Immunotherapy of Congenital SIV Infection.

DTIC Science & Technology

1996-10-01

replication-impaired viruses / threshold hypothesis diseases ©1996 Academic Press Ltd Live attenuated virus vaccines have been developed against...members of different virus families and protect against various human viral diseases including Problems for HIV-1 vaccine development poliomyelitis, mumps... Progress has been made also during year 02 on another aspect that will be a major benefit to primate vaccine research. We have developed highly

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.

Progress on adenovirus-vectored universal influenza vaccines.

PubMed

Xiang, Kui; Ying, Guan; Yan, Zhou; Shanshan, Yan; Lei, Zhang; Hongjun, Li; Maosheng, Sun

2015-01-01

Influenza virus (IFV) infection causes serious health problems and heavy financial burdens each year worldwide. The classical inactivated influenza virus vaccine (IIVV) and live attenuated influenza vaccine (LAIV) must be updated regularly to match the new strains that evolve due to antigenic drift and antigenic shift. However, with the discovery of broadly neutralizing antibodies that recognize conserved antigens, and the CD8(+) T cell responses targeting viral internal proteins nucleoprotein (NP), matrix protein 1 (M1) and polymerase basic 1 (PB1), it is possible to develop a universal influenza vaccine based on the conserved hemagglutinin (HA) stem, NP, and matrix proteins. Recombinant adenovirus (rAd) is an ideal influenza vaccine vector because it has an ideal stability and safety profile, induces balanced humoral and cell-mediated immune responses due to activation of innate immunity, provides 'self-adjuvanting' activity, can mimic natural IFV infection, and confers seamless protection against mucosal pathogens. Moreover, this vector can be developed as a low-cost, rapid-response vaccine that can be quickly manufactured. Therefore, an adenovirus vector encoding conserved influenza antigens holds promise in the development of a universal influenza vaccine. This review will summarize the progress in adenovirus-vectored universal flu vaccines and discuss future novel approaches.

Which Dengue Vaccine Approach Is the Most Promising, and Should We Be Concerned about Enhanced Disease after Vaccination? The Challenges of a Dengue Vaccine.

PubMed

Screaton, Gavin; Mongkolsapaya, Juthathip

2017-07-17

A dengue vaccine has been pursued for more than 50 years and, unlike other flaviviral vaccines such as that against yellow fever, progress has been slow. In this review, we describe progress toward the first licensed dengue vaccine Dengvaxia, which does not give complete protection against disease. The antibody response to the dengue virion is reviewed, highlighting immunodominant yet poorly neutralizing responses in the context of a highly dynamic structurally flexible dengue virus particle. Finally, we review recent evidence for cross-reactivity between antibody responses to Zika and dengue viruses, which may further complicate the development of broadly protective dengue virus vaccines. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

Effect of vaccination against leptospirosis on the frequency, days to recurrence and progression of disease in horses with equine recurrent uveitis.

PubMed

Rohrbach, Barton W; Ward, Daniel A; Hendrix, Diane V H; Cawrse-Foss, Margaret; Moyers, Tammy D

2005-01-01

To evaluate the effect of vaccination against leptospirosis on frequency and days to recurrence of uveitis and progression of disease in horses with equine recurrent uveitis (ERU). Forty-one horses with ERU. Horses were randomly assigned to experimental (vaccinated) or control groups. Vaccine containing six serovars of Leptospira or placebo was administered, an ophthalmic examination performed and blood samples drawn on days 0, 28, 180 and 365. Antibody titers were measured against each serovar. Recurrence of uveitis was verified by ophthalmic examination. Results of the initial and final ophthalmic examinations were compared and progression of disease defined as an increase in extent of synechiae, or development of new or progression of an existing cataract. Vaccination increased the average geometric mean serum antibody titer from 225 on day 0, to 4077 and 593 on days 28 and 180, respectively. After the second vaccination, days to first recurrence was significantly longer (median 126 days; range 24-231 days) when compared with controls (median 86 days; range 14-192 days, P=0.04). Recurrence of ERU was observed among 7/20 (35%) vaccinated horses and 12/21 (57%) controls; however, this difference was not statistically significant (P=0.061, OR 0.25, 95% CI 0.06, 1.07). More horses in the experimental group 13/20 (65%) experienced progression of disease when compared with controls 12/21(57%); however, this difference was statistically nonsignificant (P=0.35). Vaccine significantly increased days to recurrence, but failed to slow the progression of disease. These data do not support the use of vaccination against leptospirosis as adjunct therapy for the routine treatment of horses with ERU.

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.

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.

In vitro Studies of Sandfly Fever Viruses and Their Potential Significance for Vaccine Development.

DTIC Science & Technology

1981-02-01

34 - "’: / AD In vitro Studies of Sandfly Fever Viruses and Their Potential Significance for Vaccine Development Annual Progress Report by CO Jonathan F. Smith...Significance for Vaccine 1 gR1 Development 6 WPW"a EOTHmaei AUTHOV&PSI CONTRACt OR GRANT NUMSERWa Jonahan . Smth, h.D.DAMD-17-78-C-8056 P6EftJrPORim...antibodies, post-translational processing, Immunoprecipitation, antigen purification, In vitro translation, passive transfer, vaccines _26. AEISTRACTMO

[Rabies vaccines: Current status and prospects for development].

PubMed

Starodubova, E S; Preobrazhenskaia, O V; Kuzmenko, Y V; Latanova, A A; Yarygina, E I; Karpov, V L

2015-01-01

Rabies is an infectious disease among humans and animals that remains incurable, despite its longstanding research history. The only way to prevent the disease is prompt treatment, including vaccination as an obligatory component and administration of antirabies immunoglobulin as a supplement. Since the first antirabies vaccination performed in the 19th century, a large number of different rabies vaccines have been developed. Progress in molecular biology and biotechnology enabled the development of effective and safe technologies of vaccine production. Currently, new-generation vaccines are being developed based on recombinant rabies virus strains or on the production of an individual recombinant rabies antigen-glycoprotein (G protein), either as a component of nonpathogenic viruses, or in plants, or in the form of DNA vaccines. In this review, the main modern trends in the development of rabies vaccines have been discussed.

The global roadmap for advancing development of vaccines against sexually transmitted infections: Update and next steps.

PubMed

Gottlieb, Sami L; Deal, Carolyn D; Giersing, Birgitte; Rees, Helen; Bolan, Gail; Johnston, Christine; Timms, Peter; Gray-Owen, Scott D; Jerse, Ann E; Cameron, Caroline E; Moorthy, Vasee S; Kiarie, James; Broutet, Nathalie

2016-06-03

In 2014, the World Health Organization, the US National Institutes of Health, and global technical partners published a comprehensive roadmap for development of new vaccines against sexually transmitted infections (STIs). Since its publication, progress has been made in several roadmap activities: obtaining better epidemiologic data to establish the public health rationale for STI vaccines, modeling the theoretical impact of future vaccines, advancing basic science research, defining preferred product characteristics for first-generation vaccines, and encouraging investment in STI vaccine development. This article reviews these overarching roadmap activities, provides updates on research and development of individual vaccines against herpes simplex virus, Chlamydia trachomatis, Neisseria gonorrhoeae, and Treponema pallidum, and discusses important next steps to advance the global roadmap for STI vaccine development. Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

Engineered human vaccines

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

Sandhu, J.S.

1994-01-01

The limitations of human vaccines in use at present and the design requirements for a new generation of human vaccines are discussed. The progress in engineering of human vaccines for bacteria, viruses, parasites, and cancer is reviewed, and the data from human studies with the engineered vaccines are discussed, especially for cancer and AIDS vaccines. The final section of the review deals with the possible future developments in the field of engineered human vaccines and the requirement for effective new human adjuvants.

HSV-2 Vaccine: Current Status and Insight into Factors for Developing an Efficient Vaccine

PubMed Central

Zhu, Xiao-Peng; Muhammad, Zaka S.; Wang, Jian-Guang; Lin, Wu; Guo, Shi-Kun; Zhang, Wei

2014-01-01

Herpes simplex virus type 2 (HSV-2), a globally sexually transmitted virus, and also one of the main causes of genital ulcer diseases, increases susceptibility to HIV-1. Effective vaccines to prevent HSV-2 infection are not yet available, but are currently being developed. To facilitate this process, the latest progress in development of these vaccines is reviewed in this paper. A summary of the most promising HSV-2 vaccines tested in animals in the last five years is presented, including the main factors, and new ideas for developing an effective vaccine from animal experiments and human clinical trials. Experimental results indicate that future HSV-2 vaccines may depend on a strategy that targets mucosal immunity. Furthermore, estradiol, which increases the effectiveness of vaccines, may be considered as an adjuvant. Therefore, this review is expected to provide possible strategies for development of future HSV-2 vaccines. PMID:24469503

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.

Mucosal Vaccine Development Based on Liposome Technology

PubMed Central

Norling, Karin; Bally, Marta; Höök, Fredrik

2016-01-01

Immune protection against infectious diseases is most effective if located at the portal of entry of the pathogen. Hence, there is an increasing demand for vaccine formulations that can induce strong protective immunity following oral, respiratory, or genital tract administration. At present, only few mucosal vaccines are found on the market, but recent technological advancements and a better understanding of the principles that govern priming of mucosal immune responses have contributed to a more optimistic view on the future of mucosal vaccines. Compared to live attenuated vaccines, subcomponent vaccines, most often protein-based, are considered safer, more stable, and less complicated to manufacture, but they require the addition of nontoxic and clinically safe adjuvants to be effective. In addition, another limiting factor is the large antigen dose that usually is required for mucosal vaccines. Therefore, the combination of mucosal adjuvants with the recent progress in nanoparticle technology provides an attractive solution to these problems. In particular, the liposome technology is ideal for combining protein antigen and adjuvant into an effective mucosal vaccine. Here, we describe and discuss recent progress in nanoparticle formulations using various types of liposomes that convey strong promise for the successful development of the next generation of mucosal vaccines. PMID:28127567

Reducing empiricism in malaria vaccine design.

PubMed

Moorthy, Vasee S; Kieny, Marie Paule

2010-03-01

Gains in the control of malaria and the promising progress of a malaria vaccine that is partly efficacious do not reduce the need for a high-efficacy vaccine in the longer term. Evidence supports the feasibility of developing a highly efficacious malaria vaccine. However, design of candidate malaria vaccines remains empirical and is necessarily based on many unproven assumptions because much of the knowledge needed to design vaccines and to predict efficacy is not available. Data to inform key questions of vaccine science might allow the design of vaccines to progress to a less empirical stage, for example through availability of assay results associated with vaccine efficacy. We discuss six strategic gaps in knowledge that contribute to empiricism in the design of vaccines. Comparative evaluation, assay and model standardisation, greater sharing of information, collaboration and coordination between groups, and rigorous evaluation of existing datasets are steps that can be taken to enable reductions in empiricism over time. 2010 Elsevier Ltd. All rights reserved.

Universal influenza vaccines, a dream to be realized soon.

PubMed

Zhang, Han; Wang, Li; Compans, Richard W; Wang, Bao-Zhong

2014-04-29

Due to frequent viral antigenic change, current influenza vaccines need to be re-formulated annually to match the circulating strains for battling seasonal influenza epidemics. These vaccines are also ineffective in preventing occasional outbreaks of new influenza pandemic viruses. All these challenges call for the development of universal influenza vaccines capable of conferring broad cross-protection against multiple subtypes of influenza A viruses. Facilitated by the advancement in modern molecular biology, delicate antigen design becomes one of the most effective factors for fulfilling such goals. Conserved epitopes residing in virus surface proteins including influenza matrix protein 2 and the stalk domain of the hemagglutinin draw general interest for improved antigen design. The present review summarizes the recent progress in such endeavors and also covers the encouraging progress in integrated antigen/adjuvant delivery and controlled release technology that facilitate the development of an affordable universal influenza vaccine.

Universal Influenza Vaccines, a Dream to Be Realized Soon

PubMed Central

Zhang, Han; Wang, Li; Compans, Richard W.; Wang, Bao-Zhong

2014-01-01

Due to frequent viral antigenic change, current influenza vaccines need to be re-formulated annually to match the circulating strains for battling seasonal influenza epidemics. These vaccines are also ineffective in preventing occasional outbreaks of new influenza pandemic viruses. All these challenges call for the development of universal influenza vaccines capable of conferring broad cross-protection against multiple subtypes of influenza A viruses. Facilitated by the advancement in modern molecular biology, delicate antigen design becomes one of the most effective factors for fulfilling such goals. Conserved epitopes residing in virus surface proteins including influenza matrix protein 2 and the stalk domain of the hemagglutinin draw general interest for improved antigen design. The present review summarizes the recent progress in such endeavors and also covers the encouraging progress in integrated antigen/adjuvant delivery and controlled release technology that facilitate the development of an affordable universal influenza vaccine. PMID:24784572

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.

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.

Progress in Developing Virus-like Particle Influenza Vaccines

PubMed Central

Quan, Fu-Shi; Lee, Young-Tae; Kim, Ki-Hye; Kim, Min-Chul; Kang, Sang-Moo

2016-01-01

Summary Recombinant vaccines based on virus-like particles (VLPs) or nanoparticles have been successful in their safety and efficacy in preclinical and clinical studies. The technology of expressing enveloped VLP vaccines has combined with molecular engineering of proteins in membrane-anchor and immunogenic forms mimicking the native conformation of surface proteins on the enveloped viruses. This review summarizes recent developments in influenza VLP vaccines against seasonal, pandemic, and avian influenza viruses from the perspective of use in humans. The immunogenicity and efficacies of influenza VLP vaccine in the homologous and cross-protection were reviewed. Discussions include limitations of current influenza vaccination strategies and future directions to confer broadly cross protective new influenza vaccines as well as vaccination. PMID:27058302

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.

Refining the approach to vaccines against influenza A viruses with pandemic potential

PubMed Central

Czako, Rita; Subbarao, Kanta

2015-01-01

Vaccination is the most effective strategy for prevention and control of influenza. Timely production and deployment of seasonal influenza vaccines is based on an understanding of the epidemiology of influenza and on global disease and virologic surveillance. Experience with seasonal influenza vaccines guided the initial development of pandemic influenza vaccines. A large investment in pandemic influenza vaccines in the last decade has resulted in much progress and a body of information that can now be applied to refine the established paradigm. Critical and complementary considerations for pandemic influenza vaccines include improved assessment of the pandemic potential of animal influenza viruses, proactive development and deployment of pandemic influenza vaccines, and application of novel platforms and strategies for vaccine production and administration. PMID:26587050

Working towards dengue as a vaccine-preventable disease: challenges and opportunities.

