis was performed using a model constructed in Microsoft(®)Excel, based on a previously-published dynamic transmission model of HPV vaccination and published European epidemiological data on incidence of HPV-related diseases. The incremental benefits of vaccinating 12-year old girls and boys versus girls-only vaccination was assessed (70% vaccine coverage were assumed for both). Sensitivity analyses around vaccine coverage and duration of protection were performed. Compared with screening alone, girls-only vaccination led to 84% reduction in HPV 16/18-related carcinomas in females and a 61% reduction in males. Vaccination of girls and boys led to a 90% reduction in HPV 16/18-related carcinomas in females and 86% reduction in males versus screening alone. Relative to a girls-only program, vaccination of girls and boys led to a reduction in female and male HPV-related carcinomas of 40% and 65%, respectively and a reduction in the incidence of HPV 6/11-related genital warts of 58% for females and 71% for males versus girls-only vaccination. In Europe, the vaccination of 12-year old boys and girls against HPV 6, 11, 16 and 18 would be associated with substantial additional clinical benefits in terms of reduced incidence of HPV-related genital warts and carcinomas versus girls-only vaccination. The incremental benefits of adding boys vaccination

  5. [Phase II clinical trial of autologous dendritic cell vaccine with immunologic adjuvant in cutaneous melanoma patients].

    PubMed

    Baldueva, I A; Novik, A V; Moiseenko, V M; Nekhaeva, T L; Danilova, A B; Danilov, A O; Protsenko, S A; Petrova, T Iu; Uleĭskaia, G I; Shchekina, L A; Semenova, A I; Mikhaĭlichenko, T D; Teletaeva, G M; Zhabina, A S; Volkov, N V; Komarov, Iu I

    2012-01-01

    This paper describes the clinical results and immunologic changes in cutaneous melanoma patients receiving active specific immunotherapy with autologous dendritic cell vaccine (DCV) in combination with cyclophosphamide used as immunologic adjuvant. Twenty eight patients with morphologically verified stage III-IV cutaneous melanoma receiving therapy in N. N. Petrov Research Institute of Oncology between 2008 and 2011 were included in the study. All patients signed an informed consent form. Nineteen patients (67,9%) received DCV in therapeutic setting, 9 (32,1%) received it in adjuvant setting. DCV therapy was well tolerated. No serious adverse events were registered. Frequent adverse events included Grade 1-2 unspecific symptoms (fever, fatigue, flu-like symptoms) observed in 22% patients after 3,5% of vaccinations. In therapeutic settings the use DCV lead to clinical effect (PR+SD) in 36,6% of patients. PR was observed in 5% of (95% CI 0-15%) patients, SD in 31,6% (95% CI 13-56%). Duration of the objective responses was 168-965+days. Addition of immunologic adjuvant (cyclophosphamide 300 mg/m2 IV 2 hours) 3 days before vaccination increased its efficacy. In this patients group (n=12) the therapy lead to clinical benefit in 42% (95% CI 17-69%) of cases, median time to progression was 91 (95% CI 55-126) days. This regimen was selected for adjuvant therapy. In the adjuvant therapy group (n=9) the median time to progression was 112 (95% CI 58-166) days. Immunologic monitoring showed correlation ofT- and B-cell immune response with DCV clinical efficacy (p<0,05), no correlation with delayed hypersensivity reaction was observed (p>0,1). DCV is well tolerated and shows immunological and clinical response in stage III-IV skin melanoma patients.

  6. The biopolitics of reproductive technologies beyond the clinic: localizing HPV vaccines in India.

    PubMed

    Towghi, Fouzieyha

    2013-01-01

    The human papillomavirus (HPV) vaccine research and marketing in India exemplifies the privatization of public sectors and global assemblages of novel actors and public-private partnerships in service delivery and pharmaceutical marketing. Drawing on ethnographic research, in this article I examine how the molecularized conception of cervical cancer and the simultaneous global rise of the HPV vaccine is redefining the meaning of prevention, the role of the state, and blurring the relationship between health care and health research in India. In 2009, two Indian states began "demonstration projects" to vaccinate 30,000 girls. The subsequent deaths of a number of girls exposed inherent problems with the projects. For many health activists, the vaccine has potentially grave consequences for India's public health system. This case demonstrates how biopolitical actors, and the drive for biocapital, can create a public health campaign that might in the end place women's health and the public health system at a greater risk.

  7. Antiradiation Vaccine: Technology Development- Radiation Tolerance,Prophylaxis, Prevention And Treatment Of Clinical Presentation After Heavy Ion Irradiation.

    NASA Astrophysics Data System (ADS)

    Popov, Dmitri; Maliev, Slava; Jones, Jeffrey

    Introduction: Research in the field of biological effects of heavy charged particles is necessary for both heavy-ion therapy (hadrontherapy) and protection from the exposure to galactic cosmic radiation in long-term manned space missions.[Durante M. 2004] In future crew of long-term manned missions could operate in exremely high hadronic radiation areas of space and will not survive without effective radiation protection. An Antiradiation Vaccine (AV) must be an important part of a countermeasures regimen for efficient radiation protection purposes of austronauts-cosmonauts-taukonauts: immune-prophylaxis and immune-therapy of acute radiation toxic syndromes developed after heavy ion irradiation. New technology developed (AV) for the purposes of radiological protection and improvement of radiation tolerance and it is quite important to create protective immune active status which prevent toxic reactions inside a human body irradiated by high energy hadrons.[Maliev V. et al. 2006, Popov D. et al.2008]. High energy hadrons produce a variety of secondary particles which play an important role in the energy deposition process, and characterise their radiation qualities [Sato T. et al. 2003] Antiradiation Vaccine with specific immune-prophylaxis by an anti-radiation vaccine should be an important part of medical management for long term space missions. Methods and experiments: 1. Antiradiation vaccine preparation standard, mixture of toxoid form of Radiation Toxins [SRD-group] which include Cerebrovascular RT Neurotoxin, Cardiovascular RT Neurotoxin, Gastrointestinal RT Neurotoxin, Hematopoietic RT Hematotoxin. Radiation Toxins of Radiation Determinant Group isolated from the central lymph of gamma-irradiated animals with Cerebrovascular, Cardiovascular, Gastro-intestinal, Hematopoietic forms of ARS. Devices for radiation are "Panorama", "Puma". 2. Heavy ion exposure was accomplished at Department of Research Institute of Nuclear Physics, Dubna, Russia. The heavy ions

  8. Implementation research: reactive mass vaccination with single-dose oral cholera vaccine, Zambia.

    PubMed

    Poncin, Marc; Zulu, Gideon; Voute, Caroline; Ferreras, Eva; Muleya, Clara Mbwili; Malama, Kennedy; Pezzoli, Lorenzo; Mufunda, Jacob; Robert, Hugues; Uzzeni, Florent; Luquero, Francisco J; Chizema, Elizabeth; Ciglenecki, Iza

    2018-02-01

    To describe the implementation and feasibility of an innovative mass vaccination strategy - based on single-dose oral cholera vaccine - to curb a cholera epidemic in a large urban setting. In April 2016, in the early stages of a cholera outbreak in Lusaka, Zambia, the health ministry collaborated with Médecins Sans Frontières and the World Health Organization in organizing a mass vaccination campaign, based on single-dose oral cholera vaccine. Over a period of 17 days, partners mobilized 1700 health ministry staff and community volunteers for community sensitization, social mobilization and vaccination activities in 10 townships. On each day, doses of vaccine were delivered to vaccination sites and administrative coverage was estimated. Overall, vaccination teams administered 424 100 doses of vaccine to an estimated target population of 578 043, resulting in an estimated administrative coverage of 73.4%. After the campaign, few cholera cases were reported and there was no evidence of the disease spreading within the vaccinated areas. The total cost of the campaign - 2.31 United States dollars (US$) per dose - included the relatively low cost of local delivery - US$ 0.41 per dose. We found that an early and large-scale targeted reactive campaign using a single-dose oral vaccine, organized in response to a cholera epidemic within a large city, to be feasible and appeared effective. While cholera vaccines remain in short supply, the maximization of the number of vaccines in response to a cholera epidemic, by the use of just one dose per member of an at-risk community, should be considered.

  9. A review of vaccine development and research for industry animals in Korea

    PubMed Central

    Lee, Nak-Hyung; Lee, Jung-Ah; Park, Seung-Yong; Song, Chang-Seon; Choi, In-Soo

    2012-01-01

    Vaccination has proven to be the most cost-effective strategy for controlling a wide variety of infectious diseases in humans and animals. For the last decade, veterinary vaccines have been substantially developed and demonstrated their effectiveness against many diseases. Nevertheless, new vaccines are greatly demanded to effectively control newly- and re-emerging pathogens in livestock. However, development of veterinary vaccines is a challenging task, in part, due to a variety of pathogens, hosts, and the uniqueness of host-susceptibility to each pathogen. Therefore, novel concepts of vaccines should be explored to overcome the limitation of conventional vaccines. There have been greatly advanced in the completion of genomic sequencing of pathogens, the application of comparative genomic and transcriptome analysis. This would facilitate to open opportunities up to investigate a new generation of vaccines; recombinant subunit vaccine, virus-like particle, DNA vaccine, and vector-vehicle vaccine. Currently, such types of vaccines are being actively explored against various livestock diseases, affording numerous advantages over conventional vaccines, including ease of production, immunogenicity, safety, and multivalency in a single shot. In this articles, the authors present the current status of the development of veterinary vaccines at large as well as research activities conducted in Korea. PMID:23596575

  10. Adversomics: a new paradigm for vaccine safety and design

    PubMed Central

    Whitaker, Jennifer A.; Ovsyannikova, Inna G.; Poland, Gregory A.

    2015-01-01

    Summary Despite the enormous population benefits of routine vaccination, vaccine adverse events and reactions, whether real or perceived, have posed one of the greatest barriers to vaccine acceptance—and thus to infectious disease prevention—worldwide. A truly integrated clinical, translational, and basic science approach is required to understand the mechanisms behind vaccine adverse events, predict them, and then apply this knowledge to new vaccine design approaches that decrease, or avoid, these events. The term “adversomics” was first introduced in 2009 and refers to the study of vaccine adverse reactions using immunogenomics and systems biology approaches. In this review, we present the current state of adversomics research, review known associations and mechanisms of vaccine adverse events/reactions, and outline a plan for the further development of this emerging research field. PMID:25937189

  11. Herpes Zoster Vaccine in the Long-Term Care Setting: A Clinical and Logistical Conundrum.

    PubMed

    Schafer, Katherine Montag; Reidt, Shannon

    2016-01-01

    Advancing age is associated with an increased risk of herpes zoster (shingles) infection and latent effects such as postherpetic neuralgia. The herpes zoster vaccine is recommended in those 60 years of age and older and has been shown to prevent both the primary disease and associated complications. While this recommendation applies to those living in long-term care facilities, there is little clinical evidence to support use in this population. Additionally, there are logistical barriers that may complicate the use of the vaccine. The article examines the evidence for vaccinating residents in long-term care facilities and discusses logistical barriers to vaccination. Pharmacists and providers may consider life expectancy and other factors when evaluating which patients should receive the vaccination.

  12. Viral load and clinical disease enhancement associated with a lentivirus cytotoxic T lymphocyte vaccine regimen

    PubMed Central

    Mealey, Robert H.; Leib, Steven R.; Littke, Matt H.; Wagner, Bettina; Horohov, David W.; McGuire, Travis C.

    2009-01-01

    Effective DNA-based vaccines against lentiviruses will likely induce CTL against conserved viral proteins. Equine infectious anemia virus (EIAV) infects horses worldwide, and serves as a useful model for lentiviral immune control. Although attenuated live EIAV vaccines have induced protective immune responses, DNA-based vaccines have not. In particular, DNA-based vaccines have had limited success in inducing CTL responses against intracellular pathogens in the horse. We hypothesized that priming with a codon-optimized plasmid encoding EIAV Gag p15/p26 with co-administration of a plasmid encoding an equine IL-2/IgG fusion protein as a molecular adjuvant, followed by boosting with a vaccinia vector expressing Gag p15/p26, would induce protective Gag-specific CTL responses. Although the regimen induced Gag-specific CTL in four of seven vaccinated horses, CTL were not detected until after the vaccinia boost, and protective effects were not observed in EIAV challenged vaccinates. Unexpectedly, vaccinates had significantly higher viral loads and more severe clinical disease, associated with the presence of vaccine-induced CTL. It was concluded that 1.) further optimization of the timing and route of DNA immunization was needed for efficient CTL priming in vivo, 2.) co-administration of the IL-2/IgG plasmid did not enhance CTL priming by the Gag p15/p26 plasmid, 3.) vaccinia vectors are useful for lentivirus-specific CTL induction in the horse, 4.) Gag-specific CTL alone are either insufficient or a more robust Gag-specific CTL response is needed to limit EIAV viremia and clinical disease, and 5.) CTL-inducing vaccines lacking envelope immunogens can result in lentiviral disease enhancement. Although the mechanisms for enhancement associated with this vaccine regimen remain to be elucidated, these results have important implications for development of lentivirus T cell vaccines. PMID:19368787

  13. Strengthening capacity for AIDS vaccine research: analysis of the Pfizer Global Health Fellows Program and the International AIDS Vaccine Initiative

    PubMed Central

    2013-01-01

    Background Industry partnerships can help leverage resources to advance HIV/AIDS vaccine research, service delivery, and policy advocacy goals. This often involves capacity building for international and local non-governmental organizations (NGOs). International volunteering is increasingly being used as a capacity building strategy, yet little is known about how corporate volunteers help to improve performance of NGOs in the fight against HIV/AIDS. Methods This case study helps to extend our understanding by analyzing how the Pfizer Global Health Fellows (GHF) program helped develop capacity of the International AIDS Vaccine Initiative (IAVI), looking specifically at Fellowship activities in South Africa, Kenya, and Uganda. From 2005–2009, 8 Pfizer GHF worked with IAVI and local research centers to strengthen capacity to conduct and monitor vaccine trials to meet international standards and expand trial activities. Data collection for the case study included review of Fellow job descriptions, online journals, evaluation reports, and interviews with Fellows and IAVI staff. Qualitative methods were used to analyze factors which influenced the process and outcomes of capacity strengthening. Results Fellows filled critical short-term expert staffing needs at IAVI as well as providing technical assistance and staff development activities. Capacity building included assistance in establishing operating procedures for the start-up period of research centers; training staff in Good Clinical Practice (GCP); developing monitoring capacity (staff and systems) to assure that centers are audit-ready at all times; and strategic planning for data management systems. Factors key to the success of volunteering partnerships included similarities in mission between the corporate and NGO partners, expertise and experience of Fellows, and attitudes of partner organization staff. Conclusion By developing standard operating procedures, ensuring that monitoring and regulatory

  14. Strengthening capacity for AIDS vaccine research: analysis of the Pfizer Global Health Fellows program and the International AIDS Vaccine Initiative.

    PubMed

    Vian, Taryn; Koseki, Sayaka; Feeley, Frank G; Beard, Jennifer

    2013-10-02

    Industry partnerships can help leverage resources to advance HIV/AIDS vaccine research, service delivery, and policy advocacy goals. This often involves capacity building for international and local non-governmental organizations (NGOs). International volunteering is increasingly being used as a capacity building strategy, yet little is known about how corporate volunteers help to improve performance of NGOs in the fight against HIV/AIDS. This case study helps to extend our understanding by analyzing how the Pfizer Global Health Fellows (GHF) program helped develop capacity of the International AIDS Vaccine Initiative (IAVI), looking specifically at Fellowship activities in South Africa, Kenya, and Uganda. From 2005-2009, 8 Pfizer GHF worked with IAVI and local research centers to strengthen capacity to conduct and monitor vaccine trials to meet international standards and expand trial activities. Data collection for the case study included review of Fellow job descriptions, online journals, evaluation reports, and interviews with Fellows and IAVI staff. Qualitative methods were used to analyze factors which influenced the process and outcomes of capacity strengthening. Fellows filled critical short-term expert staffing needs at IAVI as well as providing technical assistance and staff development activities. Capacity building included assistance in establishing operating procedures for the start-up period of research centers; training staff in Good Clinical Practice (GCP); developing monitoring capacity (staff and systems) to assure that centers are audit-ready at all times; and strategic planning for data management systems. Factors key to the success of volunteering partnerships included similarities in mission between the corporate and NGO partners, expertise and experience of Fellows, and attitudes of partner organization staff. By developing standard operating procedures, ensuring that monitoring and regulatory compliance systems were in place, training

  15. Clinical evaluation of a new measles-mumps-rubella combined live virus vaccine in the Dominican Republic*

    PubMed Central

    Ehrenkranz, N. Joel; Ventura, Arnoldo K.; Medler, Edward M.; Jackson, Joseph E.; Kenny, Michael T.

    1975-01-01

    Over 900 children were enrolled in a double-blind placebo-controlled clinical study of measles (Schwarz strain), mumps (Jeryl Lynn strain), and rubella (Cendehill strain) trivalent vaccine. The trivalent vaccine caused about the same degree of reactivity as is generally associated with the Schwarz strain measles vaccine. Paired sera from triplesusceptible vaccinees had seroconversion rates of 99% for measles, 94% for mumps, and 93% for rubella. The results of this study show that this trivalent vaccine is as well tolerated and as effective as its component vaccines. PMID:764997

  16. Implementation research: reactive mass vaccination with single-dose oral cholera vaccine, Zambia

    PubMed Central

    Zulu, Gideon; Voute, Caroline; Ferreras, Eva; Muleya, Clara Mbwili; Malama, Kennedy; Pezzoli, Lorenzo; Mufunda, Jacob; Robert, Hugues; Uzzeni, Florent; Luquero, Francisco J; Chizema, Elizabeth; Ciglenecki, Iza

    2018-01-01

    Abstract Objective To describe the implementation and feasibility of an innovative mass vaccination strategy – based on single-dose oral cholera vaccine – to curb a cholera epidemic in a large urban setting. Method In April 2016, in the early stages of a cholera outbreak in Lusaka, Zambia, the health ministry collaborated with Médecins Sans Frontières and the World Health Organization in organizing a mass vaccination campaign, based on single-dose oral cholera vaccine. Over a period of 17 days, partners mobilized 1700 health ministry staff and community volunteers for community sensitization, social mobilization and vaccination activities in 10 townships. On each day, doses of vaccine were delivered to vaccination sites and administrative coverage was estimated. Findings Overall, vaccination teams administered 424 100 doses of vaccine to an estimated target population of 578 043, resulting in an estimated administrative coverage of 73.4%. After the campaign, few cholera cases were reported and there was no evidence of the disease spreading within the vaccinated areas. The total cost of the campaign – 2.31 United States dollars (US$) per dose – included the relatively low cost of local delivery – US$ 0.41 per dose. Conclusion We found that an early and large-scale targeted reactive campaign using a single-dose oral vaccine, organized in response to a cholera epidemic within a large city, to be feasible and appeared effective. While cholera vaccines remain in short supply, the maximization of the number of vaccines in response to a cholera epidemic, by the use of just one dose per member of an at-risk community, should be considered. PMID:29403111

  17. In "Step" with HIV Vaccines? A Content Analysis of Local Recruitment Campaigns for an International HIV Vaccine Study.

    PubMed

    Frew, Paula M; Macias, Wendy; Chan, Kayshin; Harding, Ashley C

    2009-01-01

    During the past two decades of the HIV/AIDS pandemic, several recruitment campaigns were designed to generate community involvement in preventive HIV vaccine clinical trials. These efforts utilized a blend of advertising and marketing strategies mixed with public relations and community education approaches to attract potential study participants to clinical trials (integrated marketing communications). Although more than 30,000 persons worldwide have participated in preventive HIV vaccine studies, no systematic analysis of recruitment campaigns exists. This content analysis study was conducted to examine several United States and Canadian recruitment campaigns for one of the largest-scale HIV vaccine trials to date (the "Step Study"). This study examined persuasive features consistent with the Elaboration Likelihood Model (ELM) including message content, personal relevance of HIV/AIDS and vaccine research, intended audiences, information sources, and other contextual features. The results indicated variation in messages and communication approaches with gay men more exclusively targeted in these regions. Racial/ethnic representations also differed by campaign. Most of the materials promote affective evaluation of the information through heuristic cueing. Implications for subsequent campaigns and research directions are discussed.

  18. Clinical experience with respiratory syncytial virus vaccines.

    PubMed

    Piedra, Pedro A

    2003-02-01

    Respiratory syncytial virus (RSV) infection is at times associated with life-threatening lower respiratory tract illness in infancy. Severe infection during the first year of life may be an important risk factor or indicator for the development of asthma in early childhood. Severe infections primarily occur in healthy infants, and young infants and children with specific risk factors. However, RSV causes respiratory infections in all age groups. Indeed it is now recognized that RSV disease is responsible for significant morbidity and mortality in the geriatric population. RSV infection remains difficult to treat, and prevention is a worldwide goal. For this reason there has been an intensive effort to develop an effective and safe RSV vaccine. Initial infection with RSV affords limited protection to reinfection, yet repeated episodes decrease the risk for lower respiratory tract illness. In the 20 years from 1960 to 1980, trials of several candidate RSV vaccines failed to attain the desired safety and protection against natural infection. Some vaccine types either failed to elicit immunogenicity, as with the live subcutaneous vaccine, or resulted in exaggerated disease on natural exposure to the virus, as with the formalin-inactivated (FI) type. Currently vaccine candidates are being developed based on the molecular virology of RSV. Recent formulations of candidate RSV vaccines have focused on subunit vaccines [such as purified fusion protein (PFP)], subunit vaccines combined with nonspecific immune activating adjuvants, live attenuated vaccines (including cold passaged, temperature-sensitive or cpts mutants), genetically engineered live attenuated vaccines and polypeptide vaccines.

  19. Matched Case-Control Study of Effectiveness of Live, Attenuated S79 Mumps Virus Vaccine against Clinical Mumps▿

    PubMed Central

    Fu, Chuanxi; Liang, Jianhua; Wang, Ming

    2008-01-01

    Mumps virus infection is a potentially serious viral infection of childhood and early adulthood. In China, live, attenuated S79 mumps virus vaccine has been licensed for pediatric use since 1990. There has been no assessment of its efficacy. Thus, the objective of this study was to determine the effectiveness of live, attenuated S79 mumps virus vaccine against clinical mumps. Cases were selected from the China Information System for Disease Control and Prevention during September 2004 to March 2005. Each case was matched to a control by gender, age, and area of residency. In all, 469 cases and 469 controls were enrolled in the study. Vaccination information was obtained from the Children's EPI Administrative Computerized System. Vaccine effectiveness (VE) was calculated for one or two doses of S79 vaccine, with 95% confidence intervals (CI). VE of mumps virus vaccine for one dose versus none was protection of 86.0% (95% CI, 77.2% to 91.5%) of recipients, and VE was much higher in the first 4 years than in the 5 to 12 years after vaccination. The S79 vaccine can effectively prevent clinical mumps, and a second dose of mumps virus vaccine is necessary for the protection of children in China. PMID:18667635

  20. Ethical Challenges and Lessons Learned During the Clinical Development of a Group A Meningococcal Conjugate Vaccine.

    PubMed

    Martellet, Lionel; Sow, Samba O; Diallo, Aldiouma; Hodgson, Abraham; Kampmann, Beate; Hirve, Siddhivinayak; Tapia, Milagritos; Haidara, Fadima Cheick; Ndiaye, Assane; Diarra, Bou; Ansah, Patrick Odum; Akinsola, Adebayo; Idoko, Olubukola T; Adegbola, Richard A; Bavdekar, Ashish; Juvekar, Sanjay; Viviani, Simonetta; Enwere, Godwin C; Marchetti, Elisa; Chaumont, Julie; Makadi, Marie-Francoise; Pallardy, Flore; Kulkarni, Prasad S; Preziosi, Marie-Pierre; LaForce, F Marc

    2015-11-15

    The group A meningococcal vaccine (PsA-TT) clinical development plan included clinical trials in India and in the West African region between 2005 and 2013. During this period, the Meningitis Vaccine Project (MVP) accumulated substantial experience in the ethical conduct of research to the highest standards. Because of the public-private nature of the sponsorship of these trials and the extensive international collaboration with partners from a diverse setting of countries, the ethical review process was complex and required strategic, timely, and attentive communication to ensure the smooth review and approval for the clinical studies. Investigators and their site teams fostered strong community relationships prior to, during, and after the studies to ensure the involvement and the ownership of the research by the participating populations. As the clinical work proceeded, investigators and sponsors responded to specific questions of informed consent, pregnancy testing, healthcare, disease prevention, and posttrial access. Key factors that led to success included (1) constant dialogue between partners to explore and answer all ethical questions; (2) alertness and preparedness for emerging ethical questions during the research and in the context of evolving international ethics standards; and (3) care to assure that approaches were acceptable in the diverse community contexts. Many of the ethical issues encountered during the PsA-TT clinical development are familiar to groups conducting field trials in different cultural settings. The successful approaches used by the MVP clinical team offer useful examples of how these problems were resolved. ISRCTN17662153 (PsA-TT-001); ISRTCN78147026 (PsA-TT-002); ISRCTN87739946 (PsA-TT-003); ISRCTN46335400 (PsA-TT-003a); ISRCTN82484612 (PsA-TT-004); CTRI/2009/091/000368 (PsA-TT-005); PACTR ATMR2010030001913177 (PsA-TT-006); PACTR201110000328305 (PsA-TT-007). © The Author 2015. Published by Oxford University Press on behalf of

  1. Advanced Clinical Decision Support for Vaccine Adverse Event Detection and Reporting.

    PubMed

    Baker, Meghan A; Kaelber, David C; Bar-Shain, David S; Moro, Pedro L; Zambarano, Bob; Mazza, Megan; Garcia, Crystal; Henry, Adam; Platt, Richard; Klompas, Michael

    2015-09-15

    Reporting of adverse events (AEs) following vaccination can help identify rare or unexpected complications of immunizations and aid in characterizing potential vaccine safety signals. We developed an open-source, generalizable clinical decision support system called Electronic Support for Public Health-Vaccine Adverse Event Reporting System (ESP-VAERS) to assist clinicians with AE detection and reporting. ESP-VAERS monitors patients' electronic health records for new diagnoses, changes in laboratory values, and new allergies following vaccinations. When suggestive events are found, ESP-VAERS sends the patient's clinician a secure electronic message with an invitation to affirm or refute the message, add comments, and submit an automated, prepopulated electronic report to VAERS. High-probability AEs are reported automatically if the clinician does not respond. We implemented ESP-VAERS in December 2012 throughout the MetroHealth System, an integrated healthcare system in Ohio. We queried the VAERS database to determine MetroHealth's baseline reporting rates from January 2009 to March 2012 and then assessed changes in reporting rates with ESP-VAERS. In the 8 months following implementation, 91 622 vaccinations were given. ESP-VAERS sent 1385 messages to responsible clinicians describing potential AEs. Clinicians opened 1304 (94.2%) messages, responded to 209 (15.1%), and confirmed 16 for transmission to VAERS. An additional 16 high-probability AEs were sent automatically. Reported events included seizure, pleural effusion, and lymphocytopenia. The odds of a VAERS report submission during the implementation period were 30.2 (95% confidence interval, 9.52-95.5) times greater than the odds during the comparable preimplementation period. An open-source, electronic health record-based clinical decision support system can increase AE detection and reporting rates in VAERS. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society

  2. History of incomplete vaccination may associate with occurrence of hemorrhagic fever with renal syndrome with relieved clinical symptoms.

    PubMed

    Chen, Yunru; Yang, Xueliang; Ye, Feng; Chen, Tianyan; Liu, Zhengwen; Zhao, Yingren

    2016-07-01

    This retrospective study is aimed to investigate the clinical features of the patients with history of incomplete vaccination against hemorrhagic fever with renal syndrome (HFRS). Data of 140 cases of hospitalized patients with HFRS were collected. The patients were divided into incomplete vaccinated group (n = 10) and unvaccinated group (n = 130) according to vaccination status. Demographic, clinical, and laboratory characteristics of the two groups' patients were compared through t test, Pearson χ(2) test, and Mann-Whitney test. In comparison with the unvaccinated group, the incidence rate of vomiting and hypotensive-shock, the white blood cell (WBC) and platelet count, the level of blood urea nitrogen and albumin, total number of dialysis and hospitalization cost of patients in the incomplete vaccinated group have statistically significant differences. HFRS disease may still occur in individuals with a history of HFRS incomplete vaccination although the symptoms may be mild. Effective vaccination against HFRS needs sufficient doses and booster shot of the vaccine. © 2015 Wiley Periodicals, Inc.

  3. Travellers' profile, travel patterns and vaccine practices--a 10-year prospective study in a Swiss Travel Clinic.

    PubMed

    Boubaker, Rim; Meige, Pierrette; Mialet, Catherine; Buffat, Chantal Ngarambe; Uwanyiligira, Mediatrice; Widmer, Francine; Rochat, Jacynthe; Fossati, Annie Hérard; Souvannaraj-Blanchant, Manisinh; Payot, Sylvie; Rochat, Laurence; de Vallière, Serge; Genton, Blaise; D'Acremont, Valérie

    2016-01-01

    The travel clinic in Lausanne serves a catchment area of 700 000 of inhabitants and provides pre- and post-travel consultations. This study describes the profile of attendees before departure, their travel patterns and the travel clinic practices in terms of vaccination over time. We included all pre-travel first consultation data recorded between November 2002 and December 2012 by a custom-made program DIAMM/G. We analysed client profiles, travel characteristics and vaccinations prescribed over time. Sixty-five thousand and forty-six client-trips were recorded. Fifty-one percent clients were female. Mean age was 32 years. In total, 0.1% were aged <1 year and 0.2% ≥80 years. Forty-six percent of travellers had pre-existing medical conditions. Forty-six percent were travelling to Africa, 35% to Asia, 20% to Latin America and 1% (each) to Oceania and Europe; 19% visited more than one country. India was the most common destination (9.6% of travellers) followed by Thailand (8.6%) and Kenya (6.4%). Seventy-three percent of travellers were planning to travel for ≤ 4 weeks. The main reasons for travel were tourism (75%) and visiting friends and relatives (18%). Sixteen percent were backpackers. Pre-travel advice were sought a median of 29 days before departure. Ninety-nine percent received vaccine(s). The most frequently administered vaccines were hepatitis A (53%), tetanus-diphtheria (46%), yellow fever (39%), poliomyelitis (38%) and typhoid fever (30%). The profile of travel clinic attendees was younger than the general Swiss population. A significant proportion of travellers received vaccinations that are recommended in the routine national programme. These findings highlight the important role of travel clinics to (i) take care of an age group that has little contact with general practitioners and (ii) update vaccination status. The most commonly prescribed travel-related vaccines were for hepatitis A and yellow fever. The question remains to know whether

  4. Vaccination of healthcare workers: A review

    PubMed Central

    Haviari, Skerdi; Bénet, Thomas; Saadatian-Elahi, Mitra; André, Philippe; Loulergue, Pierre; Vanhems, Philippe

    2015-01-01

    Vaccine-preventable diseases are a significant cause of morbidity and mortality. As new vaccines are proving to be effective and as the incidence of some infections decreases, vaccination practices are changing. Healthcare workers (HCWs) are particularly exposed to and play a role in nosocomial transmission, which makes them an important target group for vaccination. Most vaccine-preventable diseases still carry a significant risk of resurgence and have caused outbreaks in recent years. While many professional societies favor vaccination of HCWs as well as the general population, recommendations differ from country to country. In turn, vaccination coverage varies widely for each microorganism and for each country, making hospitals and clinics vulnerable to outbreaks. Vaccine mandates and non-mandatory strategies are the subject of ongoing research and controversies. Optimal approaches to increase coverage and turn the healthcare workforce into an efficient barrier against infectious diseases are still being debated. PMID:26291642

  5. 75 FR 47602 - Clinical Studies of Safety and Effectiveness of Orphan Products Research Project Grant (R01)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-06

    ...] Clinical Studies of Safety and Effectiveness of Orphan Products Research Project Grant (R01) AGENCY: Food... product will be superior to the existing therapy. FDA provides grants for clinical studies on safety and... vaccine annually) and an explanation of how the proposed study will either help support product approval...

  6. Effectiveness of one dose of mumps vaccine against clinically diagnosed mumps in Guangzhou, China, 2006-2012.

    PubMed

    Fu, Chuanxi; Xu, Jianxiong; Cai, Yuanjun; He, Qing; Zhang, Chunhuan; Chen, Jian; Dong, Zhiqiang; Hu, Wensui; Wang, Hui; Zhu, Wei; Wang, Ming

    2013-12-01

    Although mumps-containing vaccines were introduced in China in 1990s, mumps continues to be a public health concern due to the lack of decline in reported mumps cases. To assess the mumps vaccine effectiveness (VE) in Guangzhou, China, we performed a 1:1 matched case-control study. Among children in Guangzhou aged 8 mo to 12 y during 2006 to 2012, we matched one healthy child to each child with clinically diagnosed mumps. Cases with clinically diagnosed mumps were identified from surveillance sites system and healthy controls were randomly sampled from the Children's Expanded Programmed Immunization Administrative Computerized System in Guangzhou. Conditional logistic regression was used to calculate VE. We analyzed the vaccination information for 1983 mumps case subjects and 1983 matched controls and found that the overall VE for 1 dose of mumps vaccine, irrespective of the manufacture, was 53.6% (95% confidence interval [CI], 41.0-63.5%) to children aged 8 mo to 12 y. This post-marketing mumps VE study found that immunization with one dose of the mumps vaccine confers partial protection against mumps disease. Evaluation of the VE for the current mumps vaccines, introduction of a second dose of mumps vaccine, and assessment of modifications to childhood immunization schedules is essential.

  7. Phase II and III Clinical Studies of Diphtheria-Tetanus-Acellular Pertussis Vaccine Containing Inactivated Polio Vaccine Derived from Sabin Strains (DTaP-sIPV).

    PubMed

    Okada, Kenji; Miyazaki, Chiaki; Kino, Yoichiro; Ozaki, Takao; Hirose, Mizuo; Ueda, Kohji

    2013-07-15

    Phase II and III clinical studies were conducted to evaluate immunogenicity and safety of a novel DTaP-IPV vaccine consisting of Sabin inactivated poliovirus vaccine (sIPV) and diphtheria-tetanus-acellular pertussis vaccine (DTaP). A Phase II study was conducted in 104 healthy infants using Formulation H of the DTaP-sIPV vaccine containing high-dose sIPV (3, 100, and 100 D-antigen units for types 1, 2, and 3, respectively), and Formulations M and L, containing half and one-fourth of the sIPV in Formulation H, respectively. Each formulation was administered 3 times for primary immunization and once for booster immunization. A Phase III study was conducted in 342 healthy infants who received either Formulation M + oral polio vaccine (OPV) placebo or DTaP + OPV. The OPV or OPV placebo was orally administered twice between primary and booster immunizations. Formulation M was selected as the optimum dose. In the Phase III study, the seropositive rate was 100% for all Sabin strains after primary immunization, and the neutralizing antibody titer after booster immunization was higher than in the control group (DTaP + OPV). All adverse reactions were clinically acceptable. DTaP-sIPV was shown to be a safe and immunogenic vaccine. JapicCTI-121902 for Phase II study, JapicCTI-101075 for Phase III study (http://www.clinicaltrials.jp/user/cte_main.jsp).

  8. A new multivalent (DHPPi/L4R) canine combination vaccine prevents infection, shedding and clinical signs following experimental challenge with four Leptospira serovars.

    PubMed

    Wilson, Stephen; Stirling, Catrina; Thomas, Anne; King, Vickie; Plevová, Edita; Chromá, Ludmila; Siedek, Elisabeth; Illambas, Joanna; Salt, Jeremy; Sture, Gordon

    2013-06-28

    Although effective vaccines have been developed against the common Leptospira serovars, they are still reported in clinical cases, while others are increasingly prevalent. The results from four challenge studies following vaccination of dogs with a new combination vaccine (DHPPi/L4R) containing inactivated L. serovars, L. canicola, L. icterohaemorrhagiae, L. bratislava and L. grippotyphosa conducted to satisfy the requirements of the European Pharmacopoeia monograph (01/2008:0447), are reported. Six week old dogs received two vaccinations, three weeks apart, and were challenged 25 days later with different isolates of the L. serovars. Clinical observations were recorded, and blood, urine and tissue samples were collected for analysis. Following challenge, non-vaccinated dogs demonstrated various clinical signs, while no vaccinated dogs were affected; significant differences in mean clinical scores were observed. Measurable antibody titres to each Leptospira antigen were seen in vaccinated dogs 21 days following the first vaccination, with further increases in antibody titres observed following challenge with the respective Leptospira strain. Non-vaccinated dogs remained seronegative until challenge. Leptospira were re-isolated from the blood, urine, kidney and liver of all non-vaccinated dogs following challenge. In contrast no vaccinated dogs had Leptospira re-isolated from the same tissues. Significant differences were seen in number of days with positive isolation (blood and urine) and in number of dogs with positive samples (kidney and liver). In conclusion, vaccination of dogs with the new vaccine induces protective immunity 25 days after second vaccination with protection against infection, renal infection and clinical signs following challenge. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Current barriers, challenges and opportunities for the development of effective STI vaccines: point of view of vaccine producers, biotech companies and funding agencies.

    PubMed

    Dodet, Betty

    2014-03-20

    Several barriers limit the development of vaccines against sexually transmitted diseases (STIs). Critical scientific information is missing that makes the feasibility and the likelihood of success of vaccines against genital herpes, chlamydia, gonorrhea and trichomonas uncertain: the immunity induced by natural infection is absent or imperfect which seriously limits the capacity to define the types of immune responses that an effective vaccine must induce. Reliable animal models are lacking and a number of crucial clinical questions are still unanswered about the goal of these vaccines and definition of endpoints for clinical trials. In the absence of a clear recognition of the need for vaccines against these diseases, there is no motivation for public or private research and industry to invest in the development of vaccines against STIs. The STI burden should be evaluated not only in terms of mortality and morbidity, but also in terms of economic and psycho-social impact. A global public-private consortium could mobilize the joint efforts of all stakeholders involved in the research, development and implementation of STI vaccines of the public and private sectors; ensure that sufficient resources are applied to R&D of vaccines against these STIs; and provide the pull-push forces that are necessary to overcome the barriers to develop safe and effective vaccines against these diseases. Copyright © 2014. Published by Elsevier Ltd.

  10. New Kids on the Block: RNA-Based Influenza Virus Vaccines.

    PubMed

    Scorza, Francesco Berlanda; Pardi, Norbert

    2018-04-01

    RNA-based immunization strategies have emerged as promising alternatives to conventional vaccine approaches. A substantial body of published work demonstrates that RNA vaccines can elicit potent, protective immune responses against various pathogens. Consonant with its huge impact on public health, influenza virus is one of the best studied targets of RNA vaccine research. Currently licensed influenza vaccines show variable levels of protection against seasonal influenza virus strains but are inadequate against drifted and pandemic viruses. In recent years, several types of RNA vaccines demonstrated efficacy against influenza virus infections in preclinical models. Additionally, comparative studies demonstrated the superiority of some RNA vaccines over the currently used inactivated influenza virus vaccines in animal models. Based on these promising preclinical results, clinical trials have been initiated and should provide valuable information about the translatability of the impressive preclinical data to humans. This review briefly describes RNA-based vaccination strategies, summarizes published preclinical and clinical data, highlights the roadblocks that need to be overcome for clinical applications, discusses the landscape of industrial development, and shares the authors' personal perspectives about the future of RNA-based influenza virus vaccines.

  11. HIV vaccine research--South Africa's ethical-legal framework and its ability to promote the welfare of trial participants.

    PubMed

    Strode, Ann; Slack, Catherine; Mushariwa, Muriel

    2005-08-01

    An effective ethical-legal framework for the conduct of research is critical. We describe five essential components of such a system, review the extent to which these components have been realised in South Africa, present brief implications for the ethical conduct of clinical trials of HIV vaccines in South Africa and make recommendations. The components of an effective ethical-legal system that we propose are the existence of scientific ethical and policy-making structures that regulate research; research ethics committees (RECs) that ethically review research; national ethical guidelines and standards; laws protecting research participants; and mechanisms to enforce and monitor legal rights and ethical standards. We conclude that the ethical-legal framework has, for the most part, the necessary institutions, and certain necessary guidelines but does not have many of the laws needed to protect and promote the rights of persons participating in research, including HIV vaccine trials. Recommendations made include advocacy measures to finalise and implement legislation, development of regulations, analysis and comparison of ethical guidelines, and the development of measures to monitor ethical-legal rights at trial sites.

  12. Influence of clinical outcome and outcome period definitions on estimates of absolute clinical and economic benefits of influenza vaccination in community dwelling elderly persons.

    PubMed

    Nichol, K L; Nordin, J; Mullooly, J

    2006-03-06

    Studies assessing the clinical and economic benefits of vaccination in the elderly have used different clinical outcomes (e.g. hospitalizations for pneumonia or influenza versus hospitalizations for respiratory and cardiovascular causes) and different outcome periods (e.g. peak versus total influenza season) on which to base estimates of clinical effectiveness and cost effectiveness. We explored the implications of these varying approaches by comparing two health economic analysis models of influenza vaccination of community-dwelling elderly persons. We developed computerized models using clinical data from 3 large US HMOs for the 1998-1999 and 1999-2000 influenza seasons. The primary health economic model used a broad definition of clinical events and outcome period and included hospitalizations for all respiratory and cardiovascular events that occurred during the entire influenza season. The alternative model used more restrictive definitions and included pneumonia or influenza hospitalizations occurring during the peak influenza season. The results of Monte Carlo simulation showed that, with the more inclusive primary model, influenza vaccination resulted in net medical care cost savings due to fewer respiratory or cardiovascular hospitalizations of Dollars 71/person vaccinated (5th-95th percentile Dollars 32-118) and net savings of Dollars 809/year of life saved (5th-95th percentile Dollars 331-1450). In contrast, the alternate model found costs of Dollars 3.50/person vaccinated (5th-95th percentile Dollars -11 to 5) and net costs of Dollars 91/year of life saved (5th-95th percentile Dollars -309 to 126). Our findings confirm that influenza vaccination of the elderly is most likely cost saving and supports policies and programs that advocate routine immunization of all persons 65 and older. They also highlight how different outcome definitions can influence the results of health economic analyses.

  13. Herpes zoster and vaccination: a clinical review.

    PubMed

    Adams, Erin N; Parnapy, Sarah; Bautista, Philip

    2010-05-01

    Herpes zoster, herpes zoster vaccine, and the cost-effectiveness of the vaccine are reviewed. Herpes zoster infection is estimated to affect one in three people during their lifetime. Two thirds of people who develop this disease are over age 60 years. Postherpetic neuralgia (PHN) is the most common complication of herpes zoster, occurring in 10-18% of patients. The associated chronic pain can be very debilitating, affecting patients' quality of life. The pain may last for months or years and is difficult to treat, leading to increased health care costs and morbidity. To prevent herpes zoster, a live attenuated vaccine was developed and approved for marketing in 2006 for individuals age > or = 60 years. The safety and efficacy of the vaccine were evaluated in the Shingles Prevention Study in 38,546 adults age > or = 60 years. Compared with placebo, administration of the vaccine resulted in a 51.3% reduction in the incidence of herpes zoster and a 66.5% reduction in the incidence of PHN (p < 0.001 for both comparisons). A single dose of the vaccine is approximately $162 and is not covered by all insurance plans. Several studies evaluated the cost-effectiveness of the vaccine, which was found to be most beneficial in individuals age 70 years or older. The use of the vaccine appears to reduce health care costs and protect the public health. The herpes zoster vaccine is effective in preventing herpes zoster and decreasing the incidence of complications. However, insurance coverage may hinder eligible patients from receiving the vaccination.

  14. Considerations for the rational design of a Chlamydia vaccine.

    PubMed

    Liang, Steven; Bulir, David; Kaushic, Charu; Mahony, James

    2017-04-03

    Chlamydia trachomatis is the leading cause of preventable blindness and the most common bacterial sexually transmitted infection. Remarkable progress in vaccine research over the past six decades has led to the advancement of novel C. trachomatis vaccine candidates into clinical trials. However, many questions regarding the role of specific cellular populations and molecular mechanisms in protective immunity against human C. trachomatis genital tract infections remain unanswered. Biomarkers of vaccine induced protective immunity are elusive in humans, while a cautionary message on the translatability of data obtained from current animal models has emanated from vaccine research and development efforts against other important human pathogens. In this commentary, we highlight recent advances in Chlamydia vaccine development and discuss their implications in the context of a rational approach to the design of a human C. trachomatis vaccine.