PubMed

Shrivastava, Ambuj; Tripathi, Nagesh K; Dash, Paban K; Parida, Manmohan

2017-10-01

Dengue is an emerging viral disease that affects the human population around the globe. Recent advancements in dengue virus research have opened new avenues for the development of vaccines against dengue. The development of a vaccine against dengue is a challenging task because any of the four serotypes of dengue viruses can cause disease. The development of a dengue vaccine aims to provide balanced protection against all the serotypes. Several dengue vaccine candidates are in the developmental stages such as inactivated, live attenuated, recombinant subunit, and plasmid DNA vaccines. Area covered: The authors provide an overview of the progress made in the development of much needed dengue vaccines. The authors include their expert opinion and their perspectives for future developments. Expert opinion: Human trials of a live attenuated tetravalent chimeric vaccine have clearly demonstrated its potential as a dengue vaccine. Other vaccine candidate molecules such as DENVax, a recombinant chimeric vaccine andTetraVax, are at different stages of development at this time. The authors believe that the novel strategies for testing and improving the immune response of vaccine candidates in humans will eventually lead to the development of a successful dengue vaccine in future.

Ebolavirus Vaccines for Humans and Apes

PubMed Central

Fausther-Bovendo, Hugues; Mulangu, Sabue

2012-01-01

Due to high case fatality proportions, person-to-person transmission, and potential use in bioterrorism, the development of a vaccine against ebolavirus remains a top priority. Although no licensed vaccine or treatment against ebolavirus is currently available, progress in preclinical testing of countermeasures has been made. Here, we will review ebolavirus vaccine candidates and considerations for their use in humans and wild apes. PMID:22560007

Vaccines to combat the neglected tropical diseases.

PubMed

Bethony, Jeffrey M; Cole, Rhea N; Guo, Xiaoti; Kamhawi, Shaden; Lightowlers, Marshall W; Loukas, Alex; Petri, William; Reed, Steven; Valenzuela, Jesus G; Hotez, Peter J

2011-01-01

The neglected tropical diseases (NTDs) represent a group of parasitic and related infectious diseases such as amebiasis, Chagas disease, cysticercosis, echinococcosis, hookworm, leishmaniasis, and schistosomiasis. Together, these conditions are considered the most common infections in low- and middle-income countries, where they produce a level of global disability and human suffering equivalent to better known conditions such as human immunodeficiency virus/acquired immunodeficiency syndrome and malaria. Despite their global public health importance, progress on developing vaccines for NTD pathogens has lagged because of some key technical hurdles and the fact that these infections occur almost exclusively in the world's poorest people living below the World Bank poverty line. In the absence of financial incentives for new products, the multinational pharmaceutical companies have not embarked on substantive research and development programs for the neglected tropical disease vaccines. Here, we review the current status of scientific and technical progress in the development of new neglected tropical disease vaccines, highlighting the successes that have been achieved (cysticercosis and echinococcosis) and identifying the challenges and opportunities for development of new vaccines for NTDs. Also highlighted are the contributions being made by non-profit product development partnerships that are working to overcome some of the economic challenges in vaccine manufacture, clinical testing, and global access. © 2010 John Wiley & Sons A/S.

Vaccines to combat the neglected tropical diseases

PubMed Central

Bethony, Jeffrey M.; Cole, Rhea N.; Guo, Xiaoti; Kamhawi, Shaden; Lightowlers, Marshall W.; Loukas, Alex; Petri, William; Reed, Steven; Valenzuela, Jesus G.; Hotez, Peter J.

2012-01-01

Summary The neglected tropical diseases (NTDs) represent a group of parasitic and related infectious diseases such as amebiasis, Chagas disease, cysticercosis, echinococcosis, hookworm, leishmaniasis, and schistosomiasis. Together, these conditions are considered the most common infections in low- and middle-income countries, where they produce a level of global disability and human suffering equivalent to better known conditions such as human immunodeficiency virus/acquired immunodeficiency syndrome and malaria. Despite their global public health importance, progress on developing vaccines for NTD pathogens has lagged because of some key technical hurdles and the fact that these infections occur almost exclusively in the world’s poorest people living below the World Bank poverty line. In the absence of financial incentives for new products, the multinational pharmaceutical companies have not embarked on substantive research and development programs for the neglected tropical disease vaccines. Here, we review the current status of scientific and technical progress in the development of new neglected tropical disease vaccines, highlighting the successes that have been achieved (cysticercosis and echinococcosis) and identifying the challenges and opportunities for development of new vaccines for NTDs. Also highlighted are the contributions being made by non-profit product development partnerships that are working to overcome some of the economic challenges in vaccine manufacture, clinical testing, and global access. PMID:21198676

Cloning and Expression of Genes for Dengue Virus Type-2 Encoded-Antigens for Rapid Diagnosis and Vaccine Development

DTIC Science & Technology

1988-10-31

00 0 Cloning and Expression of Genes for Dengue Virus (Type-2 Encoded-Antigens for Rapid ODiagnosis and Vaccine DevelopmentN| ANNUAL PROGRESS REPORT...11. TITLE (include Security Classification) Cloning and Expression of Genes f or Dengue Virus Type 2 Fncoded Antigens for Rapid Diagnosis and Vaccine ...epidemics in Central and South Americas and the Caribbean is a cause of major concern. An effective vaccine is not available to protect individuals

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.

Recombinant and epitope-based vaccines on the road to the market and implications for vaccine design and production.

PubMed

Oyarzún, Patricio; Kobe, Bostjan

2016-03-03

Novel vaccination approaches based on rational design of B- and T-cell epitopes - epitope-based vaccines - are making progress in the clinical trial pipeline. The epitope-focused recombinant protein-based malaria vaccine (termed RTS,S) is a next-generation approach that successfully reached phase-III trials, and will potentially become the first commercial vaccine against a human parasitic disease. Progress made on methods such as recombinant DNA technology, advanced cell-culture techniques, immunoinformatics and rational design of immunogens are driving the development of these novel concepts. Synthetic recombinant proteins comprising both B- and T-cell epitopes can be efficiently produced through modern biotechnology and bioprocessing methods, and can enable the induction of large repertoires of immune specificities. In particular, the inclusion of appropriate CD4+ T-cell epitopes is increasingly considered a key vaccine component to elicit robust immune responses, as suggested by results coming from HIV-1 clinical trials. In silico strategies for vaccine design are under active development to address genetic variation in pathogens and several broadly protective "universal" influenza and HIV-1 vaccines are currently at different stages of clinical trials. Other methods focus on improving population coverage in target populations by rationally considering specificity and prevalence of the HLA proteins, though a proof-of-concept in humans has not been demonstrated yet. Overall, we expect immunoinformatics and bioprocessing methods to become a central part of the next-generation epitope-based vaccine development and production process.

Prospects for new viral vaccines.

PubMed

Marmion, B P

1980-08-11

Animal virology has made outstanding contributions to preventive medicine by the development of vaccines for the control of infectious disease in man and animals. Cost-benefit analysis indicates substantial savings in health care costs from the control of diseases such as smallpox, poliomyelitis, yellow fever and measels. Areas for further development include vaccines for influenza (living, attenuated virus), the herpes group (varicella: cytomegalovirus), respiratory syncytial virus, rotavirus and hepatitis A, B, and non A/non B. The general options for vaccine formulation are discussed with particular emphasis on approaches with the use of viral genetics to 'tailor make' vaccine viruses with defined growth potential in laboratory systems, low pathogenicity, and defined antigens. Current progress with the development of an inactivated hepatitis B vaccine is reviewed as a case study in vaccine development. The impact of recent experiments in cloning hepatitis B virus DNA in E. coli on the production of a purified viral polypeptide vaccine is assessed.

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

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.

Progress towards development of an HIV vaccine: report of the AIDS Vaccine 2009 Conference.

PubMed

Ross, Anna Laura; Bråve, Andreas; Scarlatti, Gabriella; Manrique, Amapola; Buonaguro, Luigi

2010-05-01

The search for an HIV/AIDS vaccine is steadily moving ahead, generating and validating new concepts in terms of novel vectors for antigen delivery and presentation, new vaccine and adjuvant strategies, alternative approaches to design HIV-1 antigens for eliciting protective cross-neutralising antibodies, and identification of key mechanisms in HIV infection and modulation of the immune system. All these different perspectives are contributing to the unprecedented challenge of developing a protective HIV-1 vaccine. The high scientific value of this massive effort is its great impact on vaccinology as a whole, providing invaluable scientific information for the current and future development of new preventive vaccine as well as therapeutic knowledge-based infectious-disease and cancer vaccines. Copyright 2010 Elsevier Ltd. All rights reserved.

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

Ebolavirus vaccines for humans and apes.

PubMed

Fausther-Bovendo, Hugues; Mulangu, Sabue; Sullivan, Nancy J

2012-06-01

Because of high case fatality proportions, person-to-person transmission, and potential use in bioterrorism, the development of a vaccine against ebolavirus remains a top priority. Although no licensed vaccine or treatment against ebolavirus is currently available, progress in preclinical testing of countermeasures has been made. Here, we will review ebolavirus vaccine candidates and considerations for their use in humans and wild apes. Published by Elsevier B.V.

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.

New approaches for Helicobacter vaccine development--difficulties and progress.

PubMed

Jagusztyn-Krynicka, Elzbieta K; Godlewska, Renata

2008-01-01

Despite the enormous progress in understanding the process of bacterial pathogenesis and interactions of pathogens with eucaryotic cells the infectious diseases still remain the main cause of human premature deaths. It is now recognized that Helicobacter pylori infects about half of the world's population. Based on results of clinical studies the World Health Organization has assigned H. pylori as a class I carcinogen. The review presents new achievements aimed at construction efficient and safe anti-Helicobacter vaccine. We discuss the new global technologies such as immunoproteomics employed for selecting new candidates for vaccine construction as well as new vaccine delivery systems. The review presents also our knowledge concerning H. pylori interaction with immune system which might facilitate modulation of the host immune system by specific adjuvant included into vaccine.

The Children's Vaccine Initiative and vaccine supply: the role of the public sector.

PubMed

van Noort, R B

1992-01-01

'Children represent the most vulnerable segment of every society--and they are our present and future. Good health, especially of children, promotes personal and national development. Scientific progress, matched with improved capacities of all countries to immunize their children, provides an unparalleled opportunity to save additional lives and prevent additional millions of disabilities annually through a Children's Vaccine Initiative.' (The Netherlands Minister for Development Co-operation.)

Development of Leishmania vaccines: predicting the future from past and present experience

PubMed Central

Mutiso, Joshua Muli; Macharia, John Chege; Kiio, Maria Ndunge; Ichagichu, James Maina; Rikoi, Hitler; Gicheru, Michael Muita

2013-01-01

Leishmaniasis is a disease that ranges in severity from skin lesions to serious disfigurement and fatal systemic infection. Resistance to infection is associated with a T-helper-1 immune response that activates macrophages to kill the intracellular parasite in a nitric oxide-dependent manner. Conversely, disease progression is generally associated with a T-helper-2 response that activates humoral immunity. Current control is based on chemotherapeutic treatments which are expensive, toxic and associated with high relapse and resistance rates. Vaccination remains the best hope for control of all forms of the disease, and the development of a safe, effective and affordable antileishmanial vaccine is a critical global public-health priority. Extensive evidence from studies in animal models indicates that solid protection can be achieved by immunization with defined subunit vaccines or live-attenuated strains of Leishmania. However, to date, no vaccine is available despite substantial efforts by many laboratories. Major impediments in Leishmania vaccine development include: lack of adequate funding from national and international agencies, problems related to the translation of data from animal models to human disease, and the transition from the laboratory to the field. Furthermore, a thorough understanding of protective immune responses and generation and maintenance of the immunological memory, an important but least-studied aspect of antiparasitic vaccine development, during Leishmania infection is needed. This review focuses on the progress of the search for an effective vaccine against human and canine leishmaniasis. PMID:23554800

Immunogenicity and efficacy of three recombinant subunit Pasteurella multocida toxin vaccines against progressive atrophic rhinitis in pigs

USGS Publications Warehouse

Liao, Chih-Ming; Huang, Chienjin; Hsuan, Shih-Ling; Chen, Zeng-Weng; Lee, Wei-Cheng; Liu, Cheng-I; Winton, James R.; Chien, Maw-Sheng

2006-01-01

Three short fragments of recombinant subunit Pasteurella multocida toxin (rsPMT) were constructed for evaluation as candidate vaccines against progressive atrophic rhinitis (PAR) of swine. PMT-specific antibody secreting cells and evidence of cellular immunity were detected in rsPMT-immunized pigs following authentic PMT challenge or homologous antigen booster. Piglets immunized with rsPMT fragments containing either the N-terminal or the C-terminal portions of PMT developed high titers of neutralizing antibodies. Pregnant sows immunized with rsPMT had higher levels of maternal antibodies in their colostrum than did those immunized with a conventional PAR-toxoid vaccine. Offspring from rsPMT vaccinated sows had better survival after challenge with a five-fold lethal dose of authentic PMT and had better growth performance after challenge with a sublethal dose of toxin. Our findings indicate these non-toxic rsPMT proteins are attractive candidates for development of a subunit vaccine against PAR in pigs.

An Overview of Current Approaches Toward the Treatment and Prevention of West Nile Virus Infection.

PubMed

Acharya, Dhiraj; Bai, Fengwei

2016-01-01

The persistence of West Nile virus (WNV) infections throughout the USA since its inception in 1999 and its continuous spread throughout the globe calls for an urgent need of effective treatments and prevention measures. Although the licensing of several WNV vaccines for veterinary use provides a proof of concept, similar efforts on the development of an effective vaccine for humans remain still unsuccessful. Increased understanding of biology and pathogenesis of WNV together with recent technological advancements have raised hope that an effective WNV vaccine may be available in the near future. In addition, rapid progress in the structural and functional characterization of WNV and other flaviviral proteins have provided a solid base for the design and development of several classes of inhibitors as potential WNV therapeutics. Moreover, the therapeutic monoclonal antibodies demonstrate an excellent efficacy against WNV in animal models and represent a promising class of WNV therapeutics. However, there are some challenges as to the design and development of a safe and efficient WNV vaccine or therapeutic. In this chapter, we discuss the current approaches, progress, and challenges toward the development of WNV vaccines, therapeutic antibodies, and antiviral drugs.

Genome-based approaches to develop vaccines against bacterial pathogens.

PubMed

Serruto, Davide; Serino, Laura; Masignani, Vega; Pizza, Mariagrazia

2009-05-26

Bacterial infectious diseases remain the single most important threat to health worldwide. Although conventional vaccinology approaches were successful in conferring protection against several diseases, they failed to provide efficacious solutions against many others. The advent of whole-genome sequencing changed the way to think about vaccine development, enabling the targeting of possible vaccine candidates starting from the genomic information of a single bacterial isolate, with a process named reverse vaccinology. As the genomic era progressed, reverse vaccinology has evolved with a pan-genome approach and multi-strain genome analysis became fundamental for the design of universal vaccines. This review describes the applications of genome-based approaches in the development of new vaccines against bacterial pathogens.