  15. Current advances in research and clinical applications of PLGA-based nanotechnology

    PubMed Central

    Lü, Jian-Ming; Wang, Xinwen; Marin-Muller, Christian; Wang, Hao; Lin, Peter H; Yao, Qizhi; Chen, Changyi

    2009-01-01

    Co-polymer poly(lactic-co-glycolic acid) (PLGA) nanotechnology has been developed for many years and has been approved by the US FDA for the use of drug delivery, diagnostics and other applications of clinical and basic science research, including cardiovascular disease, cancer, vaccine and tissue engineering. This article presents the more recent successes of applying PLGA-based nanotechnologies and tools in these medicine-related applications. It focuses on the possible mechanisms, diagnosis and treatment effects of PLGA preparations and devices. This updated information will benefit to both new and established research scientists and clinical physicians who are interested in the development and application of PLGA nanotechnology as new therapeutic and diagnostic strategies for many diseases. PMID:19435455

  16. From bench to almost bedside: the long road to a licensed Ebola virus vaccine.

    PubMed

    Wong, Gary; Mendoza, Emelissa J; Plummer, Francis A; Gao, George F; Kobinger, Gary P; Qiu, Xiangguo

    2018-02-01

    The Ebola virus (EBOV) disease epidemic during 2014-16 in West Africa has accelerated the clinical development of several vaccine candidates that have demonstrated efficacy in the gold standard nonhuman primate (NHP) model, namely cynomolgus macaques. Areas covered: This review discusses the pre-clinical research and if available, clinical evaluation of the currently available EBOV vaccine candidates, while emphasizing the translatability of pre-clinical data generated in the NHP model to clinical data in humans. Expert opinion: Despite the existence of many successful EBOV vaccine candidates in the pre-clinical stages, only two platforms became the focus of Phase 2/3 efficacy trials in Liberia, Sierra Leone, and Guinea near the peak of the epidemic: the Vesicular stomatitis virus (VSV)-vectored vaccine and the chimpanzee adenovirus type 3 (ChAd3)-vectored vaccine. The results of three distinct clinical trials involving these candidates may soon pave the way for a licensed, safe and efficacious EBOV vaccine to help combat future epidemics.

  17. From bench to almost bedside: The long road to a licensed Ebola virus vaccine

    PubMed Central

    Wong, Gary; Mendoza, Emelissa J.; Plummer, Francis A.; Gao, George F.; Kobinger, Gary P.; Qiu, Xiangguo

    2018-01-01

    Introduction The Ebola virus (EBOV) disease epidemic during 2014-16 in West Africa has accelerated the clinical development of several vaccine candidates that have demonstrated efficacy in the gold standard nonhuman primate (NHP) model, namely cynomolgus macaques. Areas covered This review discusses the pre-clinical research and if available, clinical evaluation of the currently available EBOV vaccine candidates, while emphasizing the translatability of pre-clinical data generated in the NHP model to clinical data in humans. Expert opinion Despite the existence of many successful EBOV vaccine candidates in the pre-clinical stages, only two platforms became the focus of Phase 2/3 efficacy trials in Liberia, Sierra Leone, and Guinea near the peak of the epidemic: the Vesicular stomatitis virus (VSV)-vectored vaccine and the chimpanzee adenovirus type 3 (ChAd3)-vectored vaccine. The results of three distinct clinical trials involving these candidates may soon pave the way for a licensed, safe and efficacious EBOV vaccine to help combat future epidemics. PMID:29148858

  18. Incentives and disincentives to participate in prophylactic HIV vaccine research.

    PubMed

    Jenkins, R A; Temoshok, L R; Virochsiri, K

    1995-05-01

    An anonymous cross-sectional paper-and-pencil survey was used to assess incentives and disincentives to participate in a Phase I preventive human immunodeficiency virus (HIV) vaccine trial in a potential Thai target population. A total of 255 persons employed in health care service and research settings completed questionnaires after attending informational briefings regarding the proposed vaccine product and the planned trial procedures. Willingness to participate was related to self-perceived benefits from joining a preventive vaccine trial, as well as to concerns about product safety and social discrimination that might result from participation. The distinction between positive results of enzyme-linked immunosorbent assay from vaccine administration and positivity from HIV infection was unclear for many participants. Men were more willing to participate than women, and there was a trend toward greater willingness to participate in those who were less educated. Preparations for preventive vaccine trials may be more successful if they emphasize personal benefits of trial participation, clearly address safety issues, and consider ways to prevent social discrimination against participants.

  19. Characteristics of a large mumps outbreak: Clinical severity, complications and association with vaccination status of mumps outbreak cases.

    PubMed

    Zamir, C Stein; Schroeder, H; Shoob, H; Abramson, N; Zentner, G

    2015-01-01

    In recent years, large mumps outbreaks, involving mainly adolescents and young adults, have re-emerged in several countries. We investigated a large mumps outbreak, evaluated the association between mumps clinical severity (complications, hospitalization) and vaccination status (number of previous measles, mumps and rubella - MMR vaccine doses), and assessed vaccine effectiveness. The first mumps cases emerged in an ultra-orthodox boys' school in Jerusalem and were epidemiologically linked to the mumps outbreak in New York. Overall, 3130 mumps cases were notified in the Jerusalem district during September 2009-August 2011 (median age 13y, 64% males). Most cases were reported from community clinics. Patients with systemic symptoms and/or complications (419, 13.4%) were either hospitalized (n = 79) or treated in an emergency medical center (n = 340). The main complications included orchitis (3.8% males> age 12y) and meningoencephalitis (0.5%). The mumps virus genotype was G5. The distribution of previous MMR vaccine doses (n = 0,1,2) was: 24.8%, 28.3% and 46.9%, respectively. The number of previous vaccine doses was inversely associated with clinical severity. Adjusted values for MMR vaccine effectiveness against complications were estimated as 52.1% (95% CI -4 -78%) for one vaccine dose and 62.7% (95% CI 25.7-81.3%) for 2 doses. The outbreak was characterized by predominance of male students; the majority of whom had been previously vaccinated. The reported complication rate was relatively low. Vaccination status was associated with age and disease severity. The combination of limited mumps vaccine effectiveness and the specific school setting (dense learning and living conditions) probably contributed to the disease spread.

  20. Characteristics of a large mumps outbreak: Clinical severity, complications and association with vaccination status of mumps outbreak cases

    PubMed Central

    Zamir, C Stein; Schroeder, H; Shoob, H; Abramson, N; Zentner, G

    2015-01-01

    In recent years, large mumps outbreaks, involving mainly adolescents and young adults, have re-emerged in several countries. We investigated a large mumps outbreak, evaluated the association between mumps clinical severity (complications, hospitalization) and vaccination status (number of previous measles, mumps and rubella - MMR vaccine doses), and assessed vaccine effectiveness. The first mumps cases emerged in an ultra-orthodox boys' school in Jerusalem and were epidemiologically linked to the mumps outbreak in New York. Overall, 3130 mumps cases were notified in the Jerusalem district during September 2009-August 2011 (median age 13y, 64% males). Most cases were reported from community clinics. Patients with systemic symptoms and/or complications (419, 13.4%) were either hospitalized (n = 79) or treated in an emergency medical center (n = 340). The main complications included orchitis (3.8% males> age 12y) and meningoencephalitis (0.5%). The mumps virus genotype was G5. The distribution of previous MMR vaccine doses (n = 0,1,2) was: 24.8%, 28.3% and 46.9%, respectively. The number of previous vaccine doses was inversely associated with clinical severity. Adjusted values for MMR vaccine effectiveness against complications were estimated as 52.1% (95% CI −4 −78%) for one vaccine dose and 62.7% (95% CI 25.7–81.3%) for 2 doses. The outbreak was characterized by predominance of male students; the majority of whom had been previously vaccinated. The reported complication rate was relatively low. Vaccination status was associated with age and disease severity. The combination of limited mumps vaccine effectiveness and the specific school setting (dense learning and living conditions) probably contributed to the disease spread. PMID:25874726

  1. The clinical and economic benefits of school-based quadrivalent HPV vaccination in Singapore.

    PubMed

    Tay, Sun Kuie; Hsu, Tun-Ying; Shcheprov, Andrei; Walia, Anuj; Kulkarni, Amit S

    2017-05-01

    To investigate the clinical and economic impacts of school-based administration of the quadrivalent HPV vaccine. A retrospective health-economic analysis was conducted using data collected in Singapore between 2004 and 2005. A dynamic transmission model was adapted for universal vaccination that provided 80% coverage among students aged 11-12 years. Strategy 1 involved only girls, with a 5-year catch-up vaccination to provide 50% coverage among those aged 13-17 years. Strategy 2 included both girls and boys with no catch-up vaccination. Outcomes included the predicted incidence of HPV-related disease over 100 years. Current coverage was assumed to be 5%. Strategy 1 would reduce cervical intraepithelial neoplasia grade 1 (CIN1) by 63.8%, cervical intraepithelial neoplasia grade 2-3 (CIN2-3) by 62.9%, cervical cancer by 50.9%, and genital warts by 78.0% (female individuals) and 73.6% (male individuals). Strategy 2 would reduce CIN1 by 64.0%, CIN2-3 by 63.1%, cervical cancer by 50.7%, and genital warts by 79.9% (female individuals) and 80.1% (male individuals). The incremental cost-effectiveness ratio was S$12 464 for strategy 1 and $27 837 for Strategy 2. These values decreased to $7477 and $22 574, respectively, if a two-dose regimen was adapted. School-based quadrivalent HPV vaccination offered clinical and economic benefits, and is cost-effective in Singapore. © 2017 International Federation of Gynecology and Obstetrics.

  2. Lessons learned from a review of the development of selected vaccines. National Vaccine Advisory Committee.

    PubMed

    Peter, G; des Vignes-Kendrick, M; Eickhoff, T C; Fine, A; Galvin, V; Levine, M M; Maldonado, Y A; Marcuse, E K; Monath, T P; Osborn, J E; Plotkin, S; Poland, G A; Quinlisk, M P; Smith, D R; Sokol, M; Soland, D B; Whitley-Williams, P N; Williamson, D E; Breiman, R F

    1999-10-01

    Although the vaccine research and development network in the United States remains vibrant, its continued success requires maintaining harmonious interaction among its many components. Changing one component is likely to affect the system overall. An examination of case studies of the development of selected vaccines would allow an examination of the network as a whole. This article presents conclusions drawn from the case study review undertaken. Successful development of vaccines is a time-intensive process requiring years of commitment from a network of scientists and a continuum of regulatory and manufacturing entities. We undertook this work to shed light on how well the vaccine development system in the United States performs. The National Vaccine Advisory Committee examined the research and development pathways of several vaccines that reached licensure expeditiously (hepatitis B vaccine, Haemophilus influenzae type b conjugate vaccines); some that became licensed only after considerable delay (oral typhoid Ty21a vaccine, varicella vaccine); some that are at the point of imminent or recent licensure (reassortant Rhesus rotavirus vaccine, which was licensed by the Food and Drug Administration on August 30, 1998) or near submission for licensure (intranasal cold adapted influenza vaccine); and one for which clinical development is slow because of hurdles that must be overcome (respiratory syncytial virus vaccines). Some common themes emerged from the reviews of these vaccine "case histories": the expediting influence of a strong scientific base and rationale; the need for firm quantitation of disease burden and clear identification of target populations; the critical role played by individuals or teams who act as "champions" to overcome the inevitable obstacles; availability of relevant animal models, high-quality reagents and standardized assays to measure immune response; the absolute requirement for well designed, meticulously executed clinical trials of

  3. Assessment of maternal antibody decay and response to canine parvovirus vaccination using a clinic-based enzyme-linked immunosorbent assay.

    PubMed

    Waner, T; Naveh, A; Wudovsky, I; Carmichael, L E

    1996-10-01

    Interference caused by maternal antibodies is considered a major cause of canine parvovirus (CPV) vaccination failure. In this study, an immunoblot clinic-based enzyme-linked immunosorbent assay (ELISA) method was used to detect CPV antibodies in sera of pregnant bitches and their offspring to study the response of pups to vaccination. With a easily accessible procedure for CPV antibody determination, the veterinarian should be able to gauge the response of pups after vaccination. The validity of the technique was tested in parallel against the standard hemagglutination inhibition (HI) test. Results of the ELISA were correlated with those of the standard HI method for quantification of CPV antibodies. With the ELISA, successfully immunized pups were identified, allowing for a more reliable and cost-effective program of vaccination. This simple clinic-based test could be used for the assessment of vaccination status of pups during the critical phase of 6 to about 16 weeks of age. This study is the first in which vaccination response to CPV in pups was followed, using a clinic-based ELISA for CPV antibody monitoring.

  4. Zika virus vaccines.

    PubMed

    Abbink, Peter; Stephenson, Kathryn E; Barouch, Dan H

    2018-06-19

    The recent epidemic of Zika virus (ZIKV) in the Americas has revealed the devastating consequences of ZIKV infection, particularly in pregnant women. Congenital Zika syndrome, characterized by malformations and microcephaly in neonates as well as developmental challenges in children, highlights the need for the development of a safe and effective vaccine. Multiple vaccine candidates have been developed and have shown promising results in both animal models and phase I clinical trials. However, important challenges remain for the clinical development of these vaccines. In this Progress article, we discuss recent preclinical studies and lessons learned from first-in-human clinical trials with ZIKV vaccines.

  5. Vaccine stabilization: research, commercialization, and potential impact.

    PubMed

    Kristensen, Debra; Chen, Dexiang; Cummings, Ray

    2011-09-22

    All vaccines are susceptible to damage by elevated temperatures and many are also damaged by freezing. The distribution, storage, and use of vaccines therefore present challenges that could be reduced by enhanced thermostability, with resulting improvements in vaccine effectiveness. Formulation and processing technologies exist that can improve the stability of vaccines at temperature extremes, however, customization is required for individual vaccines and results are variable. Considerations affecting decisions about stabilization approaches include development cost, manufacturing cost, and the ease of use of the final product. Public sector agencies can incentivize vaccine developers to prioritize stabilization efforts through advocacy and by implementing policies that increase demand for thermostable vaccines. Copyright © 2011 Elsevier Ltd. All rights reserved.

  6. An open-label, single arm, phase III clinical study to evaluate the efficacy and safety of CJ smallpox vaccine in previously vaccinated healthy adults.

    PubMed

    Kim, Nak-Hyun; Kang, Yu Min; Kim, Gayeon; Choe, Pyoeng Gyun; Song, Jin Su; Lee, Kwang-Hee; Seong, Baik-Lin; Park, Wan Beom; Kim, Nam Joong; Oh, Myoung-don

    2013-10-25

    The increased possibility of bioterrorism has led to reinitiation of smallpox vaccination. In Korea, more than 30 years have passed since the last smallpox vaccinations, and even people who were previously vaccinated are not regarded as adequately protected against smallpox. We evaluated the efficacy and safety of CJ-50300, a newly developed cell culture-derived smallpox vaccine, in healthy adults previously vaccinated against smallpox. We conducted an open label, single arm, phase III clinical trial to evaluate the efficacy and safety of CJ-50300. Healthy volunteers, previously vaccinated against smallpox, born between 1950 and 1978 were enrolled. CJ-50300 was administered with a bifurcated needle over the deltoid muscle according to the recommended method. The rate of the cutaneous take reaction, humoral immunogenicity, and safety of the vaccine was assessed. Of 145 individuals enrolled for vaccination, 139 completed the study. The overall rates of cutaneous take reactions and humoral immunogenicity were 95.0% (132/139) and 88.5% (123/139), respectively. Although 95.9% (139/145) reported adverse events related to vaccination, no serious adverse reactions were observed. CJ-50300 can be used safely and effectively in healthy adults previously vaccinated against smallpox. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Tuberculosis vaccines: time to think about the next generation.

    PubMed

    Kaufmann, Stefan H E

    2013-04-01

    Efforts over the last 2 decades have led to a rich research and development pipeline of tuberculosis (TB) vaccines. Although none of the candidates has successfully completed the clinical trial pipeline, many are under advanced clinical assessment. These vaccines aim at prevention of active TB, with most of them being considered for preexposure with recent additions for postexposure or multistage administration. A few therapeutic vaccines are under clinical assessment, as well. Preexposure vaccination with the licensed TB vaccine BCG prevents severe forms of TB in children but not in adolescents and adults. The current vaccine pipeline does not include strategies which prevent or eliminate infection with the causative agent Mycobacterium tuberculosis (Mtb). Rather in a best-case scenario, they are quantitatively superior to BCG in preventing active TB over prolonged periods of time, ideally lifelong in the face of latent Mtb infection. Qualitatively superior vaccines should be capable of preventing or eliminating Mtb infection, in this way eliminating the risk of TB reactivation. The time is now ripe to exploit radically new strategies to achieve this goal. Copyright © 2013. Published by Elsevier Ltd.

  8. Current Status of Syphilis Vaccine Development: Need, Challenges, Prospects

    PubMed Central

    Cameron, Caroline E.; Lukehart, Sheila A.

    2013-01-01

    Syphilis is a multistage disease caused by the invasive spirochete Treponema pallidum subsp. pallidum. Despite inexpensive and effective antibiotic therapy, syphilis remains a prevalent disease in developing countries and has re-emerged as a public health threat in developed nations. In addition to the medical burden imparted by infectious syphilis, congenital syphilis is considered the most significant infectious disease affecting fetuses and newborns worldwide, and individuals afflicted with syphilis have an enhanced risk for HIV transmission and acquisition. The global disease burden of syphilis and failure of decades of public health efforts to stem the incidence of disease highlight the need for an effective syphilis vaccine. Although challenges associated with T. pallidum research have impeded understanding of this pathogen, the existence of a relevant animal model has enabled insight into the correlates of disease protection. Complete protection against infection has been achieved in the animal model using an extended immunization regimen of γ-irradiated T. pallidum, demonstrating the importance of treponemal surface components in generation of protective immunity and the feasibility of syphilis vaccine development. Syphilis is a prime candidate for development of a successful vaccine due to the (1) research community’s accumulated knowledge of immune correlates of protection; (2) existence of a relevant animal model that enables effective pre-clinical analyses; (3) universal penicillin susceptibility of T. pallidum which enhances the attractiveness of clinical vaccine trials; and (4) significant public health benefit a vaccine would have on reduction of infectious/congenital syphilis and HIV rates. Critical personnel, research and market gaps need to be addressed before the goal of a syphilis vaccine can be realized, including recruitment of additional researchers to the T. pallidum research field with a proportional increase in research funding

  9. Smallpox vaccines for biodefense: need and feasibility.

    PubMed

    Artenstein, Andrew W; Grabenstein, John D

    2008-10-01

    Smallpox, eradicated as a cause of natural disease through an intensive global effort in the later part of the 20th Century, has resurfaced as a possible agent of bioterrorism. For this reason, there is renewed interest in smallpox vaccines. Live vaccinia virus, an orthopoxvirus related to smallpox, has a long and successful clinical track record as an effective smallpox vaccine; however, its use is associated with uncommon yet serious adverse events. This has led to a surge of recent research into newer-generation smallpox vaccines with improved safety profiles and retained efficacy. This article will review the history of smallpox vaccines, assess the status of newer-generation vaccines and examine the overall risk-versus-benefit profile of smallpox vaccination.

  10. A brief history of HIV vaccine research: stepping back to the drawing board?

    PubMed

    Miedema, Frank

    2008-09-12

    In September 2007, it was announced that the most promising HIV vaccine trial had to be stopped because it had failed to show the protection that was hoped for. Here, the history of HIV vaccine development from the discovery of HIV-1 in 1983 until 2008, the underlying ideas on protective immunity to HIV and potential avenues for vaccine research are discussed.

  11. Primary care pediatricians' perceptions of vaccine refusal in europe.

    PubMed

    Grossman, Zachi; van Esso, Diego; Del Torso, Stefano; Hadjipanayis, Adamos; Drabik, Anna; Gerber, Andreas; Miron, Dan

    2011-03-01

    An electronic survey assessing primary care pediatricians' estimations and practices regarding parents' vaccination refusal was sent to 395 members of the European Academy of Pediatrics Research in Ambulatory Setting network, with a response rate of 87%. Of respondents who vaccinate in the clinic, 93% estimated the total vaccine refusal rate as <1%. Of all respondents, 69% prefer a shared decision-making approach to handle refusing parents.

  12. Ethical considerations in HIV prevention and vaccine research in resource-limited settings.

    PubMed

    Garner, Samual A; Anude, Chuka J; Adams, Elizabeth; Dawson, Liza

    2014-09-01

    HIV prevention research has been facing increasing ethical and operational challenges. Factors influencing the design and conduct of HIV prevention trials include a rapidly changing evidence base, new biomedical prevention methods and modalities being tested, a large diversity of countries, sites and populations affected by HIV and participating in trials, and challenges of developing and making available products that will be feasible and affordable for at-risk populations. To discuss these challenges, a meeting, Ethical considerations around novel combination prevention modalities in HIV prevention and vaccine trials in resource-limited settings, was convened by NIH/NIAID/Division of AIDS on April 22-23, 2013. Several themes emerged from the meeting: (1) because of both trial design and ethical complexities, choosing prevention packages and designing combination prevention research trials will need to be evaluated on a case by case basis in different clinical trials, countries, and health systems; (2) multilevel stakeholder engagement from the beginning is vital to a fair and transparent process and also to designing ethical and relevant trials; (3) research should generally be responsive to a host country's needs, and sponsors and stakeholders should work together to address potential barriers to future access; and finally, (4) another meeting including a broader group of stakeholders is needed to address many of the outstanding ethical issues raised by this meeting. We offer an overview of the meeting and the key discussion points and recommendations to help guide the design and conduct of future HIV prevention and vaccine research in resource-limited settings.

  13. Research on subgroups is not research on equity attributes: Evidence from an overview of systematic reviews on vaccination.

    PubMed

    Bosch-Capblanch, Xavier; Zuske, Meike-Kathrin; Auer, Christian

    2017-06-07

    Equity remains a priority in the international health development agenda. However, major inequities in vaccination coverage jeopardise the achievement of the Sustainable Development Goals. We aim at comprehensively describing how research has addressed equity issues related to vaccination. We carried out an overview of systematic reviews (SRs) that explicitly explored the effects of interventions to improve vaccination in any context; for any vaccine and, in any language. We followed standard research synthesis methods to systematically search for SR, assess them for inclusion and extracting relevant data, particularly on vaccination related outcomes. To gather evidence on equity issues addressed in the SR, we used the PROGRESS-plus framework. Our search obtained 2,003 hits which resulted in 54 included SRs, published between 1994 and 2014. The quality of SRs was generally poor, with less than half complying with most of the quality criteria. Reported vaccines included, by order of frequency, influenza and Expanded Programme on Immunisation vaccines. The types of interventions more frequently reported were related to vaccination delivery strategies, financial support and information, education and communication. Most of the SRs suggested effects favouring intervention groups as opposed to comparison groups. The most frequently reported equity attribute was 'place of residence' and the least reported equity attributes were sexual orientation and religion. Very few estimates of effects actually measured differences or changes between groups having those attributes and all of them referred to the place of residence. No data was found about reducing equity gaps for vulnerable groups or minorities, or attributes such as sexual orientation, education or specific religious groups. Although research on vulnerable populations as a subgroup is abundant, it fails to report on the interventions that will actually reduce inequities and consider how redistribution of health care

  14. Sequence and immunogenicity of a clinically approved novel measles virus vaccine vector

    PubMed Central

    Zuniga, Amando; Liniger, Mathias; Morin, Teldja Neige Azzouz; Marty, René R.; Wiegand, Marian; Ilter, Orhan; Weibel, Sara; Billeter, Martin A.; Knuchel, Marlyse C.; Naim, Hussein Y.

    2013-01-01

    The measles virus vaccine (MVbv) is a clinically certified and well-tolerated vaccine strain that has been given both parenterally and mucosally. It has been extensively used in children and has proven to be safe and effective in eliciting protective immunity. This specific strain was therefore chosen to generate a measles viral vector. The genome of the commercial MVbv vaccine strain was isolated, sequenced and a plasmid, p(+)MVb, enabling transcription of the viral antigenome and rescue of MVb, was constructed. Phylogenic and phenotypic analysis revealed that MVbv and the rescued MVb constitute another evolutionary branch within the hitherto classified measles vaccines. Plasmid p(+)MVb was modified by insertion of artificial MV-type transcription units (ATUs) for the generation of recombinant viruses (rMVb) expressing additional proteins. Replication characteristics and immunogenicity of rMVb vectors were similar to the parental MVbv and to other vaccine strains. The expression of the additional proteins was stable over 10 serial virus transfers, which corresponds to an amplification greater than 1020. The excellent safety record and its efficient application as aerosol may add to the usefulness of the derived vectors. PMID:23324616

  15. Subviral Particle as Vaccine and Vaccine Platform

    PubMed Central

    Tan, Ming; Jiang, Xi

    2014-01-01

    Recombinant subvirual particles retain similar antigenic features of their authentic viral capsids and thus have been applied as nonreplicating subunit vaccines against viral infection and illness. Additionally, the self-assembled, polyvalent subviral particles are excellent platforms to display foreign antigens for immune enhancement for vaccine development. These subviral particle-based vaccines are noninfectious and thus safer than the conventional live attenuated and inactivated vaccines. While several VLP vaccines are available in the markets, numerous others, including dual vaccines against more than one pathogen, are under clinical or preclinical development. This article provides an update of these efforts. PMID:24662314

  16. Factors influencing women's attitudes towards antenatal vaccines, group B Streptococcus and clinical trial participation in pregnancy: an online survey

    PubMed Central

    McQuaid, Fiona; Stevens, Zoe; Plumb, Jane; Hughes, Rhona; Voysey, Merryn; Heath, Paul T; Snape, Matthew D

    2016-01-01

    Objectives To explore factors influencing the likelihood of antenatal vaccine acceptance of both routine UK antenatal vaccines (influenza and pertussis) and a hypothetical group B Streptococcus (GBS) vaccine in order to improve understanding of how to optimise antenatal immunisation acceptance, both in routine use and clinical trials. Setting An online survey distributed to women of childbearing age in the UK. Participants 1013 women aged 18–44 years in England, Scotland and Wales. Methods Data from an online survey conducted to gauge the attitudes of 1013 women of childbearing age in England, Scotland and Wales to antenatal vaccination against GBS were further analysed to determine the influence of socioeconomic status, parity and age on attitudes to GBS immunisation, using attitudes to influenza and pertussis vaccines as reference immunisations. Factors influencing likelihood of participation in a hypothetical GBS vaccine trial were also assessed. Results Women with children were more likely to know about each of the 3 conditions surveyed (GBS: 45% vs 26%, pertussis: 79% vs 63%, influenza: 66% vs 54%), to accept vaccination (GBS: 77% vs 65%, pertussis: 79% vs 70%, influenza: 78% vs 68%) and to consider taking part in vaccine trials (37% vs 27% for a hypothetical GBS vaccine tested in 500 pregnant women). For GBS, giving information about the condition significantly increased the number of respondents who reported that they would be likely to receive the vaccine. Health professionals were the most important reported source of information. Conclusions Increasing awareness about GBS, along with other key strategies, would be required to optimise the uptake of a routine vaccine, with a specific focus on informing women without previous children. More research specifically focusing on acceptability in pregnant women is required and, given the value attached to input from healthcare professionals, this group should be included in future studies. PMID:27098824

  17. Large animal models for vaccine development and testing.

    PubMed

    Gerdts, Volker; Wilson, Heather L; Meurens, Francois; van Drunen Littel-van den Hurk, Sylvia; Wilson, Don; Walker, Stewart; Wheler, Colette; Townsend, Hugh; Potter, Andrew A

    2015-01-01

    The development of human vaccines continues to rely on the use of animals for research. Regulatory authorities require novel vaccine candidates to undergo preclinical assessment in animal models before being permitted to enter the clinical phase in human subjects. Substantial progress has been made in recent years in reducing and replacing the number of animals used for preclinical vaccine research through the use of bioinformatics and computational biology to design new vaccine candidates. However, the ultimate goal of a new vaccine is to instruct the immune system to elicit an effective immune response against the pathogen of interest, and no alternatives to live animal use currently exist for evaluation of this response. Studies identifying the mechanisms of immune protection; determining the optimal route and formulation of vaccines; establishing the duration and onset of immunity, as well as the safety and efficacy of new vaccines, must be performed in a living system. Importantly, no single animal model provides all the information required for advancing a new vaccine through the preclinical stage, and research over the last two decades has highlighted that large animals more accurately predict vaccine outcome in humans than do other models. Here we review the advantages and disadvantages of large animal models for human vaccine development and demonstrate that much of the success in bringing a new vaccine to market depends on choosing the most appropriate animal model for preclinical testing. © The Author 2015. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  18. Clinical outcome and cerebrospinal fluid profiles in patients with tick-borne encephalitis and prior vaccination history.

    PubMed

    Lenhard, Thorsten; Ott, Daniela; Jakob, Nurith J; Martinez-Torres, Francisco; Grond-Ginsbach, Caspar; Meyding-Lamadé, Uta

    2018-05-01

    Tick-borne encephalitis (TBE) is endemic in southern and eastern districts of Germany. Approximately 10-14% of the infected individuals suffer from long-term disability and in 1.5-3.6% the course is fatal. Two well-tolerated vaccines are available, which provide high protection and which have been confirmed in several field studies. Here we investigate clinical course, long-term outcome and cerebrospinal fluid (CSF) characteristics of TBE cases with a prior history of any vaccination as well as real vaccination breakthrough (VBT). A case series of 11 patients with a prior history of vaccination, part of a recently published lager cohort of 111 TBE cases. Evaluation included clinical data, degree of disability (modified RANKIN scale, mRS) and analysis of CSF and serum samples. Furthermore, metadata for extended analysis on clinical outcome of TBE with VBT were analysed. One patient had a clear VBT and ten of them had irregular vaccinations schedules (IVS). Infection severity did not differ in patients with IVS as compared to a non-vaccinated control cohort (median mRS: both 3.0) but these patients showed a stronger cellular immune response as measured by CSF pleocytosis (IVS, 205 cells/μL versus non-vaccinated control, 114 cell/μL, P < 0.05) and by differential pattern of CSF (intrathecal) immunoglobulin synthesis. However, shift analysis of VBT metadata using linear-by-linear association revealed a more serious course of TBE in patients with VBT than in a non-vaccinated control cohort (χ 2  = 9.95, P = 0.002). Furthermore, ordinal logistic regression analysis showed that VBT patients had an age-corrected, 2.65 fold (CI: 1.110-6.328; χ 2  = 4.813; p = 0.028) significant higher risk to suffer from moderate or severe infections, respectively. A history of IVS surprisingly seems to have no impact on the clinical course of TBE but may leave marks in the specific brain immune response. VBT patients, however, carry an age-independent, significant

  19. Does influenza vaccination improve pregnancy outcome? Methodological issues and research needs.

    PubMed

    Savitz, David A; Fell, Deshayne B; Ortiz, Justin R; Bhat, Niranjan

    2015-11-25

    Evidence that influenza vaccination during pregnancy is safe and effective at preventing influenza disease in women and their children through the first months of life is increasing. Several reports of reduced risk of adverse outcomes associated with influenza vaccination have generated interest in its potential for improving pregnancy outcome. Gavi, the Vaccine Alliance, estimates maternal influenza immunization programs in low-income countries would have a relatively modest impact on mortality compared to other new or under-utilized vaccines, however the impact would be substantially greater if reported vaccine effects on improved pregnancy outcomes were accurate. Here, we examine the available evidence and methodological issues bearing on the relationship between influenza vaccination and pregnancy outcome, particularly preterm birth and fetal growth restriction, and summarize research needs. Evidence for absence of harm associated with vaccination at a point in time is not symmetric with evidence of benefit, given the scenario in which vaccination reduces risk of influenza disease and, in turn, risk of adverse pregnancy outcome. The empirical evidence for vaccination preventing influenza in pregnant women is strong, but the evidence that influenza itself causes adverse pregnancy outcomes is inconsistent and limited in quality. Studies of vaccination and pregnancy outcome have produced mixed evidence of potential benefit but are limited in terms of influenza disease assessment and control of confounding, and their analytic methods often fail to fully address the longitudinal nature of pregnancy and influenza prevalence. We recommend making full use of results of randomized trials, re-analysis of existing observational studies to account for confounding and time-related factors, and quantitative assessment of the potential benefits of vaccination in improving pregnancy outcome, all of which should be informed by the collective engagement of experts in influenza

  20. [Typhoid fever in school children: by what measures is the modification of the clinical course due to oral vaccination?].

    PubMed

    Contreras, R; Ferreccio, C; Sotomayor, V; Astroza, L; Berríos, G; Ortiz, E; Palomino, C; Prenzel, I; Pinto, M E; Levine, M

    1992-02-01

    The clinical course of infection by Salmonellae was compared between patients who had been vaccinated against typhoid fever using the Ty21a vaccine and those who had not. Of 2566 bacteriological confirmed cases 84% were infected with S typhi, 14% with S paratyphi B and 2% with S paratyphi A. Among patients with typhoid fever, 34% were treated in hospital, 3.5% had relapses, 5.4% developed complications and 1 patient died (0.05%). Among patients with paratyphoid fever, 18% were treated in hospital, 0.6% had relapses, 1.4% developed complications and there were no deaths. These figures were similar among vaccinated and non-vaccinated cases. A slightly greater proportion of vaccinated cases were treated in hospital (38 vs 30%). Thus, use of oral vaccination against typhoid fever does not alter the clinical course of infection with Salmonellae.

  1. Vaccine and Drug Ontology Studies (VDOS 2014).

    PubMed

    Tao, Cui; He, Yongqun; Arabandi, Sivaram

    2016-01-01

    The "Vaccine and Drug Ontology Studies" (VDOS) international workshop series focuses on vaccine- and drug-related ontology modeling and applications. Drugs and vaccines have been critical to prevent and treat human and animal diseases. Work in both (drugs and vaccines) areas is closely related - from preclinical research and development to manufacturing, clinical trials, government approval and regulation, and post-licensure usage surveillance and monitoring. Over the last decade, tremendous efforts have been made in the biomedical ontology community to ontologically represent various areas associated with vaccines and drugs - extending existing clinical terminology systems such as SNOMED, RxNorm, NDF-RT, and MedDRA, developing new models such as the Vaccine Ontology (VO) and Ontology of Adverse Events (OAE), vernacular medical terminologies such as the Consumer Health Vocabulary (CHV). The VDOS workshop series provides a platform for discussing innovative solutions as well as the challenges in the development and applications of biomedical ontologies for representing and analyzing drugs and vaccines, their administration, host immune responses, adverse events, and other related topics. The five full-length papers included in this 2014 thematic issue focus on two main themes: (i) General vaccine/drug-related ontology development and exploration, and (ii) Interaction and network-related ontology studies.

  2. Air conditioning a vaccine laboratory. [Connaught Medical Research Laboratory, Toronto, Canada

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ross J.

    1976-05-01

    In 1974, the new Bacterial Vaccine Building of Connaught Medical Research Laboratories, Toronto, Canada, was opened to produce such vaccines as pertussis, typhoid, paratyphoids, and cholera and such toxoids as staphylococcus, diphtheria, and tetanus. It also produces other medicinal products. The layout of the complex and the air conditioning system necessary in all zones are described and schematically shown. (MCW)

  3. Newcastle disease virus vectored vaccines as bivalent or antigen delivery vaccines

    PubMed Central

    2017-01-01

    Recent advances in reverse genetics techniques make it possible to manipulate the genome of RNA viruses such as Newcastle disease virus (NDV). Several NDV vaccine strains have been used as vaccine vectors in poultry, mammals, and humans to express antigens of different pathogens. The safety, immunogenicity, and protective efficacy of these NDV-vectored vaccines have been evaluated in pre-clinical and clinical studies. The vaccines are safe in mammals, humans, and poultry. Bivalent NDV-vectored vaccines against pathogens of economic importance to the poultry industry have been developed. These bivalent vaccines confer solid protective immunity against NDV and other foreign antigens. In most cases, NDV-vectored vaccines induce strong local and systemic immune responses against the target foreign antigen. This review summarizes the development of NDV-vectored vaccines and their potential use as a base for designing other effective vaccines for veterinary and human use. PMID:28775971

  4. Social Justice and HIV Vaccine Research in the Age of Pre-Exposure Prophylaxis and Treatment as Prevention

    PubMed Central

    Bailey, Theodore C.; Sugarman, Jeremy

    2014-01-01

    The advent of pre-exposure prophylaxis (PrEP) and treatment as prevention (TasP) as means of HIV prevention raises issues of justice concerning how most fairly and equitably to apportion resources in support of the burgeoning variety of established HIV treatment and prevention measures and further HIV research, including HIV vaccine research. We apply contemporary approaches to social justice to assess the ethical justification for allocating resources in support of HIV vaccine research given competing priorities to support broad implementation of HIV treatment and prevention measures, including TasP and PrEP. We argue that there is prima facie reason to believe that a safe and effective preventive HIV vaccine would offer a distinct set of ethically significant benefits not provided by current HIV treatment or prevention methods. It is thereby possible to justify continued support for HIV vaccine research despite tension with priorities for treatment, prevention, and other research. We then consider a counter-argument to such a justification based on the uncertainty of successfully developing a safe and effective preventive HIV vaccine. Finally, we discuss how HIV vaccine research might now be ethically designed and conducted given the new preventive options of TasP and PrEP, focusing on the ethically appropriate standard of prevention for HIV vaccine trials. PMID:24033297

  5. Safety issues from a Phase 3 clinical trial of a live-attenuated chimeric yellow fever tetravalent dengue vaccine.

    PubMed

    Halstead, Scott B

    2018-02-26

    A tetravalent live-attenuated 3-dose vaccine composed of chimeras of yellow fever 17D and the four dengue viruses (CYD, also called Dengvaxia) completed phase 3 clinical testing in over 35,000 children leading to a recommendation that vaccine be administered to >/ = 9 year-olds residing in highly dengue- endemic countries. When clinical trial results were assessed 2 years after the first dose, vaccine efficacy among seropositives was high, but among seronegatives efficacy was marginal. Breakthrough dengue hospitalizations of vaccinated children occurred continuously over a period of 4-5 years post 3rd dose in an age distribution suggesting these children had been vaccinated when seronegative. This surmise was validated recently when the manufacturer reported that dengue NS1 IgG antibodies were absent in sera from hospitalized vaccinated children, an observation consistent with their having received Dengvaxia when seronegative. Based upon published efficacy data and in compliance with initial published recommendations by the manufacturer and WHO the Philippine government undertook to vaccinate 800,000-plus 9 year-olds starting in April 2016. Eighteen months later, dengue hospitalizations and a deaths were reported among vaccinated children. The benefits of administering Dengvaxia predicted by the manufacturer, WHO and others derive from scoring dengue hospitalizations of vaccinated children as vaccine failures rather than as vaccine enhanced dengue disease. Recommended regimens for administration of Dengvaxia should have been structured to warn of and avoid serious adverse events.

  6. Overcoming barriers to HPV vaccination: A randomized clinical trial of a culturally-tailored, media intervention among African American girls.

    PubMed

    DiClemente, Ralph J; Murray, Colleen Crittenden; Graham, Tracie; Still, Julia

    2015-01-01

    Although genital HPV is the most prevalent STI in the US, rates of vaccination uptake among high-risk subgroups remain low. Investigations of vaccine compliance have mainly targeted mother-daughter dyads, which in some settings may prove difficult. This study examines an innovative culturally tailored, computer-delivered media-based strategy to promote HPV vaccine uptake. Data, inclusive of sociodemographics, sexual behaviors, knowledge, attitudes, and beliefs about HPV and vaccination were collected via ACASI from 216 African American adolescent females (ages 14-18 years) seeking services in family planning and STI public health clinics in metropolitan Atlanta. Data were obtained prior to randomization and participation in an interactive media-based intervention designed to increase HPV vaccination uptake. Medical record abstraction was conducted 7 month post-randomization to assess initial vaccine uptake and compliance. Participants in the intervention were more compliant to vaccination relative to a placebo comparison condition (26 doses vs. Seventeen doses; p=0.12). However, vaccination series initiation and completion were lower than the national average. Thorough evaluation is needed to better understand factors facilitating HPV vaccine uptake and compliance, particularly perceived susceptibility and the influence of the patient-provider encounter in a clinical setting.

  7. HIV vaccines advocacy: the role of UNAIDS. Research and accessibility.

    PubMed

    Piot, P

    1996-01-01

    This article presents an interview with Dr. Peter Piot, executive director of the Joint UN Program on HIV/AIDS (UNAIDS) on the role of UNAIDS in the advocacy of HIV vaccines. Piot stressed that an efficient HIV vaccine, truly protective against HIV infection, could make all the difference in the campaign against AIDS. To this effect, the role of the UNAIDS is to carry out advocacy in favor of research as well as to collaborate with the diverse private initiatives that already exist. Commenting on the issue of guaranteed accessibility of HIV vaccine for developing countries, Piot states that it is possible to sell the product through seeking the support of donor organizations. When vaccine trials in a country are supported, it will also be made sure that the basic guarantees exist for making that product accessible to the population. Moreover, considering the impact of the pandemic on the business and economic community, Piot emphasized that alliance between the public and private sector is necessary in the struggle against AIDS. In general, the role of UNAIDS in the evaluation of a preventive vaccine for HIV is centered around communication, impact on community, and impact on prevention programs.

  8. Vaccines for the 21st century

    PubMed Central

    Delany, Isabel; Rappuoli, Rino; De Gregorio, Ennio

    2014-01-01

    In the last century, vaccination has been the most effective medical intervention to reduce death and morbidity caused by infectious diseases. It is believed that vaccines save at least 2–3 million lives per year worldwide. Smallpox has been eradicated and polio has almost disappeared worldwide through global vaccine campaigns. Most of the viral and bacterial infections that traditionally affected children have been drastically reduced thanks to national immunization programs in developed countries. However, many diseases are not yet preventable by vaccination, and vaccines have not been fully exploited for target populations such as elderly and pregnant women. This review focuses on the state of the art of recent clinical trials of vaccines for major unmet medical needs such as HIV, malaria, TB, and cancer. In addition, we describe the innovative technologies currently used in vaccine research and development including adjuvants, vectors, nucleic acid vaccines, and structure-based antigen design. The hope is that thanks to these technologies, more diseases will be addressed in the 21st century by novel preventative and therapeutic vaccines. PMID:24803000

  9. Effectiveness of one dose of mumps vaccine against clinically diagnosed mumps in Guangzhou, China, 2006–2012

    PubMed Central

    Fu, Chuanxi; Xu, Jianxiong; Cai, Yuanjun; He, Qing; Zhang, Chunhuan; Chen, Jian; Dong, Zhiqiang; Hu, Wensui; Wang, Hui; Zhu, Wei; Wang, Ming

    2013-01-01

    Although mumps-containing vaccines were introduced in China in 1990s, mumps continues to be a public health concern due to the lack of decline in reported mumps cases. To assess the mumps vaccine effectiveness (VE) in Guangzhou, China, we performed a 1:1 matched case-control study. Among children in Guangzhou aged 8 mo to 12 y during 2006 to 2012, we matched one healthy child to each child with clinically diagnosed mumps. Cases with clinically diagnosed mumps were identified from surveillance sites system and healthy controls were randomly sampled from the Children’s Expanded Programmed Immunization Administrative Computerized System in Guangzhou. Conditional logistic regression was used to calculate VE. We analyzed the vaccination information for 1983 mumps case subjects and 1983 matched controls and found that the overall VE for 1 dose of mumps vaccine, irrespective of the manufacture, was 53.6% (95% confidence interval [CI], 41.0–63.5%) to children aged 8 mo to 12 y. This post-marketing mumps VE study found that immunization with one dose of the mumps vaccine confers partial protection against mumps disease. Evaluation of the VE for the current mumps vaccines, introduction of a second dose of mumps vaccine, and assessment of modifications to childhood immunization schedules is essential. PMID:23955378

  10. Consensus on the Development of Vaccines against Naturally Acquired Melioidosis

    PubMed Central

    Funnell, Simon G.P.; Torres, Alfredo G.; Morici, Lisa A.; Brett, Paul J.; Dunachie, Susanna; Atkins, Timothy; Altmann, Daniel M.; Bancroft, Gregory; Peacock, Sharon J.