Measurements of Immune Responses for Establishing Correlates of Vaccine Protection Against HIV

PubMed Central

Burgers, Wendy A.; Manrique, Amapola; McKinnon, Lyle R.; Reynolds, Matthew R.; Rolland, Morgane; Blish, Catherine; Chege, Gerald K.; Curran, Rhonda; Fischer, William; Herrera, Carolina; Sather, D. Noah

2012-01-01

Abstract Well-defined correlates of protective immunity are an essential component of rational vaccine development. Despite years of basic science and three HIV vaccine efficacy trials, correlates of immunological protection from HIV infection remain undefined. In December 2010, a meeting of scientists engaged in basic and translational work toward developing HIV-1 vaccines was convened. The goal of this meeting was to discuss current opportunities and optimal approaches for defining correlates of protection, both for ongoing and future HIV-1 vaccine candidates; specific efforts were made to engage young scientists. We discuss here the highlights from the meeting regarding the progress made and the way forward for a protective HIV-1 vaccine. PMID:21861777

Current strategic thinking for the development of a trivalent alphavirus vaccine for human use.

PubMed

Wolfe, Daniel N; Heppner, D Gray; Gardner, Shea N; Jaing, Crystal; Dupuy, Lesley C; Schmaljohn, Connie S; Carlton, Kevin

2014-09-01

Vaccinations against the encephalitic alphaviruses (western, eastern, and Venezuelan equine encephalitis virus) are of significant interest to biological defense, public health, and agricultural communities alike. Although vaccines licensed for veterinary applications are used in the Western Hemisphere and attenuated or inactivated viruses have been used under Investigational New Drug status to protect at-risk personnel, there are currently no licensed vaccines for use in humans. Here, we will discuss the need for a trivalent vaccine that can protect humans against all three viruses, recent progress to such a vaccine, and a strategy to continue development to Food and Drug Administration licensure. © The American Society of Tropical Medicine and Hygiene.

IT-26IDENTIFICATION OF PSEUDO-PROGRESSION IN NEW DIAGNOSED GLIOBLASTOMA (GBM) IN A RANDOMIZED PHASE 2 OF ICT-107: MRI AND PATHOLOGY CORRELATION

PubMed Central

Phuphanich, Surasak; Yu, John; Bannykh, Serguei; Zhu, Jay-Jiguang

2014-01-01

BACKGROUND: Previously reports of pseudo-progression in patients with brain tumor after therapeutic vaccines in pediatric and adult glioma (Pollack, JCO online on June 2, 2014 and Okada, JCO Jan 20, 2011; 29: 330-336) demonstrated that RANO criteria for tumor progression may not be adequate for immunotherapy trials. Similar observations were also seen in other checkpoint inhibitor in melanoma and NSLSC. METHODS: We identified 2 patients, who developed tumor progression by RANO criteria, underwent surgery following enrollment in a phase 2 randomized ICT-107 (an autologous vaccine consisting of patient dendritic cells pulsed with peptides from AIM-2, TRP-2, HER2/neu, IL-13Ra2, gp100, MAGE1) after radiation and Temozolomide (TMZ). RESULTS: The first case is a 69 years old Chinese male, who underwent 1st surgery of gross total resection right occipital GBM on 10/26/2011. Subsequently he received 19 cycles of TMZ and 9 vaccines/placebo. MRI from 7/2/2013 showed enhancement surrounding surgical cavity. After 2nd surgery, pathology showed only rare residual tumor cells with macrophages and positive CD 8 cells. He continued on this vaccine program and MRI showed more progression with finger-like extension into parietal lobe 4 months later. The 3rd surgery also showed extensive reactive changes with no active tumor cells. For 2nd case, a 62 years old male, who underwent first surgery on 7/11/2011 of right temporal lobe, developed 2 areas of enhancement after 6 cycles of TMZ and 7 vaccines/placebo on 4/18/2012. With 2nd surgery, pathology showed reactive gliosis without active tumor. The subject continued in this trial. CONCLUSION: Pseudo-progression was confirmed by pathology in these 2 patients at 20 and 9 months which were delayed comparing to pseudo-progression observed in patients treated with concurrent XRT/TMZ (3-6 months). Future iRANO criteria development is essential for immunotherapy trials. Accurately identifying and managing such patients is necessary to avoid premature termination of therapy.

Development of a metabolically active, non-replicating sporozoite vaccine to prevent Plasmodium falciparum malaria.

PubMed

Hoffman, Stephen L; Billingsley, Peter F; James, Eric; Richman, Adam; Loyevsky, Mark; Li, Tao; Chakravarty, Sumana; Gunasekera, Anusha; Chattopadhyay, Rana; Li, Minglin; Stafford, Richard; Ahumada, Adriana; Epstein, Judith E; Sedegah, Martha; Reyes, Sharina; Richie, Thomas L; Lyke, Kirsten E; Edelman, Robert; Laurens, Matthew B; Plowe, Christopher V; Sim, B Kim Lee

2010-01-01

Immunization of volunteers by the bite of mosquitoes carrying radiation-attenuated Plasmodium falciparum sporozoites protects greater than 90% of such volunteers against malaria, if adequate numbers of immunizing biting sessions and sporozoite-infected mosquitoes are used. Nonetheless, until recently it was considered impossible to develop, license and commercialize a live, whole parasite P. falciparum sporozoite (PfSPZ) vaccine. In 2003 Sanaria scientists reappraised the potential impact of a metabolically active, non-replicating PfSPZ vaccine, and outlined the challenges to producing such a vaccine. Six years later, significant progress has been made in overcoming these challenges. This progress has enabled the manufacture and release of multiple clinical lots of a 1(st) generation metabolically active, non-replicating PfSPZ vaccine, the Sanaria PfSPZ Vaccine, submission of a successful Investigational New Drug application to the US Food and Drug Administration, and initiation of safety, immunogenicity and protective efficacy studies in volunteers in MD, US. Efforts are now focused on how best to achieve submission of a successful Biologics License Application and introduce the vaccine to the primary target population of African children in the shortest possible period of time. This will require implementation of a systematic, efficient clinical development plan. Short term challenges include optimizing the (1) efficiency and scale up of the manufacturing process and quality control assays, (2) dosage regimen and method of administration, (3) potency of the vaccine, and (4) logistics of delivering the vaccine to those who need it most, and finalizing the methods for vaccine stabilization and attenuation. A medium term goal is to design and build a facility for manufacturing highly potent and stable vaccine for pivotal Phase 3 studies and commercial launch.

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

Complexity of Human Antibody Response to Dengue Virus: Implication for Vaccine Development.

PubMed

Tsai, Wen-Yang; Lin, Hong-En; Wang, Wei-Kung

2017-01-01

The four serotypes of dengue virus (DENV) are the leading cause of arboviral diseases in humans. Decades of efforts have made remarkable progress in dengue vaccine development. Despite the first dengue vaccine (dengvaxia from Sanofi Pasteur), a live-attenuated tetravalent chimeric yellow fever-dengue vaccine, has been licensed by several countries since 2016, its overall moderate efficacy (56.5-60.8%) in the presence of neutralizing antibodies during the Phase 2b and 3 trials, lower efficacy among dengue naïve compared with dengue experienced individuals, and increased risk of hospitalization among young children during the follow-up highlight the need for a better understanding of humoral responses after natural DENV infection. Recent studies of more than 300 human monoclonal antibodies (mAbs) against DENV have led to the discovery of several novel epitopes on the envelope protein recognized by potent neutralizing mAbs. This information together with in-depth studies on polyclonal sera and B-cells following natural DENV infection has tremendous implications for better immunogen design for a safe and effective dengue vaccine. This review outlines the progress in our understanding of mouse mAbs, human mAbs, and polyclonal sera against DENV envelope and precursor membrane proteins, two surface proteins involved in vaccine development, following natural infection; analyses of these discoveries have provided valuable insight into new strategies involving molecular technology to induce more potent neutralizing antibodies and less enhancing antibodies for next-generation dengue vaccine development.

Complexity of Human Antibody Response to Dengue Virus: Implication for Vaccine Development

PubMed Central

Tsai, Wen-Yang; Lin, Hong-En; Wang, Wei-Kung

2017-01-01

The four serotypes of dengue virus (DENV) are the leading cause of arboviral diseases in humans. Decades of efforts have made remarkable progress in dengue vaccine development. Despite the first dengue vaccine (dengvaxia from Sanofi Pasteur), a live-attenuated tetravalent chimeric yellow fever-dengue vaccine, has been licensed by several countries since 2016, its overall moderate efficacy (56.5–60.8%) in the presence of neutralizing antibodies during the Phase 2b and 3 trials, lower efficacy among dengue naïve compared with dengue experienced individuals, and increased risk of hospitalization among young children during the follow-up highlight the need for a better understanding of humoral responses after natural DENV infection. Recent studies of more than 300 human monoclonal antibodies (mAbs) against DENV have led to the discovery of several novel epitopes on the envelope protein recognized by potent neutralizing mAbs. This information together with in-depth studies on polyclonal sera and B-cells following natural DENV infection has tremendous implications for better immunogen design for a safe and effective dengue vaccine. This review outlines the progress in our understanding of mouse mAbs, human mAbs, and polyclonal sera against DENV envelope and precursor membrane proteins, two surface proteins involved in vaccine development, following natural infection; analyses of these discoveries have provided valuable insight into new strategies involving molecular technology to induce more potent neutralizing antibodies and less enhancing antibodies for next-generation dengue vaccine development. PMID:28775720

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.

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

Delivering vaccines to the people who need them most

PubMed Central

Barocchi, Michèle Anne; Rappuoli, Rino

2015-01-01

Thanks to the Global Alliance for Vaccines and Immunization (GAVI), the Vaccine Fund and the Bill & Melinda Gates Foundation, the global health community has made enormous progress in providing already existing vaccines to developing countries. However, there still exists a gap to develop vaccines for which there is no market in the Western world, owing to low economic incentives for the private sector to justify the investments necessary for vaccine development. In many cases, industry has the technologies, but lacks the impetus to direct resources to develop these vaccine products. The present emergency with the Ebola vaccine provides us an excellent example where a vaccine was feasible several years ago, but the global health community waited for a humanitarian disaster to direct efforts and resources to develop this vaccine. In the beginning of 2015, the first large-scale trials of two experimental vaccines against Ebola virus disease have begun in West Africa. During the past few years, several institutions have dedicated efforts to the development of vaccines against diseases present only in low-income countries. These include the International Vaccine Institute, the Novartis Vaccines Institute for Global Health, the Hilleman Institute, the Sabin Vaccine Institute and the Infectious Disease Research Institute. Nevertheless, solving this problem requires a more significant global effort than that currently invested. These efforts include a clear policy, global coordination of funds dedicated to the development of neglected disease and an agreement on regulatory strategies and incentives for the private sector. PMID:25964460

DNA vaccines in veterinary use

PubMed Central

Redding, Laurel; Werner, David B

2015-01-01

DNA vaccines represent a new frontier in vaccine technology. One important application of this technology is in the veterinary arena. DNA vaccines have already gained a foothold in certain fields of veterinary medicine. However, several important questions must be addressed when developing DNA vaccines for animals, including whether or not the vaccine is efficacious and cost effective compared with currently available options. Another important question to consider is how to apply this developing technology in a wide range of different situations, from the domestic pet to individual fish in fisheries with several thousand animals, to wildlife programs for disease control. In some cases, DNA vaccines represent an interesting option for vaccination, while in others, currently available options are sufficient. This review will examine a number of diseases of veterinary importance and the progress being made in DNA vaccine technology relevant to these diseases, and we compare these with the conventional treatment options available. PMID:19722897

Progress, Prospects, and Problems in Epstein-Barr Virus Vaccine Development

PubMed Central

Balfour, Henry H.

2014-01-01

Epstein-Barr virus (EBV) is responsible for a farrago of acute and chronic human diseases including cancer. A prophylactic vaccine could reduce this disease burden. Several EBV vaccines have been given to humans but none has been sufficiently studied to establish safety and efficacy. EBV vaccine development has been hampered by the lack of an animal model other than subhuman primates, proprietary issues, selection of an appropriate adjuvant, and failure to reach consensus on what an EBV vaccine could or should actually achieve. A recent conference at the U.S. National Institutes of Health emphasizing the global importance of EBV vaccine and advocating a phase 3 trial to prevent infectious mononucleosis should encourage research that could eventually lead to its licensure. PMID:24632197

Global Foot-and-Mouth Disease Research Update and Gap Analysis: 1 - Overview of Global Status and Research Needs.

PubMed

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

2016-06-01

The Global Foot-and-mouth disease (FMD) Research Alliance periodically reviews the state of FMD research to assess progress and to identify new priorities. In this supplement we provide an update of global FMD research, comprising (i) this overview paper, which includes background information with key findings, and papers covering (ii) epidemiology, wildlife and economics, (iii) vaccines, (iv) diagnostics, (v) biotherapeutics and disinfectants, (vi) immunology and (vii) pathogenesis and molecular biology. FMD research publications were reviewed (2011-2015) and activity updates were obtained from 33 FMD research institutes from around the world. Although a continual threat, FMD has been effectively controlled in much of the world using existing tools. However, control remains a challenge in most developing countries, where little has been done to understand the ongoing burden of FMD. More research is needed to support control in endemically infected countries, particularly robust field studies. Traditional FMD vaccines have several limitations including short duration and spectrum of protection, cold chain requirements, and the costs and biosecurity risks associated with vaccine production. Significant progress has been made in the development of novel vaccine candidates, particularly in the use of recombinant vaccines and virus-like particles as an alternative to traditional inactivated whole virus vaccines. Continued investment is needed to turn these developments into improved vaccines produced at scale. Increased knowledge of cellular and mucosal immunity would benefit vaccine development, as would further advances in our ability to enhance vaccine capsid stability. Developments in molecular biology and phylogenetics underlie many of the recent advances in FMD research, including improved vaccines and diagnostics, and improved understanding of FMD epidemiology. Tools for genetic analyses continue to become both more powerful and more affordable enabling them to be used to address an ever-expanding range of questions. This rapidly advancing field potentiates many areas of FMD research and should be prioritized. © 2016 Blackwell Verlag GmbH.

A 2020 vision for vaccines against HIV, tuberculosis and malaria.

PubMed

Rappuoli, Rino; Aderem, Alan

2011-05-26

Acquired immune deficiency syndrome (AIDS), malaria and tuberculosis collectively cause more than five million deaths per year, but have nonetheless eluded conventional vaccine development; for this reason they represent one of the major global public health challenges as we enter the second decade of the twenty-first century. Recent trials have provided evidence that it is possible to develop vaccines that can prevent infection by human immunodeficiency virus (HIV) and malaria. Furthermore, advances in vaccinology, including novel adjuvants, prime-boost regimes and strategies for intracellular antigen presentation, have led to progress in developing a vaccine against tuberculosis. Here we discuss these advances and suggest that new tools such as systems biology and structure-based antigen design will lead to a deeper understanding of mechanisms of protection which, in turn, will lead to rational vaccine development. We also argue that new and innovative approaches to clinical trials will accelerate the availability of these vaccines.

A multiantigen vaccine targeting neu, IGFBP-2, and IGF-IR prevents tumor progression in mice with preinvasive breast disease.

PubMed

Disis, Mary L; Gad, Ekram; Herendeen, Daniel R; Lai, Vy Phan-; Park, Kyong Hwa; Cecil, Denise L; O'Meara, Megan M; Treuting, Piper M; Lubet, Ronald A

2013-12-01

A multiantigen multipeptide vaccine, targeting proteins expressed in preinvasive breast lesions, can stimulate type I CD4(+) T cells which have been shown to be deficient in both patients with breast cancer and mice that develop mammary tumors. Transgenic mice (TgMMTV-neu) were immunized with a multiantigen peptide vaccine specific for neu, insulin-like growth factor-binding protein 2 and insulin-like growth factor receptor-I at a time when some of the animals already had preinvasive lesions (18 weeks of age). Although immunization with each individual antigen was partially effective in inhibiting tumor growth, immunization with the multiantigen vaccine was highly effective, blocking development of palpable lesions in 65% of mice and slowing tumor growth in the infrequent palpable tumors, which did arise. Protection was mediated by CD4(+) T cells, and the few slow-growing tumors that did develop demonstrated a significant increase in intratumoral CD8(+) T cells as compared with controls (P = 0.0007). We also combined the vaccine with agents that were, by themselves, partially effective inhibitors of tumor progression in this model; lapatinib and the RXR agonist bexarotene. Although the combination of lapatinib and vaccination performed similarly to vaccination alone (P = 0.735), bexarotene and vaccination significantly enhanced disease-free survival (P < 0.0001), and approximately 90% of the mice showed no pathologic evidence of carcinomas at one year. The vaccine also demonstrated significant clinical efficacy in an additional transgenic model of breast cancer (TgC3(I)-Tag). Chemoimmunoprevention combinations may be an effective approach to breast cancer prevention even when the vaccine is administered in the presence of subclinical disease.

Development of a transmission-blocking malaria vaccine: progress, challenges, and the path forward.

PubMed

Nunes, Julia K; Woods, Colleen; Carter, Terrell; Raphael, Theresa; Morin, Merribeth J; Diallo, Diadier; Leboulleux, Didier; Jain, Sanjay; Loucq, Christian; Kaslow, David C; Birkett, Ashley J

2014-09-29

New interventions are needed to reduce morbidity and mortality associated with malaria, as well as to accelerate elimination and eventual eradication. Interventions that can break the cycle of parasite transmission, and prevent its reintroduction, will be of particular importance in achieving the eradication goal. In this regard, vaccines that interrupt malaria transmission (VIMT) have been highlighted as an important intervention, including transmission-blocking vaccines that prevent human-to-mosquito transmission by targeting the sexual, sporogonic, or mosquito stages of the parasite (SSM-VIMT). While the significant potential of this vaccine approach has been appreciated for decades, the development and licensure pathways for vaccines that target transmission and the incidence of infection, as opposed to prevention of clinical malaria disease, remain ill-defined. This article describes the progress made in critical areas since 2010, highlights key challenges that remain, and outlines important next steps to maximize the potential for SSM-VIMTs to contribute to the broader malaria elimination and eradication objectives. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Vaccines and immunization strategies for dengue prevention

PubMed Central

Liu, Yang; Liu, Jianying; Cheng, Gong

2016-01-01

Dengue is currently the most significant arboviral disease afflicting tropical and sub-tropical countries worldwide. Dengue vaccines, such as the multivalent attenuated, chimeric, DNA and inactivated vaccines, have been developed to prevent dengue infection in humans, and they function predominantly by stimulating immune responses against the dengue virus (DENV) envelope (E) and nonstructural-1 proteins (NS1). Of these vaccines, a live attenuated chimeric tetravalent DENV vaccine developed by Sanofi Pasteur has been licensed in several countries. However, this vaccine renders only partial protection against the DENV2 infection and is associated with an unexplained increased incidence of hospitalization for severe dengue disease among children younger than nine years old. In addition to the virus-based vaccines, several mosquito-based dengue immunization strategies have been developed to interrupt the vector competence and effectively reduce the number of infected mosquito vectors, thus controlling the transmission of DENV in nature. Here we summarize the recent progress in the development of dengue vaccines and novel immunization strategies and propose some prospective vaccine strategies for disease prevention in the future. PMID:27436365

Collaborative studies on the development of national reference standards for potency determination of H7N9 influenza vaccine

PubMed Central

Li, Changgui; Xu, Kangwei; Hashem, Anwar; Shao, Ming; Liu, Shuzhen; Zou, Yong; Gao, Qiang; Zhang, Yongchao; Yuan, Liyong; Xu, Miao; Li, Xuguang; Wang, Junzhi

2015-01-01

The outbreak of human infections of a novel avian influenza virus A (H7N9) prompted the development of the vaccines against this virus. Like all types of influenza vaccines, H7N9 vaccine must be tested for its potency prior to being used in humans. However, the unavailability of international reference reagents for the potency determination of H7N9 vaccines substantially hinders the progress in vaccine development. To facilitate clinical development, we enlisted 5 participants in a collaborative study to develop critical reagents used in Single Radial Immunodiffusion (SRID), the currently acceptable assay for potency determination of influenza vaccine. Specifically, the hemagglutinin (HA) content of one vaccine bulk for influenza A (H7N9), herein designated as Primary Liquid Standard (PLS), was determined by SDS-PAGE. In addition, the freeze-dried antigen references derived from PLS were prepared to enhance the stability for long term storage. The final HA content of lyophilized antigen references were calibrated against PLS by SRID assay in a collaborative study. Importantly, application of these national reference standards to potency analyses greatly facilitated the development of H7N9 vaccines in China. PMID:25970793

Update on progress in HIV vaccine development.

PubMed

Watkins, David I

2012-01-01

The 19th Conference on Retroviruses and Opportunistic Infections heralded the arrival of a new crop of potent, broadly neutralizing antibodies against HIV. This advance has given the entire vaccine field enormous hope that it will be possible one day to develop an antibody-based vaccine for HIV. However, substantial obstacles still exist in the induction of these antibodies by vaccination, given the enormous number of somatic mutations needed to develop these highly efficient antibodies. It is likely that follicular helper T cells will be involved in the development of these antibodies, and this will be a key area of interest in the future. Cellular immune responses will also be an important part of any vaccine regimen. Evidence showed that protection provided by an attenuated vaccine correlated with the frequency of vaccine-induced helper cells and killer cells, underlining the importance of these key immune cells. An alternative approach to the development of potent neutralizing antibodies was presented as part of an update on the Thai Phase III Vaccine Trial RV144. Data were shown suggesting that binding antibodies may play a role in protection from HIV infection.

Current challenges in the development of vaccines for pneumonic plague

PubMed Central

Smiley, Stephen T

2008-01-01

Inhalation of Yersinia pestis bacilli causes pneumonic plague, a rapidly progressing and exceptionally virulent disease. Extensively antibiotic-resistant Y. pestis strains exist and we currently lack a safe and effective pneumonic plague vaccine. These facts raise concern that Y. pestis may be exploited as a bioweapon. Here, I review the history and status of plague vaccine research and advocate that pneumonic plague vaccines should strive to prime both humoral and cellular immunity. PMID:18324890

Characterization of Prostate-Specific Membrane Antigen (PSMA) for Use in Therapeutic and Diagnostic Strategies against Prostate Cancer

DTIC Science & Technology

2000-07-01

Copenhagen, Copenhagen, Denmark To develop adjuvant therapy for glioma patients vaccination by autologous Neovascularization of blood vessels is...on the physiology of solid Vaccines : Novel Antigens and Vectors I tumors and their response to treatment. #5056 DNA VACCINATION OF BRAIN TUMOR...involvement of Mtsl(S1 0OA4) Cal’-binding protein in DNA vaccination with irradiation of tumor. The induced immunological processes tumour progression and

Researchers See New Patterns in Spread of AIDS Virus; Progress in Development of a Vaccine Sparks Optimism.

ERIC Educational Resources Information Center

Wheeler, David L.

1990-01-01

Reports presented at the Sixth International Conference on Aids are summarized including efforts to develop a vaccine, expansion of the epidemic into new areas, the high rate of infection among Romanian children, the crisis in Africa, and evidence of relapsing behaviors among homosexual men in the United States. (MLW)

Live attenuated pre-erythrocytic malaria vaccines.

PubMed

Keitany, Gladys J; Vignali, Marissa; Wang, Ruobing

2014-01-01

Although recent control measures have significantly reduced malaria cases and deaths in many endemic areas, an effective vaccine will be essential to eradicate this parasitic disease. Malaria vaccine strategies developed to date focus on different phases of the parasite's complex life cycle in the human host and mosquito vector, and include both subunit-based and whole-parasite vaccines. This review focuses on the 3 live-attenuated malaria vaccination strategies that have been tested in humans to date, and discusses their progress, challenges and the immune correlates of protection that have been identified.

Impact of BRICS' investment in vaccine development on the global vaccine market.

PubMed

Kaddar, Miloud; Milstien, Julie; Schmitt, Sarah

2014-06-01

Brazil, the Russian Federation, India, China and South Africa--the countries known as BRICS--have made considerable progress in vaccine production, regulation and development over the past 20 years. In 1993, all five countries were producing vaccines but the processes used were outdated and non-standardized, there was little relevant research and there was negligible international recognition of the products. By 2014, all five countries had strong initiatives for the development of vaccine technology and had greatly improved their national regulatory capacity. South Africa was then the only BRICS country that was not completely producing vaccines. South Africa is now in the process of re-establishing its own vaccine production and passing beyond the stage of simply importing, formulating and filling vaccine bulks. Changes in the public sector's price per dose of selected vaccines, the global market share represented by products from specific manufacturers, and the attractiveness, for multinational companies, of partnership and investment opportunities in BRICS companies have all been analysed. The results indicate that the BRICS countries have had a major impact on vaccine price and availability, with much of that impact attributable to the output of Indian vaccine manufacturers. China is expected to have a greater impact soon, given the anticipated development of Chinese vaccine manufacturers in the near future. BRICS' accomplishments in the field of vaccine development are expected to reshape the global vaccine market and accelerate access to vaccines in the developing world. The challenge is to turn these expectations into strategic actions and practical outcomes.

Development of respiratory syncytial virus (RSV) vaccines for infants.

PubMed

Gerretsen, Hannah E; Sande, Charles J

2017-06-01

2017 will mark the 60 th anniversary since the first isolation of RSV in children. In spite of concerted efforts over all these years, the goal of developing an effective vaccine against paediatric RSV disease has remained elusive. One of the main hurdles standing in the way of an effective vaccine is the fact that the age incidence of severe disease peaks within the first 3 months of life, providing limited opportunity for intervention. In addition to this complexity, the spectre of failed historical vaccines, which increased the risk of illness and death upon subsequent natural infection, has substantially increased the safety criteria against which modern vaccines will be assessed. This review traces the history of RSV vaccine development for young infants and analyses the potential reasons for the failure of historic vaccines. It also discusses recent breakthroughs in vaccine antigen design and the progressive evolution of platforms for the delivery of these antigens to seronegative infants. © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Therapeutic vaccination to treat chronic infectious diseases

PubMed Central

Boukhebza, Houda; Bellon, Nadine; Limacher, Jean Marc; Inchauspé, Geneviève

2012-01-01

A famous milestone in the vaccine field has been the first successful vaccination against smallpox, in 1798, by Edward Jenner. Using the vaccinia cowpox virus, Jenner was able to protect vaccinees from variola or smallpox. The Modified Virus Ankara (MVA) poxvirus strain has been one of the vaccines subsequently developed to prevent smallpox infection and was selected by the US government in their Biodefense strategy. Progress in molecular biology and immunology associated with MVA infection has led to the development of MVA as vaccine platform, both in the field of preventive and therapeutic vaccines. This later class of therapeutics has witnessed growing interest that has translated into an increasing number of vaccine candidates reaching the clinics. Among those, MVA-based therapeutic vaccines have addressed four major chronic infections including viral hepatitis, AIDS, human papillomavirus-linked pathologies and tuberculosis. Clinical trials encompass phase 1 and 2 and have started to show significant results and promises. PMID:22894957

The role of human papillomavirus vaccines in cervical neoplasia.

PubMed

Stern, P L; Faulkner, R; Veranes, E C; Davidson, E J

2001-10-01

Cervical cancer is the second most common cause of cancer-related death in women, in some developing countries accounting for the highest cancer mortality. The evidence for the association of high-risk human papillomavirus types with the aetiology of cervical neoplasia is firmly established, human papillomavirus being detected in virtually all cervical cancers. The risk of progression of precursor cervical intra-epithelial neoplasia lesions is associated with persistence of human papillomavirus infection. One strategy for the management of cervical neoplasia worldwide could be the development of prophylactic and/or therapeutic human papillomavirus vaccines. This chapter will discuss the natural history of human papillomavirus infection, viral immunity and the clinical course of resultant disease as the background to the effective design and use of human papillomavirus vaccines for protection or therapy. The progress of ongoing phase I and II clinical trials for several different vaccine preparations and the challenges for establishing their future use will be discussed. Copyright 2001 Harcourt Publishers Ltd.

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.

[Animal experimentation in the discovery and production of veterinary vaccines].

PubMed

Audonnet, J Ch; Lechenet, J; Verschuere, B

2007-08-01

Veterinary vaccine research, development and production facilities must aim to improve animal welfare, respond to public concerns and meet regulatory requirements, while at the same time fulfilling their objective of producing evermore effective and safer vaccines. The use of animal experimentation for the development of new veterinary vaccines is inevitable, as no in vitro model can predict a candidate vaccine's ability to induce protection in the target species. Against the backdrop of ethical and regulatory constraints, constant progress is being made in creating the best possible conditions for animal experimentation. Keeping up to date with the constant changes in the field of animal ethics requires a particular effort on the part of the pharmaceutical industry, which must make careful changes to product registration documentation in accordance with each new development.

Severe post-vaccination reaction to 17D yellow fever vaccine in Nigeria.

PubMed

Oyelami, S A; Olaleye, O D; Oyejide, C O; Omilabu, S A; Fatunla, B A

1994-01-01

An unusual outbreak of post-vaccination reactions to 17D yellow fever vaccine occurred at Shaki, Nigeria, in May 1987. Twenty-five of the affected people were treated at the Baptist Hospital Shaki. The patients presented with rapidly progressing swelling of the left arm with associated fever and other constitutional symptoms few hours after inoculation with the vaccine. Some of the patients developed gangrene of the affected limb, five of them went into coma and died. Poor hygiene and improper handling of vaccine as well as contamination of vaccine from the source are possible causes. A review of vaccine delivery strategies especially at local community levels; sound training, supervision of vaccinators and health education are strongly recommended to prevent reoccurrence of similar reactions.

Delivering vaccines to the people who need them most.