    2015-01-01

    Several candidates for a vaccine against Burkholderia pseudomallei, the causal bacterium of melioidosis, have been developed, and a rational approach is now needed to select and advance candidates for testing in relevant nonhuman primate models and in human clinical trials. Development of such a vaccine was the topic of a meeting in the United Kingdom in March 2014 attended by international candidate vaccine developers, researchers, and government health officials. The focus of the meeting was advancement of vaccines for prevention of natural infection, rather than for protection from the organism’s known potential for use as a biological weapon. A direct comparison of candidate vaccines in well-characterized mouse models was proposed. Knowledge gaps requiring further research were identified. Recommendations were made to accelerate the development of an effective vaccine against melioidosis. PMID:25992835

  11. Safety and preliminary immunogenicity of Cuban pneumococcal conjugate vaccine candidate in healthy children: a randomized phase I clinical trial.

    PubMed

    Dotres, Carlos P; Puga, Rinaldo; Ricardo, Yariset; Broño, Carmen R; Paredes, Beatriz; Echemendía, Vladimir; Rosell, Sandra; González, Nadezhda; García-Rivera, Dagmar; Valdés, Yury; Goldblatt, David; Vérez-Bencomo, Vicente

    2014-09-15

    A new heptavalent conjugate vaccine (PCV7-TT) is under development in Cuba. PCV7-TT contains 2 μg of serotypes 1, 5, 14, 18C, 19F, 23F and 4 μg of 6B, each one conjugated to tetanus toxoid (TT). This vaccine was designed with the serotypes that cause most invasive pneumococcal diseases (IPD) worldwide. In the present study, we investigated the safety and explored the immunogenicity of PCV7-TT during a controlled, randomized and double blind clinical trial phase I in 4-5-year-old children. PCV7-TT was well tolerated and as safe as Synflorix used as control vaccine. Following a single-dose vaccination, all individual serotypes included in PCV7-TT induced statistically significant increase of IgG GMC and OPA GMT. These are the first clinical results of PCV7-TT in children and they pave the way toward next clinical trials in children and infants. This clinical trial was published in the Cuban Public Register of Clinical Trials with code RPCEC00000173. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Dendritic cell based vaccines: progress in immunotherapy studies for prostate cancer.

    PubMed

    Ragde, Haakon; Cavanagh, William A; Tjoa, Benjamin A

    2004-12-01

    No effective treatment is currently available for metastatic prostate cancer. Dendritic cell (DC) based cancer vaccine research has emerged from the laboratories to human clinical trials. We describe progress in the development of DC based prostate cancer vaccine. The literature was reviewed for major contributions to a growing number of studies that demonstrate the potential of DC based immunotherapeutics for prostate cancer. Background topics relating to DC based immunotherapy theory and practice are also addressed. DCs have been recognized as the most efficient antigen presenting cells that have the capacity to initiate naive T cell response in vitro and in vivo. During their differentiation and maturation pathways, dendritic cells can efficiently capture, process and present antigens for T cell activation. These characteristics make DC an attractive choice as the cellular adjuvant for cancer vaccines. Advances in DC generation, loading, and maturation methodologies have made it possible to generate clinical grade vaccines for various human trials. More than 100 DC vaccine trials, including 7 studies of patients with advanced prostate cancer have been reported to date. These vaccines were generally well tolerated with no significant adverse toxicity reported. Clinical responders have been identified in these studies. The new prospects opened by DC based vaccines for prostate cancer are fascinating. When compared to conventional treatments, DC vaccinations have few side effects. Improvements in patient selection, vaccine delivery strategies, immune monitoring and vaccine manufacturing will be crucial in moving DC based prostate cancer vaccines closer to the clinics.

  13. Travel Pattern and Prescription Analysis at a Single Travel Clinic Specialized for Yellow Fever Vaccination in South Korea.

    PubMed

    Chin, Bum Sik; Kim, Jae Yoon; Gianella, Sara; Lee, Myunghee

    2016-03-01

    Travel-related risks for infectious diseases vary depending on travel patterns such as purpose, destination, and duration. In this study, we describe the patterns of travel and prescription of vaccines as well as malaria prophylaxis medication (MPM) at a travel clinic in South Korea to identify the gaps to fill for the optimization of pre-travel consultation. A cohort of travel clinic visitors in 2011 was constructed and early one-third of the visitors of each month were reviewed. During the study period, 10,009 visited the travel clinic and a retrospective chart review was performed for 3,332 cases for analysis of travel patterns and prescriptions. People receiving yellow fever vaccine (YFV) (n = 2,933) were traveling more frequently for business and tourism and less frequently for providing non-medical service or research/education compared to the 399 people who did not receive the YFV. Overall, most people were traveling to Eastern Africa, South America, and Western Africa, while South-Eastern Asia was the most common destination for the non-YFV group. Besides YFV, the typhoid vaccine was the most commonly prescribed (54.2%), while hepatitis A presented the highest coverage (74.7%) considering the natural immunity, prior and current vaccination history. Additionally, 402 (82.5%) individuals received a prescription for MPM among the 487 individuals travelling to areas with high-risk of malaria infection. Age over 55 was independently associated with receiving MPM prescription, while purpose of providing service and travel duration over 10 days were associated with no MPM prescription, despite travelling to high-risk areas. Eastern Africa and South America were common travel destinations among the visitors to a travel clinic for YFV, and most of them were travelling for tourism and business. For the individuals who are traveling to areas with high-risk for malaria, more proactive approach might be required in case of younger age travelers, longer duration, and

  14. Travel Pattern and Prescription Analysis at a Single Travel Clinic Specialized for Yellow Fever Vaccination in South Korea

    PubMed Central

    Gianella, Sara

    2016-01-01

    Background Travel-related risks for infectious diseases vary depending on travel patterns such as purpose, destination, and duration. In this study, we describe the patterns of travel and prescription of vaccines as well as malaria prophylaxis medication (MPM) at a travel clinic in South Korea to identify the gaps to fill for the optimization of pre-travel consultation. Materials and Methods A cohort of travel clinic visitors in 2011 was constructed and early one-third of the visitors of each month were reviewed. During the study period, 10,009 visited the travel clinic and a retrospective chart review was performed for 3,332 cases for analysis of travel patterns and prescriptions. Results People receiving yellow fever vaccine (YFV) (n = 2,933) were traveling more frequently for business and tourism and less frequently for providing non-medical service or research/education compared to the 399 people who did not receive the YFV. Overall, most people were traveling to Eastern Africa, South America, and Western Africa, while South-Eastern Asia was the most common destination for the non-YFV group. Besides YFV, the typhoid vaccine was the most commonly prescribed (54.2%), while hepatitis A presented the highest coverage (74.7%) considering the natural immunity, prior and current vaccination history. Additionally, 402 (82.5%) individuals received a prescription for MPM among the 487 individuals travelling to areas with high-risk of malaria infection. Age over 55 was independently associated with receiving MPM prescription, while purpose of providing service and travel duration over 10 days were associated with no MPM prescription, despite travelling to high-risk areas. Conclusion Eastern Africa and South America were common travel destinations among the visitors to a travel clinic for YFV, and most of them were travelling for tourism and business. For the individuals who are traveling to areas with high-risk for malaria, more proactive approach might be required in

  15. Mucosal vaccination with recombinant poxvirus vaccines protects ferrets against symptomatic CDV infection.

    PubMed

    Welter, J; Taylor, J; Tartaglia, J; Paoletti, E; Stephensen, C B

    1999-01-28

    Canine distemper virus (CDV) infection of ferrets causes a disease characterized by fever, erythema, conjunctivitis and leukocytopenia, similar clinically to measles except for the fatal neurologic sequelae of CDV. We vaccinated juvenile ferrets twice at 4-week intervals by the intranasal or intraduodenal route with attenuated vaccinia (NYVAC) or canarypox virus (ALVAC) constructs containing the CDV hemagglutinin and fusion genes. Controls were vaccinated with the same vectors expressing rabies glycoprotein. Animals were challenged intranasally 4 weeks after the second vaccination with virulent CDV. Body weights, white blood cell (WBC) counts and temperatures were monitored and ferrets were observed daily for clinical signs of infection. WBCs were assayed for the presence of viral RNA by RT-PCR. Intranasally vaccinated animals survived challenge with no virologic or clinical evidence of infection. Vaccination by the intraduodenal route did not provide complete protection. All control animals developed typical distemper. Ferrets can be effectively protected against distemper by mucosal vaccination with poxvirus vaccines.

  16. School-Located Vaccination Clinics: Then and Now

    ERIC Educational Resources Information Center

    Mazyck, Donna

    2010-01-01

    School-located vaccination has a long history in the United States. The 2008 Advisory Committee on Immunization Practices (ACIP) recommendation for annual influenza vaccination of all children 6 months through 18 years of age adds approximately 30 million individuals to the overall cohort recommended to have a yearly vaccination. The ability to…

  17. Safety of live vaccines on immunosuppressive or immunomodulatory therapy-a retrospective study in three Swiss Travel Clinics.

    PubMed

    Huber, Fabienne; Ehrensperger, Benoît; Hatz, Christoph; Chappuis, François; Bühler, Silja; Eperon, Gilles

    2018-01-01

    Patients increasingly benefit from immunosuppressive/immunomodulatory medications for a range of conditions allowing them a lifestyle similar to healthy individuals, including travel. However, the administration of live vaccines to immunodeficient patients bears the risk of replication of the attenuated vaccine microorganism. Therefore, live vaccines are generally contraindicated on immunosuppression. Data on live vaccinations on immunosuppressive/immunomodulatory medication are scarce. We identified all travellers seeking pre-travel advice in three Swiss travel clinics with a live vaccine during immunosuppressive/immunomodulatory therapy to ascertain experienced side effects. A retrospective and multi-centre study design was chosen to increase the sample size. This study was conducted in the travel clinics of the University of Zurich; the Swiss TPH, Basel; and Geneva University Hospitals. Travellers on immunosuppressive/immunomodulatory therapy who received live vaccines [yellow fever vaccination (YFV), measles/mumps/rubella (MMR), varicella and/ or oral typhoid vaccination (OTV)] between 2008 and 2015 were identified and interviewed. A total of 60 age- and sex-matched controls (matched to Basel/Zurich travel clinics travellers) were included. Overall, 197 patients were identified. And 116 patients (59%) and 60 controls were interviewed. YFV was administered 92 times, MMR 21 times, varicella 4 times and OTV 6 times to patients on immunosuppressive/immunomodulatory therapy. Most common medications were corticosteroids (n = 45), mesalazine (n = 28) and methotrexate (n = 19). Live vaccines were also administered on biological treatment, e.g. TNF-alpha inhibitors (n = 8). Systemic reactions were observed in 12.2% of the immunosuppressed vs 13.3% of controls; local reactions in 7.8% of the immunosuppressed vs 11.7% of controls. In controls, all reactions were mild/moderate. In the immunosuppressed, 2/21 severe reactions occurred: severe local pain on interferon

  18. Effectiveness of an oral cholera vaccine campaign to prevent clinically-significant cholera in Odisha State, India.

    PubMed

    Wierzba, Thomas F; Kar, Shantanu K; Mogasale, Vijayalaxmi V; Kerketta, Anna S; You, Young Ae; Baral, Prameela; Khuntia, Hemant K; Ali, Mohammad; Kim, Yang Hee; Rath, Shyam Bandhu; Bhattachan, Anuj; Sah, Binod

    2015-05-15

    A clinical trial conducted in India suggests that the oral cholera vaccine, Shanchol, provides 65% protection over five years against clinically-significant cholera. Although the vaccine is efficacious when tested in an experimental setting, policymakers are more likely to use this vaccine after receiving evidence demonstrating protection when delivered to communities using local health department staff, cold chain equipment, and logistics. We used a test-negative, case-control design to evaluate the effectiveness of a vaccination campaign using Shanchol and validated the results using a cohort approach that addressed disparities in healthcare seeking behavior. The campaign was conducted by the local health department using existing resources in a cholera-endemic area of Puri District, Odisha State, India. All non-pregnant residents one year of age and older were offered vaccine. Over the next two years, residents seeking care for diarrhea at one of five health facilities were asked to enroll following informed consent. Cases were patients seeking treatment for laboratory-confirmed V. cholera-associated diarrhea. Controls were patients seeking treatment for V. cholerae negative diarrhea. Of 51,488 eligible residents, 31,552 individuals received one dose and 23,751 residents received two vaccine doses. We identified 44 V. cholerae O1-associated cases and 366 non V. cholerae diarrhea controls. The adjusted protective effectiveness for persons receiving two doses was 69.0% (95% CI: 14.5% to 88.8%), which is similar to the adjusted estimates obtained from the cohort approach. A statistical trend test suggested a single dose provided a modicum of protection (33%, test for trend, p=0.0091). This vaccine was found to be as efficacious as the results reported from a clinical trial when administered to a rural population using local health personnel and resources. This study provides evidence that this vaccine should be widely deployed by public health departments in

  19. Design and rationale for the Influenza vaccination After Myocardial Infarction (IAMI) trial. A registry-based randomized clinical trial.

    PubMed

    Fröbert, Ole; Götberg, Matthias; Angerås, Oskar; Jonasson, Lena; Erlinge, David; Engstrøm, Thomas; Persson, Jonas; Jensen, Svend E; Omerovic, Elmir; James, Stefan K; Lagerqvist, Bo; Nilsson, Johan; Kåregren, Amra; Moer, Rasmus; Yang, Cao; Agus, David B; Erglis, Andrejs; Jensen, Lisette O; Jakobsen, Lars; Christiansen, Evald H; Pernow, John

    2017-07-01

    Registry studies and case-control studies have demonstrated that the risk of acute myocardial infarction (AMI) is increased following influenza infection. Small randomized trials, underpowered for clinical end points, indicate that future cardiovascular events can be reduced following influenza vaccination in patients with established cardiovascular disease. Influenza vaccination is recommended by international guidelines for patients with cardiovascular disease, but uptake is varying and vaccination is rarely prioritized during hospitalization for AMI. The Influenza vaccination After Myocardial Infarction (IAMI) trial is a double-blind, multicenter, prospective, registry-based, randomized, placebo-controlled, clinical trial. A total of 4,400 patients with ST-segment elevation myocardial infarction (STEMI) or non-STEMI undergoing coronary angiography will randomly be assigned either to in-hospital influenza vaccination or to placebo. Baseline information is collected from national heart disease registries, and follow-up will be performed using both registries and a structured telephone interview. The primary end point is a composite of time to all-cause death, a new AMI, or stent thrombosis at 1 year. The IAMI trial is the largest randomized trial to date to evaluate the effect of in-hospital influenza vaccination on death and cardiovascular outcomes in patients with STEMI or non-STEMI. The trial is expected to provide highly relevant clinical data on the efficacy of influenza vaccine as secondary prevention after AMI. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  20. Rhodococcus equi (Prescottella equi) vaccines; the future of vaccine development.

    PubMed

    Giles, C; Vanniasinkam, T; Ndi, S; Barton, M D

    2015-09-01

    For decades researchers have been targeting prevention of Rhodococcus equi (Rhodococcus hoagui/Prescottella equi) by vaccination and the horse breeding industry has supported the ongoing efforts by researchers to develop a safe and cost effective vaccine to prevent disease in foals. Traditional vaccines including live, killed and attenuated (physical and chemical) vaccines have proved to be ineffective and more modern molecular-based vaccines including the DNA plasmid, genetically attenuated and subunit vaccines have provided inadequate protection of foals. Newer, bacterial vector vaccines have recently shown promise for R. equi in the mouse model. This article describes the findings of key research in R. equi vaccine development and looks at alternative methods that may potentially be utilised. © 2014 EVJ Ltd.

  1. Progress in the development of photodynamic-therapy-generated cancer vaccines

    NASA Astrophysics Data System (ADS)

    Korbelik, Mladen; Sun, Jinghai

    2003-07-01

    Upon giving an outline on vaccines in general, their history and priorities for future development, this paper gives a brief summary of the advances in the generation of cancer vaccines from the first attempts made over 100 years ago to those currently evaluted in clinical trials. This is followed by discussing hte intitial achievements in the investigation of cancer vaccines generated by photodynamic therapy (PDT). Recent contributions from our research to the understanding of how PDT-generated cancer vaccines work and their advantages compared to other types of cancer vaccines are discussed.

  2. Large-scale adenovirus and poxvirus-vectored vaccine manufacturing to enable clinical trials.

    PubMed

    Kallel, Héla; Kamen, Amine A

    2015-05-01

    Efforts to make vaccines against infectious diseases and immunotherapies for cancer have evolved to utilize a variety of heterologous expression systems such as viral vectors. These vectors are often attenuated or engineered to safely deliver genes encoding antigens of different pathogens. Adenovirus and poxvirus vectors are among the viral vectors that are most frequently used to develop prophylactic vaccines against infectious diseases as well as therapeutic cancer vaccines. This mini-review describes the trends and processes in large-scale production of adenovirus and poxvirus vectors to meet the needs of clinical applications. We briefly describe the general principles for the production and purification of adenovirus and poxvirus viral vectors. Currently, adenovirus and poxvirus vector manufacturing methods rely on well-established cell culture technologies. Several improvements have been evaluated to increase the yield and to reduce the overall manufacturing cost, such as cultivation at high cell densities and continuous downstream processing. Additionally, advancements in vector characterization will greatly facilitate the development of novel vectored vaccine candidates. Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. The time-course of protection of the RTS,S vaccine against malaria infections and clinical disease.

    PubMed

    Penny, Melissa A; Pemberton-Ross, Peter; Smith, Thomas A

    2015-11-04

    Recent publications have reported follow-up of the RTS,S/AS01 malaria vaccine candidate Phase III trials at 11 African sites for 32 months (or longer). This includes site- and time-specific estimates of incidence and efficacy against clinical disease with four different vaccination schedules. These data allow estimation of the time-course of protection against infection associated with two different ages of vaccination, both with and without a booster dose. Using an ensemble of individual-based stochastic models, each trial cohort in the Phase III trial was simulated assuming many different hypothetical profiles for the vaccine efficacy against infection in time, for both the primary course and boosting dose and including the potential for either exponential or non-exponential decay. The underlying profile of protection was determined by Bayesian fitting of these model predictions to the site- and time-specific incidence of clinical malaria over 32 months (or longer) of follow-up. Using the same stochastic models, projections of clinical efficacy in each of the sites were modelled and compared to available observed trial data. The initial protection of RTS,S immediately following three doses is estimated as providing an efficacy against infection of 65 % (when immunizing infants aged 6-12 weeks old) and 91 % (immunizing children aged 5-17 months old at first vaccination). This protection decays relatively rapidly, with an approximately exponential decay for the 6-12 weeks old cohort (with a half-life of 7.2 months); for the 5-17 months old cohort a biphasic decay with a similar half-life is predicted, with an initial rapid decay followed by a slower decay. The boosting dose was estimated to return protection to an efficacy against infection of 50-55 % for both cohorts. Estimates of clinical efficacy by trial site are consistent with those reported in the trial for all cohorts. The site- and time-specific clinical observations from the RTS,S/AS01 trial data allowed

  4. VIOLIN: vaccine investigation and online information network.

    PubMed

    Xiang, Zuoshuang; Todd, Thomas; Ku, Kim P; Kovacic, Bethany L; Larson, Charles B; Chen, Fang; Hodges, Andrew P; Tian, Yuying; Olenzek, Elizabeth A; Zhao, Boyang; Colby, Lesley A; Rush, Howard G; Gilsdorf, Janet R; Jourdian, George W; He, Yongqun

    2008-01-01

    Vaccines are among the most efficacious and cost-effective tools for reducing morbidity and mortality caused by infectious diseases. The vaccine investigation and online information network (VIOLIN) is a web-based central resource, allowing easy curation, comparison and analysis of vaccine-related research data across various human pathogens (e.g. Haemophilus influenzae, human immunodeficiency virus (HIV) and Plasmodium falciparum) of medical importance and across humans, other natural hosts and laboratory animals. Vaccine-related peer-reviewed literature data have been downloaded into the database from PubMed and are searchable through various literature search programs. Vaccine data are also annotated, edited and submitted to the database through a web-based interactive system that integrates efficient computational literature mining and accurate manual curation. Curated information includes general microbial pathogenesis and host protective immunity, vaccine preparation and characteristics, stimulated host responses after vaccination and protection efficacy after challenge. Vaccine-related pathogen and host genes are also annotated and available for searching through customized BLAST programs. All VIOLIN data are available for download in an eXtensible Markup Language (XML)-based data exchange format. VIOLIN is expected to become a centralized source of vaccine information and to provide investigators in basic and clinical sciences with curated data and bioinformatics tools for vaccine research and development. VIOLIN is publicly available at http://www.violinet.org.

  5. In “Step” with HIV Vaccines? A Content Analysis of Local Recruitment Campaigns for an International HIV Vaccine Study

    PubMed Central

    Frew, Paula M.; Macias, Wendy; Chan, Kayshin; Harding, Ashley C.

    2009-01-01

    During the past two decades of the HIV/AIDS pandemic, several recruitment campaigns were designed to generate community involvement in preventive HIV vaccine clinical trials. These efforts utilized a blend of advertising and marketing strategies mixed with public relations and community education approaches to attract potential study participants to clinical trials (integrated marketing communications). Although more than 30,000 persons worldwide have participated in preventive HIV vaccine studies, no systematic analysis of recruitment campaigns exists. This content analysis study was conducted to examine several United States and Canadian recruitment campaigns for one of the largest-scale HIV vaccine trials to date (the “Step Study”). This study examined persuasive features consistent with the Elaboration Likelihood Model (ELM) including message content, personal relevance of HIV/AIDS and vaccine research, intended audiences, information sources, and other contextual features. The results indicated variation in messages and communication approaches with gay men more exclusively targeted in these regions. Racial/ethnic representations also differed by campaign. Most of the materials promote affective evaluation of the information through heuristic cueing. Implications for subsequent campaigns and research directions are discussed. PMID:19609373

  6. Advancing a vaccine to prevent human schistosomiasis.

    PubMed

    Merrifield, Maureen; Hotez, Peter J; Beaumier, Coreen M; Gillespie, Portia; Strych, Ulrich; Hayward, Tara; Bottazzi, Maria Elena

    2016-06-03

    Several candidate human schistosomiasis vaccines are in different stages of preclinical and clinical development. The major targets are Schistosoma haematobium (urogenitial schistosomiasis) and Schistosoma mansoni (intestinal schistosomiasis) that account for 99% of the world's 252 million cases, with 90% of these cases in Africa. Two recombinant S. mansoni vaccines - Sm-TSP-2 and Sm-14 are in Phase 1 trials, while Smp80 (calpain) is undergoing testing in non-human primates. Sh28GST, also known as Bilhvax is in advanced clinical development for S. haematobium infection. The possibility remains that some of these vaccines may cross-react to target both schistosome species. These vaccines were selected on the basis of their protective immunity in preclinical challenge models, through human immune-epidemiological studies or both. They are being advanced through a combination of academic research institutions, non-profit vaccine product development partnerships, biotechnology companies, and developing country vaccine manufacturers. In addition, new schistosome candidate vaccines are being identified through bioinformatics, OMICs approaches, and moderate throughput screening, although the full potential of reverse vaccinology for schistosomiasis has not yet been realized. The target product profiles of these vaccines vary but many focus on vaccinating children, in some cases following mass treatment with praziquantel, also known as vaccine-linked chemotherapy. Several regulatory pathways have been proposed, some of which rely on World Health Organization prequalification. Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

  7. Characterization of a whole, inactivated influenza (H5N1) vaccine.

    PubMed

    Tada, Yoshikazu

    2008-11-01

    Effective vaccines against the highly pathogenic influenza A/H5N1 virus are being developed worldwide. In Japan, two adjuvanted, inactivated, whole-virion influenza vaccines were recently developed and licensed as mock-up, pre-pandemic vaccine formulations by the Ministry of Health and Labor Welfare of Japan. During the vaccine design and development process, various obstacles were overcome and, in this report, we introduce the non clinical production, immunogenicity data in human and development process that was associated with egg-derived adjuvanted, inactivated, whole-virion influenza A (H5N1) vaccine. Pilot lots of H5N1 vaccine were produced using the avirulent H5N1 reference strain A/Vietnam/1194/2004 (H5N1) NIBRG-14 and administered following adsorption with aluminum hydroxide as an adjuvant. Quality control and formulation stability tests were performed before clinical trials were initiated (phase I-III). The research foundation for microbial diseases of Osaka University (BIKEN) carried out vaccine production, quality control, stability testing and the phase I clinical trial in addition to overseeing the licensing of this vaccine. Mitsubishi Chemical Safety Institute Ltd. carried out the non clinical pharmacological toxicity and safety studies and the Japanese medical association carried out the phase II/III trials. Phase I-III trials took place in 2006. The production processes were well controlled by established tests and validations. Vaccine quality was confirmed by quality control, stability and pre-clinical tests, and the vaccine was approved as a mock-up, pre-pandemic vaccine by the Ministry of Health and Labor Welfare of Japan. Numerous safety and efficacy procedures were carried out prior to the approval of the described vaccine formulation. Some of these procedures were of particular importance e.g., vaccine development, validation, and quality control tests that included strict monitoring of the hemagglutinin (HA) content of the vaccine

  8. Advances in inducing adaptive immunity using cell-based cancer vaccines: Clinical applications in pancreatic cancer.

    PubMed

    Kajihara, Mikio; Takakura, Kazuki; Kanai, Tomoya; Ito, Zensho; Matsumoto, Yoshihiro; Shimodaira, Shigetaka; Okamoto, Masato; Ohkusa, Toshifumi; Koido, Shigeo

    2016-05-14

    The incidence of pancreatic ductal adenocarcinoma (PDA) is on the rise, and the prognosis is extremely poor because PDA is highly aggressive and notoriously difficult to treat. Although gemcitabine- or 5-fluorouracil-based chemotherapy is typically offered as a standard of care, most patients do not survive longer than 1 year. Therefore, the development of alternative therapeutic approaches for patients with PDA is imperative. As PDA cells express numerous tumor-associated antigens that are suitable vaccine targets, one promising treatment approach is cancer vaccines. During the last few decades, cell-based cancer vaccines have offered encouraging results in preclinical studies. Cell-based cancer vaccines are mainly generated by presenting whole tumor cells or dendritic cells to cells of the immune system. In particular, several clinical trials have explored cell-based cancer vaccines as a promising therapeutic approach for patients with PDA. Moreover, chemotherapy and cancer vaccines can synergize to result in increased efficacies in patients with PDA. In this review, we will discuss both the effect of cell-based cancer vaccines and advances in terms of future strategies of cancer vaccines for the treatment of PDA patients.

  9. Translating nanoparticulate-personalized cancer vaccines into clinical applications: case study with RNA-lipoplexes for the treatment of melanoma.

    PubMed

    Grabbe, Stephan; Haas, Heinrich; Diken, Mustafa; Kranz, Lena M; Langguth, Peter; Sahin, Ugur

    2016-10-01

    The development of nucleic acid based vaccines against cancer has gained considerable momentum through the advancement of modern sequencing technologies and on novel RNA-based synthetic drug formats, which can be readily adapted following identification of every patient's tumor-specific mutations. Furthermore, affordable and individual 'on demand' production of molecularly optimized vaccines should allow their application in large groups of patients. This has resulted in the therapeutic concept of an active personalized cancer vaccine, which has been brought into clinical testing. Successful trials have been performed by intranodal administration of sterile isotonic solutions of synthetic RNA vaccines. The second generation of RNA vaccines which is currently being developed encompasses intravenously injectable RNA nanoparticle formulations (lipoplexes), made up from lipid excipients, denoted RNA (LIP) . A first product that has made its way from bench to bedside is a therapeutic vaccine for intravenous administration based on a fixed set of four RNA lipoplex drug products, each encoding for one shared tumor antigen (Lipoplex Melanoma RNA Immunotherapy, 'Lipo-MERIT'). This article describes the steps for translating these novel RNA nanomedicines into clinical trials.

  10. EV-A71 vaccine licensure: a first step for multivalent enterovirus vaccine to control HFMD and other severe diseases

    PubMed Central

    Mao, Qunying; Wang, Yiping; Bian, Lianlian; Xu, Miao; Liang, Zhenglun

    2016-01-01

    Enteroviruses (EVs) are the most common viral agents in humans. Although most infections are mild or asymptomatic, there is a wide spectrum of clinical manifestations that may be caused by EV infections with varying degrees of severity. Among these viruses, EV-A71 and coxsackievirus (CV) CV-A16 from group A EVs attract the most attention because they are responsible for hand, foot and mouth disease (HFMD). Other EV-A viruses such as CV-A6 and CV-A10 were also reported to cause HFMD outbreaks in several countries or regions. Group B EVs such as CV-B3, CV-B5 and echovirus 30 were reported to be the main pathogens responsible for myocarditis and encephalitis epidemics and were also detected in HFMD patients. Vaccines are the best tools to control infectious diseases. In December 2015, China's Food and Drug Administration approved two inactivated EV-A71 vaccines for preventing severe HFMD.The CV-A16 vaccine and the EV-A71-CV-A16 bivalent vaccine showed substantial efficacy against HFMD in pre-clinical animal models. Previously, research on EV-B group vaccines was mainly focused on CV-B3 vaccine development. Because the HFMD pathogen spectrum has changed, and the threat from EV-B virus-associated severe diseases has gradually increased, it is necessary to develop multivalent HFMD vaccines. This study summarizes the clinical symptoms of diseases caused by EVs, such as HFMD, myocarditis and encephalitis, and the related EV vaccine development progress. In conclusion, developing multivalent EV vaccines should be strongly recommended to prevent HFMD, myocarditis, encephalitis and other severe diseases. PMID:27436364

  11. EV-A71 vaccine licensure: a first step for multivalent enterovirus vaccine to control HFMD and other severe diseases.

    PubMed

    Mao, Qunying; Wang, Yiping; Bian, Lianlian; Xu, Miao; Liang, Zhenglun

    2016-07-20

    Enteroviruses (EVs) are the most common viral agents in humans. Although most infections are mild or asymptomatic, there is a wide spectrum of clinical manifestations that may be caused by EV infections with varying degrees of severity. Among these viruses, EV-A71 and coxsackievirus (CV) CV-A16 from group A EVs attract the most attention because they are responsible for hand, foot and mouth disease (HFMD). Other EV-A viruses such as CV-A6 and CV-A10 were also reported to cause HFMD outbreaks in several countries or regions. Group B EVs such as CV-B3, CV-B5 and echovirus 30 were reported to be the main pathogens responsible for myocarditis and encephalitis epidemics and were also detected in HFMD patients. Vaccines are the best tools to control infectious diseases. In December 2015, China's Food and Drug Administration approved two inactivated EV-A71 vaccines for preventing severe HFMD.The CV-A16 vaccine and the EV-A71-CV-A16 bivalent vaccine showed substantial efficacy against HFMD in pre-clinical animal models. Previously, research on EV-B group vaccines was mainly focused on CV-B3 vaccine development. Because the HFMD pathogen spectrum has changed, and the threat from EV-B virus-associated severe diseases has gradually increased, it is necessary to develop multivalent HFMD vaccines. This study summarizes the clinical symptoms of diseases caused by EVs, such as HFMD, myocarditis and encephalitis, and the related EV vaccine development progress. In conclusion, developing multivalent EV vaccines should be strongly recommended to prevent HFMD, myocarditis, encephalitis and other severe diseases.

  12. Clinical Features of Post-Vaccination Guillain-Barré Syndrome (GBS) in Korea

    PubMed Central

    2017-01-01

    Guillain-Barré syndrome (GBS) is the most common immune-mediated polyradiculoneuropathy and it is also the most commonly reported severe adverse event following immunization in adults. To evaluate the results of clinical and laboratory features of GBS after vaccination in Korea, we analyzed the claims-based data from 2002 to 2014 using materials collected for the Advisory Committee Vaccination Injury Compensation (ACVIC) meeting including, clinical features, nerve conduction studies (NCSs), cerebrospinal fluid (CSF) profiles, treatment, and outcomes. Forty-eight compensated GBS cases (median age, 15 years; interquartile range [IQR], 13–51; male:female ratio, 1:1) of 68 suspected GBS were found following immunization and all of them with influenza immunizations with either monovalent (n = 35) or trivalent (n = 13). Among them, 30 cases fulfilled the Brighton criteria level 1–3 (62.5%). The median duration between the onset of symptoms to nadir, duration of the nadir, and total admission period were 3 (IQR, 2–7 days), 2 (IQR, 1–5 days), and 14 (IQR, 6–33 days) days, respectively. The most frequently reported symptom was quadriparesis which was present in 36 cases (75%) at nadir. CSF examination revealed albuminocytologic dissociation in 25.0% and NCS was abnormal in 61.8%. After treatment, most of them showed improvement. Clinical features were similar to typical post-infectious GBS and there were both demyelinating and axonal forms suggesting heterogeneous pathogenic mechanism. In order to improve the diagnostic certainty of post-vaccination GBS, careful documentation of clinical features and timely diagnostic work-up with follow-up studies are needed. PMID:28581273

  13. Protective efficacy of standard Edmonston-Zagreb measles vaccination in infants aged 4.5 months: interim analysis of a randomised clinical trial.

    PubMed

    Martins, Cesário L; Garly, May-Lill; Balé, Carlito; Rodrigues, Amabelia; Ravn, Henrik; Whittle, Hilton C; Lisse, Ida M; Aaby, Peter

    2008-07-24

    To examine the protective efficacy of measles vaccination in infants in a low income country before 9 months of age. Randomised clinical trial. 1333 infants aged 4.5 months: 441 in treatment group and 892 in control group. Urban area in Guinea-Bissau. Measles vaccination using standard titre Edmonston-Zagreb vaccine at 4.5 months of age. Vaccine efficacy against measles infection, admission to hospital for measles, and measles mortality before standard vaccination at 9 months of age. 28% of the children tested at 4.5 months of age had protective levels of maternal antibodies against measles at enrolment. After early vaccination against measles 92% had measles antibodies at 9 months of age. A measles outbreak offered a unique situation for testing the efficacy of early measles vaccination. During the outbreak, 96 children developed measles; 19% of unvaccinated children had measles before 9 months of age. The monthly incidence of measles among the 441 children enrolled in the treatment arm was 0.7% and among the 892 enrolled in the control arm was 3.1%. Early vaccination with the Edmonston-Zagreb measles vaccine prevented infection; vaccine efficacy for children with serologically confirmed measles and definite clinical measles was 94% (95% confidence interval 77% to 99%), for admissions to hospital for measles was 100% (46% to 100%), and for measles mortality was 100% (-42% to 100%). The number needed to treat to prevent one case of measles between ages 4.5 months and 9 months during the epidemic was 7.2 (6.8 to 9.2). The treatment group tended to have lower overall mortality (mortality rate ratio 0.18, 0.02 to 1.36) although this was not significant. In low income countries, maternal antibody levels against measles may be low and severe outbreaks of measles can occur in infants before the recommended age of vaccination at 9 months. Outbreaks of measles may be curtailed by measles vaccination using the Edmonston-Zagreb vaccine as early as 4.5 months of age. TRIAL

  14. Smallpox vaccine: problems and prospects.

    PubMed

    Poland, Gregory A; Neff, John M

    2003-11-01

    Smallpox justifiably is feared because of its morbidity and mortality. Wide-spread population-level susceptibility to smallpox exists, and the only effective tool against the virus is a live, attenuated vaccine that is highly reactogenic and controversial. A significant minority of the population has contraindications that prevent preexposure use of this vaccine. Newer, safer, and equally immunogenic vaccines must be developed and licensed. Several live, attenuated vaccines are in clinical trials. Although these vaccines may prove to be less reactogenic, they still may not be administered safely to a significant portion of the population because they contain live, attenuated viruses. Newer vaccines will be needed if routine preexposure vaccination is to be instituted universally. The idea of a subunit or peptide-based vaccine is appealing, because it obviates potential safety concerns. It may be possible to use a more-attenuated, live vaccine strain for a large segment of the population on a preexposure basis and accept the morbidity and mortality that would result from its use on a postexposure basis, if necessary. The need for widespread population-level protection against variola infection is apparent. The use of the new biology tools to predict or define who might experience serious reactions to the smallpox vaccine and why these reactions occur is an area ripe for additional research. The reason why an individual develops postvaccinal encephalitis remains unknown, and the development is unpredictable and untreatable. In the future, if the mechanism behind such adverse events is defined, it may be possible to screen persons who are likely to experience such events. Although the authors remain proponents for use of the vaccine in alignment with the CDC vaccination program and recommendations, the previous concerns indicate that new knowledge must be gained and shared. Further research on attenuated vaccines and nonliving or peptide vaccines with equal efficacy

  15. Cell culture-derived influenza vaccines from Vero cells: a new horizon for vaccine production.

    PubMed

    Montomoli, Emanuele; Khadang, Baharak; Piccirella, Simona; Trombetta, Claudia; Mennitto, Elisa; Manini, Ilaria; Stanzani, Valerio; Lapini, Giulia

    2012-05-01

    In the 20th century, three influenza pandemics killed approximately 100 million people. The traditional method of influenza vaccine manufacturing is based on using chicken eggs. However, the necessity of the availability of millions of fertile eggs in the event of a pandemic has led research to focus on the development of cell culture-derived vaccines, which offer shorter lead-in times and greater flexibility of production. So far, the cell substrates being evaluated and in use include Vero, Madin-Darby canine kidney, PER.C6 and insect cells. However, Vero cells are the most widely accepted among others. This review introduces briefly the concepts of advanced cell culture-derived influenza vaccine production and highlights the advantages of these vaccines in terms of efficiency, speed and immunogenicity based on the clinical data obtained from different studies.

  16. The NIAID Division of AIDS enterprise information system: integrated decision support for global clinical research programs

    PubMed Central

    Gupta, Nitin; Varghese, Suresh; Virkar, Hemant

    2011-01-01

    The National Institute of Allergy and Infectious Diseases (NIAID) Division of AIDS (DAIDS) Enterprise Information System (DAIDS-ES) is a web-based system that supports NIAID in the scientific, strategic, and tactical management of its global clinical research programs for HIV/AIDS vaccines, prevention, and therapeutics. Different from most commercial clinical trials information systems, which are typically protocol-driven, the DAIDS-ES was built to exchange information with those types of systems and integrate it in ways that help scientific program directors lead the research effort and keep pace with the complex and ever-changing global HIV/AIDS pandemic. Whereas commercially available clinical trials support systems are not usually disease-focused, DAIDS-ES was specifically designed to capture and incorporate unique scientific, demographic, and logistical aspects of HIV/AIDS treatment, prevention, and vaccine research in order to provide a rich source of information to guide informed decision-making. Sharing data across its internal components and with external systems, using defined vocabularies, open standards and flexible interfaces, the DAIDS-ES enables NIAID, its global collaborators and stakeholders, access to timely, quality information about NIAID-supported clinical trials which is utilized to: (1) analyze the research portfolio, assess capacity, identify opportunities, and avoid redundancies; (2) help support study safety, quality, ethics, and regulatory compliance; (3) conduct evidence-based policy analysis and business process re-engineering for improved efficiency. This report summarizes how the DAIDS-ES was conceptualized, how it differs from typical clinical trial support systems, the rationale for key design choices, and examples of how it is being used to advance the efficiency and effectiveness of NIAID's HIV/AIDS clinical research programs. PMID:21816958

  17. The NIAID Division of AIDS enterprise information system: integrated decision support for global clinical research programs.

    PubMed

    Kagan, Jonathan M; Gupta, Nitin; Varghese, Suresh; Virkar, Hemant

    2011-12-01

    The National Institute of Allergy and Infectious Diseases (NIAID) Division of AIDS (DAIDS) Enterprise Information System (DAIDS-ES) is a web-based system that supports NIAID in the scientific, strategic, and tactical management of its global clinical research programs for HIV/AIDS vaccines, prevention, and therapeutics. Different from most commercial clinical trials information systems, which are typically protocol-driven, the DAIDS-ES was built to exchange information with those types of systems and integrate it in ways that help scientific program directors lead the research effort and keep pace with the complex and ever-changing global HIV/AIDS pandemic. Whereas commercially available clinical trials support systems are not usually disease-focused, DAIDS-ES was specifically designed to capture and incorporate unique scientific, demographic, and logistical aspects of HIV/AIDS treatment, prevention, and vaccine research in order to provide a rich source of information to guide informed decision-making. Sharing data across its internal components and with external systems, using defined vocabularies, open standards and flexible interfaces, the DAIDS-ES enables NIAID, its global collaborators and stakeholders, access to timely, quality information about NIAID-supported clinical trials which is utilized to: (1) analyze the research portfolio, assess capacity, identify opportunities, and avoid redundancies; (2) help support study safety, quality, ethics, and regulatory compliance; (3) conduct evidence-based policy analysis and business process re-engineering for improved efficiency. This report summarizes how the DAIDS-ES was conceptualized, how it differs from typical clinical trial support systems, the rationale for key design choices, and examples of how it is being used to advance the efficiency and effectiveness of NIAID's HIV/AIDS clinical research programs.

  18. Dengue vaccination during pregnancy - An overview of clinical trials data.

    PubMed

    Skipetrova, Anna; Wartel, Tram Anh; Gailhardou, Sophia

    2018-04-28

    The live, attenuated, tetravalent dengue vaccine (CYD-TDV) is licensed in several endemic countries and contraindicated during pregnancy. Inadvertent vaccination during pregnancy may occur during clinical trials that include women of childbearing age. The potential risk associated with dengue vaccination in pregnancy remains unknown. We describe pregnancy outcomes following inadvertent dengue vaccination in pregnancy from CYD-TDV trial data. Data were collected from trials conducted as part of the CYD-TDV clinical development. Women who received CYD-TDV or placebo during the pre-specified pregnancy risk window (from 30 days before the date of their last menstrual period to end of pregnancy) were considered as exposed; pregnancies occurring in non-risk periods during the trials were considered to be non-exposed. Pregnancy losses were defined as abortion (spontaneous or unspecified), death in utero, and stillbirth. 615 pregnancies were reported from 19 CYD-TDV trials: 404 in the CYD-TDV arm, and 211 in the placebo arm. Exposure could not be determined for 7 pregnancies (5, CYD-TDV; 2, placebo). In the CYD-TDV arm, 58 pregnancies were considered as exposed. Most of these (n = 47, 81%) had healthy live births; 6 (10.3%) had pregnancy losses; 3 underwent elective termination and 2 had unknown outcome. In the placebo group, 30 pregnancies were considered exposed. Most of these (n = 25, 83%) had healthy births; 4 (13.3%) had pregnancy losses; and 1 had elective termination. Among non-exposed pregnancies, most resulted in healthy live births; 23/341 (6.7%) in the CYD-TDV group and 17/179 (9.5%) in the placebo group had pregnancy losses. Most reported pregnancy losses were in women considered high-risk for adverse pregnancy outcome, primarily due to young age. In the small dataset assessed, no evidence of increased adverse pregnancy outcomes has been identified from inadvertent immunization of women in early pregnancy with CYD-TDV compared with the control group

  19. Vaccines today, vaccines tomorrow: a perspective.

    PubMed

    Loucq, Christian

    2013-01-01

    Vaccines are considered as one of the major contributions of the 20th century and one of the most cost effective public health interventions. The International Vaccine Institute has as a mission to discover, develop and deliver new and improved vaccines against infectious diseases that affects developing nations. If Louis Pasteur is known across the globe, vaccinologists like Maurice Hilleman, Jonas Salk and Charles Mérieux are known among experts only despite their contribution to global health. Thanks to a vaccine, smallpox has been eradicated, polio has nearly disappeared, Haemophilus influenzae B, measles and more recently meningitis A are controlled in many countries. While a malaria vaccine is undergoing phase 3, International Vaccine Institute, in collaboration with an Indian manufacturer has brought an oral inactivated cholera vaccine to pre-qualification. The field of vaccinology has undergone major changes thanks to philanthropists such as Bill and Melinda Gates, initiatives like the Decade of Vaccines and public private partnerships. Current researches on vaccines have more challenging targets like the dengue viruses, malaria, human immunodeficiency virus, the respiratory syncytial virus and nosocomial diseases. Exciting research is taking place on new adjuvants, nanoparticles, virus like particles and new route of administration. An overcrowded infant immunization program, anti-vaccine groups, immunizing a growing number of elderlies and delivering vaccines to difficult places are among challenges faced by vaccinologists and global health experts.