PubMed

Barocchi, Michèle Anne; Rappuoli, Rino

2015-06-19

Thanks to the Global Alliance for Vaccines and Immunization (GAVI), the Vaccine Fund and the Bill & Melinda Gates Foundation, the global health community has made enormous progress in providing already existing vaccines to developing countries. However, there still exists a gap to develop vaccines for which there is no market in the Western world, owing to low economic incentives for the private sector to justify the investments necessary for vaccine development. In many cases, industry has the technologies, but lacks the impetus to direct resources to develop these vaccine products. The present emergency with the Ebola vaccine provides us an excellent example where a vaccine was feasible several years ago, but the global health community waited for a humanitarian disaster to direct efforts and resources to develop this vaccine. In the beginning of 2015, the first large-scale trials of two experimental vaccines against Ebola virus disease have begun in West Africa. During the past few years, several institutions have dedicated efforts to the development of vaccines against diseases present only in low-income countries. These include the International Vaccine Institute, the Novartis Vaccines Institute for Global Health, the Hilleman Institute, the Sabin Vaccine Institute and the Infectious Disease Research Institute. Nevertheless, solving this problem requires a more significant global effort than that currently invested. These efforts include a clear policy, global coordination of funds dedicated to the development of neglected disease and an agreement on regulatory strategies and incentives for the private sector. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

New generation of oral mucosal vaccines targeting dendritic cells

PubMed Central

Owen, Jennifer L.; Sahay, Bikash; Mohamadzadeh, Mansour

2013-01-01

As most infectious organisms gain entry at mucosal surfaces, there is a great deal of interest in developing vaccines that elicit effective mucosal immune responses against pathogen challenge. Targeted vaccination is one of the most effective methods available to prevent and control infectious diseases. Mucosal vaccines can offer lower costs, better accessibility, needle free delivery, and a higher capacity for mass immunizations during pandemics. Both local mucosal immunity and robust systemic responses can be achieved through mucosal vaccination. Recent progress in understanding the molecular and cellular components of the mucosal immune system have allowed for the development of a novel mucosal vaccine platform utilizing specific dendritic cell-targeting peptides and orally administered lactobacilli to elicit efficient antigen specific immune responses against infections, including B. anthracis in experimental models of disease. PMID:23835515

[Research progress of the molecule mechanisms of Ebola virus infection of cells].

PubMed

Shi, Ming; Shen, Yu-Qing

2013-01-01

Ebola virus can cause severe Ebola hemorrhagic fever. The mortality rate is 90 percent. Up till now, there is no effective vaccine or treatment of Ebola virus infection. Relaed researches on Ebola virus have become a hot topic in virology. The understanding of molecular mechanisms of Ebola virus infection of cells are important for the development of vaccine and anti-virus drugs. Therefore, this review summarized the recent research progress on the mechanisms of Ebola virus infection.

Financing children's vaccines.

PubMed

Nelson, E Anthony S; Sack, David; Wolfson, Lara; Walker, Damian G; Seng, Lim Fong; Steele, Duncan

2009-11-20

A 2006 Commonwealth Association of Paediatric Gastroenterology and Nutrition workshop on financing children's vaccines highlighted the potential for vaccines to control diarrhoea and other diseases as well as spur economic development through better health. Clear communication of vaccination value to decision-makers is required, together with sustainable funding mechanisms. GAVI and partners have made great progress providing funding for vaccines for children in the poorest countries but other solutions may be required to achieve the same gains in middle- and high-income countries. World Health Organization has a wealth of freely available country-level data on immunisation that academics and advocates can use to communicate the economic and health benefits of vaccines to decision-makers.

Progress with new malaria vaccines.

PubMed Central

Webster, Daniel; Hill, Adrian V. S.

2003-01-01

Malaria is a parasitic disease of major global health significance that causes an estimated 2.7 million deaths each year. In this review we describe the burden of malaria and discuss the complicated life cycle of Plasmodium falciparum, the parasite responsible for most of the deaths from the disease, before reviewing the evidence that suggests that a malaria vaccine is an attainable goal. Significant advances have recently been made in vaccine science, and we review new vaccine technologies and the evaluation of candidate malaria vaccines in human and animal studies worldwide. Finally, we discuss the prospects for a malaria vaccine and the need for iterative vaccine development as well as potential hurdles to be overcome. PMID:14997243

Progress and prospects for L2-based human papillomavirus vaccines

PubMed Central

Jiang, Rosie T; Schellenbacher, Christina; Chackerian, Bryce; Roden, Richard B.S.

2016-01-01

Summary Human papillomavirus (HPV) is a worldwide public health problem, particularly in resource-limited countries. Fifteen high-risk genital HPV types are sexually transmitted and cause 5% of all cancers worldwide, primarily cervical, anogenital and oropharyngeal carcinomas. Skin HPV types are generally associated with benign disease, but a subset is linked to non-melanoma skin cancer. Licensed HPV vaccines based on virus-like particles (VLPs) derived from L1 major capsid antigen of key high risk HPVs are effective at preventing these infections but do not cover cutaneous types and are not therapeutic. Vaccines targeting L2 minor capsid antigen, some using capsid display, adjuvant and fusions with early HPV antigens or Toll-like receptor agonists, are in development to fill these gaps. Progress and challenges with L2-based vaccines are summarized. PMID:26901354

Immunisation registers in Canada: progress made, current situation, and challenges for the future.

PubMed

Laroche, J A; Diniz, A J

2012-04-26

Immunisation registers have the capacity to capture data on the administration of vaccine doses at the individual level within the population and represent an important tool in assessing immunisation coverage and vaccine uptake. In 1999, the National Advisory Committee on Immunization recommended that a network of immunisation registers be established in Canada. The Canadian Immunization Registry Network (CIRN) was established to coordinate the development of standards and facilitate the sharing of knowledge and experience to develop a national network of such registers. In 2003, the National Immunization Strategy identified immunisation registers as an important component in improving national immunisation surveillance. In addition, there has been consistent public and professional interest in a national immunisation register being available and considerable progress has been made in developing technologies to facilitate the capture of immunisation-related data. More specifically, the automated identification of vaccines, through the use of barcodes on vaccines, will facilitate collection of data related to administered vaccine doses. Nevertheless, challenges remain in the implementation of immunisation registers in all Canadian provinces and territories such that Canada still does not currently have a fully functional network of immunisation registers with the capacity to be interoperable between jurisdictions and to allow for data to be captured at the national level.

Accelerating vaccine development and deployment: report of a Royal Society satellite meeting

PubMed Central

Bregu, Migena; Draper, Simon J.; Hill, Adrian V. S.; Greenwood, Brian M.

2011-01-01

The Royal Society convened a meeting on the 17th and 18th November 2010 to review the current ways in which vaccines are developed and deployed, and to make recommendations as to how each of these processes might be accelerated. The meeting brought together academics, industry representatives, research sponsors, regulators, government advisors and representatives of international public health agencies from a broad geographical background. Discussions were held under Chatham House rules. High-throughput screening of new vaccine antigens and candidates was seen as a driving force for vaccine discovery. Multi-stakeholder, small-scale manufacturing facilities capable of rapid production of clinical grade vaccines are currently too few and need to be expanded. In both the human and veterinary areas, there is a need for tiered regulatory standards, differentially tailored for experimental and commercial vaccines, to allow accelerated vaccine efficacy testing. Improved cross-fertilization of knowledge between industry and academia, and between human and veterinary vaccine developers, could lead to more rapid application of promising approaches and technologies to new product development. Identification of best-practices and development of checklists for product development plans and implementation programmes were seen as low-cost opportunities to shorten the timeline for vaccine progression from the laboratory bench to the people who need it. PMID:21893549

Impact of BRICS’ investment in vaccine development on the global vaccine market

PubMed Central

Milstien, Julie; Schmitt, Sarah

2014-01-01

Abstract Brazil, the Russian Federation, India, China and South Africa – the countries known as BRICS – have made considerable progress in vaccine production, regulation and development over the past 20 years. In 1993, all five countries were producing vaccines but the processes used were outdated and non-standardized, there was little relevant research and there was negligible international recognition of the products. By 2014, all five countries had strong initiatives for the development of vaccine technology and had greatly improved their national regulatory capacity. South Africa was then the only BRICS country that was not completely producing vaccines. South Africa is now in the process of re-establishing its own vaccine production and passing beyond the stage of simply importing, formulating and filling vaccine bulks. Changes in the public sector’s price per dose of selected vaccines, the global market share represented by products from specific manufacturers, and the attractiveness, for multinational companies, of partnership and investment opportunities in BRICS companies have all been analysed. The results indicate that the BRICS countries have had a major impact on vaccine price and availability, with much of that impact attributable to the output of Indian vaccine manufacturers. China is expected to have a greater impact soon, given the anticipated development of Chinese vaccine manufacturers in the near future. BRICS’ accomplishments in the field of vaccine development are expected to reshape the global vaccine market and accelerate access to vaccines in the developing world. The challenge is to turn these expectations into strategic actions and practical outcomes. PMID:24940018

Global Foot-and-Mouth Disease Research Update and Gap Analysis: 4 - Diagnostics.

PubMed

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

2016-06-01

This study assessed knowledge gaps in foot-and-mouth disease (FMD) research in the field of diagnostics. The study took the form of a literature review (2011-15) combined with research updates collected in 2014 from 33 institutes from around the world. Findings were used to identify priority areas for future FMD research. Molecular and genetic technologies, including sequencing, are developing at an increasing rate both in terms of capability and affordability. These advances potentiate progress in many other fields of research, from vaccine development to epidemiology. The development of RT-LAMP represents an important breakthrough allowing greater use and access to molecular diagnostics. It is now possible to determine virus serotype using PCR, although only for certain virus pools, continued progress is needed to cover the global spectrum of FMD viruses. Progress has also been made in the development of pen-side rapid diagnostics, some with the ability to determine serotype. However, further advances in pen-side serotype or strain determination would benefit both FMD-free countries and endemic countries with limited access to well-resourced laboratories. Novel sampling methods that show promise include air sampling and baited ropes, the latter may aid sampling in wildlife and swine. Studies of infrared thermography for the early detection of FMD have not been encouraging, although investigations are ongoing. Multiplex tests have been developed that are able to simultaneously screen for multiple pathogens with similar clinical signs. Crucial for assessing FMDV freedom, tests exist to detect animals that have been infected with FMDV regardless of vaccination status; however, limitations exist, particularly when testing previously vaccinated animals. Novel vaccines are being developed with complementary DIVA tests for this purpose. Research is also needed to improve the current imprecise approaches to FMD vaccine matching. The development of simple, affordable tests increases access to FMD diagnostics, greatly benefiting regions with limited laboratory capacity. © 2016 Blackwell Verlag GmbH.

[Vaccine for human immunodeficiency virus (HIV)--relevance of these days].

PubMed

Laiskonis, Alvydas; Pukenyte, Evelina

2005-01-01

Since 1980 more than 25 million people have died from acquired immunodeficiency syndrome (AIDS), which results from infection with human immunodeficiency virus (HIV). Number of new cases increases very threateningly. One and the most effective method to stop the progress of epidemic is the development of the vaccine for HIV. There is the presentation of the first stage of the vaccine for HIV testing (structure, methodology), which is now on trial in St. Pierre hospital, Brussels University. HIV characteristics which inflame the process of the vaccine development, historical facts and facts about vaccines on trial in these days are reviewed in this article. More than 10,000 volunteers have been participating in various clinical trials since 1987. The development of the vaccine is a very difficult, long-terming (about 8-10 years) and costly process. The process of the vaccine testing is very difficult in developing countries where the infection spreads the most rapidly. Available data confirm that the vaccine must be multi-componential, inducing cellular, humoral immunity against various subtypes of HIV. The vaccine cannot protect fully but the changes of the natural infection course could decrease virulence, distance the stage of AIDS, and retard the spread of the epidemic.

Measles virus infection of human keratinocytes: Possible link between measles and atopic dermatitis.

PubMed

Gourru-Lesimple, Geraldine; Mathieu, Cyrille; Thevenet, Thomas; Guillaume-Vasselin, Vanessa; Jégou, Jean-François; Boer, Cindy G; Tomczak, Katarzyna; Bloyet, Louis-Marie; Giraud, Celine; Grande, Sophie; Goujon, Catherine; Cornu, Catherine; Horvat, Branka

2017-05-01

Measles virus (MV) infection is marked with a skin rash in the acute phase of the disease, which pathogenesis remains poorly understood. Moreover, the association between measles and progression of skin diseases, such as atopic dermatitis (AD), is still elusive. We have thus analysed the susceptibility of human keratinocytes to MV infection and explore the potential relationship between MV vaccination and the pathogenesis the AD. We performed immunovirological characterisation of MV infection in human keratinocytes and then tested the effect of live attenuated measles vaccine on the progression of AD in adult patients, in a prospective, double-blind study. We showed that both human primary keratinocytes and the keratinocyte cell line HaCaT express MV receptors and could be infected by MV. The infection significantly modulated the expression of several keratinocyte-produced cytokines, known to be implicated in the pathogenesis of inflammatory allergic diseases, including AD. We then analysed the relationship between exposure to MV by vaccination and the progression of AD in 20 adults during six weeks. We found a significant decrease in CCL26 and thymic stromal lymphopoietin (TSLP) mRNA in biopsies from acute lesions of vaccinated patients, suggesting MV-induced modulation of skin cytokine expression. Clinical analysis revealed a transient improvement of SCORAD index in vaccinated compared to placebo-treated patients, two weeks after vaccination. Altogether, these results clearly demonstrate that keratinocytes are susceptible to MV infection, which could consequently modulate their cytokine production, resulting with a beneficial effect in the progression of AD. This study provides thus a proof of concept for the vaccination therapy in AD and may open new avenues for the development of novel strategies in the treatment of this allergic disease. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

NIAID meeting report: improving malaria vaccine strategies through the application of immunological principles.

PubMed

Mo, Annie X Y; Augustine, Alison Deckhut

2014-02-26

A highly efficacious vaccine to prevent malaria infection or clinical disease is still far from reality despite several decades of intensive effort and a growing global commitment in malaria vaccine development. Further understanding of the mechanisms required for induction of effective host immune responses and maintenance of long-term protective immunity is needed to facilitate rational approaches for vaccine design and evaluation. The National Institute of Allergy and Infectious Diseases (NIAID) conducted a workshop on June 18-19, 2012 with experts in the fields of malaria vaccine development, malaria immunology, and basic immunology to address issues associated with improving our current understanding of malaria vaccine immunity. This report summarizes the discussion and major recommendations generated by the workshop participants regarding the application of recent advances in basic immunology and state-of-the-art immunological tools to improve progress and help address current challenges and knowledge gaps in malaria vaccine development. Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

An adjuvant-modulated vaccine response in human whole blood

PubMed Central

Hakimi, Jalil; Azizi, Ali; Ausar, Salvador F.; Todryk, Stephen M.; Rahman, Nausheen; Brookes, Roger H.

2017-01-01

ABSTRACT The restimulation of an immune memory response by in vitro culture of blood cells with a specific antigen has been used as a way to gauge immunity to vaccines for decades. In this commentary we discuss a less appreciated application to support vaccine process development. We report that human whole blood from pre-primed subjects can generate a profound adjuvant-modulated, antigen-specific response to several different vaccine formulations. The response is able to differentiate subtle changes in the quality of an immune memory response to vaccine formulations and can be used to select optimal conditions relating to a particular manufacture process step. While questions relating to closeness to in vivo vaccination remain, the approach is another big step nearer to the more relevant human response. It has special importance for new adjuvant development, complementing other preclinical in vivo and in vitro approaches to considerably de-risk progression of novel vaccines before and throughout early clinical development. Broader implications of the approach are discussed. PMID:28605295

Making new vaccines affordable: a comparison of financing processes used to develop and deploy new meningococcal and pneumococcal conjugate vaccines.