  20. HIV Vaccines

    MedlinePlus

    ... an NIH-supported clinical trial was launched to test a modified HIV vaccine. This current vaccine trial, called HVTN 702, is testing whether an experimental vaccine regimen safely prevents HIV infection among South African adults. Learn more in this blog post and in the video below. /* // ** // */ Why Do We ...

  1. Polyvalent Vaccines Targeting Oncogenic Driver Pathways

    Cancer.gov

    Mary L. (Nora) Disis, MD, is the Athena Distinguished Professor of Breast Cancer Research and Associate Dean for Translational Health Sciences in the University of Washington (UW) School of Medicine. She is a Professor of Medicine and Adjunct Professor of Pathology and Obstetrics and Gynecology at UW, and a Member of the Fred Hutchinson Cancer Research Center (FHCRC). She is also an American Cancer Society Clinical Professor and a Komen Scholar. In addition to directing work in the Tumor Vaccine Group, Dr. Disis is the Director of the Institute of Translational Health Sciences and the Director for the Center for Translational Medicine in Women’s Health at the UW. Dr. Disis is an expert in breast and ovarian cancer immunology and translational research. She is one of the pioneering investigators who discovered that HER-2/neu is a tumor antigen. Her work has led to several clinical trials which evaluate boosting immunity to HER-2/neu with cancer vaccines. Her research interest is in the discovery of new molecular immunologic targets in solid tumors for the development of vaccine and cellular therapy for the treatment and prevention of common malignancies. Dr. Disis is a member of Alpha Omega Alpha and the American Society of Clinical Investigation. She is also the Editor-in-Chief for JAMA Oncology, and is a member of several committees and task forces for both the American Society of Clinical Oncology (ASCO) and the American Association for Cancer Research (AACR). Dr. Disis received her MD from the University of Nebraska Medical School and completed a residency and chief residency in Internal Medicine at the University of Illinois in Chicago and her fellowship in oncology at UW/FHCRC.

  2. Hegemonic structure of basic, clinical and patented knowledge on Ebola research: a US army reductionist initiative.

    PubMed

    Fajardo-Ortiz, David; Ortega-Sánchez-de-Tagle, José; Castaño, Victor M

    2015-04-19

    Ebola hemorrhagic fever (Ebola) is still a highly lethal infectious disease long affecting mainly neglected populations in sub-Saharan Africa. Moreover, this disease is now considered a potential worldwide threat. In this paper, we present an approach to understand how the basic, clinical and patent knowledge on Ebola is organized and intercommunicated and what leading factor could be shaping the evolution of the knowledge translation process for this disease. A combination of citation network analysis; analysis of Medical heading Subject (MeSH) and Gene Ontology (GO) terms, and quantitative content analysis for patents and scientific literature, aimed to map the organization of Ebola research was carried out. We found six putative research fronts (i.e. clusters of high interconnected papers). Three research fronts are basic research on Ebola virus structural proteins: glycoprotein, VP40 and VP35, respectively. There is a fourth research front of basic research papers on pathogenesis, which is the organizing hub of Ebola research. A fifth research front is pre-clinical research focused on vaccines and glycoproteins. Finally, a clinical-epidemiology research front related to the disease outbreaks was identified. The network structure of patent families shows that the dominant design is the use of Ebola virus proteins as targets of vaccines and other immunological treatments. Therefore, patents network organization resembles the organization of the scientific literature. Specifically, the knowledge on Ebola would flow from higher (clinical-epidemiology) to intermediated (cellular-tissular pathogenesis) to lower (molecular interactions) levels of organization. Our results suggest a strong reductionist approach for Ebola research probably influenced by the lethality of the disease. On the other hand, the ownership profile of the patent families network and the main researches relationship with the United State Army suggest a strong involvement of this military

  3. 17DD yellow fever vaccine: a double blind, randomized clinical trial of immunogenicity and safety on a dose-response study.

    PubMed

    Martins, Reinaldo M; Maia, Maria de Lourdes S; Farias, Roberto Henrique G; Camacho, Luiz Antonio B; Freire, Marcos S; Galler, Ricardo; Yamamura, Anna Maya Yoshida; Almeida, Luiz Fernando C; Lima, Sheila Maria B; Nogueira, Rita Maria R; Sá, Gloria Regina S; Hokama, Darcy A; de Carvalho, Ricardo; Freire, Ricardo Aguiar V; Pereira Filho, Edson; Leal, Maria da Luz Fernandes; Homma, Akira

    2013-04-01

    To verify if the Bio-Manguinhos 17DD yellow fever vaccine (17DD-YFV) used in lower doses is as immunogenic and safe as the current formulation. Doses from 27,476 IU to 587 IU induced similar seroconversion rates and neutralizing antibodies geometric mean titers (GMTs). Immunity of those who seroconverted to YF was maintained for 10 mo. Reactogenicity was low for all groups. Young and healthy adult males (n = 900) were recruited and randomized into 6 groups, to receive de-escalating doses of 17DD-YFV, from 27,476 IU to 31 IU. Blood samples were collected before vaccination (for neutralization tests to yellow fever, serology for dengue and clinical chemistry), 3 to 7 d after vaccination (for viremia and clinical chemistry) and 30 d after vaccination (for new yellow fever serology and clinical chemistry). Adverse events diaries were filled out by volunteers during 10 d after vaccination. Volunteers were retested for yellow fever and dengue antibodies 10 mo later. Seropositivity for dengue was found in 87.6% of volunteers before vaccination, but this had no significant influence on conclusions. In young healthy adults Bio-Manguinhos/Fiocruz yellow fever vaccine can be used in much lower doses than usual. INTERNATIONAL REGISTER: ISRCTN 38082350.

  4. Development of Novel Faster-Dissolving Microneedle Patches for Transcutaneous Vaccine Delivery

    PubMed Central

    Ono, Akihiko; Ito, Sayami; Sakagami, Shun; Saito, Mio; Quan, Ying-Shu; Kamiyama, Fumio; Hirobe, Sachiko; Okada, Naoki

    2017-01-01

    Microneedle (MN) patches are promising for transcutaneous vaccination because they enable vaccine antigens to physically penetrate the stratum corneum via low-invasive skin puncturing, and to be effectively delivered to antigen-presenting cells in the skin. In second-generation MN patches, the dissolving MNs release the loaded vaccine antigen into the skin. To shorten skin application time for clinical practice, this study aims to develop novel faster-dissolving MNs. We designed two types of MNs made from a single thickening agent, carboxymethylcellulose (CMC) or hyaluronan (HN). Both CMC-MN and HN-MN completely dissolved in rat skin after a 5-min application. In pre-clinical studies, both MNs could demonstrably increase antigen-specific IgG levels after vaccination and prolong antigen deposition compared with conventional injections, and deliver antigens into resected human dermal tissue. In clinical research, we demonstrated that both MNs could reliably and safely puncture human skin without any significant skin irritation from transepidermal water loss measurements and ICDRG (International Contact Dermatitis Research Group) evaluation results. PMID:28771172

  5. Effective influenza vaccines for children

    PubMed Central

    Banzhoff, Angelika; Stoddard, Jeffrey J.

    2012-01-01

    Seasonal influenza causes clinical illness and hospitalization in all age groups; however, conventional inactivated vaccines have only limited efficacy in young children. MF59®, an oil-in-water emulsion adjuvant, has been used since the 1990s to enhance the immunogenicity of influenza vaccines in the elderly, a population with waning immune function due to immunosenescence.   Clinical trials now provide information to support a favorable immunogenicity and safety profile of MF59-adjuvanted influenza vaccine in young children. Published data indicate that Fluad®, a trivalent seasonal influenza vaccine with MF59, was immunogenic and well tolerated in young children, with a benefit/risk ratio that supports routine clinical use. A recent clinical trial also shows that Fluad provides high efficacy against PCR-confirmed influenza. Based on the results of clinical studies in children, the use of MF59-adjuvanted vaccine offers the potential to enhance efficacy and make vaccination a viable prevention and control strategy in this population. PMID:22327501

  6. Attitudes towards antenatal vaccination, Group B streptococcus and participation in clinical trials: Insights from focus groups and interviews of parents and healthcare professionals.

    PubMed

    McQuaid, Fiona; Pask, Sophie; Locock, Louise; Davis, Elizabeth; Stevens, Zoe; Plumb, Jane; Snape, Matthew D

    2016-07-25

    Antenatal vaccination has become a part of routine care during pregnancy in the UK and worldwide, leading to improvements in health for both pregnant women and their infants. However, uptake remains sub-optimal. Other antenatal vaccines targeting major neonatal pathogens, such as Group B streptococcus (GBS), the commonest cause of sepsis and meningitis in the neonatal period, are undergoing clinical trials but more information is needed on how to improve acceptance of such vaccines. Qualitative study using focus groups and interviews; involving 14 pregnant women, 8 mothers with experience of GBS, and 28 maternity healthcare professionals. Questions were asked regarding antenatal vaccines, knowledge of GBS, attitudes to a potential future GBS vaccine and participation in antenatal vaccine trials. All participants were very cautious about vaccination during pregnancy, with harm to the baby being a major concern. Despite this, the pregnant women and parents with experience of GBS were open to the idea of an antenatal GBS vaccine and participating in research, while the maternity professionals were less positive. Major barriers identified included lack of knowledge about GBS and the reluctance of maternity professionals to be involved. In order for a future GBS vaccine to be acceptable to both pregnant women and the healthcare professionals advising them, a major awareness campaign would be required with significant focus on convincing and training maternity professionals. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. Improving human papilloma virus vaccination rates throughout military treatment facilities.

    PubMed

    Dawson, Rachel; Lemmon, Keith; Trivedi, Nidhi J; Hansen, Shana

    2018-03-07

    The four objectives of this study were to (1) educate military healthcare providers on HPV disease and vaccine, (2) assess short term recall of information presented at educational sessions, (3) assess provider comfort level with the vaccine, and (4) assess improvement in HPV vaccination rates. Standardized interactive educational sessions were conducted at military primary care clinics with pre- and post-educational quizzes administered before and immediately following the sessions. Provider attitudes were assessed using Likert scale questionnaires. Vaccination rates in children and young adolescents ages 11-18 at one of the participating regions that had a champion and started a Quality Improvement (QI) project were assessed at baseline, at 3-months and at 6-months post sessions. 200 providers were reached at 48 primary care clinics during May 2014 through October 2015 with 200 quizzes and Likert scale questionnaires returned. There was increase in knowledge following the educational sessions as revealed in the pre- and post- test scores [t(57) = -5.04, p < 0.001]. There was a significant overall increase in comfort in answering patients' and parents' questions about HPV vaccine [p = 0.003]. There was a significant increase in the number of vaccines given at all the clinics 3-months after the educational sessions at the region who had a champion dedicated to monitoring vaccine rates and ensuring implementation efforts [p = 0.01] and started a QI project. This increase was not sustained at 6-months [p = 0.324]. Improvement in provider short term knowledge recall and comfort level in answering parents' questions was seen. We found that educational sessions can improve HPV vaccination rates in military clinics that have a vaccine champion for up to 3-months. Further research into the effects of having clinic vaccine champions is critical. Copyright © 2018. Published by Elsevier Ltd.

  8. National Institute of Allergy and Infectious Diseases workshop report: "Chlamydia vaccines: The way forward".

    PubMed

    Zhong, Guangming; Brunham, Robert C; de la Maza, Luis M; Darville, Toni; Deal, Carolyn

    2017-10-31

    Chlamydia trachomatis (Ct), an intracellular pathogen, is the most common bacterial sexually transmitted infection. In addition to acute cervicitis and urethritis, Ct can lead to serious sequelae of significant public health burden including pelvic inflammatory disease (PID) and infertility. Ct control efforts have not resulted in desired outcomes such as reduced incidence and reinfection, and this highlights the need for the development of an effective Ct vaccine. To this end, NIAID organized a workshop to consider the current status of Ct vaccine research and address critical questions in Ct vaccine design and clinical testing. Topics included the goal(s) of a vaccine and the feasibility of achieving these goals, animal models of infection including mouse and nonhuman primate (NHP) models, and correlates of protection to guide vaccine design. Decades of research have provided both whole cell-based and subunit vaccine candidates for development. At least one is currently in clinical development and efforts now need to be directed toward further development of the most attractive candidates. Overall, the discussions and presentations from the workshop highlighted optimism about the current status of Ct vaccine research and detailed the remaining gaps and questions needed to move vaccines forward. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Current status of syphilis vaccine development: need, challenges, prospects.

    PubMed

    Cameron, Caroline E; Lukehart, Sheila A

    2014-03-20

    Syphilis is a multistage disease caused by the invasive spirochete Treponema pallidum subsp. pallidum. Despite inexpensive and effective antibiotic therapy, syphilis remains a prevalent disease in developing countries and has re-emerged as a public health threat in developed nations. In addition to the medical burden imparted by infectious syphilis, congenital syphilis is considered the most significant infectious disease affecting fetuses and newborns worldwide, and individuals afflicted with syphilis have an enhanced risk for HIV transmission and acquisition. The global disease burden of syphilis and failure of decades of public health efforts to stem the incidence of disease highlight the need for an effective syphilis vaccine. Although challenges associated with T. pallidum research have impeded understanding of this pathogen, the existence of a relevant animal model has enabled insight into the correlates of disease protection. Complete protection against infection has been achieved in the animal model using an extended immunization regimen of γ-irradiated T. pallidum, demonstrating the importance of treponemal surface components in generation of protective immunity and the feasibility of syphilis vaccine development. Syphilis is a prime candidate for development of a successful vaccine due to the (1) research community's accumulated knowledge of immune correlates of protection; (2) existence of a relevant animal model that enables effective pre-clinical analyses; (3) universal penicillin susceptibility of T. pallidum which enhances the attractiveness of clinical vaccine trials; and (4) significant public health benefit a vaccine would have on reduction of infectious/congenital syphilis and HIV rates. Critical personnel, research and market gaps need to be addressed before the goal of a syphilis vaccine can be realized, including recruitment of additional researchers to the T. pallidum research field with a proportional increase in research funding

  10. Non-clinical immuno-toxicological evaluation of HER1 cancer vaccine in non-human primates: a 12-month study.

    PubMed

    Barro, Ana M Bada; Rivero, Arianna Iglesias; Goñi, Avelina León; Navarro, Bárbara O González; Angarica, Meilis Mesa; Ramírez, Belinda Sánchez; Bedoya, Darel Martínez; Triana, Consuelo González; Rodríguez, Axel Mancebo; Parada, Ángel Casacó

    2012-12-17

    Human epidermal growth factor receptor (HER1) constitutes a tumor associated antigen. Its overexpression in many epithelial tumors has been associated with bad prognosis and poor survival. Cancer vaccine based on the extracellular domain (ECD) of HER1 and adjuvated in very small sized proteoliposomes (VSSP) and Montanide ISA 51-VG is a new and complementary approach for the treatment of epithelial tumors. The present study deals with the immunogenicity of this vaccine in Macaca fascicularis monkeys and evaluation of its toxicity during 12 months. Twelve monkeys were randomized into two groups of 3 animals per sex: control and vaccinated. Treated monkeys received 9 doses of vaccination and were daily inspected for clinical signs. Body weight, rectal temperature, cardiac and respiratory rates were measured during the study. Humoral immune response, clinical pathology parameters and delayed type hypensensitivity were analyzed. Skin biopsy was performed at the end of the study in all animals. Animal's survival in the study was 100% (n=12). Local reactions were observed at the administration site of four treated animals (n=6), with two showing slight inflammatory cutaneous damage. Clinical pathology parameters were not affected. HER1 vaccine induced high IgG antibodies titers in the treated animals even when DTH was not observed. The induced antibodies recognized HER1+ tumor cell lines, decreased HER1 phosphorylation and showed anti-proliferative and pro-apoptotic effects in H125 cells. In general the present study showed that HER1 vaccine induced specific immune response in M. fascicularis monkeys and was well tolerated, suggesting it could be safely used in clinical studies in epithelial cancer patients. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Methodology and lessons-learned from the efficacy clinical trial of the pentavalent rotavirus vaccine in Bangladesh.

    PubMed

    Zaman, K; Yunus, M; El Arifeen, Shams; Azim, Tasnim; Faruque, A S G; Huq, Ehsanul; Hossain, Ilias; Luby, Stephen P; Victor, John C; Dallas, Michael J; Lewis, Kristen D C; Rivers, Stephen B; Steele, A Duncan; Neuzil, Kathleen M; Ciarlet, Max; Sack, David A

    2012-04-27

    An efficacy clinical trial with pentavalent rotavirus vaccine (PRV), RotaTeq(®), was conducted at Matlab field site of ICDDR,B, Bangladesh from March 2007 to March 2009. The methodology, including operation logistics, and lessons-learned are described in this report. Vaccination was organized at 41 fixed-site clinics twice/month. A total of 1136 infants were randomized 1:1 to receive 3 doses of PRV/placebo at approximately 6-, 10-, and 14-weeks of age with routine vaccines of the Expanded Programme on Immunization (EPI) schedule. Twelve field-workers routinely visited study participants for safety and efficacy follow-up. The study was conducted following good clinical practices and maintaining cold-chain requirements. There were no temperature deviations of clinical vaccine supplies. Data entry was done using the source documents to a central database developed by the sponsor which was linked to web. Among enrolled infants, 1128 (99.3%) received 3 doses of PRV/placebo and efficacy follow-up was conducted for a median of 554 days. For the evaluation of immunogenicity, blood samples were collected from 150 participants predose 1 and from 147 (98%) of the same participants post dose 3. Stool samples were collected from 778 (99.9%) acute gastroenteritis episodes among children who reported to diarrhoea treatment centres. Thirty-nine serious adverse events, including 6 deaths, occurred among study participants. The efficacy of PRV against severe rotavirus gastroenteritis was 42.7% through the entire follow-up period; serum anti-rotavirus IgA response was 78.1%. Inclement weather, difficult transportation, and movement of study participants were some of the challenges identified. This is the first vaccine trial in rural Bangladesh with online data entry. The study was well accepted in the community and was completed successfully. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Approaches to Preventative and Therapeutic HIV vaccines

    PubMed Central

    Gray, Glenda E.; Laher, Fatima; Lazarus, Erica; Ensoli, Barbara; Corey, Lawrence

    2016-01-01

    Novel strategies are being researched to discover vaccines to prevent and treat HIV-1. Nonefficacious preventative vaccine approaches include bivalent recombinant gp120 alone, HIV gene insertion into an Adenovirus 5 (Ad5) virus vector and the DNA prime/Ad5 boost vaccine regimen. However, the ALVAC-HIV prime/AIDSVAX® B/E gp120 boost regimen showed 31.2% efficacy at 3.5 years, and is being investigated as clade C constructs with an additional boost. Likewise, although multiple therapeutic vaccines have failed in the past, in a non-placebo controlled trial, a Tat vaccine demonstrated immune cell restoration, reduction of immune activation, and reduced HIV-1 DNA viral load. Monoclonal antibodies for passive immunization or treatment show promise, with VRC01 entering advanced clinical trials. PMID:26985884

  13. Pre-clinical evaluation of a replication-competent recombinant adenovirus serotype 4 vaccine expressing influenza H5 hemagglutinin.

    PubMed

    Alexander, Jeff; Ward, Simone; Mendy, Jason; Manayani, Darly J; Farness, Peggy; Avanzini, Jenny B; Guenther, Ben; Garduno, Fermin; Jow, Lily; Snarsky, Victoria; Ishioka, Glenn; Dong, Xin; Vang, Lo; Newman, Mark J; Mayall, Tim

    2012-01-01

    Influenza virus remains a significant health and social concern in part because of newly emerging strains, such as avian H5N1 virus. We have developed a prototype H5N1 vaccine using a recombinant, replication-competent Adenovirus serotype 4 (Ad4) vector, derived from the U.S. military Ad4 vaccine strain, to express the hemagglutinin (HA) gene from A/Vietnam/1194/2004 influenza virus (Ad4-H5-Vtn). Our hypothesis is that a mucosally-delivered replicating Ad4-H5-Vtn recombinant vector will be safe and induce protective immunity against H5N1 influenza virus infection and disease pathogenesis. The Ad4-H5-Vtn vaccine was designed with a partial deletion of the E3 region of Ad4 to accommodate the influenza HA gene. Replication and growth kinetics of the vaccine virus in multiple human cell lines indicated that the vaccine virus is attenuated relative to the wild type virus. Expression of the HA transgene in infected cells was documented by flow cytometry, western blot analysis and induction of HA-specific antibody and cellular immune responses in mice. Of particular note, mice immunized intranasally with the Ad4-H5-Vtn vaccine were protected against lethal H5N1 reassortant viral challenge even in the presence of pre-existing immunity to the Ad4 wild type virus. Several non-clinical attributes of this vaccine including safety, induction of HA-specific humoral and cellular immunity, and efficacy were demonstrated using an animal model to support Phase 1 clinical trial evaluation of this new vaccine.

  14. Sustainable development of a GCP-compliant clinical trials platform in Africa: the malaria clinical trials alliance perspective.

    PubMed

    Ogutu, Bernhards R; Baiden, Rita; Diallo, Diadier; Smith, Peter G; Binka, Fred N

    2010-04-20

    The Malaria Clinical Trials Alliance (MCTA), a programme of INDEPTH network of demographic surveillance centres, was launched in 2006 with two broad objectives: to facilitate the timely development of a network of centres in Africa with the capacity to conduct clinical trials of malaria vaccines and drugs under conditions of good clinical practice (GCP); and to support, strengthen and mentor the centres in the network to facilitate their progression towards self-sustaining clinical research centres. Sixteen research centres in 10 African malaria-endemic countries were selected that were already working with the Malaria Vaccine Initiative (MVI) or the Medicines for Malaria Venture (MMV). All centres were visited to assess their requirements for research capacity development through infrastructure strengthening and training. Support provided by MCTA included: laboratory and facility refurbishment; workshops on GCP, malaria diagnosis, strategic management and media training; and training to support staff to undertake accreditation examinations of the Association of Clinical Research Professionals (ACRP). Short attachments to other network centres were also supported to facilitate sharing practices within the Alliance. MCTA also played a key role in the creation of the African Media & Malaria Research Network (AMMREN), which aims to promote interaction between researchers and the media for appropriate publicity and media reporting of research and developments on malaria, including drug and vaccine trials. In three years, MCTA strengthened 13 centres to perform GCP-compliant drug and vaccine trials, including 11 centres that form the backbone of a large phase III malaria vaccine trial. MCTA activities have demonstrated that centres can be brought up to GCP compliance on this time scale, but the costs are substantial and there is a need for further support of other centres to meet the growing demand for clinical trial capacity. The MCTA experience also indicates that

  15. Sustainable development of a GCP-compliant clinical trials platform in Africa: the Malaria Clinical Trials Alliance perspective

    PubMed Central

    2010-01-01

    Background The Malaria Clinical Trials Alliance (MCTA), a programme of INDEPTH network of demographic surveillance centres, was launched in 2006 with two broad objectives: to facilitate the timely development of a network of centres in Africa with the capacity to conduct clinical trials of malaria vaccines and drugs under conditions of good clinical practice (GCP); and to support, strengthen and mentor the centres in the network to facilitate their progression towards self-sustaining clinical research centres. Case description Sixteen research centres in 10 African malaria-endemic countries were selected that were already working with the Malaria Vaccine Initiative (MVI) or the Medicines for Malaria Venture (MMV). All centres were visited to assess their requirements for research capacity development through infrastructure strengthening and training. Support provided by MCTA included: laboratory and facility refurbishment; workshops on GCP, malaria diagnosis, strategic management and media training; and training to support staff to undertake accreditation examinations of the Association of Clinical Research Professionals (ACRP). Short attachments to other network centres were also supported to facilitate sharing practices within the Alliance. MCTA also played a key role in the creation of the African Media & Malaria Research Network (AMMREN), which aims to promote interaction between researchers and the media for appropriate publicity and media reporting of research and developments on malaria, including drug and vaccine trials. Conclusion In three years, MCTA strengthened 13 centres to perform GCP-compliant drug and vaccine trials, including 11 centres that form the backbone of a large phase III malaria vaccine trial. MCTA activities have demonstrated that centres can be brought up to GCP compliance on this time scale, but the costs are substantial and there is a need for further support of other centres to meet the growing demand for clinical trial capacity. The

  16. HIV-1 Tat-based vaccines: from basic science to clinical trials.

    PubMed

    Fanales-Belasio, Emanuele; Cafaro, Aurelio; Cara, Andrea; Negri, Donatella R M; Fiorelli, Valeria; Butto, Stefano; Moretti, Sonia; Maggiorella, Maria Teresa; Baroncelli, Silvia; Michelini, Zuleika; Tripiciano, Antonella; Sernicola, Leonardo; Scoglio, Arianna; Borsetti, Alessandra; Ridolfi, Barbara; Bona, Roberta; Ten Haaft, Peter; Macchia, Iole; Leone, Pasqualina; Pavone-Cossut, Maria Rosaria; Nappi, Filomena; Vardas, Eftyhia; Magnani, Mauro; Laguardia, Elena; Caputo, Antonella; Titti, Fausto; Ensoli, Barbara

    2002-09-01

    Vaccination against human immunodeficiency virus (HIV)-1 infection requires candidate antigen(s) (Ag) capable of inducing an effective, broad, and long-lasting immune response against HIV-1 despite mutation events leading to differences in virus clades. The HIV-1 Tat protein is more conserved than envelope proteins, is essential in the virus life cycle and is expressed very early upon virus entry. In addition, both humoral and cellular responses to Tat have been reported to correlate with a delayed progression to disease in both humans and monkeys. This suggested that Tat is an optimal target for vaccine development aimed at controlling virus replication and blocking disease onset. Here are reviewed the results of our studies including the effects of the Tat protein on monocyte-derived dendritic cells (MDDCs) that are key antigen-presenting cells (APCs), and the results from vaccination trials with both the Tat protein or tat DNA in monkeys. We provide evidence that the HIV-1 Tat protein is very efficiently taken up by MDDCs and promotes T helper (Th)-1 type immune responses against itself as well as other Ag. In addition, a Tat-based vaccine elicits an immune response capable of controlling primary infection of monkeys with the pathogenic SHIV89.6P at its early stages allowing the containment of virus spread. Based on these results and on data of Tat conservation and immune cross-recognition in field isolates from different clades, phase I clinical trials are being initiated in Italy for both preventive and therapeutic vaccination.

  17. Long-term clinical and immunological effects of p53-SLP® vaccine in patients with ovarian cancer.

    PubMed

    Leffers, Ninke; Vermeij, Renee; Hoogeboom, Baukje-Nynke; Schulze, Ute R; Wolf, Rinze; Hamming, Ineke E; van der Zee, Ate G; Melief, Kees J; van der Burg, Sjoerd H; Daemen, Toos; Nijman, Hans W

    2012-01-01

    Vaccine-induced p53-specific immune responses were previously reported to be associated with improved response to secondary chemotherapy in patients with small cell lung cancer. We investigated long-term clinical and immunological effects of the p53-synthetic long peptide (p53-SLP®) vaccine in patients with recurrent ovarian cancer. Twenty patients were immunized with the p53-SLP® vaccine between July 2006 and August 2007. Follow-up information on patients was obtained. Clinical responses to secondary chemotherapy after p53-SLP® immunizations were determined by computerized tomography and/or tumor marker levels (CA125). Disease-specific survival was compared to a matched historical control group. Immune responses were analyzed by flow cytometry, proliferation assay, interferon gamma (IFN-γ) ELISPOT and/or cytokine bead array. Lymphocytes cultured from skin biopsy were analyzed by flow cytometry and proliferation assay. Of 20 patients treated with the p53-SLP® vaccine, 17 were subsequently treated with chemotherapy. Eight of these patients volunteered another blood sample. No differences in clinical response rates to secondary chemotherapy or disease-specific survival were observed between immunized patients and historical controls (p = 0.925, resp. p = 0.601). p53-specific proliferative responses were observed in 5/8 patients and IFN-γ production in 2/7 patients. Lymphocytes cultured from a prior injection site showing inflammation during chemotherapy did not recognize p53-SLP®. Thus, treatment with the p53-SLP® vaccine does not affect responses to secondary chemotherapy or survival, although p53-specific T-cells do survive chemotherapy. Copyright © 2011 UICC.

  18. Southern Hemisphere Influenza and Vaccine Effectiveness Research and Surveillance

    PubMed Central

    Huang, Qiu Sue; Turner, Nikki; Baker, Michael G; Williamson, Deborah A; Wong, Conroy; Webby, Richard; Widdowson, Marc-Alain

    2015-01-01

    The 2009 influenza A(H1N1)pdm09 pandemic highlighted the need for improved scientific knowledge to support better pandemic preparedness and seasonal influenza control. The Southern Hemisphere Influenza and Vaccine Effectiveness Research and Surveillance (SHIVERS) project, a 5-year (2012–2016) multiagency and multidisciplinary collaboration, aimed to measure disease burden, epidemiology, aetiology, risk factors, immunology, effectiveness of vaccination and other prevention strategies for influenza and other respiratory infectious diseases of public health importance. Two active, prospective, population-based surveillance systems were established for monitoring influenza and other respiratory pathogens among those hospitalized patients with acute respiratory illness and those enrolled patients seeking consultations at sentinel general practices. In 2015, a sero-epidemiological study will use a sample of patients from the same practices. These data will provide a full picture of the disease burden and risk factors from asymptomatic infections to severe hospitalized disease and deaths and related economic burden. The results during the first 2 years (2012–2013) provided scientific evidence to (a) support a change to NZ's vaccination policy for young children due to high influenza hospitalizations in these children; (b) contribute to the revision of the World Health Organization's case definition for severe acute respiratory illness for global influenza surveillance; and (c) contribute in part to vaccine strain selection using vaccine effectiveness assessment in the prevention of influenza-related consultations and hospitalizations. In summary, SHIVERS provides valuable international platforms for supporting seasonal influenza control and pandemic preparedness, and responding to other emerging/endemic respiratory-related infections. PMID:25912617

  19. Active Vaccines for Alzheimer Disease Treatment.

    PubMed

    Sterner, Rosalie M; Takahashi, Paul Y; Yu Ballard, Aimee C

    2016-09-01

    Vaccination against peptides specific to Alzheimer disease may generate an immune response that could help inhibit disease and symptom progression. PubMed and Scopus were searched for clinical trial articles, review articles, and preclinical studies relevant to the field of active Alzheimer disease vaccines and raw searches yielded articles ranging from 2016 to 1973. ClinicalTrials.gov was searched for active Alzheimer disease vaccine trials. Manual research and cross-referencing from reviews and original articles was performed. First generation Aβ42 phase 2a trial in patients with mild to moderate Alzheimer disease resulted in cases of meningoencephalitis in 6% of patients, so next generation vaccines are working to target more specific epitopes to induce a more controlled immune response. Difficulty in developing these vaccines resides in striking a balance between providing a vaccine that induces enough of an immune response to actually clear protein sustainably but not so much of a response that results in excess immune activation and possibly adverse effects such as meningoencephalitis. Although much work still needs to be done in the field to make this a practical possibility, the enticing allure of being able to treat or even prevent the extraordinarily impactful disease that is Alzheimer disease makes the idea of active vaccination for Alzheimer disease very appealing and something worth striving toward. Copyright © 2016 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

  20. Malaria vaccine R&D in the Decade of Vaccines: breakthroughs, challenges and opportunities.

    PubMed

    Birkett, Ashley J; Moorthy, Vasee S; Loucq, Christian; Chitnis, Chetan E; Kaslow, David C

    2013-04-18

    While recent progress has been made in reducing malaria mortality with other interventions, vaccines are still urgently needed to further reduce the incidence of clinical disease, including during pregnancy, and to provide "herd protection" by blocking parasite transmission. The most clinically advanced candidate, RTS,S, is presently undergoing Phase 3 evaluation in young African children across 13 clinical sites in eight African countries. In the 12-month period following vaccination, RTS,S conferred approximately 50% protection from clinical Plasmodium falciparum disease in children aged 5-17 months, and approximately 30% protection in children aged 6-12 weeks when administered in conjunction with Expanded Program for Immunization (EPI) vaccines. The development of more highly efficacious vaccines to prevent clinical disease caused by both P. falciparum and Plasmodium vivax, as well as vaccines to support elimination efforts by inducing immunity that blocks malaria parasite transmission, are priorities. Some key barriers to malaria vaccine development include: a paucity of well-characterized target immunogens and an absence of clear correlates of protection to enable vaccine development targeting all stages of the P. falciparum and P. vivax lifecycles; a limited number of safe and effective delivery systems, including adjuvants, that induce potent, long-lived protective immunity, be it by antibody, CD4+, and/or CD8+ T cell responses; and, for vaccines designed to provide "herd protection" by targeting sexual stage and/or mosquito antigens, the lack of a clear clinical and regulatory pathway to licensure using non-traditional endpoints. Recommendations to overcome these, and other key challenges, are suggested in this document. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Accelerating Next Generation Vaccine Development for Global Disease Prevention

    PubMed Central

    Koff, Wayne C; Burton, Dennis R.; R.Johnson, Philip; Walker, Bruce D.; King, Charles R.; Nabel, Gary J.; Ahmed, Rafi; Bhan, Maharaj Kishan; Plotkin, Stanley A.

    2014-01-01

    Summary Vaccines are among the greatest successes in the history of public health. However, past strategies for vaccine development are unlikely to succeed in the future against major global diseases such as AIDS, TB, and malaria. For such diseases, the correlates of protection are poorly defined and the pathogens evade immune detection and/or exhibit extensive genetic variability. Recent advances have heralded in a new era of vaccine discovery. However, translation of these advances into vaccines remains impeded by lack of understanding of key vaccinology principles in humans. We review these advances towards vaccine discovery and suggest that for accelerating successful vaccine development, new human immunology-based clinical research initiatives be implemented with the goal of elucidating and more effectively inducing vaccine-induced protective immune responses. PMID:23723240

  2. The success of microneedle-mediated vaccine delivery into skin

    PubMed Central

    Marshall, Sarah; Sahm, Laura J.; Moore, Anne C.

    2016-01-01

    ABSTRACT Microneedles (MNs) are designed to specifically target the outermost, skin barrier layer, the stratum corneum, creating transient pathways for minimally invasive transcutaneous delivery. It is reported that MNs can facilitate delivery without stimulating the pain receptors or damaging blood vessels that lie beneath, thus being perceived as painless and associated with reduced bleeding. This immunocompetence of the skin, coupled with its ease of access, makes this organ an attractive vaccination site. The purpose of this review was to collate primary scientific literature pertaining to MN-mediated in vivo vaccination programmes. A total of 62 original research articles are presented, compiling vaccination strategies in 6 different models (mouse, rat, guinea pig, rabbit, pig, macaque and human). Vaccines tested span a wide range of viral, bacterial and protozoan pathogens and includes 7 of the 13 vaccine-preventable diseases, as defined by the WHO. This review highlights the paucity of available clinical trial data. MN-delivered vaccines have demonstrated safety and immunogenicity in pre-clinical models and boast desirable attributes such as painless administration, thermostability, dose-sparing capacity and the potential for self-administration. These advantages should contribute to enhanced global vaccine access. PMID:27050528

  3. Reasons for non-adherence to vaccination at mother and child care clinics (MCCs) in Lambaréné, Gabon.

    PubMed

    Schwarz, Norbert G; Gysels, Marjolein; Pell, Christopher; Gabor, Julian; Schlie, Meike; Issifou, Saadou; Lell, Bertrand; Kremsner, Peter G; Grobusch, Martin P; Pool, Robert

    2009-08-27

    The aim of this paper is to explore attitudes of mothers towards childhood vaccinations and reasons for non-attendance and non-adherence to mother-child clinics (MCCs). Forty in-depth interviews with mothers of children under 5 years of age revealed positive attitudes towards vaccination that seem at odds with the region's observed low vaccination coverage. Important reasons for MCC non-attendance included distance to the MCC, transport costs, negative experiences at MCCs (such as interactions with unfriendly staff) and mothers' feeling of shame provoked by different, often poverty-associated reasons such as attending the clinic with a dirty or poorly clothed child.

  4. Time will tell: community acceptability of HIV vaccine research before and after the “Step Study” vaccine discontinuation

    PubMed Central

    Frew, Paula M; Mulligan, Mark J; Hou, Su-I; Chan, Kayshin; del Rio, Carlos

    2010-01-01

    Objective This study examines whether men-who-have-sex-with-men (MSM) and transgender (TG) persons’ attitudes, beliefs, and risk perceptions toward human immunodeficiency virus (HIV) vaccine research have been altered as a result of the negative findings from a phase 2B HIV vaccine study. Design We conducted a cross-sectional survey among MSM and TG persons (N = 176) recruited from community settings in Atlanta from 2007 to 2008. The first group was recruited during an active phase 2B HIV vaccine trial in which a candidate vaccine was being evaluated (the “Step Study”), and the second group was recruited after product futility was widely reported in the media. Methods Descriptive statistics, t tests, and chi-square tests were conducted to ascertain differences between the groups, and ordinal logistic regressions examined the influences of the above-mentioned factors on a critical outcome, future HIV vaccine study participation. The ordinal regression outcomes evaluated the influences on disinclination, neutrality, and inclination to study participation. Results Behavioral outcomes such as future recruitment, event attendance, study promotion, and community mobilization did not reveal any differences in participants’ intentions between the groups. However, we observed greater interest in HIV vaccine study screening (t = 1.07, P < 0.05) and enrollment (t = 1.15, P < 0.05) following negative vaccine findings. Means on perceptions, attitudes, and beliefs did not differ between the groups. Before this development, only beliefs exhibited a strong relationship on the enrollment intention (β = 2.166, P = 0.002). However, the effect disappeared following negative trial results, with the positive assessment of the study-site perceptions being the only significant contributing factor on enrollment intentions (β = 1.369, P = 0.011). Conclusion Findings show greater enrollment intention among this population in the wake of negative efficacy findings from the Step

  5. Lymphoma immunotherapy: vaccines, adoptive cell transfer and immunotransplant

    PubMed Central

    Brody, Joshua; Levy, Ronald

    2017-01-01

    Therapy for non-Hodgkin lymphoma has benefited greatly from basic science and clinical research such that chemotherapy and monoclonal antibody therapy have changed some lymphoma subtypes from uniformly lethal to curable, but the majority of lymphoma patients remain incurable. Novel therapies with less toxicity and more specific targeting of tumor cells are needed and immunotherapy is among the most promising of these. Recently completed randomized trials of idiotype vaccines and earlier-phase trials of other vaccine types have shown the ability to induce antitumor T cells and some clinical responses. More recently, trials of adoptive transfer of antitumor T cells have demonstrated techniques to increase the persistence and antitumor effect of these cells. Herein, we discuss lymphoma immunotherapy clinical trial results and what lessons can be taken to improve their effect, including the combination of vaccination and adoptive transfer in an approach we have dubbed ‘immunotransplant’. PMID:20636025

  6. Parents, adolescents, children and the human papillomavirus vaccine: a review.

    PubMed

    Walhart, T

    2012-09-01

    Human papillomavirus (HPV) is a sexually transmitted infection (STI). HPV is the most common sexually transmitted infection worldwide. It is also the most common STI in adolescents. This highlights a great clinical and public health concern that must be addressed. Parents are typically involved in the clinical decision-making process of vaccine administration to children and adolescents. Therefore, understanding the acceptability of the HPV vaccination as a method to prevent STIs and certain cancers is critical.   To present the three primary themes that emerged from the literature: parental attitudes, parental beliefs and parental barrier towards vaccinating children and adolescents with the HPV vaccine. A literature search using Scopus to determine parents' attitudes and beliefs towards vaccinating children and adolescents with the HPV vaccine. The initial search included the key search terms of 'children' and 'HPV vaccine'. The publication year was limited from 2006 to present. The three themes greatly influence parents' decisions to vaccinate their children. In the future, more attention needs to be paid to specific subgroups. Future research should include groups that are currently under-represented: fathers, urban populations, low socio-economic status and ethnic minorities. Since nurses worldwide are often sought as healthcare resources by parents in the clinical decision-making process, their understanding of the attitude, beliefs and barriers parents have towards the HPV vaccine is paramount. © 2012 The Author. International Nursing Review © 2012 International Council of Nurses.

  7. Development of replication-deficient adenovirus malaria vaccines.

    PubMed

    Hollingdale, Michael R; Sedegah, Martha; Limbach, Keith

    2017-03-01

    Malaria remains a major threat to endemic populations and travelers, including military personnel to these areas. A malaria vaccine is feasible, as radiation attenuated sporozoites induce nearly 100% efficacy. Areas covered: This review covers current malaria clinical trials using adenoviruses and pre-clinical research. Heterologous prime-boost regimens, including replication-deficient human adenovirus 5 (HuAd5) carrying malaria antigens, are efficacious. However, efficacy appears to be adversely affected by pre-existing anti-HuAd5 antibodies. Current strategies focus on replacing HuAd5 with rarer human adenoviruses or adenoviruses isolated from non-human primates (NHPs). The chimpanzee adenovirus ChAd63 is undergoing evaluation in clinical trials including infants in malaria-endemic areas. Key antigens have been identified and are being used alone, in combination, or with protein subunit vaccines. Gorilla adenoviruses carrying malaria antigens are also currently being evaluated in preclinical models. These replacement adenovirus vectors will be successfully used to develop vaccines against malaria, as well as other infectious diseases. Expert commentary: Simplified prime-boost single shot regimens, dry-coated live vector vaccines or silicon microneedle arrays could be developed for malaria or other vaccines. Replacement vectors with similar or superior immunogenicity have rapidly advanced, and several are now in extensive Phase 2 and beyond in malaria as well as other diseases, notably Ebola.

  8. A Phase-1 Clinical Trial of a DNA Vaccine for Venezuelan Equine Encephalitis Delivered by Intramuscular or Intradermal Electroporation

    DTIC Science & Technology

    2016-05-25

    A Phase 1 clinical trial of a DNA vaccine for Venezuelan equine encephalitis delivered by intramuscular or intradermal electroporation Drew... vaccines against VEEV available in the United States. We developed a candidate DNA vaccine expressing the E3-E2-6K-E1 genes of VEEV (pWRG/VEEV) and...groups and were vaccinated with high and low doses of pWRG/VEE or a saline placebo by intramuscular (IM) or intradermal (ID) electroporation (EP

  9. Influenza Vaccine Research funded by the European Commission FP7-Health-2013-Innovation-1 project.

    PubMed

    Liu, Heng; Frijlink, Henderik W; Huckriede, Anke; van Doorn, Eva; Schmidt, Ed; Leroy, Odile; Rimmelzwaan, Guus; McCullough, Keneth; Whelan, Mike; Hak, Eelko

    2016-11-21

    Due to influenza viruses continuously displaying antigenic variation, current seasonal influenza vaccines must be updated annually to include the latest predicted strains. Despite all the efforts put into vaccine strain selection, vaccine production, testing, and administration, the protective efficacy of seasonal influenza vaccines is greatly reduced when predicted vaccine strains antigenically mismatch with the actual circulating strains. Moreover, preparing for a pandemic outbreak is a challenge, because it is unpredictable which strain will cause the next pandemic. The European Commission has funded five consortia on influenza vaccine development under the Seventh Framework Programme for Research and Technological Development (FP7) in 2013. The call of the EU aimed at developing broadly protective influenza vaccines. Here we review the scientific strategies used by the different consortia with respect to antigen selection, vaccine delivery system, and formulation. The issues related to the development of novel influenza vaccines are discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Progress and challenges in TB vaccine development

    PubMed Central

    Voss, Gerald; Casimiro, Danilo; Neyrolles, Olivier; Williams, Ann; Kaufmann, Stefan H.E.; McShane, Helen; Hatherill, Mark; Fletcher, Helen A

    2018-01-01

    The Bacille Calmette Guerin (BCG) vaccine can provide decades of protection against tuberculosis (TB) disease, and although imperfect, BCG is proof that vaccine mediated protection against TB is a possibility. A new TB vaccine is, therefore, an inevitability; the question is how long will it take us to get there? We have made substantial progress in the development of vaccine platforms, in the identification of antigens and of immune correlates of risk of TB disease. We have also standardized animal models to enable head-to-head comparison and selection of candidate TB vaccines for further development.  To extend our understanding of the safety and immunogenicity of TB vaccines we have performed experimental medicine studies to explore route of administration and have begun to develop controlled human infection models. Driven by a desire to reduce the length and cost of human efficacy trials we have applied novel approaches to later stage clinical development, exploring alternative clinical endpoints to prevention of disease outcomes. Here, global leaders in TB vaccine development discuss the progress made and the challenges that remain. What emerges is that, despite scientific progress, few vaccine candidates have entered clinical trials in the last 5 years and few vaccines in clinical trials have progressed to efficacy trials. Crucially, we have undervalued the knowledge gained from our “failed” trials and fostered a culture of risk aversion that has limited new funding for clinical TB vaccine development. The unintended consequence of this abundance of caution is lack of diversity of new TB vaccine candidates and stagnation of the clinical pipeline. We have a variety of new vaccine platform technologies, mycobacterial antigens and animal and human models.  However, we will not encourage progression of vaccine candidates into clinical trials unless we evaluate and embrace risk in pursuit of vaccine development. PMID:29568497

  11. Progress and challenges in TB vaccine development.

    PubMed

    Voss, Gerald; Casimiro, Danilo; Neyrolles, Olivier; Williams, Ann; Kaufmann, Stefan H E; McShane, Helen; Hatherill, Mark; Fletcher, Helen A

    2018-01-01

    The Bacille Calmette Guerin (BCG) vaccine can provide decades of protection against tuberculosis (TB) disease, and although imperfect, BCG is proof that vaccine mediated protection against TB is a possibility. A new TB vaccine is, therefore, an inevitability; the question is how long will it take us to get there? We have made substantial progress in the development of vaccine platforms, in the identification of antigens and of immune correlates of risk of TB disease. We have also standardized animal models to enable head-to-head comparison and selection of candidate TB vaccines for further development.  To extend our understanding of the safety and immunogenicity of TB vaccines we have performed experimental medicine studies to explore route of administration and have begun to develop controlled human infection models. Driven by a desire to reduce the length and cost of human efficacy trials we have applied novel approaches to later stage clinical development, exploring alternative clinical endpoints to prevention of disease outcomes. Here, global leaders in TB vaccine development discuss the progress made and the challenges that remain. What emerges is that, despite scientific progress, few vaccine candidates have entered clinical trials in the last 5 years and few vaccines in clinical trials have progressed to efficacy trials. Crucially, we have undervalued the knowledge gained from our "failed" trials and fostered a culture of risk aversion that has limited new funding for clinical TB vaccine development. The unintended consequence of this abundance of caution is lack of diversity of new TB vaccine candidates and stagnation of the clinical pipeline. We have a variety of new vaccine platform technologies, mycobacterial antigens and animal and human models.  However, we will not encourage progression of vaccine candidates into clinical trials unless we evaluate and embrace risk in pursuit of vaccine development.