PubMed

Hargreaves, James R; Greenwood, Brian; Clift, Charles; Goel, Akshay; Roemer-Mahler, Anne; Smith, Richard; Heymann, David L

2011-11-26

Mechanisms to increase access to health products are varied and controversial. Two innovative mechanisms have been used to accelerate the development of low-price supply lines for conjugate vaccines. The Meningitis Vaccine Project is a so-called push mechanism that facilitated technology transfer to an Indian company to establish capacity to manufacture a vaccine. The Advanced Market Commitment for pneumococcal vaccines is a so-called pull mechanism that guarantees companies a supplement paid in addition to the purchase price for vaccines for a specific period. We compare these approaches, identifying key dimensions of each and considering their potential for replication. We also discuss issues that the Global Alliance for Vaccines and Immunisation (GAVI) face now that these new vaccines are available. Progress towards GAVI's strategic aims is needed and funding is crucial. Approaches that decrease the financial pressure on GAVI and greatly increase political and financial engagement by low-income countries should also be considered. Copyright © 2011 Elsevier Ltd. All rights reserved.

A brief history of the global effort to develop a preventive HIV vaccine.

PubMed

Esparza, José

2013-08-02

Soon after HIV was discovered as the cause of AIDS in 1983-1984, there was an expectation that a preventive vaccine would be rapidly developed. In trying to achieve that goal, three successive scientific paradigms have been explored: induction of neutralizing antibodies, induction of cell mediated immunity, and exploration of combination approaches and novel concepts. Although major progress has been made in understanding the scientific basis for HIV vaccine development, efficacy trials have been critical in moving the field forward. In 2009, the field was reinvigorated with the modest results obtained from the RV144 trial conducted in Thailand. Here, we review those vaccine development efforts, with an emphasis on events that occurred during the earlier years. The goal is to provide younger generations of scientists with information and inspiration to continue the search for an HIV vaccine. Copyright © 2013 The Author. Published by Elsevier Ltd.. All rights reserved.

Not All Antigens Are Created Equally: Progress, Challenges, and Lessons Associated with Developing a Vaccine for Leishmaniasis

PubMed Central

Reed, Steven G.

2017-01-01

ABSTRACT From experimental models and the analyses of patients, it is well documented that antigen-specific T cells are critical for protection against Leishmania infection. Effective vaccines require both targeting to the pathogen and an immune stimulant to induce maturation of appropriate immune responses. While a great number of antigens have been examined as vaccine candidates against various Leishmania species, few have advanced to human or canine clinical trials. With emphasis on antigen expression, in this minireview we discuss some of the vaccine platforms that are currently being explored for the development of Leishmania vaccines. It is clear that the vaccine platform of choice can have a significant impact upon the level of protection induced by particular antigens, and we provide and highlight some examples for which the vaccine system used has impacted the protective efficacy imparted. PMID:28515135

Not All Antigens Are Created Equally: Progress, Challenges, and Lessons Associated with Developing a Vaccine for Leishmaniasis.

PubMed

Duthie, Malcolm S; Reed, Steven G

2017-07-01

From experimental models and the analyses of patients, it is well documented that antigen-specific T cells are critical for protection against Leishmania infection. Effective vaccines require both targeting to the pathogen and an immune stimulant to induce maturation of appropriate immune responses. While a great number of antigens have been examined as vaccine candidates against various Leishmania species, few have advanced to human or canine clinical trials. With emphasis on antigen expression, in this minireview we discuss some of the vaccine platforms that are currently being explored for the development of Leishmania vaccines. It is clear that the vaccine platform of choice can have a significant impact upon the level of protection induced by particular antigens, and we provide and highlight some examples for which the vaccine system used has impacted the protective efficacy imparted. Copyright © 2017 American Society for Microbiology.

Recent advances in microparticle and nanoparticle delivery vehicles for mucosal vaccination.

PubMed

McNeela, E A; Lavelle, E C

2012-01-01

The great potential of mucosal vaccination is widely accepted but progress in the clinical development of subunit mucosal vaccines has been disappointing. Of the available approaches, the use of polymer-based microparticles is attractive because these delivery vehicles can be specifically tailored for vaccines and they offer the potential for integration of adjuvant. Here we address recent developments in the use of particulates as mucosal vaccines and the potential of novel targeting strategies, formulation approaches and adjuvant combinations to enhance the efficacy of particle-based mucosal vaccines. This review discusses the current status of mucosal vaccines based on particles and highlights several of the strategies that are currently under investigation for improving their immunogenicity. These include enhancing the stability of formulations in the luminal environment, increasing uptake by specifically targeting particles to mucosal inductive sites, and augmenting immunogenicity through co-formulation with immunostimulatory agents.

Malaria vaccines and the new malaria agenda.

PubMed

Greenwood, B M; Targett, G A T

2011-11-01

The development of an effective malaria vaccine has taken many decades, but there is now a good chance that the first malaria vaccine will be licensed within the next few years. However, this vaccine (RTS,S) will not be fully effective, and more efficacious, second-generation vaccines will be needed. Good progress is being made in the development of potential vaccines directed at each of the three main stages of the parasite's life cycle, with a variety of different approaches, but many challenges remain, e.g. overcoming the problem of polymorphism in many key parasite antigens. It is likely vaccines that are effective enough to block transmission, and thus contribute to increasing drives towards malaria elimination, will need to contain antigens from different stages of the parasite's life cycle. © 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.

Efforts to monitor Global progress on individual and community demand for immunization: Development of definitions and indicators for the Global Vaccine Action Plan Strategic Objective 2.

PubMed

Hickler, Benjamin; MacDonald, Noni E; Senouci, Kamel; Schuh, Holly B

2017-06-16

The Second Strategic Objective of the Global Vaccine Action Plan, "individuals and communities understand the value of vaccines and demand immunization as both their right and responsibility", differs from the other five in that it does not focus on supply-side aspects of immunization programs but rather on public demand for vaccines and immunization services. This commentary summarizes the work (literature review, consultations with experts, and with potential users) and findings of the UNICEF/World Health Organization Strategic Objective 2 informal Working Group on Vaccine Demand, which developed a definition for demand and indicators related to Strategic Objective 2. Demand for vaccines and vaccination is a complex concept that is not external to supply systems but rather encompasses the interaction between human behaviors and system structure and dynamics. Copyright © 2017. Published by Elsevier Ltd.

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.

Development of inactivated poliovirus vaccine from Sabin strains: A progress report.

PubMed

Okayasu, Hiromasa; Sein, Carolyn; Hamidi, Ahd; Bakker, Wilfried A M; Sutter, Roland W

2016-11-01

The Global Polio Eradication Initiative (GPEI) has seen significant progress since it began in 1988, largely due to the worldwide use of oral poliovirus vaccine (OPV). In order to achieve polio eradication the global cessation of OPV is necessary because OPV contains live attenuated poliovirus, which in rare circumstances could re-gain wild poliovirus (WPV) characteristics with potential to establish transmission. The GPEI endgame strategy for the period 2013-2018 recommends the globally synchronised sequential cessation of the Sabin strains contained in the OPV, starting with type 2 Sabin. The withdrawal of Sabin type 2 took place in April 2016, with the introduction of at least one dose of inactivated poliovirus vaccine (IPV) as a risk mitigation strategy. The introduction of IPV into 126 countries since 2013 has required a rapid scale-up of IPV production by the two manufacturers supplying the global public sector market. This scale-up has been fraught with challenges, resulting in reductions of 40-50% of initial supply commitments. Consequently, 22 countries will not be supplied until 2018, and another 23 countries will experience serious stock-outs. In the last decade repeated calls-for-action were made to the global community to invigorate their vision and investment in developing "new poliovirus vaccines" including the development of IPV from less-virulent strains, such as Sabin-IPV (S-IPV). The conventional Salk-IPV production is limited to high-income industrialized-country manufacturers due to the containment requirements (i.e., high sanitation, low force-of-poliovirus-infection, and high population immunity). The use of Sabin strains in the production of S-IPV carries a lower biosafety risk, and was determined to be suitable for production in developing countries, expanding the manufacturing base and making IPV more affordable and accessible in the long term. Significant progress in the S-IPV has been made since 2006. S-IPV is now licensed as S-IPV in Japan and as standalone S-IPV in China, demonstrating the feasibility of this vaccine. In addition, production process improvements can further reduce the cost of production. The latter are critical to the economic success of this vaccine in the global market. We summarize the progress made to date in S-IPV technology, the scientific data and economic evidence in support of S-IPV development. Copyright © 2016 International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

Vaccine process technology.

PubMed

Josefsberg, Jessica O; Buckland, Barry

2012-06-01

The evolution of vaccines (e.g., live attenuated, recombinant) and vaccine production methods (e.g., in ovo, cell culture) are intimately tied to each other. As vaccine technology has advanced, the methods to produce the vaccine have advanced and new vaccine opportunities have been created. These technologies will continue to evolve as we strive for safer and more immunogenic vaccines and as our understanding of biology improves. The evolution of vaccine process technology has occurred in parallel to the remarkable growth in the development of therapeutic proteins as products; therefore, recent vaccine innovations can leverage the progress made in the broader biotechnology industry. Numerous important legacy vaccines are still in use today despite their traditional manufacturing processes, with further development focusing on improving stability (e.g., novel excipients) and updating formulation (e.g., combination vaccines) and delivery methods (e.g., skin patches). Modern vaccine development is currently exploiting a wide array of novel technologies to create safer and more efficacious vaccines including: viral vectors produced in animal cells, virus-like particles produced in yeast or insect cells, polysaccharide conjugation to carrier proteins, DNA plasmids produced in E. coli, and therapeutic cancer vaccines created by in vitro activation of patient leukocytes. Purification advances (e.g., membrane adsorption, precipitation) are increasing efficiency, while innovative analytical methods (e.g., microsphere-based multiplex assays, RNA microarrays) are improving process understanding. Novel adjuvants such as monophosphoryl lipid A, which acts on antigen presenting cell toll-like receptors, are expanding the previously conservative list of widely accepted vaccine adjuvants. As in other areas of biotechnology, process characterization by sophisticated analysis is critical not only to improve yields, but also to determine the final product quality. From a regulatory perspective, Quality by Design (QbD) and Process Analytical Technology (PAT) are important initiatives that can be applied effectively to many types of vaccine processes. Universal demand for vaccines requires that a manufacturer plan to supply tens and sometimes hundreds of millions of doses per year at low cost. To enable broader use, there is intense interest in improving temperature stability to allow for excursions from a rigid cold chain supply, especially at the point of vaccination. Finally, there is progress in novel routes of delivery to move away from the traditional intramuscular injection by syringe approach. Copyright © 2012 Wiley Periodicals, Inc.

Plant-made oral vaccines against human infectious diseases—Are we there yet?

PubMed Central

Chan, Hui-Ting; Daniell, Henry

2016-01-01

Summary Although the plant-made vaccine field started three decades ago with the promise of developing low-cost vaccines to prevent infectious disease outbreaks and epidemics around the globe, this goal has not yet been achieved. Plants offer several major advantages in vaccine generation, including low-cost production by eliminating expensive fermentation and purification systems, sterile delivery and cold storage/transportation. Most importantly, oral vaccination using plant-made antigens confers both mucosal (IgA) and systemic (IgG) immunity. Studies in the past 5 years have made significant progress in expressing vaccine antigens in edible leaves (especially lettuce), processing leaves or seeds through lyophilization and achieving antigen stability and efficacy after prolonged storage at ambient temperatures. Bioencapsulation of antigens in plant cells protects them from the digestive system; the fusion of antigens to transmucosal carriers enhances efficiency of their delivery to the immune system and facilitates successful development of plant vaccines as oral boosters. However, the lack of oral priming approaches diminishes these advantages because purified antigens, cold storage/transportation and limited shelf life are still major challenges for priming with adjuvants and for antigen delivery by injection. Yet another challenge is the risk of inducing tolerance without priming the host immune system. Therefore, mechanistic aspects of these two opposing processes (antibody production or suppression) are discussed in this review. In addition, we summarize recent progress made in oral delivery of vaccine antigens expressed in plant cells via the chloroplast or nuclear genomes and potential challenges in achieving immunity against infectious diseases using cold-chain-free vaccine delivery approaches. PMID:26387509

Molecular and chemical engineering of bacteriophages for potential medical applications.

PubMed

Hodyra, Katarzyna; Dąbrowska, Krystyna

2015-04-01

Recent progress in molecular engineering has contributed to the great progress of medicine. However, there are still difficult problems constituting a challenge for molecular biology and biotechnology, e.g. new generation of anticancer agents, alternative biosensors or vaccines. As a biotechnological tool, bacteriophages (phages) offer a promising alternative to traditional approaches. They can be applied as anticancer agents, novel platforms in vaccine design, or as target carriers in drug discovery. Phages also offer solutions for modern cell imaging, biosensor construction or food pathogen detection. Here we present a review of bacteriophage research as a dynamically developing field with promising prospects for further development of medicine and biotechnology.

Development of an anti-HIV vaccine eliciting broadly neutralizing antibodies.

PubMed

Ahmed, Yousuf; Tian, Meijuan; Gao, Yong

2017-09-12

The extreme HIV diversity posts a great challenge on development of an effective anti-HIV vaccine. To solve this problem, it is crucial to discover an appropriate immunogens and strategies that are able to prevent the transmission of the diverse viruses that are circulating in the world. Even though there have been a number of broadly neutralizing anti-HIV antibodies (bNAbs) been discovered in recent years, induction of such antibodies to date has only been observed in HIV-1 infection. Here, in this mini review, we review the progress in development of HIV vaccine in eliciting broad immune response, especially production of bNAbs, discuss possible strategies, such as polyvalent sequential vaccination, that facilitates B cell maturation leading to bNAb response.

Hookworm vaccines.

PubMed

Diemert, David J; Bethony, Jeffrey M; Hotez, Peter J

2008-01-15

Hookworm infection caused by the soil-transmitted nematodes Necator americanus and Ancylostoma duodenale is one of the most common parasitic infections worldwide. Although not directly responsible for substantial mortality, it causes significant morbidity in the form of chronic anemia and protein malnutrition. Current global control efforts based on periodic mass anthelmintic administration are unsustainable, and new control strategies must be developed. This review describes progress in the development of vaccines against hookworm infection, including the preclinical and initial clinical testing of the N. americanus Ancylostoma Secreted Protein-2 Hookworm Vaccine. Plans call for eventual development of a vaccine that will combine at least 2 hookworm antigens--one targeting the larval stage of the life cycle and another targeting the adult worm living in the gastrointestinal tract.

New generation of oral mucosal vaccines targeting dendritic cells.

PubMed

Owen, Jennifer L; Sahay, Bikash; Mohamadzadeh, Mansour

2013-12-01

As most infectious organisms gain entry at mucosal surfaces, there is a great deal of interest in developing vaccines that elicit effective mucosal immune responses against pathogen challenge. Targeted vaccination is one of the most effective methods available to prevent and control infectious diseases. Mucosal vaccines can offer lower costs, better accessibility, needle free delivery, and a higher capacity for mass immunizations during pandemics. Both local mucosal immunity and robust systemic responses can be achieved through mucosal vaccination. Recent progress in understanding the molecular and cellular components of the mucosal immune system have allowed for the development of a novel mucosal vaccine platform utilizing specific dendritic cell-targeting peptides and orally administered lactobacilli to elicit efficient antigen specific immune responses against infections, including Bacillus anthracis in experimental models of disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

Recent advances in the molecular design of synthetic vaccines

NASA Astrophysics Data System (ADS)

Jones, Lyn H.

2015-12-01

Vaccines have typically been prepared using whole organisms. These are normally either attenuated bacteria or viruses that are live but have been altered to reduce their virulence, or pathogens that have been inactivated and effectively killed through exposure to heat or formaldehyde. However, using whole organisms to elicit an immune response introduces the potential for infections arising from a reversion to a virulent form in live pathogens, unproductive reactions to vaccine components or batch-to-batch variability. Synthetic vaccines, in which a molecular antigen is conjugated to a carrier protein, offer the opportunity to circumvent these problems. This Perspective will highlight the progress that has been achieved in developing synthetic vaccines using a variety of molecular antigens. In particular, the different approaches used to develop conjugate vaccines using peptide/proteins, carbohydrates and other small molecule haptens as antigens are compared.

The recent progress in RSV vaccine technology.

PubMed

Fretzayas, Andrew; Papadopoulou, Anna; Kotzia, Doxa; Moustaki, Maria

2012-12-01

The most effective way to control RSV infection would be the development of an expedient and safe vaccine. Subunit vaccines, live attenuated RSV vaccines, plasmid DNA vaccines have been tested either in human or in mouse models without reaching the ultimate goal of efficacy and safety, at least in humans. Viruses such as adenovirus, sendai virus, measles virus were also used as vectors for the generation of RSV vaccines with promising results in animal models. Recent patents describe new techniques for the generation of candidate vaccines. These patents include virus like particles as vaccine platforms, recombinant RSVs or modified RSV F protein as component of the vaccine. Despite the number of the candidate vaccines, the new RSV vaccines should overcome many obstacles before being established as effective vaccines for the control of RSV infections especially for the young infants who are more susceptible to the virus.

Novel vaccine development strategies for inducing mucosal immunity

PubMed Central

Fujkuyama, Yoshiko; Tokuhara, Daisuke; Kataoka, Kosuke; Gilbert, Rebekah S; McGhee, Jerry R; Yuki, Yoshikazu; Kiyono, Hiroshi; Fujihashi, Kohtaro

2012-01-01

To develop protective immune responses against mucosal pathogens, the delivery route and adjuvants for vaccination are important. The host, however, strives to maintain mucosal homeostasis by responding to mucosal antigens with tolerance, instead of immune activation. Thus, induction of mucosal immunity through vaccination is a rather difficult task, and potent mucosal adjuvants, vectors or other special delivery systems are often used, especially in the elderly. By taking advantage of the common mucosal immune system, the targeting of mucosal dendritic cells and microfold epithelial cells may facilitate the induction of effective mucosal immunity. Thus, novel routes of immunization and antigen delivery systems also show great potential for the development of effective and safe mucosal vaccines against various pathogens. The purpose of this review is to introduce several recent approaches to induce mucosal immunity to vaccines, with an emphasis on mucosal tissue targeting, new immunization routes and delivery systems. Defining the mechanisms of mucosal vaccines is as important as their efficacy and safety, and in this article, examples of recent approaches, which will likely accelerate progress in mucosal vaccine development, are discussed. PMID:22380827

Strategies to advance vaccine technologies for resource-poor settings.

PubMed

Kristensen, Debra; Chen, Dexiang

2013-04-18

New vaccine platform and delivery technologies that can have significant positive impacts on the effectiveness, acceptability, and safety of immunizations in developing countries are increasingly available. Although donor support for vaccine technology development is strong, the uptake of proven technologies by the vaccine industry and demand for them by purchasers continues to lag. This article explains the challenges and opportunities associated with accelerating the availability of innovative and beneficial vaccine technologies to meet critical needs in resource-poor settings over the next decade. Progress will require increased dialog between the public and private sectors around vaccine product attributes; establishment of specifications for vaccines that mirror programmatic needs; stronger encouragement of vaccine developers to consider novel technologies early in the product development process; broader facilitation of research and access to technologies through the formation of centers of excellence; the basing of vaccine purchase decisions on immunization systems costs rather than price per dose alone; possible subsidization of early technology adoption costs for vaccine producers that take on the risks of new technologies of importance to the public sector; and the provision of data to purchasers, better enabling them to make informed decisions that take into account the value of specific product attributes. Copyright © 2012 Elsevier Ltd. All rights reserved.

Production of adenovirus vectors and their use as a delivery system for influenza vaccines

PubMed Central

Vemula, Sai V.; Mittal, Suresh K.

2010-01-01

IMPORTANCE OF THE FIELD With the emergence of highly pathogenic avian influenza H5N1 viruses that have crossed species barriers and are responsible for lethal infections in humans in many countries, there is an urgent need for the development of effective vaccines which can be produced in large quantities at a short notice and confer broad protection against these H5N1 variants. In order to meet the potential global vaccine demand in a pandemic scenario, new vaccine-production strategies must be explored in addition to the currently used egg-based technology for seasonal influenza. AREAS COVERED IN THIS REVIEW Adenovirus (Ad) based influenza vaccines represent an attractive alternative/supplement to the currently licensed egg-based influenza vaccines. Ad-based vaccines are relatively inexpensive to manufacture, and their production process does not require either chicken eggs or labor intensive and time-consuming processes necessitating enhanced biosafety facilities. Most importantly, in a pandemic situation, this vaccine strategy could offer a stockpiling option to reduce the response time before a strain-matched vaccine could be developed. WHAT THE READER WILL GAIN This review discusses Ad-vector technology and the current progress in the development of Ad-based influenza vaccines. TAKE HOME MESSAGE Ad vector-based influenza vaccines for pandemic preparedness are under development to meet the global vaccine demand. PMID:20822477

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.

Recent progress and future directions for reduction, refinement, and replacement of animal use in veterinary vaccine potency and safety testing: a report from the 2010 NICEATM-ICCVAM International Vaccine Workshop.

PubMed

Stokes, W S; Kulpa-Eddy, J; Brown, K; Srinivas, G; McFarland, R

2012-01-01

Veterinary vaccines contribute to improved animal and human health and welfare by preventing infectious diseases. However, testing necessary to ensure vaccine effectiveness and safety can involve large numbers of animals and significant pain and distress. NICEATM and ICCVAM recently convened an international workshop to review the state of the science of human and veterinary vaccine potency and safety testing, and to identify priority activities to advance new and improved methods that can further reduce, refine and replace animal use. Rabies, Clostridium sp., and Leptospira sp. vaccines were identified as the highest priorities, while tests requiring live viruses and bacteria hazardous to laboratory workers, livestock, pets, and wildlife were also considered high priorities. Priority research, development and validation activities to address critical knowledge and data gaps were identified, including opportunities to apply new science and technology. Enhanced international harmonization and cooperation and closer collaborations between human and veterinary researchers were recommended to expedite progress. Implementation of the workshop recommendations is expected to advance new methods for vaccine testing that will benefit animal welfare and ensure continued and improved protection of human and animal health.

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.

The March Toward Malaria Vaccines.

PubMed

Hoffman, Stephen L; Vekemans, Johan; Richie, Thomas L; Duffy, Patrick E

2015-12-01

In 2013 there were an estimated 584,000 deaths and 198 million clinical illnesses due to malaria, the majority in sub-Saharan Africa. Vaccines would be the ideal addition to the existing armamentarium of anti-malaria tools. However, malaria is caused by parasites, and parasites are much more complex in terms of their biology than the viruses and bacteria for which we have vaccines, passing through multiple stages of development in the human host, each stage expressing hundreds of unique antigens. This complexity makes it more difficult to develop a vaccine for parasites than for viruses and bacteria, since an immune response targeting one stage may not offer protection against a later stage, because different antigens are the targets of protective immunity at different stages. Furthermore, depending on the life cycle stage and whether the parasite is extra- or intra-cellular, antibody and/or cellular immune responses provide protection. It is thus not surprising that there is no vaccine on the market for prevention of malaria, or any human parasitic infection. In fact, no vaccine for any disease with this breadth of targets and immune responses exists. In this limited review, we focus on four approaches to malaria vaccines, (1) a recombinant protein with adjuvant vaccine aimed at Plasmodium falciparum (Pf) pre-erythrocytic stages of the parasite cycle (RTS,S/AS01), (2) whole sporozoite vaccines aimed at Pf pre-erythrocytic stages (PfSPZ Vaccine and PfSPZ-CVac), (3) prime boost vaccines that include recombinant DNA, viruses and bacteria, and protein with adjuvant aimed primarily at Pf pre-erythrocytic, but also asexual erythrocytic stages, and (4) recombinant protein with adjuvant vaccines aimed at Pf and Plasmodium vivax sexual erythrocytic and mosquito stages. We recognize that we are not covering all approaches to malaria vaccine development, or most of the critically important work on development of vaccines against P. vivax, the second most important cause of malaria. Progress during the last few years has been significant, and a first generation malaria candidate vaccine, RTS,S/AS01, is under review by the European Medicines Agency (EMA) for its quality, safety and efficacy under article 58, which allows the EMA to give a scientific opinion about products intended exclusively for markets outside of the European Union. However, much work is in progress to optimize malaria vaccines in regard to magnitude and durability of protective efficacy and the financing and practicality of delivery. Thus, we are hopeful that anti-malaria vaccines will soon be important tools in the battle against malaria. Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

The March Toward Malaria Vaccines

PubMed Central

Hoffman, Stephen L.; Vekemans, Johan; Richie, Thomas L.; Duffy, Patrick E.

2016-01-01

In 2013 there were an estimated 584,000 deaths and 198 million clinical illnesses due to malaria, the majority in sub-Saharan Africa. Vaccines would be the ideal addition to the existing armamentarium of anti-malaria tools. However, malaria is caused by parasites, and parasites are much more complex in terms of their biology than the viruses and bacteria for which we have vaccines, passing through multiple stages of development in the human host, each stage expressing hundreds of unique antigens. This complexity makes it more difficult to develop a vaccine for parasites than for viruses and bacteria, since an immune response targeting one stage may not offer protection against a later stage, because different antigens are the targets of protective immunity at different stages. Furthermore, depending on the life cycle stage and whether the parasite is extra- or intra-cellular, antibody and/or cellular immune responses provide protection. It is thus not surprising that there is no vaccine on the market for prevention of malaria, or any human parasitic infection. In fact, no vaccine for any disease with this breadth of targets and immune responses exists. In this limited review, we focus on four approaches to malaria vaccines, (1) a recombinant protein with adjuvant vaccine aimed at Plasmodium falciparum (Pf) pre-erythrocytic stages of the parasite cycle (RTS,S/AS01), (2) whole sporozoite vaccines aimed at Pf pre-erythrocytic stages (PfSPZ Vaccine and PfSPZ-CVac), (3) prime boost vaccines that include recombinant DNA, viruses and bacteria, and protein with adjuvant aimed primarily at Pf pre-erythrocytic, but also asexual erythrocytic stages, and (4) recombinant protein with adjuvant vaccines aimed at Pf and Plasmodium vivax sexual erythrocytic and mosquito stages. We recognize that we are not covering all approaches to malaria vaccine development, or most of the critically important work on development of vaccines against P. vivax, the second most important cause of malaria. Progress during the last few years has been significant, and a first generation malaria candidate vaccine, RTS,S/AS01, is under review by the European Medicines Agency (EMA) for its quality, safety and efficacy under article 58, which allows the EMA to give a scientific opinion about products intended exclusively for markets outside of the European Union. However, much work is in progress to optimize malaria vaccines in regard to magnitude and durability of protective efficacy and the financing and practicality of delivery. Thus, we are hopeful that anti-malaria vaccines will soon be important tools in the battle against malaria. PMID:26590432

The march toward malaria vaccines

PubMed Central

Hoffman, Stephen L.; Vekemans, Johan; Richie, Thomas L.; Duffy, Patrick E.

2016-01-01

In 2013 there were an estimated 584,000 deaths and 198 million clinical illnesses due to malaria, the majority in sub-Saharan Africa. Vaccines would be the ideal addition to the existing armamentarium of anti-malaria tools. However, malaria is caused by parasites, and parasites are much more complex in terms of their biology than the viruses and bacteria for which we have vaccines, passing through multiple stages of development in the human host, each stage expressing hundreds of unique antigens. This complexity makes it more difficult to develop a vaccine for parasites than for viruses and bacteria, since an immune response targeting one stage may not offer protection against a later stage, because different antigens are the targets of protective immunity at different stages. Furthermore, depending on the life cycle stage and whether the parasite is extra- or intra-cellular, antibody and/or cellular immune responses provide protection. It is thus not surprising that there is no vaccine on the market for prevention of malaria, or any human parasitic infection. In fact, no vaccine for any disease with this breadth of targets and immune responses exists. In this limited review, we focus on four approaches to malaria vaccines, (1) a recombinant protein with adjuvant vaccine aimed at Plasmodium falciparum (Pf) pre-erythrocytic stages of the parasite cycle (RTS,S/AS01), (2) whole sporozoite vaccines aimed at Pf pre-erythrocytic stages (PfSPZ Vaccine and PfSPZ-CVac), (3) prime boost vaccines that include recombinant DNA, viruses and bacteria, and protein with adjuvant aimed primarily at Pf pre-erythrocytic, but also asexual erythrocytic stages, and (4) recombinant protein with adjuvant vaccines aimed at Pf and Plasmodium vivax sexual erythrocytic and mosquito stages. We recognize that we are not covering all approaches to malaria vaccine development, or most of the critically important work on development of vaccines against P. vivax, the second most important cause of malaria. Progress during the last few years has been significant, and a first generation malaria candidate vaccine, RTS,S/AS01, is under review by the European Medicines Agency (EMA) for its quality, safety and efficacy under article 58, which allows the EMA to give a scientific opinion about products intended exclusively for markets outside of the European Union. However, much work is in progress to optimize malaria vaccines in regard to magnitude and durability of protective efficacy and the financing and practicality of delivery. Thus, we are hopeful that anti-malaria vaccines will soon be important tools in the battle against malaria. PMID:26324116

The march toward malaria vaccines.