  12. NMOSD triggered by yellow fever vaccination - An unusual clinical presentation with segmental painful erythema.

    PubMed

    Schöberl, F; Csanadi, E; Eren, O; Dieterich, M; Kümpfel, T

    2017-01-01

    Neuromyelitis Optica Spectrum Disorder (NMOSD) is an immune-mediated disease of the central nervous system with the presence of aquaporin 4-antibodies (AQP4-abs) in most cases. We describe a patient who developed NMOSD after a yellow fever vaccination. He presented to us with an unusual painful erythema Th7-9 triggered by touch in the respective skin area due to a cervical spinal cord lesion affecting the dorsolateral parts of C6/7. To our knowledge, this is the first case of NMOSD with such a clinical presentation expanding the clinical spectrum of NMOSD. It is important to be aware of that a yellow fever vaccination can trigger NMOSD. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Factors associated with hepatitis B vaccination among men who have sex with men: a systematic review of published research.

    PubMed

    Vet, Raymond; de Wit, John Bf; Das, Enny

    2017-05-01

    This systematic review identified and synthesised evidence from published research regarding personal and environmental factors associated with hepatitis B virus (HBV) vaccination uptake among gay men and other men who have sex with men (MSM) in low prevalence, high-income countries. A systematic literature search identified 18 eligible papers that addressed factors potentially associated with HBV vaccination uptake among MSM, of which 16 reported research conducted in the US. Studies assessed possible associations between HBV vaccination among MSM and socio-demographic characteristics, behavioural and social-cognitive factors and indicators of health service access. Converging evidence was found for associations between HBV vaccination and younger age, gay self-identification, and not using alcohol and drugs; evidence suggests a lack of association between HBV vaccination and ethnicity. There was converging evidence for associations between HBV vaccination and social-cognitive factors, in particular knowledge, perceived vulnerability and perceived severity regarding HBV infection, and perceived barriers to HBV vaccination. Evidence further supported associations between HBV vaccination and indicators of health service access. While research regarding factors associated with HBV vaccination among MSM remains limited, the identified correlates of HBV vaccination among MSM provide important guidance for the development of health promotion interventions to effectively increase coverage of HBV vaccination among MSM.

  14. Placebo use in vaccine trials: Recommendations of a WHO expert panel

    PubMed Central

    Rid, Annette; Saxena, Abha; Baqui, Abdhullah H.; Bhan, Anant; Bines, Julie; Bouesseau, Marie-Charlotte; Caplan, Arthur; Colgrove, James; Dhai, Ames; Gomez-Diaz, Rita; Green, Shane K.; Kang, Gagandeep; Lagos, Rosanna; Loh, Patricia; London, Alex John; Mulholland, Kim; Neels, Pieter; Pitisuttithum, Punee; Sarr, Samba Cor; Selgelid, Michael; Sheehan, Mark; Smith, Peter G.

    2014-01-01

    Vaccines are among the most cost-effective interventions against infectious diseases. Many candidate vaccines targeting neglected diseases in low- and middle-income countries are now progressing to large-scale clinical testing. However, controversy surrounds the appropriate design of vaccine trials and, in particular, the use of unvaccinated controls (with or without placebo) when an efficacious vaccine already exists. This paper specifies four situations in which placebo use may be acceptable, provided that the study question cannot be answered in an active-controlled trial design; the risks of delaying or foregoing an efficacious vaccine are mitigated; the risks of using a placebo control are justified by the social and public health value of the research; and the research is responsive to local health needs. The four situations are: (1) developing a locally affordable vaccine, (2) evaluating the local safety and efficacy of an existing vaccine, (3) testing a new vaccine when an existing vaccine is considered inappropriate for local use (e.g. based on epidemiologic or demographic factors), and (4) determining the local burden of disease. PMID:24768580

  15. [Vaccines: building on scientific excellence and dispelling false myths].

    PubMed

    Signorelli, Carlo

    2015-01-01

    The EU and Italian institutions have recently reiterated their commitment to harmonize and implement vaccination policies as a fundamental strategy for public health. Nonetheless, vaccines are losing public confidence. False myths related to vaccine adverse reactions and commercial interests, combined with the recent judgements of the Court and the "Fluad® episode", are fuelling vaccine hesitancy. In such a context, a lively debate is ongoing in Italian scientific community. Aim of this contribution is to recall the available solid scientific evidence demonstrating that vaccines are among the most effective prevention tools ever invented and recall the economic data that support the cost-effectiveness of the immunisation. As every other medicine, vaccines are registered after large and solid clinical trials have been conducted. Immunization schedules are proposed by experts in the field of clinical medicine, epidemiology and public health on the basis of the available scientific evidence, and then implemented by policy makers also taking into consideration resources allocation and financial sustainability. The false myth that vaccines are offered because of economic interests is to be dispelled;moreover, researchers, policy makers, scientific societies and the healthcare community at large should renew commitment to invest in health education and communication on vaccines, always disclosing potential conflicts of interests.

  16. Association of Escherichia coli J5-specific serum antibody responses with clinical mastitis outcome for J5 vaccinate and control dairy cattle.

    PubMed

    Wilson, David J; Mallard, Bonnie A; Burton, Jeanne L; Schukken, Ynte H; Grohn, Yrjo T

    2009-02-01

    Dairy cattle in two commercial Holstein herds were randomly selected to be vaccinated twice with J5, at approximately 60 days and 28 days before the expected calving date, or to be untreated controls. Based on whether milk production changed following clinical mastitis or whether cows were culled or died within 30 days after onset, 51 mastitis cases were classified as severe or mild. J5-specific antibody responses were evaluated by enzyme-linked immunosorbent assay of all 32 severe and 19 mild cases. The amounts of J5-specific immunoglobulin M (IgM), IgG1, and IgG2 antibodies in sera from the 27 J5 vaccinates were compared with those of the 24 controls. At drying off (before J5 vaccination), all cows had similar amounts of J5-specific antibody. Immediately after calving (approximately 28 days after the second vaccination), J5 vaccinates had significantly higher production of J5-specific IgG1 and IgG2 than controls. When cows were tested following clinical mastitis, none of the three antibody classes differed significantly between the controls and the vaccinates. Vaccinates that contracted Escherichia coli mastitis had 75% less milk loss than controls. The cows that contracted clinical mastitis later in lactation, the unvaccinated controls, and those infected with E. coli had more milk loss following mastitis. The hazards of being culled for all reasons and of being culled for mastitis were significantly lower for J5 vaccinates. Vaccination with J5 was associated with protection against milk production loss and culling following clinical mastitis, and it was also significantly associated with changes in J5-specific IgM, IgG1, and IgG2 antibodies in sera of vaccinated cows.

  17. Clinical evaluation of CpG oligonucleotides as adjuvants for vaccines targeting infectious diseases and cancer

    PubMed Central

    Scheiermann, Julia; Klinman, Dennis M.

    2014-01-01

    Synthetic oligonucleotides (ODN) that express unmethylated “CpG motifs” trigger cells that express Toll-like receptor 9. In humans this includes plasmacytoid dendritic cells and B cells. CpG ODN induce an innate immune response characterized by the production of Th1 and pro-inflammatory cytokines. Their utility as vaccine adjuvants was evaluated in a number of clinical trials. Results indicate that CpG ODN improve antigen presentation and the generation of vaccine-specific cellular and humoral responses. This work provides an up-to-date overview of the utility of CpG ODN as adjuvants for vaccines targeting infectious agents and cancer. PMID:24975812

  18. Footrot vaccines and vaccination.

    PubMed

    Dhungyel, Om; Hunter, James; Whittington, Richard

    2014-05-30

    Research on footrot in small ruminants, which is caused by Dichelobacter nodosus, has led to development of vaccines and their application for control, treatment and eradication of the disease in sheep. Footrot vaccines have evolved over decades to contain monovalent whole cell, multivalent recombinant fimbrial, and finally mono or bivalent recombinant fimbrial antigens. Initially whole cell vaccines made against the few known serogroups of D. nodosus were found to be inefficient in control of the disease in the field, which was attributed to the presence of other unidentified serogroups and also the use of inefficient adjuvants. Fimbriae or pili, which are the basis for antigenic variation, were found to be the major protective and also curative antigens but they are not cross protective between the different serogroups. Multivalent vaccines incorporating all the known serogroups have been proven to be of limited efficacy due to the phenomenon of antigenic competition. Recent studies in Nepal, Bhutan and Australia have shown that outbreak-specific vaccination which involves targeting identified serogroups with mono- or bivalent recombinant fimbrial vaccines, can be very effective in sheep and goats. Where multiple serogroups are present in a flock, antigenic competition can be overcome by sequentially targeting the serogroups with different bivalent vaccines every 3 months. A common antigen which would confer immunity to all serogroups would be the ideal immunogen but the initial studies were not successful in this area. Until universal antigen/s are available, flock specific mono or bivalent fimbrial vaccines are likely to be the most effective tool for control and eradication of footrot in sheep and goats. Future research in footrot vaccines should be focused on improving the duration of prophylaxis by incorporating new and emerging immunomodulators or adjuvants with modified delivery vehicles, discovering a common antigen and understanding the mechanisms of

  19. The impact of a novel franchise clinic network on access to medicines and vaccinations in Kenya: a cross-sectional study.

    PubMed

    Berk, Justin; Adhvaryu, Achyuta

    2012-01-01

    To study the impact of a new franchise health clinic model (The HealthStore Foundation's CFWShops) on access to vaccinations and treatment for acute illnesses in a nationally representative sample of children in Kenya. The authors used multivariate linear and count regressions to examine associations between receipt of vaccinations or treatment and proximity to a franchise health clinic, adjusting for individual, household and clinic attributes as well as region fixed effects. Demographic and Health Survey data from Kenya, 2008-2009. 6079 Kenyan children younger than 5 years, of whom 2310 reported recent acute illness. Outcomes for all children were number of polio doses received, number of DPT doses received, receipt of BCG vaccine, receipt of measles vaccine and number of total vaccinations received. Outcomes for acutely ill children were receipt of any medical treatment, treatment for fever, treatment for malaria and treatments specifically stocked by CFWShops. Children living within 30 km of a CFWShop received 0.129 (p=0.017) and 0.113 (p=0.025) more DPT and polio doses, respectively; and 0.285 more total vaccinations (p=0.023). Among acutely ill children, CFWShop proximity was associated with significant increases in the probabilities of receiving any medical treatment (0.142; p<0.001), treatment for fever (0.117; p=0.007) and treatments specifically stocked by CFWShops (0.064; p=0.015). Use of CFWShop services was not significantly different for lower-income vis-a-vis higher-income households. The franchise health clinic model could substantially increase access to essential vaccinations and treatments in low-income countries. Moreover, the model's benefits may accrue to lesser- and higher-income households alike.

  20. Influenza vaccination responses in human systemic lupus erythematosus: impact of clinical and demographic features

    PubMed Central

    Crowe, Sherry R.; Merrill, Joan T.; Vista, Evan S.; Dedeke, Amy B.; Thompson, David M.; Stewart, Scott; Guthridge, Joel M.; Niewold, Timothy B.; Franek, Beverly S.; Air, Gillian M.; Thompson, Linda F.; James, Judith A.

    2011-01-01

    Objective Vaccination against common pathogens, such as influenza, is recommended for SLE patients to decrease infections and improve health. However, most vaccination response reports are limited to evaluation of SLE patients with quiescent disease. This study focuses on understanding the clinical, serological, therapeutic, and demographic factors which influence the response to influenza vaccination in patients with a range of disease activities. Methods Blood specimens and disease activity information were collected from seventy-two SLE patients at baseline and 2, 6 and 12 weeks after influenza vaccination. Influenza-specific antibody responses were assessed for antibody concentration (Bmax), relative affinity (Ka), and hemagglutination inhibition (HAI). Using a cumulative score, the subjects were evenly divided into high and low responders. Autoantibody levels were evaluated at each time-point by immunofluorescence and standard ELISAs. Results Low responders to the vaccine were more likely to have hematologic criteria (p=0.009), exhibit more ACR criteria (p=0.05), and be on concurrent prednisone treatment (p=0.04). Interestingly, European American patients were more likely to be low responders than African Americans (p = 0.03). Following vaccination, low responders were more likely to experience disease flares (p=0.01) and to have increased ANA titers (p = 0.04). Baseline serum interferon alpha activity was significantly higher in patients that experienced a flare after vaccination compared to a matched group of patients that did not flare (p= 0.04). Conclusions Ancestral background, prednisone treatment, hematological criteria and evidence of increased disease flares were associated with low antibody responses to influenza vaccination in SLE patients. PMID:21598235

  1. Human anthelminthic vaccines: Rationale and challenges.

    PubMed

    Hotez, Peter J; Strych, Ulrich; Lustigman, Sara; Bottazzi, Maria Elena

    2016-06-24

    Helminth infections are the most common afflictions of humankind, affecting almost every single person living in profound poverty. Through mass drug administration (MDA) we have seen sharp declines in the global prevalence of some helminth infections, including lymphatic filariasis, onchocerciasis, and ascariasis. However, since 1990, there has been no appreciable decrease in the global prevalence of hookworm infection, schistosomiasis, or food-borne trematodiases. Through the activities of a non-profit product development partnerships and two research institutes, a total of five human anthelmintic vaccines for hookworm infection (two) and schistosomiasis (three) have advanced from discovery through manufacture and are now in Phase 1 clinical testing. At least three additional antigens, including two for onchocerciasis and one for schistosomiasis, are also advancing through preclinical development with the intention of moving into the clinic soon. These preventive human anthelmintic vaccines could be used as stand-alone technologies administered to infants as part of the Expanded Program on Immunization (EPI), or together with anthelmintic drugs in programs linked to MDA. Significant hurdles though could hinder the advancement of these vaccines into later-stage clinical and product development and licensure. They include the absence of a major pharma partner (and the resultant access to adjuvants and industrial scale manufacturing expertise), an uncharted roadmap for how to introduce anthelmintic vaccines into appropriate health systems, uncertain global access and regulatory strategies that might need to rely on developing country vaccine manufacturers and national regulatory authorities, and the lack of innovative financing schemes. However, the public health and economic benefits of introducing these vaccines could be massive and therefore deserve international attention and support. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Vaccines against stimulants: cocaine and MA

    PubMed Central

    Kosten, Thomas; Domingo, Coreen; Orson, Frank; Kinsey, Berma

    2014-01-01

    While the worldwide prevalence of cocaine use remains significant, medications, or small molecule approaches, to treat drug addictions have met with limited success. Anti-addiction vaccines, on the other hand, have demonstrated great potential for treating drug abuse using a distinctly different mechanism of eliciting an antibody response that blocks the pharmacological effects of drugs. We provide a review of vaccine-based approaches to treating stimulant addictions; specifically and cocaine addictions. This selective review article focuses on the one cocaine vaccine that has been into clinical trials and presents new data related to pre-clinical development of a methamphetamine (MA) vaccine. We also review the mechanism of action for vaccine induced antibodies to abused drugs, which involves kinetic slowing of brain entry as well as simple blocking properties. We present pre-clinical innovations for MA vaccines including hapten design, linkage to carrier proteins and new adjuvants beyond alum. We provide some new information on hapten structures and linkers and variations in protein carriers. We consider a carrier, outer membrance polysaccharide coat protein (OMPC), that provides some self-adjuvant through lipopolysaccharide components and provide new results with a monophosopholipid adjuvant for the more standard carrier proteins with cocaine and MA. The review then covers the clinical trials with the cocaine vaccine TA-CD. The clinical prospects for advances in this field over the next few years include a multi-site cocaine vaccine clinical trial to be reported in 2013 and phase 1 clinical trials of a MA vaccine in 2014. PMID:23509915

  3. Vaccines against stimulants: cocaine and MA.

    PubMed

    Kosten, Thomas; Domingo, Coreen; Orson, Frank; Kinsey, Berma

    2014-02-01

    While the worldwide prevalence of cocaine use remains significant, medications, or small molecule approaches, to treat drug addictions have met with limited success. Anti-addiction vaccines, on the other hand, have demonstrated great potential for treating drug abuse using a distinctly different mechanism of eliciting an antibody response that blocks the pharmacological effects of drugs. We provide a review of vaccine-based approaches to treating stimulant addictions; specifically and cocaine addictions. This selective review article focuses on the one cocaine vaccine that has been into clinical trials and presents new data related to pre-clinical development of a methamphetamine (MA) vaccine. We also review the mechanism of action for vaccine induced antibodies to abused drugs, which involves kinetic slowing of brain entry as well as simple blocking properties. We present pre-clinical innovations for MA vaccines including hapten design, linkage to carrier proteins and new adjuvants beyond alum. We provide some new information on hapten structures and linkers and variations in protein carriers. We consider a carrier, outer membrance polysaccharide coat protein (OMPC), that provides some self-adjuvant through lipopolysaccharide components and provide new results with a monophosopholipid adjuvant for the more standard carrier proteins with cocaine and MA. The review then covers the clinical trials with the cocaine vaccine TA-CD. The clinical prospects for advances in this field over the next few years include a multi-site cocaine vaccine clinical trial to be reported in 2013 and phase 1 clinical trials of a MA vaccine in 2014. © 2013 The British Pharmacological Society.

  4. Global foot-and-mouth disease research update and gap analysis: 3 - vaccines

    USDA-ARS?s Scientific Manuscript database

    In 2014, the Global Foot-and-mouth disease Research Alliance (GFRA) conducted a gap analysis of FMD research. In this paper, we report updated findings in the field of FMD vaccine research. This paper consists of the following four sections: 1) Research priorities identified in the 2010 GFRA gap ana...

  5. Minor Consent and Delivery of Adolescent Vaccines

    PubMed Central

    Ford, Carol A.; Skiles, Martha P.; English, Abigail; Cai, Jianwen; Agans, Robert P.; Stokley, Shannon; Markowitz, Lauri; Koumans, Emilia H.

    2016-01-01

    Purpose To explore whether, and to what extent, minor consent influences adolescent vaccine delivery in the United States. Methods A telephone survey was completed by 263 professionals with responsibilities for adolescent health care and/or vaccination in 43 states. Measures included perceived frequency of unaccompanied minor visits and perceived likelihood of vaccine delivery to unaccompanied minors in hypothetical scenarios that varied by adolescent age, vaccine type, visit type, and clinical setting. Results Among the 76 respondents most familiar with private primary care clinics, 47.1% reported perceptions that 17-year-old patients often present without a parent/legal guardian. Among the 104 respondents most familiar with public primary care clinics, 56.7% reported that 17-year-old patients often present alone. In response to hypothetical scenarios, approximately 30% of respondents familiar with private clinics and 50% of respondents familiar with public clinics reported perceptions that unaccompanied 17-year-old adolescents would not receive influenza, Tdap, or human papillomavirus vaccines during routine check-ups because they could not provide consent. Perceived likelihood of unaccompanied minors receiving vaccines when seen for confidential services in primary care, sexually transmitted disease, and Title X/family planning clinics varied significantly by vaccine type and clinical setting. On average, respondents reported that they would support minors having the ability to self-consent for vaccines at age 14. Conclusions The inability of minors to consent for vaccines is likely one barrier to vaccination. Interventions to increase adolescent vaccination should consider strategies that increase the ability of unaccompanied minors, particularly older minors, to receive vaccines within the context of legal, ethical, and professional guidelines. PMID:24074605

  6. [Pertussis in fully vaccinated infants and children. Are new vaccination strategies required?].

    PubMed

    Moraga-Llop, Fernando A; Mendoza-Palomar, Natàlia; Muntaner-Alonso, Antoni; Codina-Grau, Gemma; Fàbregas-Martori, Anna; Campins-Martí, Magda

    2014-04-01

    To analyse the vaccination status of children diagnosed with pertussis and to compare the clinical manifestations of fully vaccinated with unvaccinated, or incompletely-vaccinated, children. The clinical histories and vaccination cards of patients under 16years of age seen in the Emergency Room of the University Hospital Vall d'Hebron, Barcelona (Spain), for pertussis confirmed by a microbiological study were reviewed. The study period lasted from January 1, 2009 to December 31, 2011. Two hundred and twelve cases were studied: 35 in 2009, 28 in 2010 and 149 in 2011. RT-PCR was positive in 210 patients, and 73 had a positive culture. Infants under 6months of age account for 36.8% of all cases. Forty-four patients (21.5%) were not vaccinated. Forty-four (21.5%) children were between 2 and 5months of age and had received 1-2vaccine doses. One hundred and seventeen (57%) children were fully vaccinated; 76.9% (90cases) had received the last dose less than 4years ago. When clinical manifestations of the fully vaccinated patients were compared with those of the non-vaccinated or incompletely-vaccinated children, only cyanosis was found with a higher frequency in the latter group (P<.001). The age-adjusted probability of hospitalisation was significantly associated with non-vaccination (P=.001). The case mortality rate among inpatients was 1.3%. The number of pertussis cases seen in our centre has risen significantly in the last year. More than half (57%) of the patients were fully vaccinated, and 76.9% had received the last dose in the previous 4years. Other vaccination strategies, such as vaccination of adolescents, adults, and pregnant women, as well as a cocoon strategy are required to protect infants under 6months of age. More effective vaccines need to be developed. Copyright © 2012 Elsevier España, S.L. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  7. HPV vaccination to prevent cervical cancer and other HPV-associated disease: from basic science to effective interventions.

    PubMed

    Lowy, Douglas R

    2016-01-01

    Identification of HPV infection as the etiologic agent of virtually all cases of cervical cancer, as well as a proportion of other epithelial cancers, has led to development of three FDA-approved multivalent prophylactic HPV vaccines composed of virus-like particles (VLPs). This essay describes the research and development that led to the VLP vaccines; discusses their safety, efficacy, and short-term effect on HPV-associated disease; and speculates that even a single dose of these vaccines, when given to adolescents, might be able to confer long-term protection. The HPV field exemplifies how long-term funding for basic research has lead to clinical interventions with the long-term potential to eradicate most cancers attributable to HPV infection. Although this essay is the result of my receiving the 2015 Harrington Prize for Innovation in Medicine from the Harrington Discovery Institute and the American Society for Clinical Investigation, this clinical advance has depended on the research of many investigators, development of commercial vaccines by the pharmaceutical companies, and participation of many patient volunteers in the clinical trials.

  8. HPV vaccination to prevent cervical cancer and other HPV-associated disease: from basic science to effective interventions

    PubMed Central

    Lowy, Douglas R.

    2016-01-01

    Identification of HPV infection as the etiologic agent of virtually all cases of cervical cancer, as well as a proportion of other epithelial cancers, has led to development of three FDA-approved multivalent prophylactic HPV vaccines composed of virus-like particles (VLPs). This essay describes the research and development that led to the VLP vaccines; discusses their safety, efficacy, and short-term effect on HPV-associated disease; and speculates that even a single dose of these vaccines, when given to adolescents, might be able to confer long-term protection. The HPV field exemplifies how long-term funding for basic research has lead to clinical interventions with the long-term potential to eradicate most cancers attributable to HPV infection. Although this essay is the result of my receiving the 2015 Harrington Prize for Innovation in Medicine from the Harrington Discovery Institute and the American Society for Clinical Investigation, this clinical advance has depended on the research of many investigators, development of commercial vaccines by the pharmaceutical companies, and participation of many patient volunteers in the clinical trials. PMID:26727228

  9. Translating self-persuasion into an adolescent HPV vaccine promotion intervention for parents attending safety-net clinics.

    PubMed

    Baldwin, Austin S; Denman, Deanna C; Sala, Margarita; Marks, Emily G; Shay, L Aubree; Fuller, Sobha; Persaud, Donna; Lee, Simon Craddock; Skinner, Celette Sugg; Wiebe, Deborah J; Tiro, Jasmin A

    2017-04-01

    Self-persuasion is an effective behavior change strategy, but has not been translated for low-income, less educated, uninsured populations attending safety-net clinics or to promote human papillomavirus (HPV) vaccination. We developed a tablet-based application (in English and Spanish) to elicit parental self-persuasion for adolescent HPV vaccination and evaluated its feasibility in a safety-net population. Parents (N=45) of age-eligible adolescents used the self-persuasion application. Then, during cognitive interviews, staff gathered quantitative and qualitative feedback on the self-persuasion tasks including parental decision stage. The self-persuasion tasks were rated as easy to complete and helpful. We identified six question prompts rated as uniformly helpful, not difficult to answer, and generated non-redundant responses from participants. Among the 33 parents with unvaccinated adolescents, 27 (81.8%) reported deciding to get their adolescent vaccinated after completing the self-persuasion tasks. The self-persuasion application was feasible and resulted in a change in parents' decision stage. Future studies can now test the efficacy of the tablet-based application on HPV vaccination. The self-persuasion application facilitates verbalization of reasons for HPV vaccination in low literacy, safety-net settings. This self-administered application has the potential to be more easily incorporated into clinical practice than other patient education approaches. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. The role of public-sector research in the discovery of drugs and vaccines.

    PubMed

    Stevens, Ashley J; Jensen, Jonathan J; Wyller, Katrine; Kilgore, Patrick C; Chatterjee, Sabarni; Rohrbaugh, Mark L

    2011-02-10

    Historically, public-sector researchers have performed the upstream, basic research that elucidated the underlying mechanisms of disease and identified promising points of intervention, whereas corporate researchers have performed the downstream, applied research resulting in the discovery of drugs for the treatment of diseases and have carried out development activities to bring them to market. However, the boundaries between the roles of the public and private sectors have shifted substantially since the dawn of the biotechnology era, and the public sector now has a much more direct role in the applied-research phase of drug discovery. We identified new drugs and vaccines approved by the Food and Drug Administration (FDA) that were discovered by public-sector research institutions (PSRIs) and classified them according to their therapeutic category and potential therapeutic effect. We found that during the past 40 years, 153 new FDA-approved drugs, vaccines, or new indications for existing drugs were discovered through research carried out in PSRIs. These drugs included 93 small-molecule drugs, 36 biologic agents, 15 vaccines, 8 in vivo diagnostic materials, and 1 over-the-counter drug. More than half of these drugs have been used in the treatment or prevention of cancer or infectious diseases. PSRI-discovered drugs are expected to have a disproportionately large therapeutic effect. Public-sector research has had a more immediate effect on improving public health than was previously realized.

  11. The importance of the patient voice in vaccination and vaccine safety-are we listening?

    PubMed

    Holt, D; Bouder, F; Elemuwa, C; Gaedicke, G; Khamesipour, A; Kisler, B; Kochhar, S; Kutalek, R; Maurer, W; Obermeier, P; Seeber, L; Trusko, B; Gould, S; Rath, B

    2016-12-01

    Much has been written about the patient-physician relationship over the years. This relationship is essential in maintaining trust in the complex arena of modern diagnostic techniques, treatment and prevention, including vaccines and vaccine safety. However, a great deal of this material was written from the viewpoint of clinicians and academics. The patient voice may be positive or negative, fragmented or complex. Information sources are weighed and treated differently, according to the value system and risk perceptions of the individual. In post-trust societies, when people have less confidence in health authorities, communication needs to be more than a paternalistic top-down process. Notions of empowerment and individual patient choice are becoming crucial in medical care. The 'voice of the patient', which includes healthy individuals receiving vaccines, needs to be heard, considered and addressed. With respect to childhood immunizations, this will be the voice of the parent or caregiver. The key to addressing any concerns could be to listen more and to develop a communication style that is trust-based and science-informed. Regulatory agencies are encouraging clinical and patient-reported outcomes research under the umbrella of personalized medicine, and this is an important step forward. This paper attempts to reflect the paradigm shift towards increasing attention to the patient voice in vaccination and vaccine safety. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  12. Therapeutic cancer vaccines

    PubMed Central

    Melief, Cornelis J.M.; van Hall, Thorbald; Arens, Ramon; Ossendorp, Ferry; van der Burg, Sjoerd H.

    2015-01-01

    The clinical benefit of therapeutic cancer vaccines has been established. Whereas regression of lesions was shown for premalignant lesions caused by HPV, clinical benefit in cancer patients was mostly noted as prolonged survival. Suboptimal vaccine design and an immunosuppressive cancer microenvironment are the root causes of the lack of cancer eradication. Effective cancer vaccines deliver concentrated antigen to both HLA class I and II molecules of DCs, promoting both CD4 and CD8 T cell responses. Optimal vaccine platforms include DNA and RNA vaccines and synthetic long peptides. Antigens of choice include mutant sequences, selected cancer testis antigens, and viral antigens. Drugs or physical treatments can mitigate the immunosuppressive cancer microenvironment and include chemotherapeutics, radiation, indoleamine 2,3-dioxygenase (IDO) inhibitors, inhibitors of T cell checkpoints, agonists of selected TNF receptor family members, and inhibitors of undesirable cytokines. The specificity of therapeutic vaccination combined with such immunomodulation offers an attractive avenue for the development of future cancer therapies. PMID:26214521

  13. Association of serum anti-rotavirus immunoglobulin A antibody seropositivity and protection against severe rotavirus gastroenteritis: analysis of clinical trials of human rotavirus vaccine.

    PubMed

    Cheuvart, Brigitte; Neuzil, Kathleen M; Steele, A Duncan; Cunliffe, Nigel; Madhi, Shabir A; Karkada, Naveen; Han, Htay Htay; Vinals, Carla

    2014-01-01

    Clinical trials of the human rotavirus vaccine Rotarix™ (RV1) have demonstrated significant reductions in severe rotavirus gastroenteritis (RVGE) in children worldwide. However, no correlate of vaccine efficacy (VE) has yet been established. This paper presents 2 analyses which aimed to investigate whether serum anti-RV IgA measured by ELISA 1 or 2 mo post-vaccination can serve as a correlate of efficacy against RVGE: (1) In a large Phase III efficacy trial (Rota-037), the Prentice criteria for surrogate endpoints was applied to anti-RV IgA seropositivity 1 mo post-vaccination. These criteria determine whether a significant vaccine group effect can be predicted from the surrogate, namely seropositivity (anti-RV IgA concentration>20 U/mL); (2) Among other GSK-sponsored RV1 VE studies, 8 studies which assessed immunogenicity at 1 or 2 mo post-vaccination in all or a sub-cohort of enrolled subjects and had at least 10 RVGE episodes were included in a meta-analysis to measure the regression between clinical VE and VE predicted from immunogenicity (VE1). In Rota-037, anti-RV IgA seropositivity post-vaccination was associated with a lower incidence of any or severe RVGE, however, the proportion of vaccine group effect explained by seropositivity was only 43.6% and 32.7% respectively. This low proportion was due to the vaccine group effect observed in seronegative subjects. In the meta-analysis, the slope of the regression between clinical VE and VE1 was statistically significant. These two independent analyses support the hypothesis that post-vaccination anti-RV IgA seropositivity (antibody concentration ≥20 U/mL) may serve as a useful correlate of efficacy in clinical trials of RV1 vaccines.

  14. The Recombinant Bacille Calmette-Guérin Vaccine VPM1002: Ready for Clinical Efficacy Testing.

    PubMed

    Nieuwenhuizen, Natalie E; Kulkarni, Prasad S; Shaligram, Umesh; Cotton, Mark F; Rentsch, Cyrill A; Eisele, Bernd; Grode, Leander; Kaufmann, Stefan H E

    2017-01-01

    The only licensed vaccine against tuberculosis (TB), bacille Calmette-Guérin (BCG), protects against severe extrapulmonary forms of TB but is virtually ineffective against the most prevalent form of the disease, pulmonary TB. BCG was genetically modified at the Max Planck Institute for Infection Biology to improve its immunogenicity by replacing the urease C encoding gene with the listeriolysin encoding gene from Listeria monocytogenes . Listeriolysin perturbates the phagosomal membrane at acidic pH. Urease C is involved in neutralization of the phagosome harboring BCG. Its depletion allows for rapid phagosome acidification and promotes phagolysosome fusion. As a result, BCGΔ ureC :: hly (VPM1002) promotes apoptosis and autophagy and facilitates release of mycobacterial antigens into the cytosol. In preclinical studies, VPM1002 has been far more efficacious and safer than BCG. The vaccine was licensed to Vakzine Projekt Management and later sublicensed to the Serum Institute of India Pvt. Ltd., the largest vaccine producer in the world. The vaccine has passed phase I clinical trials in Germany and South Africa, demonstrating its safety and immunogenicity in young adults. It was also successfully tested in a phase IIa randomized clinical trial in healthy South African newborns and is currently undergoing a phase IIb study in HIV exposed and unexposed newborns. A phase II/III clinical trial will commence in India in 2017 to assess efficacy against recurrence of TB. The target indications for VPM1002 are newborn immunization to prevent TB as well as post-exposure immunization in adults to prevent TB recurrence. In addition, a Phase I trial in non-muscle invasive bladder cancer patients has been completed, and phase II trials are ongoing. This review describes the development of VPM1002 from the drawing board to its clinical assessment.

  15. Vaccination Against Dengue: Challenges and Current Developments.

    PubMed

    Guy, Bruno; Lang, Jean; Saville, Melanie; Jackson, Nicholas

    2016-01-01

    Dengue is a growing threat worldwide, and the development of a vaccine is a public health priority. The completion of the active phase of two pivotal efficacy studies conducted in Asia and Latin America by Sanofi Pasteur has constituted an important step. Several other approaches are under development, and whichever technology is used, vaccine developers face several challenges linked to the particular nature and etiology of dengue disease. We start our review by defining questions and potential issues linked to dengue pathology and presenting the main types of vaccine approaches that have explored these questions; some of these candidates are in a late stage of clinical development. In the second part of the review, we focus on the Sanofi Pasteur dengue vaccine candidate, describing the steps from research to phase III efficacy studies. Finally, we discuss what could be the next steps, before and after vaccine introduction, to ensure that the vaccine will provide the best benefit with an acceptable safety profile to the identified target populations.

  16. Listen to the public and fulfil their information interests - translating vaccine communication research findings into guidance for regulators.

    PubMed

    Bahri, Priya; Castillon Melero, Mireia

    2018-03-24

    Regulatory authorities have a crucial role in communicating about the vaccines they license. In terms of content and timing, their communication to the public is usually driven by data on quality, safety and efficacy. However, concerns over safety and vaccine hesitancy have emerged in some communities in various countries, and this demands a new approach to communication, starting with listening to the public debate. Reviewing communication research findings, coming in particular from the cognitive, decision-making and media sciences, constitutes one mechanism of listening and has led the European Union (EU) regulatory network to developing guidance about which common concerns and information needs of the public to address through proactive and prepared communication. The guidance has been welcomed by EU and international fora. The current article summarizes the recommendations and shares the underlying research findings, as well as a proof of concept that communication research can be valuable for regulators. It is critical that regulators integrate the communication process with product risk assessment in the framework of pharmacovigilance, to ensure that public concerns are addressed in the assessments and that information about evidence and uncertainty relating to safety is provided to the public and vaccination policy makers in a specific, clear and accurate manner. Additionally, information from regulatory authorities should support healthcare professionals in their communication with patients. Meeting the information interests of the public is the principal prerequisite for informed decisions as well as safe and effective use of vaccines and medicines overall. This is also fundamental for trust in the authorities' commitment to patient and population health. © 2018 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

  17. Understanding Vaccine Hesitancy in Canada: Results of a Consultation Study by the Canadian Immunization Research Network

    PubMed Central

    Dubé, Eve; Gagnon, Dominique; Ouakki, Manale; Bettinger, Julie A.; Guay, Maryse; Halperin, Scott; Wilson, Kumanan; Graham, Janice; Witteman, Holly O.; MacDonald, Shannon; Fisher, William; Monnais, Laurence; Tran, Dat; Gagneur, Arnaud; Guichon, Juliet; Saini, Vineet; Heffernan, Jane M.; Meyer, Samantha; Driedger, S. Michelle; Greenberg, Joshua; MacDougall, Heather

    2016-01-01

    Vaccine hesitancy” is a concept now frequently used in vaccination discourse. The increased popularity of this concept in both academic and public health circles is challenging previously held perspectives that individual vaccination attitudes and behaviours are a simple dichotomy of accept or reject. A consultation study was designed to assess the opinions of experts and health professionals concerning the definition, scope, and causes of vaccine hesitancy in Canada. We sent online surveys to two panels (1- vaccination experts and 2- front-line vaccine providers). Two questionnaires were completed by each panel, with data from the first questionnaire informing the development of questions for the second. Our participants defined vaccine hesitancy as an attitude (doubts, concerns) as well as a behaviour (refusing some / many vaccines, delaying vaccination). Our findings also indicate that both vaccine experts and front-line vaccine providers have the perception that vaccine rates have been declining and consider vaccine hesitancy an important issue to address in Canada. Diffusion of negative information online and lack of knowledge about vaccines were identified as the key causes of vaccine hesitancy by the participants. A common understanding of vaccine hesitancy among researchers, public health experts, policymakers and health care providers will better guide interventions that can more effectively address vaccine hesitancy within Canada. PMID:27257809

  18. Live-attenuated tetravalent dengue vaccines: The needs and challenges of post-licensure evaluation of vaccine safety and effectiveness.

    PubMed

    Wichmann, Ole; Vannice, Kirsten; Asturias, Edwin J; de Albuquerque Luna, Expedito José; Longini, Ira; Lopez, Anna Lena; Smith, Peter G; Tissera, Hasitha; Yoon, In-Kyu; Hombach, Joachim

    2017-10-09

    Since December 2015, the first dengue vaccine has been licensed in several Asian and Latin American countries for protection against disease from all four dengue virus serotypes. While the vaccine demonstrated an overall good safety and efficacy profile in clinical trials, some key research questions remain which make risk-benefit-assessment for some populations difficult. As for any new vaccine, several questions, such as very rare adverse events following immunization, duration of vaccine-induced protection and effectiveness when used in public health programs, will be addressed by post-licensure studies and by data from national surveillance systems after the vaccine has been introduced. However, the complexity of dengue epidemiology, pathogenesis and population immunity, as well as some characteristics of the currently licensed vaccine, and potentially also future, live-attenuated dengue vaccines, poses a challenge for evaluation through existing monitoring systems, especially in low and middle-income countries. Most notable are the different efficacies of the currently licensed vaccine by dengue serostatus at time of first vaccination and by dengue virus serotype, as well as the increased risk of dengue hospitalization among young vaccinated children observed three years after the start of vaccination in one of the trials. Currently, it is unknown if the last phenomenon is restricted to younger ages or could affect also seronegative individuals aged 9years and older, who are included in the group for whom the vaccine has been licensed. In this paper, we summarize scientific and methodological considerations for public health surveillance and targeted post-licensure studies to address some key research questions related to live-attenuated dengue vaccines. Countries intending to introduce a dengue vaccine should assess their capacities to monitor and evaluate the vaccine's effectiveness and safety and, where appropriate and possible, enhance their surveillance

  19. Vaccines against malaria-still a long way to go.

    PubMed

    Matuschewski, Kai

    2017-08-01

    Several species of Plasmodium cause a broad spectrum of human disease that range from nausea and fever to severe anemia, cerebral malaria, and multiorgan failure. In malaria-endemic countries, continuous exposure to Plasmodium sporozoite inoculations and subsequent blood infections elicit only partial and short-lived immunity, which gradually develops over many years of parasite exposure and multiple clinical episodes. The ambitious goal of malaria vaccinology over the past 70 years has been to develop an immunization strategy that mounts protection superior to naturally acquired immunity. Herein, three principal concepts in evidence-based malaria vaccine development are compared. Feasible leads are typically stand-alone subunit vaccine approaches that block Plasmodium parasite life cycle progression or parasite/host interactions, and they constitute the majority of candidates in preclinical research and early clinical testing. Integrated approaches incorporate malaria antigen(s) into licensed or emerging pediatric vaccine formulations. This strategy can complement the malaria control portfolio even if the antimalarial component is only partially effective and has led to the development of the only candidate vaccine to date, namely RTS,S-AS01. Experimental whole parasite vaccine approaches have been repeatedly shown to elicit sterile and lasting protection against identical parasite strains, but mass production, proof of broad protection against different parasite strains, and routes of vaccine delivery remain significant translational road blocks. Global access to an effective and affordable malaria vaccine will critically depend on innovative translational research that builds on a better molecular understanding of Plasmodium biology and host immunity. © 2017 Federation of European Biochemical Societies.

  20. [Seasonal flu vaccination for older people: Evaluation of the adjuvanted vaccine. Positioning report].

    PubMed

    López Mongil, Rosa; López Trigo, José Antonio; Mariano Lázaro, Alberto; Mato Chaín, Gloria; Ramos Cordero, Primitivo; Salleras Sanmartí, Luis

    2017-11-01

    Flu is a major public health problem, particularly for older people, and creates an important clinical and economic burden. A high mortality rate was reported in Spain during the period 2015 to 2016; 3,101 serious cases were hospitalised with a confirmed diagnosis of flu, of which 11% died (352 cases). Furthermore, financial and health costs are greatly increased by the complications of flu; people aged over 65 years represent approximately 64% of the total costs. Seasonal flu vaccination is the fundamental strategy, as demonstrated by cost-benefit and cost-effectiveness studies. A priority objective is to improve the vaccine's immune response and the search for and inclusion of adjuvants and immunostimulants in vaccines is a major line of research. This positioning report evaluates vaccination for older people and the importance of the adjuvanted vaccine in the elderly in strengthening immunogenicity, by means of a critical review of the literature based on the best evidence available on its immunogenicity and effectiveness, and an economic assessment. Copyright © 2017 Sociedad Española de Geriatría y Gerontología. Publicado por Elsevier España, S.L.U. All rights reserved.

  1. Safety Analysis of Leishmania Vaccine Used in a Randomized Canine Vaccine/Immunotherapy Trial.

    PubMed

    Toepp, Angela; Larson, Mandy; Grinnage-Pulley, Tara; Bennett, Carolyne; Anderson, Michael; Parrish, Molly; Fowler, Hailie; Wilson, Geneva; Gibson-Corely, Katherine; Gharpure, Radhika; Cotter, Caitlin; Petersen, Christine

    2018-05-01

    In Leishmania infantum -endemic countries, controlling infection within dogs, the domestic reservoir, is critical to public health. There is a need for safe vaccines that prevent canine progression with disease and transmission to others. Protective vaccination against Leishmania requires mounting a strong, inflammatory, Type 1 response. Three commercially available canine vaccines on the global veterinary market use saponin or inflammatory antigen components (Letifend) as a strong pro-inflammatory adjuvant. There is very little information detailing safety of saponin as an adjuvant in field trials. Safety analyses for the use of vaccine as an immunotherapeutic in asymptomatically infected animals are completely lacking. Leishmania infantum , the causative agent of canine leishmaniasis, is enzootic within U.S. hunting hounds. We assessed the safety of LeishTec ® after use in dogs from two different clinical states: 1) without clinical signs and tested negative on polymerase chain reaction and serology or 2) without clinical signs and positive for at least one Leishmania diagnostic test. Vaccine safety was assessed after all three vaccinations to quantify the number and severity of adverse events. Vaccinated animals had an adverse event rate of 3.09%, whereas placebo animals had 0.68%. Receiving vaccine was correlated with the occurrence of mild, site-specific, reactions. Occurrence of severe adverse events was not associated with having received vaccine. Infected, asymptomatic animals did not have a higher rate of adverse events. Use of vaccination is, therefore, likely to be safe in infected, asymptomatic animals.

  2. HIV vaccines in Canada: legal and ethical issues--an overview.

    PubMed

    Garmaise, David

    2002-07-01

    In July 2002 the Legal Network released an overview paper on legal and ethical issues related to an HIV vaccine in Canada. The paper, which is based on a more detailed report prepared in collaboration with the Centre for Bioethics of the Clinical Research Institute of Montréal, calls for the establishment of a Canadian HIV Vaccine Plan.

  3. Vaccine Pipeline Has Grown During The Past Two Decades With More Early-Stage Trials From Small And Medium-Size Companies.

    PubMed

    Hwang, Thomas J; Kesselheim, Aaron S

    2016-02-01

    Many serious diseases lack safe and effective vaccines. Using a large commercial database, we examined trends in global vaccine research and development and found that the proportion of new vaccine candidates entering all stages of clinical development increased by 3-5 percentage points over the past two decades. Small and medium-size companies accounted for nearly twice as many new Phase I vaccine trials compared to large companies, but late-stage (Phase III) vaccine trials were dominated by large companies. There were no significant differences between vaccines and drugs in the probability of success in clinical trials or in profitability. Small and medium-size companies, including spin-outs from academic research centers, play an important role in innovative research and discovery. Our findings suggest that policy making targeted at smaller companies, such as prizes or opportunities for public-private partnerships, could support the development of new vaccines, particularly those targeting unmet medical needs and emerging public health threats. Project HOPE—The People-to-People Health Foundation, Inc.

  4. Recent advances in the use of therapeutic cancer vaccines in genitourinary malignancies.

    PubMed

    Surolia, Ira; Gulley, James; Madan, Ravi A

    2014-12-01

    Despite a recent increase in US FDA-approved treatments, genitourinary malignancies remain a source of significant morbidity and mortality. One focus of research is the use of therapeutic cancer vaccines in these diseases, and a significant body of clinical trial experience now exists for refining vaccine strategies to enhance antitumor efficacy and develop immune-based combination regimens. In recent years, clinical data from multiple trials in genitourinary malignancies have enhanced our understanding of the potential for immunotherapy in these cancers. There are also emerging clinical strategies that combine cancer vaccines with chemotherapy, radiation, androgen-deprivation therapy and immune checkpoint inhibitors. This review is based on a search of relevant literature for data presented over the past 5 years from clinical trials of cancer vaccines in prostate, bladder and renal carcinomas. In the coming years, clinical trials informed by decades of preclinical data and emerging clinical data will help to define the role of immunotherapy in genitourinary malignancies. Combination strategies that capitalize on the immune properties of standard treatments will bring greater clinical benefits, and immune-based combinations will likely be moved to the neoadjuvant setting, where they may have optimal clinical impact.

  5. Challenges and opportunities in RSV vaccine development: Meeting report from FDA/NIH workshop.

    PubMed

    Roberts, Jeffrey N; Graham, Barney S; Karron, Ruth A; Munoz, Flor M; Falsey, Ann R; Anderson, Larry J; Marshall, V; Kim, Sonnie; Beeler, Judy A

    2016-09-22

    Respiratory syncytial virus (RSV) is the most common cause of serious acute lower respiratory illness in infants and young children and a significant cause of disease burden in the elderly and immunocompromised. There are no licensed RSV vaccines to address this significant public health need. While advances in vaccine technologies have led to a recent resurgence in RSV vaccine development, the immune correlates of protection against RSV and the immunology of vaccine-associated enhanced respiratory disease (ERD) remain poorly understood. FDA's Center for Biologics Evaluation and Research (CBER) and NIH's National Institute of Allergy and Infectious Diseases (NIAID) organized and co-sponsored an RSV Vaccines Workshop in Bethesda, Maryland on June 1 and 2, 2015. The goal of the conference was to convene scientists, regulators, and industry stakeholders to discuss approaches to RSV vaccine development within the context of three target populations - infants and children, pregnant women, and individuals >60years of age. The agenda included topics related to RSV vaccine development in general, as well as considerations specific to each target population, such as clinical and serological endpoints. The meeting focused on vaccine development for high income countries (HIC), because issues relevant to vaccine development for low and middle income countries (LMIC) have been discussed in other forums. This manuscript summarizes the discussion of clinical, scientific, and regulatory perspectives, research gaps, and lessons learned. Copyright © 2016.

  6. Emergency medicine tools to manage smallpox (vaccinia) vaccination complications: clinical practice guideline and policies and procedures.

    PubMed

    Thorne, Craig D; Hirshon, Jon Mark; Himes, Carrie D; McDiarmid, Melissa A

    2003-11-01

    In December 2002, the federal government began a program to immunize approximately 500000 civilian public health and health care workers with smallpox (vaccinia) vaccine as a part of our pre-event defense against bioterrorism. First responders will likely follow, and the general US population might be offered vaccination in the next 1 to 2 years. Recent reports that suggest the possible association of the vaccine to adverse cardiac events (including deaths), liability concerns for hospitals, and the availability of compensation for workers with vaccine complications have significantly reduced voluntary participation. Vaccinees might experience robust primary takes or serious adverse events, including viral or even bacterial cellulitides, encephalitis, progressive skin destruction, and other life-threatening complications. With the increasing prevalence of immune suppression from both diseases and immunosuppressive medications, complications might be seen in higher frequency than previously reported. Emergency medicine providers and staff must become familiar with clinical presentations and management of vaccine complications. In addition, policies and procedures must be developed to prevent unimmunized providers from inadvertently contacting the active vaccination sites of their patients and, if the providers themselves have active vaccination sites, to protect their patients and their own families.

  7. An inactivated gE-deleted pseudorabies vaccine provides complete clinical protection and reduces virus shedding against challenge by a Chinese pseudorabies variant.

    PubMed

    Wang, Jichun; Guo, Rongli; Qiao, Yongfeng; Xu, Mengwei; Wang, Zhisheng; Liu, Yamei; Gu, Yiqi; Liu, Chang; Hou, Jibo

    2016-12-07

    Since the end of 2011 an outbreak of pseudorabies affected Chinese pig herds that had been vaccinated with the commercial vaccine made of Bartha K61 strain. It is now clear that the outbreak was caused by an emergent PRV variant. Even though vaccines made of PRV Bartha K61 strain can confer certain cross protection against PRV variants based on experimental data, less than optimal clinical protection and virus shedding reduction were observed, making the control or eradication of this disease difficult. An infectious clone of PRV AH02LA strain was constructed to generate a gE deletion mutant PRV(LA-A B ) strain. PRV(LA-A B ) strain can reach a titer of 10 8.43 TCID 50 /mL (50% tissue culture infectious dose) on BHK-21 cells. To evaluate the efficiency of the inactivated vaccine made of PRV(LA-A B ) strain, thirty 3-week-old PRV-negative piglets were divided randomly into six groups for vaccination and challenge test. All five piglets in the challenge control showed typical clinical symptoms of pseudorabies post challenge. Sneezing and nasal discharge were observed in four and three piglets in groups C(vaccinated with inactivated PRV Bartha K61 strain vaccine) and D(vaccinated with live PRV Bartha K61 strain vaccine) respectively. In contrast, piglets in both groups A(vaccinated with inactivated PRV LA-AB strain vaccine) and B(vaccinated with inactivated PRV LA-A B strain vaccine with adjuvant) presented mild or no clinical symptoms. Moreover, viral titers detected via nasal swabs were approximately 100 times lower in group B than in the challenge control, and the duration of virus shedding (3-4 days) was shorter than in either the challenge control (5-10 days) or groups C and D (5-6 days). The infectious clone constructed in this study harbors the whole genome of the PRV variant AH02LA strain. The gE deletion mutant PRV(LA-A B )strain generated from PRV AH02LA strain can reach a high titer on BHK-21 cells. An inactivated vaccine of PRV LA-A B provides clinical

  8. DNA Vaccination Against Metastatic Breast Cancer

    DTIC Science & Technology

    2002-07-01

    Although DNA vaccines have shown effectiveness in clinical trials , it is essential to demonstrate pre- clinical effectiveness for anti-tumor DNA vaccines...been shown to induce strong anti-tumor immunity in mice (3). Although gene vaccines have shown effectiveness in clinical trials for infectious...stronger justification for a clinical trial . REFERENCES: 1. Fornier, M., P. Munster, and A. D. Seidman. 1999. Update on the management of advanced breast

  9. The impact of a novel franchise clinic network on access to medicines and vaccinations in Kenya: a cross-sectional study

    PubMed Central

    Adhvaryu, Achyuta

    2012-01-01

    Objectives To study the impact of a new franchise health clinic model (The HealthStore Foundation's CFWShops) on access to vaccinations and treatment for acute illnesses in a nationally representative sample of children in Kenya. Design The authors used multivariate linear and count regressions to examine associations between receipt of vaccinations or treatment and proximity to a franchise health clinic, adjusting for individual, household and clinic attributes as well as region fixed effects. Setting Demographic and Health Survey data from Kenya, 2008–2009. Participants 6079 Kenyan children younger than 5 years, of whom 2310 reported recent acute illness. Main outcome measures Outcomes for all children were number of polio doses received, number of DPT doses received, receipt of BCG vaccine, receipt of measles vaccine and number of total vaccinations received. Outcomes for acutely ill children were receipt of any medical treatment, treatment for fever, treatment for malaria and treatments specifically stocked by CFWShops. Results Children living within 30 km of a CFWShop received 0.129 (p=0.017) and 0.113 (p=0.025) more DPT and polio doses, respectively; and 0.285 more total vaccinations (p=0.023). Among acutely ill children, CFWShop proximity was associated with significant increases in the probabilities of receiving any medical treatment (0.142; p<0.001), treatment for fever (0.117; p=0.007) and treatments specifically stocked by CFWShops (0.064; p=0.015). Use of CFWShop services was not significantly different for lower-income vis-a-vis higher-income households. Conclusions The franchise health clinic model could substantially increase access to essential vaccinations and treatments in low-income countries. Moreover, the model's benefits may accrue to lesser- and higher-income households alike. PMID:22786948

  10. Ebola vaccine, therapeutics, and diagnostics.

    PubMed

    Furuyama, Wakako; Takada, Ayato

    2016-01-01

    Ebolaviruses, members of the family Filoviridae, cause severe hemorrhagic fever in humans and nonhuman primates, with human case fatality rates of up to 90%. No effective prophylaxis or treatment for Ebola virus disease (EVD) is yet commercially available. During the latest outbreak of EVD in West Africa, several unapproved drugs were used for the treatment of patients. This outbreak has indeed accelerated efforts to develop antiviral strategies and some of the vaccine and drug candidates have undergone clinical trials. This article reviews previous researches and recent advances on the development of vaccine, therapeutics, and diagnostics for EVD.

  11. "Speaking the dialect": understanding public discourse in the aftermath of an HIV vaccine trial shutdown.

    PubMed

    Newman, Peter A; Logie, Carmen; James, Llana; Charles, Tamicka; Maxwell, John; Salam, Khaled; Woodford, Michael

    2011-09-01

    We investigated how persons from key populations at higher risk of HIV exposure interpreted the process and outcomes of the Step Study HIV-1 vaccine trial, which was terminated early, and implications for willingness to participate in and community support for HIV vaccine research. We used qualitative methods and a community-based approach in 9 focus groups (n = 72) among ethnically and sexually diverse populations and 6 semistructured key informant interviews in Ontario, Canada, in 2007 to 2008. Participants construed social meaning from complex clinical and biomedical phenomena. Social representations and mental models emerged in fears of vaccine-induced infection, conceptualizations of unfair recruitment practices and increased risk behaviors among trial participants, and questioning of informed consent. Narratives of altruism and the common good demonstrated support for future trials. Public discourse on HIV vaccine trials is a productive means of interpreting complex clinical trial processes and outcomes in the context of existing beliefs and experiences regarding HIV vaccines, medical research, and historical disenfranchisement. Strategic engagement with social representations and mental models may promote meaningful community involvement in biomedical HIV prevention research.

  12. Carbohydrate-based vaccine adjuvants - discovery and development.

    PubMed

    Hu, Jing; Qiu, Liying; Wang, Xiaoli; Zou, Xiaopeng; Lu, Mengji; Yin, Jian

    2015-10-01

    The addition of a suitable adjuvant to a vaccine can generate significant effective adaptive immune responses. There is an urgent need for the development of novel po7tent and safe adjuvants for human vaccines. Carbohydrate molecules are promising adjuvants for human vaccines due to their high biocompatibility and good tolerability in vivo. The present review covers a few promising carbohydrate-based adjuvants, lipopolysaccharide, trehalose-6,6'-dibehenate, QS-21 and inulin as examples, which have been extensively studied in human vaccines in a number of preclinical and clinical studies. The authors discuss the current status, applications and strategies of development of each adjuvant and different adjuvant formulation systems. This information gives insight regarding the exciting prospect in the field of carbohydrate-based adjuvant research. Carbohydrate-based adjuvants are promising candidates as an alternative to the Alum salts for human vaccines development. Furthermore, combining two or more adjuvants in one formulation is one of the effective strategies in adjuvant development. However, further research efforts are needed to study and develop novel adjuvants systems, which can be more stable, potent and safe. The development of synthetic carbohydrate chemistry can improve the study of carbohydrate-based adjuvants.

  13. Vaccine decision-making begins in pregnancy: Correlation between vaccine concerns, intentions and maternal vaccination with subsequent childhood vaccine uptake.

    PubMed

    Danchin, M H; Costa-Pinto, J; Attwell, K; Willaby, H; Wiley, K; Hoq, M; Leask, J; Perrett, K P; O'Keefe, Jacinta; Giles, M L; Marshall, H

    2017-08-12

    Maternal and childhood vaccine decision-making begins prenatally. Amongst pregnant Australian women we aimed to ascertain vaccine information received, maternal immunisation uptake and attitudes and concerns regarding childhood vaccination. We also aimed to determine any correlation between a) intentions and concerns regarding childhood vaccination, (b) concerns about pregnancy vaccination, (c) socioeconomic status (SES) and (d) uptake of influenza and pertussis vaccines during pregnancy and routine vaccines during childhood. Women attending public antenatal clinics were recruited in three Australian states. Surveys were completed on iPads. Follow-up phone surveys were done three to six months post delivery, and infant vaccination status obtained via the Australian Childhood Immunisation Register (ACIR). Between October 2015 and March 2016, 975 (82%) of 1184 mothers consented and 406 (42%) agreed to a follow up survey, post delivery. First-time mothers (445; 49%) had significantly more vaccine concerns in pregnancy and only 73% had made a decision about childhood vaccination compared to 89% of mothers with existing children (p-value<0.001). 66% of mothers reported receiving enough information during pregnancy on childhood vaccination. In the post delivery survey, 46% and 82% of mothers reported receiving pregnancy influenza and pertussis vaccines respectively. The mother's degree of vaccine hesitancy and two attitudinal factors were correlated with vaccine uptake post delivery. There was no association between reported maternal vaccine uptake or SES and childhood vaccine uptake. First time mothers are more vaccine hesitant and undecided about childhood vaccination, and only two thirds of all mothers believed they received enough information during pregnancy. New interventions to improve both education and communication on childhood and maternal vaccines, delivered by midwives and obstetricians in the Australian public hospital system, may reduce vaccine hesitancy

  14. Burkholderia vaccines: are we moving forward?

    PubMed

    Choh, Leang-Chung; Ong, Guang-Han; Vellasamy, Kumutha M; Kalaiselvam, Kaveena; Kang, Wen-Tyng; Al-Maleki, Anis R; Mariappan, Vanitha; Vadivelu, Jamuna

    2013-01-01

    The genus Burkholderia consists of diverse species which includes both "friends" and "foes." Some of the "friendly" Burkholderia spp. are extensively used in the biotechnological and agricultural industry for bioremediation and biocontrol. However, several members of the genus including B. pseudomallei, B. mallei, and B. cepacia, are known to cause fatal disease in both humans and animals. B. pseudomallei and B. mallei are the causative agents of melioidosis and glanders, respectively, while B. cepacia infection is lethal to cystic fibrosis (CF) patients. Due to the high rate of infectivity and intrinsic resistance to many commonly used antibiotics, together with high mortality rate, B. mallei and B. pseudomallei are considered to be potential biological warfare agents. Treatments of the infections caused by these bacteria are often unsuccessful with frequent relapse of the infection. Thus, we are at a crucial stage of the need for Burkholderia vaccines. Although the search for a prophylactic therapy candidate continues, to date development of vaccines has not advanced beyond research to human clinical trials. In this article, we review the current research on development of safe vaccines with high efficacy against B. pseudomallei, B. mallei, and B. cepacia. It can be concluded that further research will enable elucidation of the potential benefits and risks of Burkholderia vaccines.

  15. Vaccines and vaccination for avian influenza in poultry

    USDA-ARS?s Scientific Manuscript database

    Avian influenza (AI) vaccines have been developed and used to protect poultry and other birds in various countries of the world. Protection is principally mediated by an immune response to the subtype-specific hemagglutinin (HA) protein. AI vaccines prevent clinical signs of disease, death, egg pr...

  16. Successes and Challenges of Vaccines to Prevent HPV-associated Cancers

    Cancer.gov

    Dr. John T. Schiller received his bachelor’s degree in Molecular Biology from the University of Wisconsin, Madison in 1975, and his master’s and PhD degrees in Microbiology from the University of Washington, Seattle, in 1978 and 1982, respectively. He is currently a NIH Distinguished Investigator and Section Chief in the Laboratory of Cellular Oncology, Center for Cancer Research, National Cancer Institute, Bethesda, MD. In his 35 years at the NCI, Dr. Schiller has studied various aspects of papillomavirus molecular biology, immunology, and epidemiology The laboratory headed by Dr. Schiller and Dr. Lowy led in the discovery, characterization, and clinical testing of virus-like particle (VLP) vaccines to prevent the HPV infections that cause cervical and other cancers. They have facilitated technology transfer to potential HPV vaccine manufactures in developing countries and provided leadership in promoting global public health issues related to the implementation of HPV vaccination. They have received numerous awards for this work including the 2007 Sabin Gold Medal Award, the 2014 National Medal of Technology and Innovation, and the 2017 Lasker~DeBakey Clinical Medical Research Award. Dr. Schiller’s current interests include basic studies of papillomavirus virion assembly and infection, the development of 2 generation HPV vaccines, and vaccines and therapies for other infectious diseases and cancers.  

  17. Association of School-Based Influenza Vaccination Clinics and School Absenteeism--Arkansas, 2012-2013

    ERIC Educational Resources Information Center

    Gicquelais, Rachel E.; Safi, Haytham; Butler, Sandra; Smith, Nathaniel; Haselow, Dirk T.

    2016-01-01

    Background: Influenza is a major cause of seasonal viral respiratory illness among school-aged children. Accordingly, the Arkansas Department of Health (ADH) coordinates >800 school-based influenza immunization clinics before each influenza season. We quantified the relationship between student influenza vaccination in Arkansas public schools…

  18. A decade of vaccinating allergic travellers: a clinical audit.

    PubMed

    McCallum, Andrew D; Duncan, Christopher J A; MacDonald, Rona; Jones, Michael E

    2011-09-01

    Adverse reactions following vaccination are rare but may include potentially fatal anaphylaxis. This audit is a retrospective review of 38 patients with a history, or potential risk, of 'vaccine allergy' referred to an Infectious Diseases Unit for vaccination over a 10 year period. A total of 59 patient encounters were recorded, of which 89.8% were uneventful. Of the 6 adverse events, 3 patients had a local reaction, 1 patient developed urticaria and 1 patient had a vasovagal episode. Only 1 patient developed anaphylaxis secondary to vaccination, and she had no prior history of vaccine allergy. Of these patients 17 had a history suggesting the need for immunological investigation but only 7 had laboratory evidence of allergy. The differential diagnosis of anaphylaxis includes vasovagal reactions and non-specific mediator release and immunological work-up of such events can help avoid such patients being incorrectly labelled as allergic. The vast majority of immunisations are uncomplicated and patients with a history of allergic reactions to vaccination may be vaccinated safely in a controlled setting. Unduly conservative guidelines risk withholding vaccines providing protection against dangerous pathogens but which can be safely administered. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Clinical experience with the meningococcal B vaccine, Bexsero(®): Prospects for reducing the burden of meningococcal serogroup B disease.

    PubMed

    Watson, Philip S; Turner, David P J

    2016-02-10

    Although rare, invasive meningococcal disease remains an important cause of mortality and morbidity in children and young adults. Vaccines have been successfully introduced to help protect against meningococcal disease caused by serogroups A, C, W and Y, but until recently, a vaccine for serogroup B (MenB) was not available. In many industrialised countries, MenB causes the majority of meningococcal disease. Moreover, MenB outbreaks occur unpredictably, particularly in high-risk populations, such as university students. In 2013, Bexsero(®) became the first broad-coverage vaccine to be licensed for active immunisation against MenB disease. Bexsero is now licensed in more than 35 countries worldwide for varying age groups, including the EU, Australia, Brazil, Canada, Chile, Uruguay and the USA. Clinical recommendations for the use of Bexsero have been published in several countries. Recommendations include use in high-risk groups, outbreak control and routine infant immunisation. Since initial licensure, considerable clinical experience has been gained. In Canada, 43,740 individuals received Bexsero during a vaccination programme in the Saguenay-Lac-Saint-Jean region of Quebec, where local disease incidence was high. In the USA, Bexsero was administered to >15,000 individuals during two college outbreaks prior to licensure, under an Investigational New Drug protocol. In the UK, the Joint Committee on Vaccination and Immunisation has recommended the inclusion of Bexsero in the routine immunisation schedule for infants. Publically funded vaccination programmes have been initiated in Italy, and there has been widespread use of the vaccine outside of publically reimbursed programmes. Overall, >1,000,000 doses of Bexsero have been distributed in 19 countries worldwide since 2013. The emerging clinical experience with Bexsero is consistent with findings from pre-licensure clinical studies, and no new safety concerns have been identified. Additional data on length of

  20. Implementation of Flu (Influenza) Vaccination into Armenian Armed Forces Pre-Emptive Vaccination Plan

    DTIC Science & Technology

    2016-12-01

    Vinci, M., Zordan, M., & Serra, G. (2006). Cost - benefit analysis of influenza vaccination in a public healthcare unit. Therapeutics and Clinical...readiness, flu morbidity, flu vaccination, pre-emptive vaccination plan, cost - benefit analysis 15. NUMBER OF PAGES 83 16. PRICE CODE 17...expenditures pose a heavy burden on the government. A cost - benefit analysis of the flu vaccination would assess whether conducting flu vaccination is

  1. Status of vaccine research and development of vaccines for Nipah virus.

    PubMed

    Satterfield, Benjamin A; Dawes, Brian E; Milligan, Gregg N

    2016-06-03

    Nipah virus (NiV) is a highly pathogenic, recently emerged paramyxovirus that has been responsible for sporadic outbreaks of respiratory and encephalitic disease in Southeast Asia. High case fatality rates have also been associated with recent outbreaks in Malaysia and Bangladesh. Although over two billion people currently live in regions in which NiV is endemic or in which the Pteropus fruit bat reservoir is commonly found, there is no approved vaccine to protect against NiV disease. This report examines the feasibility and current efforts to develop a NiV vaccine including potential hurdles for technical and regulatory assessment of candidate vaccines and the likelihood for financing. Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

  2. Template protocol for clinical trials investigating vaccines--focus on safety elements.

    PubMed

    Bonhoeffer, Jan; Imoukhuede, Egeruan B; Aldrovandi, Grace; Bachtiar, Novilia S; Chan, Eng-Soon; Chang, Soju; Chen, Robert T; Fernandopulle, Rohini; Goldenthal, Karen L; Heffelfinger, James D; Hossain, Shah; Jevaji, Indira; Khamesipour, Ali; Kochhar, Sonali; Makhene, Mamodikoe; Malkin, Elissa; Nalin, David; Prevots, Rebecca; Ramasamy, Ranjan; Sellers, Sarah; Vekemans, Johan; Walker, Kenneth B; Wilson, Pam; Wong, Virginia; Zaman, Khalequz; Heininger, Ulrich

    2013-11-12

    This document is intended as a guide to the protocol development for trials of prophylactic vaccines. The template may serve phases I-IV clinical trials protocol development to include safety relevant information as required by the regulatory authorities and as deemed useful by the investigators. This document may also be helpful for future site strengthening efforts. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Factors associated with willingness to participate in a vaccine clinical trial among elderly Hispanic patients.

    PubMed

    Rikin, Sharon; Shea, Steven; LaRussa, Philip; Stockwell, Melissa

    2017-09-01

    A population specific understanding of barriers and facilitators to participation in clinical trials could improve recruitment of elderly and minority populations. We investigated how prior exposure to clinical trials and incentives were associated with likelihood of participation in a vaccine clinical trial through a questionnaire administered to 200 elderly patients in an academic general internal medicine clinic. Wilcoxon signed rank sum test compared likelihood of participation with and without monetary incentives. Logistic regression evaluated characteristics associated with intent to participate in an influenza vaccine trial, adjusted for age, gender, language, and education history. When asked about likelihood of participation if there was monetary compensation, there was a 12.2% absolute increase in those reporting that they would not participate, with a significant difference in the distribution of likelihood before and after mentioning a monetary incentive (Wilcoxon signed rank test, p = 0.001). Those with previous knowledge of clinical trials (54.4%) were more likely to report they would participate vs. those without prior knowledge (OR 2.5, 95% CI [1.2, 5.2]). The study highlights the importance of pre-testing recruitment materials and incentives in key group populations prior to implementing clinical trials.

  4. Plant-made vaccine antigens and biopharmaceuticals

    PubMed Central

    Daniell, Henry; Singh, Nameirakpam D.; Mason, Hugh; Streatfield, Stephen J.

    2009-01-01

    Plant cells are ideal bioreactors for the production and oral delivery of vaccines and biopharmaceuticals, eliminating the need for expensive fermentation, purification, cold storage, transportation and sterile delivery. Plant-made vaccines have been developed for two decades but none has advanced beyond Phase I. However, two plant-made biopharmaceuticals are now advancing through Phase II and Phase III human clinical trials. In this review, we evaluate the advantages and disadvantages of different plant expression systems (stable nuclear and chloroplast or transient viral) and their current limitations or challenges. We provide suggestions for advancing this valuable concept for clinical applications and conclude that greater research emphasis is needed on large scale production, purification, functional characterization, oral delivery and preclinical evaluation. PMID:19836291

  5. Advances in Therapeutic Cancer Vaccines.

    PubMed

    Wong, Karrie K; Li, WeiWei Aileen; Mooney, David J; Dranoff, Glenn

    2016-01-01

    Therapeutic cancer vaccines aim to induce durable antitumor immunity that is capable of systemic protection against tumor recurrence or metastatic disease. Many approaches to therapeutic cancer vaccines have been explored, with varying levels of success. However, with the exception of Sipuleucel T, an ex vivo dendritic cell vaccine for prostate cancer, no therapeutic cancer vaccine has yet shown clinical efficacy in phase 3 randomized trials. Though disappointing, lessons learned from these studies have suggested new strategies to improve cancer vaccines. The clinical success of checkpoint blockade has underscored the role of peripheral tolerance mechanisms in limiting vaccine responses and highlighted the potential for combination therapies. Recent advances in transcriptome sequencing, computational modeling, and material engineering further suggest new opportunities to intensify cancer vaccines. This review will discuss the major approaches to therapeutic cancer vaccination and explore recent advances that inform the design of the next generation of cancer vaccines. © 2016 Elsevier Inc. All rights reserved.

  6. Vaccine preventable disease incidence as a complement to vaccine efficacy for setting vaccine policy

    PubMed Central

    Gessner, Bradford D.; Feikin, Daniel R.

    2015-01-01

    Traditionally, vaccines have been evaluated in clinical trials that establish vaccine efficacy (VE) against etiology-confirmed disease outcomes, a measure important for licensure. Yet, VE does not reflect a vaccine’s public health impact because it does not account for relative disease incidence. An additional measure that more directly establishes a vaccine’s public health value is the vaccine preventable disease incidence (VPDI), which is the incidence of disease preventable by vaccine in a given context. We describe how VE and VPDI can vary, sometimes in inverse directions, across disease outcomes and vaccinated populations. We provide examples of how VPDI can be used to reveal the relative public health impact of vaccines in developing countries, which can be masked by focus on VE alone. We recommend that VPDI be incorporated along with VE into the analytic plans of vaccine trials, as well as decisions by funders, ministries of health, and regulatory authorities. PMID:24731817

  7. Status of vaccine research and development for Shigella.

    PubMed

    Mani, Sachin; Wierzba, Thomas; Walker, Richard I

    2016-06-03

    Shigella are gram-negative bacteria that cause severe diarrhea and dysentery. In 2013, Shigella infections caused an estimated 34,400 deaths in children less than five years old and, in 2010, an estimated 40,000 deaths in persons older than five years globally. New disease burden estimates from newly deployed molecular diagnostic assays with increased sensitivity suggest that Shigella-associated morbidity may be much greater than previous disease estimates from culture-based methods. Primary prevention of this disease should be based on universal provision of potable water and sanitation methods and improved personal and food hygiene. However, an efficacious and low-cost vaccine would complement and accelerate disease reduction while waiting for universal access to water, sanitation, and hygiene improvements. This review article provides a landscape of Shigella vaccine development efforts. No vaccine is yet available, but human and animal challenge-rechallenge trials with virulent Shigella as well as observational studies in Shigella-endemic areas have shown that the incidence of disease decreases following Shigella infection, pointing to biological feasibility of a vaccine. Immunity to Shigella appears to be strain-specific, so a vaccine that covers the most commonly detected strains (i.e., S. flexneri 2a, 3a, 6, and S. sonnei) or a vaccine using cross-species conserved antigens would likely be most effective. Vaccine development and testing may be accelerated by use of animal models, such as the guinea pig keratoconjunctivitis or murine pneumonia models. Because there is no correlate of protection, however, human studies will be necessary to evaluate vaccine efficacy prior to deployment. A diversity of Shigella vaccine constructs are under development, including live attenuated, formalin-killed whole-cell, glycoconjugate, subunit, and novel antigen vaccines (e.g., Type III secretion system and outer membrane proteins). Copyright © 2016 World Health Organization

  8. Noninvasive vaccination against infectious diseases.

    PubMed

    Zheng, Zhichao; Diaz-Arévalo, Diana; Guan, Hongbing; Zeng, Mingtao

    2018-04-06

    The development of a successful vaccine, which should elicit a combination of humoral and cellular responses to control or prevent infections, is the first step in protecting against infectious diseases. A vaccine may protect against bacterial, fungal, parasitic, or viral infections in animal models, but to be effective in humans there are some issues that should be considered, such as the adjuvant, the route of vaccination, and the antigen-carrier system. While almost all licensed vaccines are injected such that inoculation is by far the most commonly used method, injection has several potential disadvantages, including pain, cross contamination, needlestick injury, under- or overdosing, and increased cost. It is also problematic for patients from rural areas of developing countries, who must travel to a hospital for vaccine administration. Noninvasive immunizations, including oral, intranasal, and transcutaneous administration of vaccines, can reduce or eliminate pain, reduce the cost of vaccinations, and increase their safety. Several preclinical and clinical studies as well as experience with licensed vaccines have demonstrated that noninvasive vaccine immunization activates cellular and humoral immunity, which protect against pathogen infections. Here we review the development of noninvasive immunization with vaccines based on live attenuated virus, recombinant adenovirus, inactivated virus, viral subunits, virus-like particles, DNA, RNA, and antigen expression in rice in preclinical and clinical studies. We predict that noninvasive vaccine administration will be more widely applied in the clinic in the near future.

  9. Vaccines for Drug Abuse

    PubMed Central

    Shen, Xiaoyun; Orson, Frank M.; Kosten, Thomas R.

    2012-01-01

    Current medications for drug abuse have had only limited success. Anti-addiction vaccines to elicit antibodies that block the pharmacological effects of drugs have great potential for treating drug abuse. We review the status for two vaccines that are undergoing clinical trials (cocaine and nicotine) and two that are still in pre-clinical development (methamphetamine and heroin). We also outline the challenges and ethical concerns for anti-addiction vaccine development and their use as future therapeutics. PMID:22130115

  10. Status of vaccine research and development of vaccines for HIV-1.

    PubMed

    Safrit, Jeffrey T; Fast, Patricia E; Gieber, Lisa; Kuipers, Hester; Dean, Hansi J; Koff, Wayne C

    2016-06-03

    Human immunodeficiency virus (HIV) is the cause of one of the most lethal pandemics in human history, although in recent years access to highly effective anti-retroviral therapy has provided new hope worldwide. Transmission of HIV by sexual contact, childbirth and injection drug use has been reduced, but 2 million are newly infected each year, and much of the transmission is from people who do not know their status. In addition to known methods, a preventive vaccine is needed to end the pandemic. The extraordinary mutability and genetic diversity of HIV is an enormous challenge, but vaccines are being designed for broad coverage. Computer-aided design of mosaic immunogens, incorporating many epitopes from the entire genome or from conserved regions aim to induce CD8+ T cells to kill virus-infected cells or inhibit virus replication, while trimeric envelope proteins or synthetic mimics aim to induce broadly reactive neutralizing antibodies similar to those cloned from some infected patients. Induction of more potent and durable responses may require new adjuvants or replicating chimeric vectors chimeras that bear HIV genes. Passive or genetic delivery of broadly neutralizing antibodies may provide broad protection and/or lead to insights for vaccine designers. Proof-of-concept trials in non-human primates and in one human efficacy trial have provided scientific clues for a vaccine that could provide broad and durable protection against HIV. The use of vaccines to destroy HIV reservoirs as part of therapy or cure is now also being explored. Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

  11. Coordination Costs for School-Located Influenza Vaccination Clinics, Maine, 2009 H1N1 Pandemic

    ERIC Educational Resources Information Center

    Asay, Garrett R. Beeler; Cho, Bo-Hyun; Lorick, Suchita A.; Tipton, Meredith L.; Dube, Nancy L.; Messonnier, Mark L.

    2012-01-01

    School nurses played a key role in Maine's school-located influenza vaccination (SLV) clinics during the 2009-2010 pandemic season. The objective of this study was to determine, from the school district perspective, the labor hours and costs associated with outside-clinic coordination activities (OCA). The authors defined OCA as labor hours spent…

  12. A booster dose of an inactivated enterovirus 71 vaccine in chinese young children: a randomized, double-blind, placebo-controlled clinical trial.

    PubMed

    Shenyu, Wang; Jingxin, Li; Zhenglun, Liang; Xiuling, Li; Qunying, Mao; Fanyue, Meng; Hua, Wang; Yuntao, Zhang; Fan, Gao; Qinghua, Chen; Yuemei, Hu; Xin, Yao; Huijie, Guo; Fengcai, Zhu

    2014-10-01

    A significant waning of enterovirus 71 (EV71) antibody titer after priming immunization with an inactivated EV71 vaccine implied the potential need for a booster dose. In this randomized, double-blind, placebo-controlled clinical trial, we recruited participants who had received at least 1 dose of priming EV71 vaccine in an early phase 2 clinical trial that was conducted in healthy infants and children aged 6-35 months. All participants were grouped according to the priming EV71 vaccine formulations (160 U, 320 U, and 640 U with adjuvant and 640 U without adjuvant) and then randomly assigned (ratio, 2:1) to receive a booster dose of vaccine or placebo within each formulation group. The primary end point was the geometric mean titer 28 days after the booster dose. A total of 773 participants were enrolled. Significantly greater immunological responses were induced by the booster shot of all 4 formulations of EV71 vaccine, compared with that induced by placebo (P < .0001). The frequencies of adverse reactions were similar between vaccine and placebo groups within each formulation group. A booster dose of EV71 vaccine 1 year after the priming EV71 immunization shows excellent immunogenicity and good safety profile. Clinical Trials Registration: NCT01734408. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. Vector-based genetically modified vaccines: Exploiting Jenner's legacy.

    PubMed

    Ramezanpour, Bahar; Haan, Ingrid; Osterhaus, Ab; Claassen, Eric

    2016-12-07

    The global vaccine market is diverse while facing a plethora of novel developments. Genetic modification (GM) techniques facilitate the design of 'smarter' vaccines. For many of the major infectious diseases of humans, like AIDS and malaria, but also for most human neoplastic disorders, still no vaccines are available. It may be speculated that novel GM technologies will significantly contribute to their development. While a promising number of studies is conducted on GM vaccines and GM vaccine technologies, the contribution of GM technology to newly introduced vaccines on the market is disappointingly limited. In this study, the field of vector-based GM vaccines is explored. Data on currently available, actually applied, and newly developed vectors is retrieved from various sources, synthesised and analysed, in order to provide an overview on the use of vector-based technology in the field of GM vaccine development. While still there are only two vector-based vaccines on the human vaccine market, there is ample activity in the fields of patenting, preclinical research, and different stages of clinical research. Results of this study revealed that vector-based vaccines comprise a significant part of all GM vaccines in the pipeline. This study further highlights that poxviruses and adenoviruses are among the most prominent vectors in GM vaccine development. After the approval of the first vectored human vaccine, based on a flavivirus vector, vaccine vector technology, especially based on poxviruses and adenoviruses, holds great promise for future vaccine development. It may lead to cheaper methods for the production of safe vaccines against diseases for which no or less perfect vaccines exist today, thus catering for an unmet medical need. After the introduction of Jenner's vaccinia virus as the first vaccine more than two centuries ago, which eventually led to the recent eradication of smallpox, this and other viruses may now be the basis for constructing vectors

  14. Adverse events in vaccinations for travelers - a 1-year prospective survey in a travel clinic in Germany.

    PubMed

    Slesak, Günther; Fleck, Ralf; Scherbaum, Helmut; Blumenstock, Gunnar; Schäfer, Johannes

    2018-01-01

    The study goal was to assess and compare adverse events (AE) of current vaccinations for travelers under 'real-life conditions'. A prospective observational online questionnaire study was performed from May 2015 till April 2016 in a travel clinic in Germany. Online questionnaire links were sent 1 week after the first vaccination date. Severity was rated on a scale from 1 to 5 (minor to very severe AE). Of 1357 vaccinees 781 (57.6%) responded to the questionnaire, corresponding to 1415 vaccinations (1-7 simultaneous vaccinations). Responders were more often female (f:m = 1.29:1). Main age groups were 20-29 years old (36.1%). Most frequent vaccinations were against rabies (277; chick embryo cell vaccine (CEC): 97, human diploid cell vaccine (HDC): 180), yellow fever (250), typhoid fever (198), meningococcal meningitis (126) and Japanese encephalitis (104). A total of 217 vaccinees (27.8%) reported AE; 82 (10.5%) rated AE as more severe (grade 3: 61, grade 4: 18, grade 5: 3). No life-threatening AE was reported. Of 157 systemic AE the most frequent were: fatigue (75), headaches (46) and pyrexia (31). Of 94 local AE most frequently reported were pain (66), myalgia (25) and swelling (12). AE after single vaccinations were more often associated with rabies vaccine (OR 2.2; 1.2-4.2). AE increased with the number of simultaneous vaccinations (single vaccination: 24.1%, 88/365; 2 vaccinations: 26.6%, 73/274, ≥3 vaccinations: 39.4%, 56/142, χ2 = 12.24, P = 0.002, CCorr = 0.18), but more severe AE showed no association with the number of vaccinations (χ2 = 5.55, P = 0.06, CCorr = 0.12). Single and simultaneous vaccinations were overall well tolerated. AE were reported more frequently with rabies vaccinations in single vaccinations. Increased numbers of simultaneous vaccinations led to some incremental AE but not to more severe AE. Simultaneous vaccinations should be encouraged to reduce missed opportunities for immunizations.

  15. Comparison of Current Regulatory Status for Gene-Based Vaccines in the U.S., Europe and Japan

    PubMed Central

    Nakayama, Yoshikazu; Aruga, Atsushi

    2015-01-01

    Gene-based vaccines as typified by plasmid DNA vaccines and recombinant viral-vectored vaccines are expected as promising solutions against infectious diseases for which no effective prophylactic vaccines exist such as HIV, dengue virus, Ebola virus and malaria, and for which more improved vaccines are needed such as tuberculosis and influenza virus. Although many preclinical and clinical trials have been conducted to date, no DNA vaccines or recombinant viral-vectored vaccines expressing heterologous antigens for human use have yet been licensed in the U.S., Europe or Japan. In this research, we describe the current regulatory context for gene-based prophylactic vaccines against infectious disease in the U.S., Europe, and Japan. We identify the important considerations, in particular, on the preclinical assessments that would allow these vaccines to proceed to clinical trials, and the differences on the regulatory pathway for the marketing authorization in each region. PMID:26344953

  16. Clinical and immunological assessment of therapeutic immunization with a subunit vaccine for recurrent ocular canine herpesvirus-1 infection in dogs.

    PubMed

    Ledbetter, Eric C; Kim, Kay; Dubovi, Edward J; Mohammed, Hussni O; Felippe, M Julia B

    2016-12-25

    Latent canine herpesvirus-1 (CHV-1) infections are common in domestic dogs and reactivation of latent virus may be associated with recurrent ocular disease. The objectives of the present study were to evaluate the ability of a subunit CHV-1 vaccine to stimulate peripheral CHV-1 specific immunity and prevent recurrent CHV-1 ocular disease and viral shedding. Mature dogs with experimentally-induced latent CHV-1 infection received a 2-dose CHV-1 vaccine series. Recurrent ocular CHV-1 infection was induced by corticosteroid administration in the prevaccinal, short-term postvaccinal (2 weeks post-vaccination), and long-term postvacccinal (34 weeks post-vaccination) periods. Immunological, virological, and clinical parameters were evaluated during each study period. Quantitative assessment of peripheral immunity included lymphocyte immunophenotyping, proliferation response, and interferon-γ production; and CHV-1 virus neutralizing antibody production. In the present study, vaccination did not prevent development of ocular disease and viral shedding; however, there was a significant decrease in clinical ocular disease scores in the short-term postvaccinal period. Significant alterations in peripheral immunity detected in the dogs during the short-term and long-term postvaccinal periods included increased T and B lymphocyte subpopulation percentage distributions, increased lymphocyte expression of major histocompatibility complex class I and II, increased CHV-1 virus neutralizing antibody titers, decreased lymphocyte proliferation, and decreased interferon-γ production. Vaccination of latently infected mature dogs with the selected subunit CHV-1 vaccine was not effective in preventing recurrent ocular CHV-1 infection and viral shedding induced by corticosteroid administration. The vaccine did induce long-term CHV-1 specific immunity and may decrease the severity of clinical ocular disease in the immediate postvaccinal period. Copyright © 2016 Elsevier B.V. All rights

  17. Vaccines, inspiring innovation in health.

    PubMed

    Pagliusi, Sonia; Dennehy, Maureen; Kim, Hun

    2018-05-19

    This report covers the topics of pandemics, epidemics and partnerships, including regulatory convergence initiatives, new technologies and novel vaccines, discussed by leading public and private sector stakeholders at the 18th Annual General Meeting (AGM) of the Developing Countries Vaccine Manufacturers' Network (DCVMN). Contributions of Gavi and the vaccine industry from emerging countries to the growing global vaccine market, by improving the supply base from manufacturers in developing countries and contributing to 58% of doses, were highlighted. The Coalition for Epidemic Preparedness Innovations (CEPI), the International Vaccine Institute (IVI) and others reported on new strategies to ensure speedy progress in preclinical and clinical development of innovative vaccines for future MERS, Zika or other outbreak response. Priorities for vaccine stockpiling, to assure readiness during emergencies and to prevent outbreaks due to re-emerging diseases such as yellow fever, cholera and poliomyelitis, were outlined. The role of partnerships in improving global vaccine access, procurement and immunization coverage, and shared concerns were reviewed. The World Health Organization (WHO) and other international collaborating partners provided updates on the Product, Price and Procurement database, the prequalification of vaccines, the control of neglected tropical diseases, particularly the new rabies elimination initiative, and regulatory convergence proposals to accelerate vaccine registration in developing countries. Updates on supply chain innovations and novel vaccine platforms were presented. The discussions enabled members and partners to reflect on efficiency of research & development, supply chain tools and trends in packaging technologies improving delivery of existing vaccines, and allowing a deeper understanding of the current public-health objectives, industry financing, and global policies, required to ensure optimal investments, alignment and stability of

  18. Cancer Vaccines: Moving Beyond Current Paradigms

    PubMed Central

    Schlom, Jeffrey; Arlen, Philip M.; Gulley, James L.

    2008-01-01

    The field of cancer vaccines is currently in an active state of preclinical and clinical investigations. While no therapeutic cancer vaccine has to date been approved by the FDA, several new paradigms are emerging from recent clinical findings in both the use of combination therapy approaches and, perhaps more importantly, in clinical trial design and endpoint analyses. This paper will review recent clinical trials involving several different cancer vaccines from which data are emerging contrasting classical “tumor response” (RECIST) criteria with “patient response” in the manifestation of increased patient survival post-vaccine therapy. Also described are several strategies in which cancer vaccines can be exploited in combination with other agents and therapeutic modalities that are quite unique when compared with “conventional” combination therapies. This is most likely due to the phenomena that (a) cancer vaccines initiate a dynamic immune process that can be exploited in subsequent therapies, and (b) both radiation and certain chemotherapeutic agents have been shown to alter the phenotype of tumor cells as to render them more susceptible to T-cell–mediated killing. Consequently, evidence is emerging from several studies in which patient cohorts who first receive a cancer vaccine (as contrasted with control cohorts) benefit clinically from subsequent therapies. PMID:17606707

  19. Workplace Vaccination and Other Factors Impacting Influenza Vaccination Decision among Employees in Israel

    PubMed Central

    Shahrabani, Shosh; Benzion, Uri

    2010-01-01

    The study examined the factors affecting the decision to be vaccinated against influenza among employees in Israel. The research, conducted in 2007/2008, included 616 employees aged 18−65 at various workplaces in Israel, among them companies that offered their employees influenza vaccination. The research questionnaire included socio-demographic characteristics, and the Health Belief Model principles. The results show that the significant factors affecting vaccination compliance include a vaccination program at workplaces, vaccinations in the past, higher levels of vaccine’s perceived benefits, and lower levels of barriers to getting the vaccine. We conclude that vaccine compliance is larger at companies with workplace vaccination programs providing easier accessibility to vaccination. PMID:20617008

  20. Evaluation of a vaccine passport to improve vaccine coverage in people living with HIV.

    PubMed

    Chadwick, D R; Corbett, K; Mann, S; Teruzzi, B; Horner, S

    2018-01-01

    An increased risk of vaccine-preventable infections (VPIs) is seen in people living with HIV (PLWH), and current vaccine coverage and immunity is variable. Vaccine passports have the potential to improve vaccine coverage. The objective was to assess how successful a vaccine passport was in improving vaccine coverage in PLWH. Baseline immunity to VPIs was established in PLWH attending a single HIV clinic and vaccinations required were determined based on the BHIVA Vaccination Guidelines (2015). The passport was completed and the PLWH informed about additional vaccines they should obtain from primary care. After 6-9 months the passport was reviewed including confirmation if vaccines were given. PLWH satisfaction with the system was evaluated by a survey. Seventy-three PLWH provided sufficient data for analysis. At baseline significant proportions of PLWH were not immune/unvaccinated to the main VPIs, especially human papillomavirus, pneumococcus and measles. After the passport was applied immunity improved significantly (56% overall, p < 0.01) for most VPIs; however, full coverage was not achieved. The system was popular with PLWH. The passport was successful in increasing vaccination coverage although full or near-full coverage was not achieved. A more successful service would probably be achieved by commissioning English HIV clinics to provide all vaccines.

  1. 'Communicate to vaccinate' (COMMVAC). building evidence for improving communication about childhood vaccinations in low- and middle-income countries: protocol for a programme of research.

    PubMed

    Lewin, Simon; Hill, Sophie; Abdullahi, Leyla H; de Castro Freire, Sara Bensaude; Bosch-Capblanch, Xavier; Glenton, Claire; Hussey, Gregory D; Jones, Catherine M; Kaufman, Jessica; Lin, Vivian; Mahomed, Hassan; Rhoda, Linda; Robinson, Priscilla; Waggie, Zainab; Willis, Natalie; Wiysonge, Charles S

    2011-12-02

    Effective provider-parent communication can improve childhood vaccination uptake and strengthen immunisation services in low- and middle-income countries (LMICs). Building capacity to improve communication strategies has been neglected. Rigorous research exists but is not readily found or applicable to LMICs, making it difficult for policy makers to use it to inform vaccination policies and practice.The aim of this project is to build research knowledge and capacity to use evidence-based strategies for improving communication about childhood vaccinations with parents and communities in LMICs. This project is a mixed methods study with six sub-studies. In sub-study one, we will develop a systematic map of provider-parent communication interventions for childhood vaccinations by screening and extracting data from relevant literature. This map will inform sub-study two, in which we will develop a taxonomy of interventions to improve provider-parent communication around childhood vaccination. In sub-study three, the taxonomy will be populated with trial citations to create an evidence map, which will also identify how evidence is linked to communication barriers regarding vaccination. In the project's fourth sub-study, we will present the interventions map, taxonomy, and evidence map to international stakeholders to identify high-priority topics for systematic reviews of interventions to improve parent-provider communication for childhood vaccination. We will produce systematic reviews of the effects of high-priority interventions in the fifth sub-study. In the sixth and final sub-study of the project, evidence from the systematic reviews will be translated into accessible formats and messages for dissemination to LMICs. This project combines evidence mapping, conceptual and taxonomy development, priority setting, systematic reviews, and knowledge transfer. It will build and share concepts, terms, evidence, and resources to aid the development of communication

  2. The therapeutic potential of plant-derived vaccines and antibodies.

    PubMed

    Rodgers, P B; Hamilton, W D; Adair, J R

    1999-03-01

    The production of recombinant proteins in plants is reviewed with a particular focus on plant-derived vaccines and antibodies for human healthcare. Issues relating to foreign gene expression, such as protein yield, localisation and glycosylation are also considered. Emphasis is placed on reporting progress with preclinical and clinical evaluation of plant-derived vaccines and antibodies. An assessment is made of the likely future direction of research and development in this area.

  3. No evidence for cross-protection of the HPV-16/18 vaccine against HPV-6/11 positivity in female STI clinic visitors.

    PubMed

    Woestenberg, Petra J; King, Audrey J; van der Sande, Marianne A B; Donken, Robine; Leussink, Suzan; van der Klis, Fiona R M; Hoebe, Christian J P A; Bogaards, Johannes A; van Benthem, Birgit H B

    2017-04-01

    Data from a vaccine trial and from post-vaccine surveillance in the United Kingdom have suggested that the bivalent HPV-16/18 vaccine offers cross-protection against HPV-6/11 and protection against anogenital warts (AGW). We studied the effect of the bivalent vaccine on genital HPV-6/11 positivity and AGW in the Netherlands. We included all vaccine-eligible women from the PASSYON study, a biennial cross-sectional study among 16- to 24-year-old sexually transmitted infection (STI) clinic attendants. Vaginal self-swabs were analyzed for type specific HPV and AGW were diagnosed at the STI-clinic. Prevalence of HPV-6 and/or HPV-11 and AGW were compared between self-reported vaccinated and unvaccinated women by log-binomial regression analysis, adjusted for demographics and risk behavior. Of the 1198 women included, 56% reported to be vaccinated at least once. Relative to unvaccinated women, the adjusted prevalence ratio (PR) for HPV-6/11 was 1.03 (95% confidence interval [CI] 0.74-1.43) for women vaccinated at least once. The crude PR for AGW was 0.67 (95% CI 0.22-2.07) for women vaccinated at least once. Adjustment did not change these results. We observed no cross-protective effect of the bivalent vaccine on genital HPV-6/11 positivity and a non-significant partially protective effect on AGW. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. Baseline mapping of Lassa fever virology, epidemiology and vaccine research and development.

    PubMed

    Hallam, Hoai J; Hallam, Steven; Rodriguez, Sergio E; Barrett, Alan D T; Beasley, David W C; Chua, Arlene; Ksiazek, Thomas G; Milligan, Gregg N; Sathiyamoorthy, Vaseeharan; Reece, Lisa M

    2018-01-01

    Lassa fever (LF) is a zoonotic disease associated with acute and potentially fatal hemorrhagic illness caused by the Lassa virus (LASV), a member of the family Arenaviridae . It is generally assumed that a single infection with LASV will produce life-long protective immunity. This suggests that protective immunity induced by vaccination is an achievable goal and that cell-mediated immunity may play a more important role in protection, at least following natural infection. Seropositive individuals in endemic regions have been shown to have LASV-specific T cells recognizing epitopes for nucleocapsid protein (NP) and glycoprotein precursor (GPC), suggesting that these will be important vaccine immunogens. The role of neutralizing antibodies in protective immunity is still equivocal as recent studies suggest a role for neutralizing antibodies. There is extensive genetic heterogeneity among LASV strains that is of concern in the development of assays to detect and identify all four LASV lineages. Furthermore, the gene disparity may complicate the synthesis of effective vaccines that will provide protection across multiple lineages. Non-human primate models of LASV infection are considered the gold standard for recapitulation of human LF. The most promising vaccine candidates to date are the ML29 (a live attenuated reassortant of Mopeia and LASV), vesicular stomatitis virus (VSV) and vaccinia-vectored platforms based on their ability to induce protection following single doses, high rates of survival following challenge, and the use of live virus platforms. To date no LASV vaccine candidates have undergone clinical evaluation.

  5. Middle East respiratory syndrome: obstacles and prospects for vaccine development

    PubMed Central

    Papaneri, Amy B.; Johnson, Reed F.; Wada, Jiro; Bollinger, Laura; Jahrling, Peter B.; Kuhn, Jens H.

    2016-01-01

    Summary The recent emergence of Middle East respiratory syndrome (MERS) highlights the need to engineer new methods for expediting vaccine development against emerging diseases. However, several obstacles prevent pursuit of a licensable MERS vaccine. First, the lack of a suitable animal model for MERS complicates in vivo testing of candidate vaccines. Second, due to the low number of MERS cases, pharmaceutical companies have little incentive to pursue MERS vaccine production as the costs of clinical trials are high. In addition, the timeline from bench research to approved vaccine use is 10 years or longer. Using novel methods and cost-saving strategies, genetically engineered vaccines can be produced quickly and cost-effectively. Along with progress in MERS animal model development, these obstacles can be circumvented or at least mitigated. PMID:25864502

  6. Self-amplifying mRNA vaccines.

    PubMed

    Brito, Luis A; Kommareddy, Sushma; Maione, Domenico; Uematsu, Yasushi; Giovani, Cinzia; Berlanda Scorza, Francesco; Otten, Gillis R; Yu, Dong; Mandl, Christian W; Mason, Peter W; Dormitzer, Philip R; Ulmer, Jeffrey B; Geall, Andrew J

    2015-01-01

    This chapter provides a brief introduction to nucleic acid-based vaccines and recent research in developing self-amplifying mRNA vaccines. These vaccines promise the flexibility of plasmid DNA vaccines with enhanced immunogenicity and safety. The key to realizing the full potential of these vaccines is efficient delivery of nucleic acid to the cytoplasm of a cell, where it can amplify and express the encoded antigenic protein. The hydrophilicity and strong net negative charge of RNA impedes cellular uptake. To overcome this limitation, electrostatic complexation with cationic lipids or polymers and physical delivery using electroporation or ballistic particles to improve cellular uptake has been evaluated. This chapter highlights the rapid progress made in using nonviral delivery systems for RNA-based vaccines. Initial preclinical testing of self-amplifying mRNA vaccines has shown nonviral delivery to be capable of producing potent and robust innate and adaptive immune responses in small animals and nonhuman primates. Historically, the prospect of developing mRNA vaccines was uncertain due to concerns of mRNA instability and the feasibility of large-scale manufacturing. Today, these issues are no longer perceived as barriers in the widespread implementation of the technology. Currently, nonamplifying mRNA vaccines are under investigation in human clinical trials and can be produced at a sufficient quantity and quality to meet regulatory requirements. If the encouraging preclinical data with self-amplifying mRNA vaccines are matched by equivalently positive immunogenicity, potency, and tolerability in human trials, this platform could establish nucleic acid vaccines as a versatile new tool for human immunization. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Optimized enzyme-linked immunosorbent assay for detecting cytomegalovirus infections during clinical trials of recombinant vaccines.

    PubMed

    Pagnon, Anke; Piras, Fabienne; Gimenez-Fourage, Sophie; Dubayle, Joseline; Arnaud-Barbe, Nadège; Hessler, Catherine; Caillet, Catherine

    2017-11-01

    In clinical trials of cytomegalovirus (CMV) glycoprotein B (gB) vaccines, CMV infection is detected by first depleting serum of anti-gB antibodies and then measuring anti-CMV antibodies with a commercially available enzyme-linked immunosorbent assay (ELISA) kit, with confirmation of positive findings by immunoblot. Identification of CMV immunoantigens for the development of an ELISA that detects specifically CMV infection in clinical samples from individuals immunized with gB vaccines. Sensitivity and specificity of ELISAs using antigenic regions of CMV proteins UL83/pp65, UL99/pp28, UL44/pp52, UL80a/pp38, UL57, and UL32/pp150 were measured. An IgG ELISA using a UL32/pp150 [862-1048] capture peptide was the most specific (93.7%) and sensitive (96.4%) for detecting CMV-specific antibodies in sera. The ELISA successfully detected CMV-specific antibodies in 22 of 22 sera of subjects who had been vaccinated with a gB vaccine but who had later been infected with CMV. The ELISA was linear over a wide range of CMV concentrations (57-16,814 ELISA units/mL) and was reproducible as indicated by a 5% intra-day and 7% inter-day coefficients of variation. The signal was specifically competed by UL32/pp150 [862-1048] peptide but not by CMV-gB or herpes simplex virus 2 glycoprotein D. Lipid and hemoglobin matrix did not interfere with the assay. The UL32/pp150 [862-1048] IgG ELISA can be used for the sensitive and specific detection of CMV infection in gB-vaccinated individuals. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Cost-effectiveness of Rotavirus vaccination in Vietnam

    PubMed Central

    Kim, Sun-Young; Goldie, Sue J; Salomon, Joshua A

    2009-01-01

    vaccines would be a cost-effective public health intervention in Vietnam. However, given the uncertainty about vaccine efficacy and potential changes in rotavirus epidemiology in local settings, further clinical research and re-evaluation of rotavirus vaccination programs may be necessary as new information emerges. PMID:19159483

  9. Laboratory tests for mumps vaccines.

    PubMed

    Minor, P D

    1997-03-01

    The action of live attenuated vaccines against mumps is poorly understood although their clinical efficacy is beyond doubt. The attenuated character of the vaccine is assured by consistency of production related to clinical trials, and limited studies of vaccine seeds in primates. Potency is assessed by infectivity in vitro and is subject to poorly understood sources of variation. Molecular biological studies are at an early stage.

  10. Intradermal delivery of vaccines: potential benefits and current challenges

    PubMed Central

    Hickling, JK; Jones, KR; Friede, M; Chen, D; Kristensen, D

    2011-01-01

    Abstract Delivery of vaccine antigens to the dermis and/or epidermis of human skin (i.e. intradermal delivery) might be more efficient than injection into the muscle or subcutaneous tissue, thereby reducing the volumes of antigen. This is known as dose-sparing and has been demonstrated in clinical trials with some, but not all, vaccines. Dose-sparing could be beneficial to immunization programmes by potentially reducing the costs of purchase, distribution and storage of vaccines; increasing vaccine availability and effectiveness. The data obtained with intradermal delivery of some vaccines are encouraging and warrant further study and development; however significant gaps in knowledge and operational challenges such as reformulation, optimizing vaccine presentation and development of novel devices to aid intradermal vaccine delivery need to be addressed. Modelling of the costs and potential savings resulting from intradermal delivery should be done to provide realistic expectations of the potential benefits and to support cases for investment. Implementation and uptake of intradermal vaccine delivery requires further research and development, which depends upon collaboration between multiple stakeholders in the field of vaccination. PMID:21379418

  11. The Evidence for Efficacy of HPV Vaccines: Investigations in Categorical Data Analysis

    ERIC Educational Resources Information Center

    Gibbs, Alison L.; Goossens, Emery T.

    2013-01-01

    Recent approval of HPV vaccines and their widespread provision to young women provide an interesting context to gain experience with the application of statistical methods in current research. We demonstrate how we have used data extracted from a meta-analysis examining the efficacy of HPV vaccines in clinical trials with students in applied…

  12. Clinical characteristics of Haemophilus influenzae meningitis in Denmark in the post-vaccination era.

    PubMed

    Pedersen, T I; Howitz, M; Ostergaard, C

    2010-05-01

    The introduction of Haemophilus influenzae type b (Hib) vaccine into the Danish childhood vaccination programme in 1993 may have influenced the epidemiology of H. influenzae meningitis (i.e. increasing frequency of other non-vaccine types; presentation in other age groups). Based on nationwide registration, clinical information and laboratory findings were collected from all 65 confirmed cases of H. influenzae meningitis during the period 1994-2005. Twenty-nine patients (45%) were <13 years old [median 15 months (range 0-147)], and 36 patients (55%) were >24 years old [median 62 years (range 25-96)]. Hib accounted for 31% (20/65) of the cases, and significantly more children were infected with Hib compared with adults [53% (16/29) vs. 11% (4/36), respectively, p 0.0003]. Overall, 38% of cases had an otogenic focus and this was thus the most frequent primary focus of infection. Among children infected with Hib, two cases (13%) were identified as true vaccine failures. Six patients (9%) died; one premature infant infected with serotype f and five adults (age 83-96 years) with non-typeable H. influenzae. Hearing loss was reported in 16% of the surviving children and in 10% of the surviving adults. The presence of a lung focus was an independent prognostic factor for an unfavourable outcome (p 0.03). In conclusion, meningitis caused by Hib has been infrequent in Denmark after introduction of the Hib vaccine in the childhood vaccination programme, and no increase in meningitis cases due to non-b type H. influenzae has been observed. Cases with H. influenzae meningitis frequently had an otogenic focus, with low risk of an unfavourable outcome.

  13. Safety and immunogenicity of a seasonal trivalent inactivated split influenza vaccine: a phase I randomized clinical trial in healthy Serbian adults

    PubMed Central

    Stevanovic, Goran; Lavadinovic, Lidija; Filipovic Vignjevic, Svetlana; Holt, Renée; Ilic, Katarina; Berlanda Scorza, Francesco; Sparrow, Erin; Stoiljkovic, Vera; Torelli, Guido; Madenwald, Tamra; Socquet, Muriel; Barac, Aleksandra; Ilieva-Borisova, Yordanka; Pelemis, Mijomir; Flores, Jorge

    2018-01-01

    ABSTRACT This study was a phase I double-blind, randomized, placebo-controlled trial to evaluate the safety and immunogenicity of a Serbian-produced seasonal trivalent split, inactivated influenza vaccine in healthy adults. The vaccine was manufactured in eggs by the Torlak Institute of Virology, Vaccines and Sera, Belgrade, Serbia and contained A/H1N1, A/H3N2 and B viruses. The clinical trial took place at the Clinical Center of Serbia in Belgrade. Sixty healthy volunteers, aged 18–45 years, were enrolled in the trial. On the day of immunization, volunteers were randomly assigned to receive either a single dose of the trivalent seasonal influenza vaccine (15 μg of hemagglutinin per strain) or placebo (phosphate-buffered saline). Subjects were monitored for adverse events through a clinical history and physical examination, and blood was taken for testing at screening and on day 8 to assess vaccine safety. Serum samples obtained before and 21 days after immunization were tested for influenza antibody titers using hemagglutination-inhibition (HAI) and microneutralization (MN) tests. No serious adverse events were reported. Pain and tenderness at the injection site were the most commonly reported symptoms in both vaccine and placebo groups. Overall, serum HAI responses of fourfold or greater magnitude were observed to H1, H3, and B antigen in 80%, 75%, and 70% of subjects, respectively. Seroprotection rates as measured by HAI were also high (100%, 100% and 86.67%, respectively, for H1, H3 and B). Thus, Torlak's seasonal trivalent influenza vaccine was not associated with adverse events, was well-tolerated and immunogenic. It should be further evaluated in clinical trials to provide sufficient safety and immunogenicity data for licensing in Serbia. PMID:29239682

  14. DNA Vaccines for Prostate Cancer

    PubMed Central

    Zahm, Christopher D.; Colluru, Viswa Teja; McNeel, Douglas G.

    2017-01-01

    DNA vaccines offer many advantages over other anti-tumor vaccine approaches due to their simplicity, ease of manufacturing, and safety. Results from several clinical trials in patients with cancer have demonstrated that DNA vaccines are safe and can elicit immune responses. However, to date few DNA vaccines have progressed beyond phase I clinical trial evaluation. Studies into the mechanism of action of DNA vaccines in terms of antigen-presenting cell types able to directly present or cross-present DNA-encoded antigens, and the activation of innate immune responses due to DNA itself, have suggested opportunities to increase the immunogenicity of these vaccines. In addition, studies into the mechanisms of tumor resistance to anti-tumor vaccination have suggested combination approaches that can increase the antitumor effect of DNA vaccines. This review focuses on these mechanisms of action and mechanisms of resistance using DNA vaccines, and how this information is being used to improve the anti-tumor effect of DNA vaccines. These approaches are then specifically discussed in the context of human prostate cancer, a disease for which DNA vaccines have been and continue to be explored as treatments. PMID:28185916

  15. Sociobehavioural research methods for the introduction of vaccines in the Diseases of the Most Impoverished Programme.

    PubMed

    Kaljee, Linda M; Pack, Rob; Pach, Al; Nyamete, Andrew; Stanton, Bonita F

    2004-09-01

    Participation in vaccination campaigns worldwide, particularly the Expanded Programme on Immunization, has increased significantly in recent years. However, there remain multiple and integrated behavioural, sociocultural and political-economic barriers to vaccination. The Diseases of the Most Impoverished (DOMI) Programme has undertaken shigellosis disease-burden studies and oral cholera and typhoid Vi polysaccharide vaccine trials in seven Asian countries. As part of these projects, sociobehavioural studies have been undertaken to determine the potential demand for vaccines for these diseases and the obstacles and enabling factors that may affect acceptance, delivery, and use of vaccines. A theoretical model of acceptance of vaccination and a triangulation of qualitative and quantitative methods have been used for fully elucidating the range of issues relating to vaccination for shigellosis, cholera, and typhoid fever. In this paper, the theoretical and methodological basis of the DOMI projects has been reviewed in a context of current sociobehavioural research on the acceptability and desirability of vaccination.

  16. Economic and clinical evaluation of a catch-up dose of 13-valent pneumococcal conjugate vaccine in children already immunized with three doses of the 7-valent vaccine in Italy.

    PubMed

    Boccalini, Sara; Azzari, Chiara; Resti, Massimo; Valleriani, Claudia; Cortimiglia, Martina; Tiscione, Emilia; Bechini, Angela; Bonanni, Paolo

    2011-11-28

    A new 13-valent conjugated polysaccharide vaccine (PCV13) against Streptococcus pneumoniae infections, which replaced the 7-valent vaccine (PCV7) in the regional immunization programmes for newborns and children who started but not completed the 3 doses schedule of PCV7, is available in Italy since 2010. The opportunity of administering a further dose of PCV13 to children under 5 years of age who had already completed their vaccination with PCV7, with the aim of extending the serotype coverage, triggered an animated scientific debate. The purpose of this study was to perform a clinical/economic evaluation of the administration of a dose of PCV13, in a catch-up programme, for children under 5 years of age, who had already received 3 doses of PCV7. A mathematical model of the clinical/economic impact of the adoption of 4 catch-up strategies with PCV13 (children up to 24, 36, 48 and 60 months old) was set up, with a vaccination coverage of 80%, versus immunization with 3 doses of PCV7 without the catch-up programme. The time span covered by the simulation was 5.5 years. The following clinical outcomes of infection were evaluated: hospitalised meningitis/sepsis, hospitalised bacteraemic pneumonias (complicated and uncomplicated), hospitalised non-bacteraemic pneumonias, and non-hospitalised pneumonias. The administration of one dose of PCV13 to children up to 60 months of age significantly reduces the number of cases of pneumococcal diseases (especially, non-hospitalised pneumonias, 80% of all events prevented, and hospitalised cases of non-bacteraemic pneumococcal pneumonias, 15% of all events prevented) and, subsequently, the relative cost for medical treatment. This results in savings for medical costs amounting to more than 1,000,000 Euros when vaccinating children under 24 months of age (up to almost 3 million Euros for children up to 60 months). More than half of those savings are attributable to avoided hospitalised cases of non-bacteraemic pneumococcal

  17. Zika virus, vaccines, and antiviral strategies.

    PubMed

    Masmejan, Sophie; Baud, David; Musso, Didier; Panchaud, Alice

    2018-06-28

    Zika virus (ZIKV) recently emerged as a global public health emergency of international concern. ZIKV is responsible for severe neurological complications in adults and infection during pregnancy and can lead to congenital Zika syndrome. There is no licensed vaccine or drug to prevent or treat ZIKV infection. Areas covered: The aim of this article is to provide an overview and update of the progress of research on anti-ZIKV vaccine and medications until the end of 2017, with a special emphasis on drugs that can be used during pregnancy. Expert commentary: Development of new vaccines and drugs is challenging and several points particular to ZIKV infections augment this difficulty: (1) Cross-reactions between ZIKV and other flaviviruses, the impact of ZIKV vaccination on subsequent flavivirus infections, and vice-versa, is unknown, (2) Drugs against ZIKV should be safe in pregnant women, and (3) Evaluation of the efficacy of vaccine and drugs against ZIKV in clinical trials phase II-IV will be complicated due to the decline of ZIKV circulation.

  18. Dose-specific efficacy of Haemophilus influenzae type b conjugate vaccines: a systematic review and meta-analysis of controlled clinical trials

    PubMed Central

    GRIFFITHS, U. K.; CLARK, A.; GESSNER, B.; MINERS, A.; SANDERSON, C.; SEDYANINGSIH, E. R.; MULHOLLAND, K. E.

    2012-01-01

    SUMMARY Global coverage of infant Haemophilus influenzae type b (Hib) vaccination has increased considerably during the past decade, partly due to GAVI Alliance donations of the vaccine to low-income countries. In settings where large numbers of children receive only one or two vaccine doses rather than the recommended three doses, dose-specific efficacy estimates are needed to predict impact. The objective of this meta-analysis is to determine Hib vaccine efficacy against different clinical outcomes after receiving one, two or three doses of vaccine. Studies were eligible for inclusion if a prospective, controlled design had been used to evaluate commercially available Hib conjugate vaccines. Eight studies were included. Pooled vaccine efficacies against invasive Hib disease after one, two or three doses of vaccine were 59%, 92% and 93%, respectively. The meta-analysis provides robust estimates for use in decision-analytical models designed to predict the impact of Hib vaccine. PMID:22583474

  19. Vaccination Programs for Endemic Infections: Modelling Real versus Apparent Impacts of Vaccine and Infection Characteristics

    NASA Astrophysics Data System (ADS)

    Ragonnet, Romain; Trauer, James M.; Denholm, Justin T.; Geard, Nicholas L.; Hellard, Margaret; McBryde, Emma S.

    2015-10-01

    Vaccine effect, as measured in clinical trials, may not accurately reflect population-level impact. Furthermore, little is known about how sensitive apparent or real vaccine impacts are to factors such as the risk of re-infection or the mechanism of protection. We present a dynamic compartmental model to simulate vaccination for endemic infections. Several measures of effectiveness are calculated to compare the real and apparent impact of vaccination, and assess the effect of a range of infection and vaccine characteristics on these measures. Although broadly correlated, measures of real and apparent vaccine effectiveness can differ widely. Vaccine impact is markedly underestimated when primary infection provides partial natural immunity, when coverage is high and when post-vaccination infectiousness is reduced. Despite equivalent efficacy, ‘all or nothing’ vaccines are more effective than ‘leaky’ vaccines, particularly in settings with high risk of re-infection and transmissibility. Latent periods result in greater real impacts when risk of re-infection is high, but this effect diminishes if partial natural immunity is assumed. Assessments of population-level vaccine effects against endemic infections from clinical trials may be significantly biased, and vaccine and infection characteristics should be considered when modelling outcomes of vaccination programs, as their impact may be dramatic.

  20. Vaccination Programs for Endemic Infections: Modelling Real versus Apparent Impacts of Vaccine and Infection Characteristics

    PubMed Central

    Ragonnet, Romain; Trauer, James M.; Denholm, Justin T.; Geard, Nicholas L.; Hellard, Margaret; McBryde, Emma S.

    2015-01-01

    Vaccine effect, as measured in clinical trials, may not accurately reflect population-level impact. Furthermore, little is known about how sensitive apparent or real vaccine impacts are to factors such as the risk of re-infection or the mechanism of protection. We present a dynamic compartmental model to simulate vaccination for endemic infections. Several measures of effectiveness are calculated to compare the real and apparent impact of vaccination, and assess the effect of a range of infection and vaccine characteristics on these measures. Although broadly correlated, measures of real and apparent vaccine effectiveness can differ widely. Vaccine impact is markedly underestimated when primary infection provides partial natural immunity, when coverage is high and when post-vaccination infectiousness is reduced. Despite equivalent efficacy, ‘all or nothing’ vaccines are more effective than ‘leaky’ vaccines, particularly in settings with high risk of re-infection and transmissibility. Latent periods result in greater real impacts when risk of re-infection is high, but this effect diminishes if partial natural immunity is assumed. Assessments of population-level vaccine effects against endemic infections from clinical trials may be significantly biased, and vaccine and infection characteristics should be considered when modelling outcomes of vaccination programs, as their impact may be dramatic. PMID:26482413

  1. Tuberculosis vaccine development at a divide.

    PubMed

    Kaufmann, Stefan H E

    2014-05-01

    Tuberculosis (TB) remains a major health threat that will only be defeated by a combination of better drugs, diagnostics and vaccines. The only licensed TB vaccine, bacille Calmette-Guérin (BCG), protects against extrapulmonary TB in infants. Novel vaccine candidates that could protect against pulmonary TB either in TB naïve or in latent TB-infected healthy individuals have been developed and are currently being assessed in clinical trials. Subunit booster vaccines are either based on viral vectors expressing TB-specific antigens or on TB-protein antigens in adjuvants. Subunit vaccines are administered on top of BCG. Replacement vaccines for BCG are recombinant viable BCG or Mycobacterium tuberculosis. Several candidates are undergoing, or will soon start, phase IIb assessment for efficacy. The first vaccine candidate, MVA85A, to complete a phase IIb trial, unfortunately failed to show protection against TB in infants. Therapeutic vaccines composed of killed mycobacterial preparations target patients with complicated TB in adjunct to drug treatment. With increasing numbers of TB vaccine candidates in clinical trials, financial, regulatory and infrastructural issues arise, which would be best tackled by a global strategy. In addition, selection of the most promising vaccine candidates for further clinical development gains increasing importance.

  2. Estimating the full public health value of vaccination.

    PubMed

    Gessner, Bradford D; Kaslow, David; Louis, Jacques; Neuzil, Kathleen; O'Brien, Katherine L; Picot, Valentina; Pang, Tikki; Parashar, Umesh D; Saadatian-Elahi, Mitra; Nelson, Christopher B

    2017-11-01

    There is an enhanced focus on considering the full public health value (FPHV) of vaccination when setting priorities, making regulatory decisions and establishing implementation policy for public health activities. Historically, a therapeutic paradigm has been applied to the evaluation of prophylactic vaccines and focuses on an individual benefit-risk assessment in prospective and individually-randomized phase III trials to assess safety and efficacy against etiologically-confirmed clinical outcomes. By contrast, a public health paradigm considers the population impact and encompasses measures of community benefits against a range of outcomes. For example, measurement of the FPHV of vaccination may incorporate health inequity, social and political disruption, disruption of household integrity, school absenteeism and work loss, health care utilization, long-term/on-going disability, the development of antibiotic resistance, and a range of non-etiologically and etiologically defined clinical outcomes. Following an initial conference at the Fondation Mérieux in mid-2015, a second conference (December 2016) was held to further describe the efficacy of using the FPHV of vaccination on a variety of prophylactic vaccines. The wider scope of vaccine benefits, improvement in risk assessment, and the need for partnership and coalition building across interventions has also been discussed during the 2014 and 2016 Global Vaccine and Immunization Research Forums and the 2016 Geneva Health Forum, as well as in numerous publications including a special issue of Health Affairs in February 2016. The December 2016 expert panel concluded that while progress has been made, additional efforts will be necessary to have a more fully formulated assessment of the FPHV of vaccines included into the evidence-base for the value proposition and analysis of unmet medical need to prioritize vaccine development, vaccine licensure, implementation policies and financing decisions. The desired

  3. Adolescent Premature Ovarian Insufficiency Following Human Papillomavirus Vaccination

    PubMed Central

    Ward, Harvey Rodrick Grenville

    2014-01-01

    Three young women who developed premature ovarian insufficiency following quadrivalent human papillomavirus (HPV) vaccination presented to a general practitioner in rural New South Wales, Australia. The unrelated girls were aged 16, 16, and 18 years at diagnosis. Each had received HPV vaccinations prior to the onset of ovarian decline. Vaccinations had been administered in different regions of the state of New South Wales and the 3 girls lived in different towns in that state. Each had been prescribed the oral contraceptive pill to treat menstrual cycle abnormalities prior to investigation and diagnosis. Vaccine research does not present an ovary histology report of tested rats but does present a testicular histology report. Enduring ovarian capacity and duration of function following vaccination is unresearched in preclinical studies, clinical and postlicensure studies. Postmarketing surveillance does not accurately represent diagnoses in adverse event notifications and can neither represent unnotified cases nor compare incident statistics with vaccine course administration rates. The potential significance of a case series of adolescents with idiopathic premature ovarian insufficiency following HPV vaccination presenting to a general practice warrants further research. Preservation of reproductive health is a primary concern in the recipient target group. Since this group includes all prepubertal and pubertal young women, demonstration of ongoing, uncompromised safety for the ovary is urgently required. This matter needs to be resolved for the purposes of population health and public vaccine confidence. PMID:26425627

  4. Milestones in contraceptive vaccines development and hurdles in their application

    PubMed Central

    Gupta, Satish Kumar; Shrestha, Abhinav; Minhas, Vidisha

    2014-01-01

    Contraceptive vaccines have been proposed for controlling the growing human population and wildlife population management. Multiple targets such as gonadotropin releasing hormone (GnRH), luteinizing hormone, follicle stimulating hormone, gonadotropin receptors, sperm-specific proteins and zona pellucida glycoproteins have been exploited to develop contraceptive vaccine and their efficacy investigated and shown in various experimental animal models. Vaccines based on GnRH have found application in immuno-castration of male pigs for prevention of boar-taint. Vaccines based on zona pellucida glycoproteins have shown promising results for population management of wild horses and white-tailed deer. Phase II clinical trials in women with β-human chorionic gonadotropin (β-hCG)-based contraceptive vaccine established proof of principle that these can be developed for human application. Block in fertility by β-hCG contraceptive vaccine was reversible. Further research inputs are required to establish the safety of contraceptive vaccines, improve their immunogenicity and to develop novel vaccine delivery platforms for providing long lasting immunity. PMID:24262991

  5. Vaccines for Nontypeable Haemophilus influenzae: the Future Is Now

    PubMed Central

    2015-01-01

    Infections due to nontypeable Haemophilus influenzae result in enormous global morbidity in two clinical settings: otitis media in children and respiratory tract infections in adults with chronic obstructive pulmonary disease (COPD). Recurrent otitis media affects up to 20% of children and results in hearing loss, delays in speech and language development and, in developing countries, chronic suppurative otitis media. Infections in people with COPD result in clinic and emergency room visits, hospital admissions, and respiratory failure. An effective vaccine would prevent morbidity, help control health care costs, and reduce antibiotic use, a major contributor to the global crisis in bacterial antibiotic resistance. The widespread use of the pneumococcal conjugate vaccines is causing a relative increase in H. influenzae otitis media. The partial protection against H. influenzae otitis media induced by the pneumococcal H. influenzae protein D conjugate vaccine represents a proof of principle of the feasibility of a vaccine for nontypeable H. influenzae. An ideal vaccine antigen should be conserved among strains, have abundant epitopes on the bacterial surface, be immunogenic, and induce protective immune responses. Several surface proteins of H. influenzae have been identified as potential vaccine candidates and are in various stages of development. With continued research, progress toward a broadly effective vaccine to prevent infections caused by nontypeable H. influenzae is expected over the next several years. PMID:25787137

  6. Safety and Immunogenicity of a Quadrivalent Meningococcal Conjugate Vaccine and Commonly Administered Vaccines After Coadministration.

    PubMed

    Gasparini, Roberto; Tregnaghi, Miguel; Keshavan, Pavitra; Ypma, Ellen; Han, Linda; Smolenov, Igor

    2016-01-01

    Given the broad age range across which the quadrivalent meningococcal conjugate vaccine MenACWY-CRM is used, coadministration with routine vaccines should be evaluated across age groups for possible immunologic interference and impact on vaccine reactogenicity and safety. We summarize data from a large population of infants, adolescents and international travelers from 10 phase 3 or 4 clinical studies to evaluate coadministration of MenACWY-CRM with commonly administered vaccines. Noninferiority analyses of immune responses were performed across studies and age groups for each vaccine. Reactogenicity and safety were also assessed. In infants, MenACWY-CRM coadministered with routine vaccines did not reduce immune responses to diphtheria, tetanus, poliovirus, hepatitis B, Haemophilus influenzae type b, pneumococcal conjugate, measles-mumps-rubella, varicella or pertussis antigens. Noninferiority criteria were not met for some pneumococcal conjugate serotypes at 7 months of age, but no consistent trends were observed. In adolescents, coadministration did not reduce immune responses to tetanus, diphtheria and human papilloma virus vaccine antigens. Noninferiority criteria for pertussis antigens were not uniformly met in infant and adolescent studies, although the clinical relevance is unclear. In adults, coadministration did not reduce immune responses to hepatitis A/B, typhoid fever, yellow fever, Japanese encephalitis and rabies antigens. Immune responses to MenACWY-CRM were not impacted by coadministration of commonly administered vaccines. Coadministration did not increase frequencies of postvaccination adverse events in any age group. With no clinically relevant vaccine interactions or impact on vaccine reactogenicity or safety, these results support the coadministration of MenACWY-CRM with routine vaccines in all age groups.

  7. Plant-based vaccines against diarrheal diseases.

    PubMed

    Tacket, Carol O

    2007-01-01

    Every year 1.6 million deaths occur due to diarrhea related to unsafe water and inadequate sanitation-the vast majority in children under 5 years old. Safe and effective vaccines against enteric infections could contribute to control of these diseases. However, purification of protective antigens for inclusion in vaccines using traditional expression systems is expensive and unattractive to vaccine manufacturers who see the vaccine market as economically uninviting. Cost is one of the persistent barriers to deployment of new vaccines to populations that need them most urgently. Transgenic plant-derived vaccines offer a new strategy for development of safe, inexpensive vaccines against diarrheal diseases. In phase 1 clinical studies, these vaccines have been safe and immunogenic without the need for a buffer or vehicle other than the plant cell. This paper describes early clinical studies evaluating oral transgenic plant vaccines against enteric infections such as enterotoxigenic E. coli infection and norovirus.

  8. Adenovirus-vectored Ebola vaccines.

    PubMed

    Gilbert, Sarah C

    2015-01-01

    The 2014 outbreak of Ebola virus disease in West Africa has highlighted the need for the availability of effective vaccines against outbreak pathogens that are suitable for use in frontline workers who risk their own health in the course of caring for those with the disease, and also for members of the community in the affected area. Along with effective contact tracing and quarantine, use of a vaccine as soon as an outbreak is identified could greatly facilitate rapid control and prevent the outbreak from spreading. This review describes the progress that has been made in producing and testing adenovirus-based Ebola vaccines in both pre-clinical and clinical studies, and considers the likely future use of these vaccines.

  9. Burkholderia vaccines: are we moving forward?

    PubMed Central

    Choh, Leang-Chung; Ong, Guang-Han; Vellasamy, Kumutha M.; Kalaiselvam, Kaveena; Kang, Wen-Tyng; Al-Maleki, Anis R.; Mariappan, Vanitha; Vadivelu, Jamuna

    2013-01-01

    The genus Burkholderia consists of diverse species which includes both “friends” and “foes.” Some of the “friendly” Burkholderia spp. are extensively used in the biotechnological and agricultural industry for bioremediation and biocontrol. However, several members of the genus including B. pseudomallei, B. mallei, and B. cepacia, are known to cause fatal disease in both humans and animals. B. pseudomallei and B. mallei are the causative agents of melioidosis and glanders, respectively, while B. cepacia infection is lethal to cystic fibrosis (CF) patients. Due to the high rate of infectivity and intrinsic resistance to many commonly used antibiotics, together with high mortality rate, B. mallei and B. pseudomallei are considered to be potential biological warfare agents. Treatments of the infections caused by these bacteria are often unsuccessful with frequent relapse of the infection. Thus, we are at a crucial stage of the need for Burkholderia vaccines. Although the search for a prophylactic therapy candidate continues, to date development of vaccines has not advanced beyond research to human clinical trials. In this article, we review the current research on development of safe vaccines with high efficacy against B. pseudomallei, B. mallei, and B. cepacia. It can be concluded that further research will enable elucidation of the potential benefits and risks of Burkholderia vaccines. PMID:23386999

  10. Frederick National Laboratory Rallies to Meet Demand for Zika Vaccine | Frederick National Laboratory for Cancer Research

    Cancer.gov

    The Frederick National Laboratory for Cancer Research is producing another round of Zika vaccine for ongoing studies to determine the best delivery method and dosage. This will lay the groundwork for additional tests to see if the vaccine prevents i

  11. Nanoparticles for transcutaneous vaccination.

    PubMed

    Hansen, Steffi; Lehr, Claus-Michael

    2012-03-01

    The living epidermis and dermis are rich in antigen presenting cells (APCs). Their activation can elicit a strong humoral and cellular immune response as well as mucosal immunity. Therefore, the skin is a very attractive site for vaccination, and an intradermal application of antigen may be much more effective than a subcutaneous or intramuscular injection. However, the stratum corneum (SC) is a most effective barrier against the invasion of topically applied vaccines. Products which have reached the stage of clinical testing, avoid this problem by injecting the nano-vaccine intradermally or by employing a barrier disrupting method and applying the vaccine to a relatively large skin area. Needle-free vaccination is desirable from a number of aspects: ease of application, improved patient acceptance and less risk of infection among them. Nanocarriers can be designed in a way that they can overcome the SC. Also incorporation into nanocarriers protects instable antigen from degradation, improves uptake and processing by APCs, and facilitates endosomal escape and nuclear delivery of DNA vaccines. In addition, sustained release systems may build a depot in the tissue gradually releasing antigen which may avoid booster doses. Therefore, nanoformulations of vaccines for transcutaneous immunization are currently a very dynamic field of research. Among the huge variety of nanocarrier systems that are investigated hopes lie on ultra-flexible liposomes, superfine rigid nanoparticles and nanocarriers, which are taken up by hair follicles. The potential and pitfalls associated with these three classes of carriers will be discussed. © 2011 The Authors; Microbial Biotechnology © 2011 Society for Applied Microbiology and Blackwell Publishing Ltd.

  12. Nanoparticles for transcutaneous vaccination

    PubMed Central

    Hansen, Steffi; Lehr, Claus‐Michael

    2012-01-01

    Summary The living epidermis and dermis are rich in antigen presenting cells (APCs). Their activation can elicit a strong humoral and cellular immune response as well as mucosal immunity. Therefore, the skin is a very attractive site for vaccination, and an intradermal application of antigen may be much more effective than a subcutaneous or intramuscular injection. However, the stratum corneum (SC) is a most effective barrier against the invasion of topically applied vaccines. Products which have reached the stage of clinical testing, avoid this problem by injecting the nano‐vaccine intradermally or by employing a barrier disrupting method and applying the vaccine to a relatively large skin area. Needle‐free vaccination is desirable from a number of aspects: ease of application, improved patient acceptance and less risk of infection among them. Nanocarriers can be designed in a way that they can overcome the SC. Also incorporation into nanocarriers protects instable antigen from degradation, improves uptake and processing by APCs, and facilitates endosomal escape and nuclear delivery of DNA vaccines. In addition, sustained release systems may build a depot in the tissue gradually releasing antigen which may avoid booster doses. Therefore, nanoformulations of vaccines for transcutaneous immunization are currently a very dynamic field of research. Among the huge variety of nanocarrier systems that are investigated hopes lie on ultra‐flexible liposomes, superfine rigid nanoparticles and nanocarriers, which are taken up by hair follicles. The potential and pitfalls associated with these three classes of carriers will be discussed. PMID:21854553

  13. Safety, tolerability, and immunogenicity of two Zika virus DNA vaccine candidates in healthy adults: randomised, open-label, phase 1 clinical trials.

    PubMed

    Gaudinski, Martin R; Houser, Katherine V; Morabito, Kaitlyn M; Hu, Zonghui; Yamshchikov, Galina; Rothwell, Ro Shauna; Berkowitz, Nina; Mendoza, Floreliz; Saunders, Jamie G; Novik, Laura; Hendel, Cynthia S; Holman, LaSonji A; Gordon, Ingelise J; Cox, Josephine H; Edupuganti, Srilatha; McArthur, Monica A; Rouphael, Nadine G; Lyke, Kirsten E; Cummings, Ginny E; Sitar, Sandra; Bailer, Robert T; Foreman, Bryant M; Burgomaster, Katherine; Pelc, Rebecca S; Gordon, David N; DeMaso, Christina R; Dowd, Kimberly A; Laurencot, Carolyn; Schwartz, Richard M; Mascola, John R; Graham, Barney S; Pierson, Theodore C; Ledgerwood, Julie E; Chen, Grace L

    2018-02-10

    The Zika virus epidemic and associated congenital infections have prompted rapid vaccine development. We assessed two new DNA vaccines expressing premembrane and envelope Zika virus structural proteins. We did two phase 1, randomised, open-label trials involving healthy adult volunteers. The VRC 319 trial, done in three centres, assessed plasmid VRC5288 (Zika virus and Japanese encephalitis virus chimera), and the VRC 320, done in one centre, assessed plasmid VRC5283 (wild-type Zika virus). Eligible participants were aged 18-35 years in VRC19 and 18-50 years in VRC 320. Participants were randomly assigned 1:1 by a computer-generated randomisation schedule prepared by the study statistician. All participants received intramuscular injection of 4 mg vaccine. In VRC 319 participants were assigned to receive vaccinations via needle and syringe at 0 and 8 weeks, 0 and 12 weeks, 0, 4, and 8 weeks, or 0, 4, and 20 weeks. In VRC 320 participants were assigned to receive vaccinations at 0, 4, and 8 weeks via single-dose needle and syringe injection in one deltoid or split-dose needle and syringe or needle-free injection with the Stratis device (Pharmajet, Golden, CO, USA) in each deltoid. Both trials followed up volunteers for 24 months for the primary endpoint of safety, assessed as local and systemic reactogenicity in the 7 days after each vaccination and all adverse events in the 28 days after each vaccination. The secondary endpoint in both trials was immunogenicity 4 weeks after last vaccination. These trials are registered with ClinicalTrials.gov, numbers NCT02840487 and NCT02996461. VRC 319 enrolled 80 participants (20 in each group), and VRC 320 enrolled 45 participants (15 in each group). One participant in VRC 319 and two in VRC 320 withdrew after one dose of vaccine, but were included in the safety analyses. Both vaccines were safe and well tolerated. All local and systemic symptoms were mild to moderate. In both studies, pain and tenderness at the injection site

  14. Immunogenicity of sanofi pasteur tetravalent dengue vaccine.

    PubMed

    Guy, Bruno

    2009-10-01

    A candidate tetravalent (TV) dengue vaccine based on the yellow fever (YF) 17D vaccine has been developed by sanofi pasteur. This dengue TV vaccine induced a controlled dendritic cell stimulation in vitro. In clinical trials, Th1 and CD8 responses were induced with an IFN-gamma/TNF-alpha ratio favouring IFN-gamma in both cases, regardless of whether the vaccine recipients were flavivirus naive or not. There was an absence of Th2 response in all cases. The Th1 response was dominated by the D4 serotype in flavivirus naive individuals after initial vaccination but broadened to include all serotypes after second vaccination. This broadened response was also observed after primary dengue TV vaccination in subjects previously administered monovalent live-attenuated dengue 1 and dengue 2 vaccines. Notably, virtually no cross-reactivity between YF 17D and dengue NS3 antigens at the CD8 level was observed. Clinical and pre-clinical results support the favourable immunogenicity and short-term safety of the dengue TV. Future studies will establish the longevity of the vaccine-induced immunity and requirements for boosters.

  15. Baseline demographic characteristics of subjects enrolled in international quadrivalent HPV (types 6/11/16/18) vaccine clinical trials.

    PubMed

    Paavonen, Jorma

    2008-06-01

    In Phase II/III trials, administration of quadrivalent human papillomavirus (HPV) (types 6/11/16/18) L1 virus-like-particle vaccine was highly effective in preventing HPV6/11/16/18-related cervical intraepithelial neoplasia and non-invasive cervical cancer in women aged 16-26 years who were naïve to these HPV types at enrollment. However, the makeup and extent of catch-up vaccination programs among young women is unclear, because a proportion of this population will likely already have been exposed to one or more vaccine-HPV-types. Herein we analyze baseline data from the quadrivalent HPV vaccine clinical trial program to investigate variables which may help shape catch-up vaccine implementation policies. Female adolescents and young adults aged 16-26 years were randomized into five clinical trials. Baseline data regarding demographics, sexual history, pregnancy history, and other characteristics were collected at enrollment. At the baseline gynecological examination during enrollment, specimens were obtained for Pap testing. Swabs of external genital, lateral vaginal, and cervical sites for HPV polymerase chain reaction (PCR) testing were taken, and serum samples were obtained for HPV serology testing. Regional analyses of data were conducted. Overall, 72% of subjects enrolled worldwide were naïve by both serology and PCR to all four vaccine HPV types. Few subjects were seropositive and/or PCR positive for more than two vaccine-related HPV types. Of all subjects with HSIL at enrollment, 78% were positive to at least one vaccine-related HPV type at enrollment. Regional differences in HPV and STD prevalence were evident. Study limitations included under-representation of women with >/=4 sexual partners and possible underestimation of prior HPV exposure. Our findings demonstrate that sexually active 16-26 year-old women with

  16. Deciphering assumptions about stepped wedge designs: the case of Ebola vaccine research.

    PubMed

    Doussau, Adélaïde; Grady, Christine

    2016-12-01

    Ethical concerns about randomising persons to a no-treatment arm in the context of Ebola epidemic led to consideration of alternative designs. The stepped wedge (SW) design, in which participants or clusters are randomised to receive an intervention at different time points, gained popularity. Common arguments in favour of using this design are (1) when an intervention is likely to do more good than harm, (2) all participants should receive the experimental intervention at some time point during the study and (3) the design might be preferable for practical reasons. We examine these assumptions when considering Ebola vaccine research. First, based on the claim that a stepped wedge design is indicated when it is likely that the intervention will do more good than harm, we reviewed published and ongoing SW trials to explore previous use of this design to test experimental drugs or vaccines, and found that SW design has never been used for trials of experimental drugs or vaccines. Given that Ebola vaccines were all experimental with no prior efficacy data, the use of a stepped wedge design would have been unprecedented. Second, we show that it is rarely true that all participants receive the intervention in SW studies, but rather, depending on certain design features, all clusters receive the intervention. Third, we explore whether the SW design is appealing for feasibility reasons and point out that there is significant complexity. In the setting of the Ebola epidemic, spatiotemporal variation may have posed problematic challenges to a stepped wedge design for vaccine research. Finally, we propose a set of points to consider for scientific reviewers and ethics committees regarding proposals for SW designs. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  17. Are vaccine strain, type or administration protocol risk factors for canine parvovirus vaccine failure?

    PubMed

    Altman, K D; Kelman, M; Ward, M P

    2017-10-01

    Canine parvovirus (CPV) is a highly contagious and worldwide cause of serious and often fatal disease in dogs, despite the widespread availability of vaccines. Which vaccine-related factors are associated with vaccination failure is largely unknown, and there are no reports from Australia. In this study - the first national population-level CPV study of its kind ever conducted - we analysed data on 594 cases of apparent CPV vaccination failure reported from an Australian national surveillance system to determine whether vaccine strain, type or administration protocol are risk factors for vaccination failures. The strain of CPV used in vaccine manufacture was not significantly associated with vaccination failure in clinical practice. The vaccine type (killed versus attenuated vaccine) for puppies diagnosed with CPV was associated with a lower mean age at time of vaccination (P=0.0495). The age at administration of the last CPV vaccination a puppy received prior to presenting with disease was a significant (P=0.0334) risk factor for vaccination failure, irrespective of whether the vaccine was marketed for a 10-week or 12-week or greater vaccination finish protocol. There was also a strong negative correlation between age at last vaccination prior to disease and vaccination failure (P<0.0001): the later a puppy received this last vaccination, the lower the risk of vaccination failure. This supports the hypothesis that the use of final vaccination in puppies at less than 16 weeks of age predisposes to vaccination failure and warrants a final age for vaccination recommendation to be at least 16 weeks for all canine parvovirus vaccines, especially in outbreak situations. The large number of cases identified in this study confirms that CPV vaccination failure is occurring in Australia. Veterinarians should consider CPV as a differential diagnosis in cases with appropriate clinical presentation, regardless of the reported vaccination status of the dog. Copyright © 2017

  18. Safety and immunogenicity of a live attenuated mumps vaccine: a phase I clinical trial.

    PubMed

    Liang, Yan; Ma, Jingchen; Li, Changgui; Chen, Yuguo; Liu, Longding; Liao, Yun; Zhang, Ying; Jiang, Li; Wang, Xuan-Yi; Che, Yanchun; Deng, Wei; Li, Hong; Cui, Xiaoyu; Ma, Na; Ding, Dong; Xie, Zhongping; Cui, Pingfang; Ji, Qiuyan; Wang, JingJing; Zhao, Yuliang; Wang, Junzhi; Li, Qihan

    2014-01-01

    Mumps, a communicable, acute and previously well-controlled disease, has had recent and occasional resurgences in some areas. A randomized, double-blind, controlled and multistep phase I study of an F-genotype attenuated mumps vaccine produced in human diploid cells was conducted. A total of 300 subjects were enrolled and divided into 4 age groups: 16-60 years, 5-16 years, 2-5 years and 8-24 months. The groups were immunized with one injection per subject. Three different doses of the F-genotype attenuated mumps vaccine, A (3.5 ± 0.25 logCCID50), B (4.25 ± 0.25 logCCID50) and C (5.0 ± 0.25 logCCID50), as well as a placebo control and a positive control of a licensed A-genotype vaccine (S79 strain) were used. The safety and immunogenicity of this vaccine were compared with those of the controls. The safety evaluation suggested that mild adverse reactions were observed in all groups. No serious adverse event (SAE) was reported throughout the trial. The immunogenicity test showed a similar seroconversion rate of the neutralizing and ELISA antibody in the 2- to 5-year-old and 8- to 24-month-old groups compared with the seroconversion rate in the positive control. The GMT of the neutralizing anti-F-genotype virus antibodies in the vaccine groups was slightly higher than that in the positive control group. The F-genotype attenuated mumps vaccine evaluated in this clinical trial was demonstrated to be safe and have effective immunogenicity vs. control.

  19. Vaccines for preventing influenza in healthy adults.

    PubMed

    Demicheli, V; Rivetti, D; Deeks, J J; Jefferson, T O

    2001-01-01

    Three different types of influenza vaccines are currently produced world wide. None is traditionally targeted to healthy adults. Despite the publication of a large number of clinical trials, there is still substantial uncertainty about the clinical effectiveness of influenza vaccines and this has negative impact on the vaccines acceptance and uptake. To identify, retrieve and assess all studies evaluating the effects of vaccines on influenza in healthy adults. To assess the effectiveness of vaccines in preventing cases of influenza in healthy adults. To estimate the frequency of adverse effects associated with influenza vaccination in healthy adults. MEDLINE was searched using the strategy of the Cochrane Acute Respiratory Infections Group. The bibliography of retrieved articles, the Cochrane Controlled Trials Register (CCTR), and EMBASE (1990 to 1997) were also searched. Handsearch of the journal Vaccine from its first issue to the end of 1997 (Jefferson and Jefferson, 1996; Jefferson, 1998). We wrote to vaccine manufacturers and first or corresponding authors of studies in the review. Any randomised or quasi-randomised studies comparing influenza vaccines in humans with placebo, control vaccines or no intervention, or comparing types, doses or schedules of influenza vaccine. Live, attenuated or killed vaccines or fractions thereof administered by any route, irrespective of antigenic configuration were considered. Only studies assessing protection from exposure to naturally occurring influenza in healthy individuals aged 14 to 60 (irrespective of influenza immune status) were considered. Both clinically defined cases and serologically confirmed cases of influenza were considered as outcomes according to the authors' definitions. Time off work, complication and hospitalisation rates were considered, together with adverse effects. Vaccine schedules were analysed including one component matching the recommended vaccine (WHO or government recommendations) for the year

  20. Vaccination Against Tuberculosis With Whole-Cell Mycobacterial Vaccines.

    PubMed

    Scriba, Thomas J; Kaufmann, Stefan H E; Henri Lambert, Paul; Sanicas, Melvin; Martin, Carlos; Neyrolles, Olivier

    2016-09-01

    Live attenuated and killed whole-cell vaccines (WCVs) offer promising vaccination strategies against tuberculosis. A number of WCV candidates, based on recombinant bacillus Calmette-Guerin (BCG), attenuated Mycobacterium tuberculosis, or related mycobacterial species are in various stages of preclinical or clinical development. In this review, we discuss the vaccine candidates and key factors shaping the development pathway for live and killed WCVs and provide an update on progress. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  1. Malaria vaccine offers hope. International / Africa.

    PubMed

    1995-03-13

    Colombian professor Manuel Patarroyo developed a new malaria vaccine (SPF66). In February 1995, WHO and the Colombian government agreed to establish a manufacturing plant in Colombia for mass production of SPF66. This vaccine is likely to be available to persons in Africa, where 90% of all annual global cases live. In fact, Africa witnesses one million of 1.5 million annual malaria cases. Many children die from malaria. An extensive clinical trial of the SPF66 vaccine in Colombia achieved a 22-77% protection rate. The young and the very old had the high protection rates. A series of human clinical trials in the Gambia and Tanzania indicate that SPF66 produces a strong immune response against malaria without any harmful side effects. The results of field tests in the Gambia and Thailand and of trials in Colombia are expected in 1995. If the vaccine could reduce the incidence of malaria by just 50%, the lives of as many as 500,000 African children could be saved. SPF66 contains a combination of synthetic peptides (=or 2 amino acids). Mass production would make it affordable (estimated $5/injection). At least five other malaria vaccines hold promise and are ready for human testing in endemic countries. SPF66 is approximately three years ahead of all other promising malaria vaccines. 20 more vaccines are in the development stage. The large scale production of SPF66 in Colombia could begin within three years. Professor Patarroyo has financed his 12-year-old research himself because he wants to protect the lives of persons in developing countries. In 1992, the Congo's president petitioned the international community at the WHO summit in Amsterdam to join the fight against malaria since it is now in a position to defeat malaria since it finished the cold war.

  2. Repeated annual influenza vaccination and vaccine effectiveness: review of evidence.

    PubMed

    Belongia, Edward A; Skowronski, Danuta M; McLean, Huong Q; Chambers, Catharine; Sundaram, Maria E; De Serres, Gaston

    2017-07-01

    Studies in the 1970s and 1980s signaled concern that repeated influenza vaccination could affect vaccine protection. The antigenic distance hypothesis provided a theoretical framework to explain variability in repeat vaccination effects based on antigenic similarity between successive vaccine components and the epidemic strain. Areas covered: A meta-analysis of vaccine effectiveness studies from 2010-11 through 2014-15 shows substantial heterogeneity in repeat vaccination effects within and between seasons and subtypes. When negative effects were observed, they were most pronounced for H3N2, especially in 2014-15 when vaccine components were unchanged and antigenically distinct from the epidemic strain. Studies of repeated vaccination across multiple seasons suggest that vaccine effectiveness may be influenced by more than one prior season. In immunogenicity studies, repeated vaccination blunts the hemagglutinin antibody response, particularly for H3N2. Expert commentary: Substantial heterogeneity in repeated vaccination effects is not surprising given the variation in study populations and seasons, and the variable effects of antigenic distance and immunological landscape in different age groups and populations. Caution is required in the interpretation of pooled results across multiple seasons, since this can mask important variation in repeat vaccination effects between seasons. Multi-season clinical studies are needed to understand repeat vaccination effects and guide recommendations.

  3. Chlamydia vaccine candidates and tools for chlamydial antigen discovery.

    PubMed

    Rockey, Daniel D; Wang, Jie; Lei, Lei; Zhong, Guangming

    2009-10-01

    The failure of the inactivated Chlamydia-based vaccine trials in the 1960s has led researchers studying Chlamydia to take cautious and rational approaches to develop safe and effective chlamydial vaccines. Subsequent research efforts focused on three areas. The first is the analysis of the immunobiology of chlamydial infection in animal models, with supporting clinical studies, to identify the immune correlates of both protective immunity and pathological responses. Second, recent radical improvements in genomics, proteomics and associated technologies have assisted in the implementation of creative approaches to search for suitable vaccine candidates. Third, progress in the analysis of host response and adjuvanticity regulating both innate and adaptive immunity at the mucosal site of infection has led to progress in the design of optimal delivery and adjuvant systems for enhancing protective immunity. Considerable progress has been made in the first two areas but research efforts to better define the factors that regulate immunity at mucosal sites of infection and to develop strategies to boost protective immunity via immunomodulation, effective delivery systems and potent adjuvants, have remained elusive. In this article, we will summarize progress in these areas with a focus on chlamydial vaccine antigen discovery, and discuss future directions towards the development of a safe and effective chlamydial vaccine.

  4. Study of adverse events following immunisation with universal and newer vaccines in the Serampore IMA Child Clinic over a period of 7 years.

    PubMed

    Das, Pradip Kumar

    2013-04-01

    Immunisation is an important part of childcare practice. It is one of the most beneficial and cost effective measures for the prevention of diseases. From the previous retrospective studies, it was evident that smallpox has been completely eradicated throughout now-a-days with the wholehearted and sincere efforts of healthcare providers by applying efficient and safe vaccine against smallpox, same is true also to polio which is now close to worldwide eradication and measles and rubella are no longer endemic in certain parts of the world. Not only has that with the introduction of safer and more efficient newer vaccines, the incidence of most other vaccine preventable disease of childhood also reduced considerably. The aim of the present study is to estimate the incidence and clinical presentation of adverse events following immunisation with universal and newer vaccines for a period of seven years using prospective active surveillance. Children under the age of 7 years were taken for universal and newer scheduled vaccinations given in the Serampore IMA Child Clinic under the supervision of the clinicians maintaining strictly the guidelines of Expanded Programme of Immunisation (Government of India). This study of adverse events following immunisation in the Serampore IMA Child Clinic confirms that the adverse events such as fever (0.37%), pain and swelling at the site of injection (0.32%0, urticarial rash (0.02%), anaphylactic shock (0.003%) are negligible. There were only two reports of anaphylaxis following preschool and infant schedule vaccines, including measles, mumps and rubella (MMR), Haemophilus influenzae type B vaccines and typhoid vaccines in approximately 52,000 infants received over a period of 7 years starting from 1st April, 2005 to 31st March, 2012 and there were no deaths or longterm effects reported during the post follow-up period in the Serampore IMA Child Clinic.

  5. Clinical study and stability assessment of a novel transcutaneous influenza vaccination using a dissolving microneedle patch.

    PubMed

    Hirobe, Sachiko; Azukizawa, Hiroaki; Hanafusa, Takaaki; Matsuo, Kazuhiko; Quan, Ying-Shu; Kamiyama, Fumio; Katayama, Ichiro; Okada, Naoki; Nakagawa, Shinsaku

    2015-07-01

    Transcutaneous immunization (TCI) is an attractive vaccination method compared with conventional injectable vaccines because it is easier to administer without pain. We developed a dissolving microneedle patch (MicroHyala, MH) made of hyaluronic acid and showed that transcutaneous vaccination using MH induced a strong immune response against various antigens in mice. In the present study, we investigated the clinical safety and efficacy of a novel transcutaneous influenza vaccine using MH (flu-MH), which contains trivalent influenza hemagglutinins (15 μg each). Subjects of the TCI group were treated transcutaneously with flu-MH, and were compared with subjects who received subcutaneous injections of a solution containing 15 μg of each influenza antigen (SCI group). No severe local or systemic adverse events were detected in either group and immune responses against A/H1N1 and A/H3N2 strains were induced equally in the TCI and SCI groups. Moreover, the efficacy of the vaccine against the B strain in the TCI group was stronger than that in the SCI group. Influenza vaccination using MH is promising for practical use as an easy and effective method to replace conventional injections systems. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Plant-Based Vaccines Against Diarrheal Diseases

    PubMed Central

    Tacket, Carol O.

    2007-01-01

    Every year 1.6 million deaths occur due to diarrhea related to unsafe water and inadequate sanitation—the vast majority in children under 5 years old. Safe and effective vaccines against enteric infections could contribute to control of these diseases. However, purification of protective antigens for inclusion in vaccines using traditional expression systems is expensive and unattractive to vaccine manufacturers who see the vaccine market as economically uninviting. Cost is one of the persistent barriers to deployment of new vaccines to populations that need them most urgently. Transgenic plant-derived vaccines offer a new strategy for development of safe, inexpensive vaccines against diarrheal diseases. In phase 1 clinical studies, these vaccines have been safe and immunogenic without the need for a buffer or vehicle other than the plant cell. This paper describes early clinical studies evaluating oral transgenic plant vaccines against enteric infections such as enterotoxigenic E. coli infection and norovirus. PMID:18528491

  7. Vaccines against poverty

    PubMed Central

    MacLennan, Calman A.; Saul, Allan

    2014-01-01

    With the 2010s declared the Decade of Vaccines, and Millennium Development Goals 4 and 5 focused on reducing diseases that are potentially vaccine preventable, now is an exciting time for vaccines against poverty, that is, vaccines against diseases that disproportionately affect low- and middle-income countries (LMICs). The Global Burden of Disease Study 2010 has helped better understand which vaccines are most needed. In 2012, US$1.3 billion was spent on research and development for new vaccines for neglected infectious diseases. However, the majority of this went to three diseases: HIV/AIDS, malaria, and tuberculosis, and not neglected diseases. Much of it went to basic research rather than development, with an ongoing decline in funding for product development partnerships. Further investment in vaccines against diarrheal diseases, hepatitis C, and group A Streptococcus could lead to a major health impact in LMICs, along with vaccines to prevent sepsis, particularly among mothers and neonates. The Advanced Market Commitment strategy of the Global Alliance for Vaccines and Immunisation (GAVI) Alliance is helping to implement vaccines against rotavirus and pneumococcus in LMICs, and the roll out of the MenAfriVac meningococcal A vaccine in the African Meningitis Belt represents a paradigm shift in vaccines against poverty: the development of a vaccine primarily targeted at LMICs. Global health vaccine institutes and increasing capacity of vaccine manufacturers in emerging economies are helping drive forward new vaccines for LMICs. Above all, partnership is needed between those developing and manufacturing LMIC vaccines and the scientists, health care professionals, and policy makers in LMICs where such vaccines will be implemented. PMID:25136089

  8. Vaccines for preventing influenza in healthy adults.

    PubMed

    Demicheli, V; Rivetti, D; Deeks, J J; Jefferson, T O

    2004-01-01

    Three different types of influenza vaccines are currently produced worldwide. None is traditionally targeted to healthy adults. Despite the publication of a large number of clinical trials, there is still substantial uncertainty about the clinical effectiveness of influenza vaccines and this has negative impact on the vaccines acceptance and uptake. To assess the effects of vaccines on influenza in healthy adults. To assess the effectiveness of vaccines in preventing cases of influenza in healthy adults. To estimate the frequency of adverse effects associated with influenza vaccination in healthy adults. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1, 2004) which contains the Cochrane Acute Respiratory Infections Group trials register; MEDLINE (January 1966 to December 2003); and EMBASE (1990 to December 2003). We wrote to vaccine manufacturers and first or corresponding authors of studies in the review. Any randomised or quasi-randomised studies comparing influenza vaccines in humans with placebo, control vaccines or no intervention, or comparing types, doses or schedules of influenza vaccine. Live, attenuated or killed vaccines or fractions thereof administered by any route, irrespective of antigenic configuration were considered. Only studies assessing protection from exposure to naturally occurring influenza in healthy individuals aged 14 to 60 (irrespective of influenza immune status) were considered. Two reviewers independently assessed trial quality and extracted data. Twenty five reports of studies involving 59,566 people were included. The recommended live aerosol vaccines reduced the number of cases of serologically confirmed influenza by 48% (95% confidence interval (CI) 24% to 64%), whilst recommended inactivated parenteral vaccines had a vaccine efficacy of 70% (95% CI 56% to 80%). The yearly recommended vaccines had low effectiveness against clinical influenza cases: 15%(95% CI 8% to 21%) and 25

  9. DNA vaccines

    NASA Astrophysics Data System (ADS)

    Gregersen, Jens-Peter

    2001-12-01

    Immunization by genes encoding immunogens, rather than with the immunogen itself, has opened up new possibilities for vaccine research and development and offers chances for new applications and indications for future vaccines. The underlying mechanisms of antigen processing, immune presentation and regulation of immune responses raise high expectations for new and more effective prophylactic or therapeutic vaccines, particularly for vaccines against chronic or persistent infectious diseases and tumors. Our current knowledge and experience of DNA vaccination is summarized and critically reviewed with particular attention to basic immunological mechanisms, the construction of plasmids, screening for protective immunogens to be encoded by these plasmids, modes of application, pharmacokinetics, safety and immunotoxicological aspects. DNA vaccines have the potential to accelerate the research phase of new vaccines and to improve the chances of success, since finding new immunogens with the desired properties is at least technically less demanding than for conventional vaccines. However, on the way to innovative vaccine products, several hurdles have to be overcome. The efficacy of DNA vaccines in humans appears to be much less than indicated by early studies in mice. Open questions remain concerning the persistence and distribution of inoculated plasmid DNA in vivo, its potential to express antigens inappropriately, or the potentially deleterious ability to insert genes into the host cell's genome. Furthermore, the possibility of inducing immunotolerance or autoimmune diseases also needs to be investigated more thoroughly, in order to arrive at a well-founded consensus, which justifies the widespread application of DNA vaccines in a healthy population.

  10. Implications of the licensure of a partially efficacious malaria vaccine on evaluating second-generation vaccines.

    PubMed

    Fowkes, Freya J I; Simpson, Julie A; Beeson, James G

    2013-10-30

    Malaria is a leading cause of morbidity and mortality, with approximately 225 million clinical episodes and >1.2 million deaths annually attributed to malaria. Development of a highly efficacious malaria vaccine will offer unparalleled possibilities for disease prevention and remains a key priority for long-term malaria control and elimination. The Malaria Vaccine Technology Roadmap's goal is to 'develop and license a first-generation malaria vaccine that has protective efficacy of more than 50%'. To date, malaria vaccine candidates have only been shown to be partially efficacious (approximately 30% to 60%). However, licensure of a partially effective vaccine will create a number of challenges for the development and progression of new, potentially more efficacious, malaria vaccines in the future. In this opinion piece we discuss the methodological, logistical and ethical issues that may impact on the feasibility and implementation of superiority, non-inferiority and equivalence trials to assess second generation malaria vaccines in the advent of the licensure of a partially efficacious malaria vaccine. Selecting which new malaria vaccines go forward, and defining appropriate methodology for assessment in logistically challenging clinical trials, is crucial. It is imperative that the scientific community considers all the issues and starts planning how second-generation malaria vaccines will advance in the advent of licensure of a partially effective vaccine.

  11. Are HPV vaccination services accessible to high-risk communities? A spatial analysis of HPV-associated cancer and Chlamydia rates and safety-net clinics.

    PubMed

    Tsui, Jennifer; Rodriguez, Hector P; Gee, Gilbert C; Escobedo, Loraine A; Kominski, Gerald F; Bastani, Roshan

    2013-12-01

    While HPV vaccines can greatly benefit adolescents and young women from high-risk areas, little is known about whether safety-net immunization services are geographically accessible to communities at greatest risk for HPV-associated diseases. We explore the spatial relationship between areas with high HPV risk and proximity to safety-net clinics from an ecologic perspective. We used cancer registry data and Chlamydia surveillance data to identify neighborhoods within Los Angeles County with high risk for HPV-associated cancers. We examined proximity to safety-net clinics among neighborhoods with the highest risk. Proximity was measured as the shortest distance between each neighborhood center and the nearest clinic and having a clinic within 3 miles of each neighborhood center. The average 5-year non-age-adjusted rates were 1,940 cases per 100,000 for Chlamydia and 60 per 100,000 for HPV-associated cancers. A large majority, 349 of 386 neighborhoods with high HPV-associated cancer rates and 532 of 537 neighborhoods with high Chlamydia rates, had a clinic within 3 miles of the neighborhood center. Clinics were more likely to be located within close proximity to high-risk neighborhoods in the inner city. High-risk neighborhoods outside of this urban core area were less likely to be near accessible clinics. The majority of high-risk neighborhoods were geographically near safety-net clinics with HPV vaccination services. Due to low rates of vaccination, these findings suggest that while services are geographically accessible, additional efforts are needed to improve uptake. Programs aimed to increase awareness about the vaccine and to link underserved groups to vaccination services are warranted.

  12. Are HPV vaccination services accessible to high-risk communities?: A spatial analysis of HPV-associated cancer and Chlamydia rates and safety-net clinics

    PubMed Central

    Tsui, Jennifer; Rodriguez, Hector P.; Gee, Gilbert C.; Escobedo, Loraine A.; Kominski, Gerald F.; Bastani, Roshan

    2013-01-01

    Purpose While HPV vaccines can greatly benefit adolescents and young women from high-risk areas, little is known about whether safety-net immunization services are geographically accessible to communities at greatest risk for HPV-associated diseases. We explore the spatial relationship between areas with high HPV risk and proximity to safety-net clinics from an ecologic perspective. Methods We used cancer registry data and Chlamydia surveillance data to identify neighborhoods within Los Angeles County with high risk for HPV-associated cancers. We examined proximity to safety-net clinics among neighborhoods with the highest risk. Proximity was measured as the shortest distance between each neighborhood center and the nearest clinic and having a clinic within 3 miles of each neighborhood center. Results The average 5-year non-age-adjusted rates were 1,940 cases per 100,000 for Chlamydia and 60 per 100,000 for HPV-associated cancers. A large majority, 349 of 386 neighborhoods with high HPV-associated cancer rates and 532 of 537 neighborhoods with high Chlamydia rates had a clinic within 3 miles of the neighborhood center. Clinics were more likely to be located within close proximity to high-risk neighborhoods in the inner city. High-risk neighborhoods outside of this urban core area were less likely to be near accessible clinics. Conclusions The majority of high-risk neighborhoods were geographically near safety-net clinics with HPV vaccination services. Due to low rates of vaccination, these findings suggest that while services are geographically accessible, additional efforts are needed to improve uptake. Programs aimed to increase awareness about the vaccine and to link underserved groups to vaccination services are warranted. PMID:24043448

  13. 17DD yellow fever vaccine

    PubMed Central

    Martins, Reinaldo M.; Maia, Maria de Lourdes S.; Farias, Roberto Henrique G.; Camacho, Luiz Antonio B.; Freire, Marcos S.; Galler, Ricardo; Yamamura, Anna Maya Yoshida; Almeida, Luiz Fernando C.; Lima, Sheila Maria B.; Nogueira, Rita Maria R.; Sá, Gloria Regina S.; Hokama, Darcy A.; de Carvalho, Ricardo; Freire, Ricardo Aguiar V.; Filho, Edson Pereira; Leal, Maria da Luz Fernandes; Homma, Akira

    2013-01-01

    Objective: To verify if the Bio-Manguinhos 17DD yellow fever vaccine (17DD-YFV) used in lower doses is as immunogenic and safe as the current formulation. Results: Doses from 27,476 IU to 587 IU induced similar seroconversion rates and neutralizing antibodies geometric mean titers (GMTs). Immunity of those who seroconverted to YF was maintained for 10 mo. Reactogenicity was low for all groups. Methods: Young and healthy adult males (n = 900) were recruited and randomized into 6 groups, to receive de-escalating doses of 17DD-YFV, from 27,476 IU to 31 IU. Blood samples were collected before vaccination (for neutralization tests to yellow fever, serology for dengue and clinical chemistry), 3 to 7 d after vaccination (for viremia and clinical chemistry) and 30 d after vaccination (for new yellow fever serology and clinical chemistry). Adverse events diaries were filled out by volunteers during 10 d after vaccination. Volunteers were retested for yellow fever and dengue antibodies 10 mo later. Seropositivity for dengue was found in 87.6% of volunteers before vaccination, but this had no significant influence on conclusions. Conclusion: In young healthy adults Bio-Manguinhos/Fiocruz yellow fever vaccine can be used in much lower doses than usual. International Register ISRCTN 38082350. PMID:23364472

  14. [Immunological surrogate endpoints to evaluate vaccine efficacy].

    PubMed

    Jin, Pengfei; Li, Jingxin; Zhou, Yang; Zhu, Fengcai

    2015-12-01

    An immunological surrogate endpoints is a vaccine-induced immune response (either humoral or cellular immune) that predicts protection against clinical endpoints (infection or disease), and can be used to evaluate vaccine efficacy in clinical vaccine trials. Compared with field efficacy trials observing clinical endpoints, immunological vaccine trials could reduce the sample size or shorten the duration of a trial, which promote the license and development of new candidate vaccines. For these reasons, establishing immunological surrogate endpoints is one of 14 Grand Challenges of Global Health of the National Institutes of Health (NIH) and the Bill and Melinda Gates Foundation. From two parts of definition and statistical methods for evaluation of surrogate endpoints, this review provides a more comprehensive description.

  15. Possibilities and challenges for developing a successful vaccine for leishmaniasis.

    PubMed

    Srivastava, Saumya; Shankar, Prem; Mishra, Jyotsna; Singh, Sarman

    2016-05-12

    Leishmaniasis is a vector-borne disease caused by different species of protozoan parasites of the genus Leishmania. It is a major health problem yet neglected tropical diseases, with approximately 350 million people worldwide at risk and more than 1.5 million infections occurring each year. Leishmaniasis has different clinical manifestations, including visceral (VL or kala-azar), cutaneous (CL), mucocutaneous (MCL), diffuse cutaneous (DCL) and post kala-azar dermal leishmaniasis (PKDL). Currently, the only mean to treat and control leishmaniasis is by rational medications and vector control. However, the number of available drugs is limited and even these are either exorbitantly priced, have toxic side effects or prove ineffective due to the emergence of resistant strains. On the other hand, the vector control methods are not so efficient. Therefore, there is an urgent need for developing a safe, effective, and affordable vaccine for the prevention of leishmaniasis. Although in recent years a large body of researchers has concentrated their efforts on this issue, yet only three vaccine candidates have gone for clinical trial, until date. These are: (i) killed vaccine in Brazil for human immunotherapy; (ii) live attenuated vaccine for humans in Uzbekistan; and (iii) second-generation vaccine for dog prophylaxis in Brazil. Nevertheless, there are at least half a dozen vaccine candidates in the pipeline. One can expect that, in the near future, the understanding of the whole genome of Leishmania spp. will expand the vaccine discovery and strategies that may provide novel vaccines. The present review focuses on the development and the status of various vaccines and potential vaccine candidates against leishmaniasis.

  16. Pills, shots, implants, vaccines: can the elusive sperm be reined in? Male contraceptive research extremely slow, but promising.

    PubMed

    1995-08-01

    Although it may be 20 years before a male contraceptive is marketed, researchers continue to explore various options. Part of the difficulty with male contraception is the fact that the oral contraceptives were so successful in women that they cornered the market. Another problem is that it is easier to control one egg per month than hundreds of millions of sperm cells each day. Another is that it is more expensive to do research on male than on female rats since the males require separate cages. The physiologic targets for male birth control are 1) the process of spermatogenesis, 2) the process of sperm maturation, and 3) the process of capacitation. The substance gossypol, which suppresses sperm without affecting androgen levels, has been the subject of male contraceptive research in the US since the 1970s. Clinical trials of gossypol are planned by a collaborative groups of investigators from developing countries. Research has also continued for more than 20 years on compounds to alter male hormone levels. The use of one such compound, testosterone enanthate, required weekly injections, so current research is centered on finding a more marketable product, such as a 3-month injectable that uses testosterone buciclate. The combination of testosterone enanthate with cyproterone acetate is also showing promise in achieving complete azoospermia in trials in men. The dosing schedule makes this regimen unmarketable, however. Protocols have also been completed for a clinical trial using two implanted rods to deliver a GnRH analog and a specially developed androgen. Work is also proceeding on the development of a GnRH vaccine and on a vaccine specific only to follicle-stimulating hormone. Other avenues of research are focusing on nifedipine, a drug used to treat high blood pressure, on mifepristone (RU-486) which temporarily blocks calcium, and on etoprine, which suppresses rapidly dividing sperm cells. Research has halted on two compounds that protect cells from

  17. “Speaking the Dialect”: Understanding Public Discourse in the Aftermath of an HIV Vaccine Trial Shutdown

    PubMed Central

    Logie, Carmen; James, LLana; Charles, Tamicka; Maxwell, John; Salam, Khaled; Woodford, Michael

    2011-01-01

    Objectives. We investigated how persons from key populations at higher risk of HIV exposure interpreted the process and outcomes of the Step Study HIV-1 vaccine trial, which was terminated early, and implications for willingness to participate in and community support for HIV vaccine research. Methods. We used qualitative methods and a community-based approach in 9 focus groups (n = 72) among ethnically and sexually diverse populations and 6 semistructured key informant interviews in Ontario, Canada, in 2007 to 2008. Results. Participants construed social meaning from complex clinical and biomedical phenomena. Social representations and mental models emerged in fears of vaccine-induced infection, conceptualizations of unfair recruitment practices and increased risk behaviors among trial participants, and questioning of informed consent. Narratives of altruism and the common good demonstrated support for future trials. Conclusions. Public discourse on HIV vaccine trials is a productive means of interpreting complex clinical trial processes and outcomes in the context of existing beliefs and experiences regarding HIV vaccines, medical research, and historical disenfranchisement. Strategic engagement with social representations and mental models may promote meaningful community involvement in biomedical HIV prevention research. PMID:21778490

  18. Guideline for collection, analysis and presentation of safety data in clinical trials of vaccines in pregnant women

    PubMed Central

    Jones, Christine E.; Munoz, Flor M.; Spiegel, Hans M.L.; Heininger, Ulrich; Zuber, Patrick L.F.; Edwards, Kathryn M.; Lambach, Philipp; Neels, Pieter; Kohl, Katrin S.; Gidudu, Jane; Hirschfeld, Steven; Oleske, James M.; Khuri-Bulos, Najwa; Bauwens, Jorgen; Eckert, Linda O.; Kochhar, Sonali; Bonhoeffer, Jan; Heath, Paul T.

    2017-01-01

    Vaccination during pregnancy is increasingly being used as an effective approach for protecting both young infants and their mothers from serious infections. Drawing conclusions from published studies in this area can be difficult because of the inability to compare vaccine trial results across different studies and settings due to the heterogeneity in the definitions of terms used to assess the safety of vaccines in pregnancy and the data collected in such studies. The guidelines proposed in this document have been developed to harmonize safety data collection in all phases of clinical trials of vaccines in pregnant women and apply to data from the mother, fetus and infant. Guidelines on the prioritization of the data to be collected is also provided to allow applicability in various geographic, cultural and resource settings, including high, middle and low-income countries. PMID:27481360

  19. Booster dose vaccination for preventing hepatitis B.

    PubMed

    Poorolajal, Jalal; Hooshmand, Elham

    2016-06-07

    Antibodies against hepatitis B surface antigen (HBsAg) wane over time following hepatitis B immunisation; hence, it is unclear whether people vaccinated in three-dose or four-dose schedules of the hepatitis B vaccine are still immune when the hepatitis B surface antibody (anti-HBs) level in their body is undetectable, or lower than the level usually considered protective. This question may potentially be answered indirectly by measuring the anamnestic immune response to a booster dose of vaccine. The term 'booster' (or revaccination) refers to an additional dose of hepatitis B vaccine (HBV) given some time post-primary vaccination to induce immune memory and improve protection against hepatitis B virus (HBV) infection. To assess the benefits and harms of booster dose hepatitis B vaccination, more than five years after the primary vaccination, for preventing HBV infection in healthy individuals previously vaccinated with the hepatitis B vaccine, and with hepatitis B surface antibody (anti-HBs) levels below 10 mIU/mL. We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index Expanded, conference databases, and reference lists of articles to January 2016. We also contacted authors of articles. In addition, we searched ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform for ongoing trials (May 2016). Randomised clinical trials addressing anamnestic immune response to a booster dose of hepatitis B vaccine, more than five years after the primary vaccination, in apparently healthy participants, vaccinated in a three-dose or four-dose schedule of the hepatitis B vaccine during the primary vaccination, without receiving an additional dose or immunoglobulin. Both review authors decided if the identified studies met the inclusion criteria or not. Primary outcomes included the proportion of participants

  20. Cervical, anal and oral HPV in an adolescent inner-city health clinic providing free vaccinations.

    PubMed

    Schlecht, Nicolas F; Burk, Robert D; Nucci-Sack, Anne; Shankar, Viswanathan; Peake, Ken; Lorde-Rollins, Elizabeth; Porter, Richard; Linares, Lourdes Oriana; Rojas, Mary; Strickler, Howard D; Diaz, Angela

    2012-01-01

    Published human papillomavirus (HPV) vaccine trials indicate efficacy is strongest for those naive to the vaccine-types. However, few high-risk young women have been followed and cervical HPV has been the predominant outcome measure. We collected cervical and anal swabs, as well as oral rinse specimens from 645 sexually active inner-city young females attending a large adolescent health-clinic in New York City that offers free care and HPV vaccination. Specimens were tested for HPV-DNA using a MY09/MY11-PCR system. Type-specific prevalence of HPV at each anatomic site was compared for individuals by vaccination dose using generalized estimating equation logistic regression models. The majority of subjects reported being of non-Caucasian (92%) and/or Hispanic ethnicity (61%). Median age was 18 years (range:14-20). All had practiced vaginal sex, a third (33%) practiced anal sex, and most (77%) had also engaged in oral sex. At enrollment, 21% had not received the vaccine and 51% had received three doses. Prevalent HPV infection at enrollment was detected in 54% of cervical, 42% of anal and 20% of oral specimens, with vaccine types present in 7%, 6% and 1% of specimens, respectively. Comparing prevalence for vaccine types, the detection of HPV in the cervix of vaccinated compared to unvaccinated adolescents was significantly reduced: HPV6/11 (odds ratio [OR] = 0.19, 95%CI:0.06-0.75), HPV16 (OR = 0.31, 95%CI:0.11-0.88) and HPV18 (OR = 0.14, 95%CI:0.03-0.75). For anal HPV, the risk of detecting vaccine types HPV6/11 (OR = 0.27, 95%CI:0.10-0.72) and HPV18(OR = 0.12, 95%CI:0.01-1.16) were significantly reduced for vaccinated adolescents however, the risk for HPV16 was not significantly decreased (OR = 0.63, 95%CI:0.18-2.20). HPV Prevalence is extremely high in inner-city female adolescents. Administration of the HPV vaccine reduced the risk for cervical HPV; however continued follow-up is required to assess the protection for HPV at all sites in