PubMed

Hoffman, Stephen L; Vekemans, Johan; Richie, Thomas L; Duffy, Patrick E

2015-11-27

In 2013 there were an estimated 584,000 deaths and 198 million clinical illnesses due to malaria, the majority in sub-Saharan Africa. Vaccines would be the ideal addition to the existing armamentarium of anti-malaria tools. However, malaria is caused by parasites, and parasites are much more complex in terms of their biology than the viruses and bacteria for which we have vaccines, passing through multiple stages of development in the human host, each stage expressing hundreds of unique antigens. This complexity makes it more difficult to develop a vaccine for parasites than for viruses and bacteria, since an immune response targeting one stage may not offer protection against a later stage, because different antigens are the targets of protective immunity at different stages. Furthermore, depending on the life cycle stage and whether the parasite is extra- or intra-cellular, antibody and/or cellular immune responses provide protection. It is thus not surprising that there is no vaccine on the market for prevention of malaria, or any human parasitic infection. In fact, no vaccine for any disease with this breadth of targets and immune responses exists. In this limited review, we focus on four approaches to malaria vaccines, (1) a recombinant protein with adjuvant vaccine aimed at Plasmodium falciparum (Pf) pre-erythrocytic stages of the parasite cycle (RTS,S/AS01), (2) whole sporozoite vaccines aimed at Pf pre-erythrocytic stages (PfSPZ Vaccine and PfSPZ-CVac), (3) prime boost vaccines that include recombinant DNA, viruses and bacteria, and protein with adjuvant aimed primarily at Pf pre-erythrocytic, but also asexual erythrocytic stages, and (4) recombinant protein with adjuvant vaccines aimed at Pf and Plasmodium vivax sexual erythrocytic and mosquito stages. We recognize that we are not covering all approaches to malaria vaccine development, or most of the critically important work on development of vaccines against P. vivax, the second most important cause of malaria. Progress during the last few years has been significant, and a first generation malaria candidate vaccine, RTS,S/AS01, is under review by the European Medicines Agency (EMA) for its quality, safety and efficacy under article 58, which allows the EMA to give a scientific opinion about products intended exclusively for markets outside of the European Union. However, much work is in progress to optimize malaria vaccines in regard to magnitude and durability of protective efficacy and the financing and practicality of delivery. Thus, we are hopeful that anti-malaria vaccines will soon be important tools in the battle against malaria. Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Ltd.. All rights reserved.

Pyrogenic renal hyperemia: the role of prostaglandins.

PubMed

Gagnon, J A; Ramwell, P W; Flamenbaum, W

1978-01-01

The intravenous administration of triple typhoid vaccine to anesthetized dogs resulted in a significant increase in renal blood flow accompanied by a modest decline in systemic blood pressure. This renal hyperemia was associated with elevated renal secretory rates of renin and prostaglandin E and F. Measurements of the intracortical distribution of radiolabeled microspheres revealed a progressive decrease in outer cortical blood flow rates and a progressive increase in inner cortical flow rates. When meclofenamate, an inhibitor of prostaglandin synthetase, was administered concomitantly with triple typhoid vaccine renal hyperemia did not develop. The renal renin secretory rate increased modestly and intracortical renal blood flow was not redistributed. The increased renal blood flow after triple typhoid vaccine administration to unanesthetized dogs was also reversed by meclofenamate. The marked increase in prostaglandin secretion by the kidney during renal hyperemia following triple typhoid vaccine administration (pyrogen), and the effect of meclofenamate, is consonant with a role for increased renal synthesis and release of prostaglandins.

Progress towards the eradication of Aujeszky's disease in New Zealand by vaccination with a subunit vaccine.

PubMed

Motha, M X; Atkinson, G; Hoyle, F P

1994-08-27

Attempts to control Aujeszky's disease by vaccination with a glycoprotein-I negative subunit vaccine have been made on nine New Zealand pig farms. Thirty-one to 42 months after the programme of vaccination began, its progress was assessed by measuring the gI-antibody response in pigs from seven of the farms. Three farms had totally eradicated the 'wild' virus infection, one farm was close to achieving complete eradication and the other three farms had made little or no progress. One of the farms which eradicated the 'wild' virus infection achieved this status in two years by combining vaccination with an intensive testing and culling programme; the other two farms had eradicated the 'wild' virus infection by a combination of vaccination and good standards of hygiene without undertaking an intensive culling programme. The farms that had made little or no progress had less satisfactory standards of hygiene and did not practise an intensive testing and culling programme.

Vaccine candidates for leishmaniasis: a review.

PubMed

Nagill, Rajeev; Kaur, Sukhbir

2011-10-01

Leishmaniasis is a diverse group of clinical syndromes caused by protozoan parasites of the genus Leishmania. The clinical manifestation of the disease varies from self-limiting cutaneous lesions to progressive visceral disease. It is estimated that 350 million people are at risk in 88 countries, with a global incidence of 1-1.5 million cases of cutaneous and 500,000 cases of visceral leishmaniasis. The key control measures mainly rely on early case detection and chemotherapy which has been hampered by the toxicity of drugs, side-effects and by the emergence of drug resistance in parasites. Control of reservoir host and vector is difficult due to operational difficulties and frequent relapses in the host. Therefore, the development of effective and affordable vaccine against leishmaniasis is highly desirable. Although considerable progress has been made over the last decade in understanding immune mechanisms underlying potential candidate antigens, including killed, live attenuated parasites, crude parasites, pure or recombinant Leishmania proteins or DNA encoding leishmanial proteins, as well as immunomodulators from sand fly saliva, very few candidate vaccines have progressed beyond the experimental stage. As such there is no vaccine against any form of human leishmaniasis. In recent years, however, much interest has been stimulated towards vaccination against leishmaniasis focused mainly on cutaneous leishmaniasis with fewer attempts against visceral leishmaniasis. Copyright © 2011 Elsevier B.V. All rights reserved.

Chimpanzee adenoviral vectors as vaccines for outbreak pathogens

PubMed Central

2017-01-01

ABSTRACT The 2014–15 Ebola outbreak in West Africa highlighted the potential for large disease outbreaks caused by emerging pathogens and has generated considerable focus on preparedness for future epidemics. Here we discuss drivers, strategies and practical considerations for developing vaccines against outbreak pathogens. Chimpanzee adenoviral (ChAd) vectors have been developed as vaccine candidates for multiple infectious diseases and prostate cancer. ChAd vectors are safe and induce antigen-specific cellular and humoral immunity in all age groups, as well as circumventing the problem of pre-existing immunity encountered with human Ad vectors. For these reasons, such viral vectors provide an attractive platform for stockpiling vaccines for emergency deployment in response to a threatened outbreak of an emerging pathogen. Work is already underway to develop vaccines against a number of other outbreak pathogens and we will also review progress on these approaches here, particularly for Lassa fever, Nipah and MERS. PMID:29083948

Progress and Challenges Associated with the Development of Ricin Toxin Subunit Vaccines

PubMed Central

Vance, David J.; Mantis, Nicholas J.

2016-01-01

Summary The past several years have seen major advances in the development of a safe and efficacious ricin toxin vaccine, including the completion of two Phase I clinical trials with two different recombinant A subunit (RTA)-based vaccines: RiVax™ and RVEc™ adsorbed to aluminum salt adjuvant, as well as a non-human primate study demonstrating that parenteral immunization with RiVax elicits a serum antibody response that was sufficient to protect against a lethal dose aerosolized ricin exposure. One of the major obstacles moving forward is assessing vaccine efficacy in humans, when neither ricin-specific serum IgG endpoint titers nor toxin-neutralizing antibody levels are accepted as definitive predictors of protective immunity. In this review we summarize ongoing efforts to leverage recent advances in our understanding of RTA-antibody interactions at the structural level to develop novel assays to predict vaccine efficacy in humans. PMID:26998662

Progress and challenges associated with the development of ricin toxin subunit vaccines.

PubMed

Vance, David J; Mantis, Nicholas J

2016-09-01

The past several years have seen major advances in the development of a safe and efficacious ricin toxin vaccine, including the completion of two Phase I clinical trials with two different recombinant A subunit (RTA)-based vaccines: RiVax™ and RVEc™ adsorbed to aluminum salt adjuvant, as well as a non-human primate study demonstrating that parenteral immunization with RiVax elicits a serum antibody response that was sufficient to protect against a lethal dose aerosolized ricin exposure. One of the major obstacles moving forward is assessing vaccine efficacy in humans, when neither ricin-specific serum IgG endpoint titers nor toxin-neutralizing antibody levels are accepted as definitive predictors of protective immunity. In this review we summarize ongoing efforts to leverage recent advances in our understanding of RTA-antibody interactions at the structural level to develop novel assays to predict vaccine efficacy in humans.

Developing live vaccines against Yersinia pestis

PubMed Central

Sun, Wei; Roland, Kenneth L.; Curtiss, Roy

2014-01-01

Three great plague pandemics caused by the gram-negative bacterium Yersinia pestis have killed nearly 200 million people and it has been linked to biowarfare in the past. Plague is endemic in many parts of the world. In addition, the risk of plague as a bioweapon has prompted increased research to develop plague vaccines against this disease. Injectable subunit vaccines are being developed in the United States and United Kingdom. However, the live attenuated Y. pestis-EV NIIEG strain has been used as a vaccine for more than 70 years in the former Soviet Union and in some parts of Asia and provides a high degree of efficacy against plague. This vaccine has not gained general acceptance because of safety concerns. In recent years, modern molecular biological techniques have been applied to Y. pestis to construct strains with specific defined mutations designed to create safe, immunogenic vaccines with potential for use in humans and as bait vaccines to reduce the load of Y. pestis in the environment. In addition, a number of live, vectored vaccines have been reported using attenuated viral vectors or attenuated Salmonella strains to deliver plague antigens. Here we summarize the progress of live attenuated vaccines against plague. PMID:21918302

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.

Replacement of glycoprotein B in alcelaphine herpesvirus 1 by its ovine herpesvirus 2 homolog: Implications in vaccine development for sheep-associated malignant catarrhal fever

USDA-ARS?s Scientific Manuscript database

Vaccine development is a top priority in malignant catarrhal fever (MCF) research. In the case of sheep-associated MCF (SA-MCF), caused by ovine herpesvirus 2 (OvHV-2), progress towards this objective has been hindered by the absence of methods to attenuate or modify the virus, since it cannot be pr...

Progress toward Development of a Vaccine against Congenital Cytomegalovirus Infection

PubMed Central

Permar, Sallie R.; Plotkin, Stanley A.

2017-01-01

ABSTRACT A vaccine against congenital human cytomegalovirus (CMV) infection is a major public health priority. Congenital CMV causes substantial long-term morbidity, particularly sensorineural hearing loss (SNHL), in newborns, and the public health impact of this infection on maternal and child health is underrecognized. Although progress toward development of a vaccine has been limited by an incomplete understanding of the correlates of protective immunity for the fetus, knowledge about some of the key components of the maternal immune response necessary for preventing transplacental transmission is accumulating. Moreover, although there have been concerns raised about observations indicating that maternal seropositivity does not fully prevent recurrent maternal CMV infections during pregnancy, it is becoming increasing clear that preconception immunity does confer some measure of protection against both CMV transmission and CMV disease (if transmission occurs) in the newborn infant. Although the immunity to CMV conferred by both infection and vaccination is imperfect, there are encouraging data emerging from clinical trials demonstrating the immunogenicity and potential efficacy of candidate CMV vaccines. In the face of the knowledge that between 20,000 and 30,000 infants are born with congenital CMV in the United States every year, there is an urgent and compelling need to accelerate the pace of vaccine trials. In this minireview, we summarize the status of CMV vaccines in clinical trials and provide a perspective on what would be required for a CMV immunization program to become incorporated into clinical practice. PMID:29046308

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 vaccine supply in developing countries. Copyright © 2018. Published by Elsevier Ltd.

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.

Implications of the licensure of a partially efficacious malaria vaccine on evaluating second-generation vaccines

PubMed Central

2013-01-01

Background 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. Discussion 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. Conclusions 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. PMID:24228861

Efficacy of a novel Pasteurella multocida vaccine against progressive atrophic rhinitis of swine

USGS Publications Warehouse

Hsuan, Shih-Ling; Liao, Chih-Ming; Huang, Chienjin; Winton, James R.; Chen, Zeng-Weng; Lee, Wei-Cheng; Liao, Jiunn-Wang; Chen, Ter-Hsin; Chiou, Chwei-Jang; Yeh, Kuang-Sheng; Chien, Maw-Sheng

2009-01-01

The efficacy of a novel vaccine composed of three short recombinant subunit Pasteurella multocida toxin (PMT) proteins in combination with a bi-valent P. multocida whole-cell bacterin (rsPMT–PM) was evaluated in field studies for prevention and control of progressive atrophic rhinitis (PAR) of swine at 15 conventional farrow-to-finish farms. Experimental piglets that were immunized twice with the rsPMT–PM vaccine developed detectable titers of neutralizing antibodies (greater than 1:8) that prevented the growth retardation and pathological lesions typically observed following challenge with authentic PMT. A total of 542 sows were vaccinated once or twice prior to parturition and serum neutralizing antibody titers were evaluated. Both single and double vaccination protocols induced neutralizing antibody titers of 1:16 or higher in 62% and 74% of sows, respectively. Notably, neither sows nor piglets at a farm experiencing a severe outbreak of PAR at the time of the vaccination trial had detectable antibody titers, but antibody titers increased significantly to 1:16 or higher in 40% of sows following double vaccination. During the year after vaccination, clinical signs of PAR decreased in fattening pigs and growth performance improved sufficiently to reduce the rearing period until marketing by 2 weeks. Collectively, these results indicate that the rsPMT–PM vaccine could be used to provide protective immunity for controlling the prevalence and severity of PAR among farm-raised swine.

New developments in flavivirus vaccines with special attention to yellow fever.

PubMed

Pugachev, Konstantin V; Guirakhoo, Farshad; Monath, Thomas P

2005-10-01

Here we review recent epidemiological trends in flavivirus diseases, findings related to existing vaccines, and new directions in flavivirus vaccine research. We emphasize the need for stepped-up efforts to stop further spread and intensification of these infections worldwide. Although the incidence and geographic distribution of flavivirus diseases have increased in recent years, human vaccines are available only for yellow fever, Japanese encephalitis, tick-borne encephalitis and Kyasanur forest disease. Factors contributing to resurgence include insufficient supplies of available vaccines, incomplete vaccination coverage and relaxation in vector control. Research has been underway for 60 years to develop effective vaccines against dengue, and recent progress is encouraging. The development of vaccines against West Nile, virus recently introduced to North America, has been initiated. In addition, there is considerable interest in improving existing vaccines with respect to increasing safety (e.g. eliminating the newly recognized syndrome of yellow fever vaccine-associated viscerotropic adverse disease), and to reducing the cost and number of doses required for effective immunization. Traditional approaches to flavivirus vaccines are still employed, while recent advancements in biotechnology produced new approaches to vaccine design, such as recombinant live virus, subunit and DNA vaccines. Live chimeric vaccines against dengue, Japanese encephalitis and West Nile based on yellow fever 17D virus (ChimeriVax) are in phase I/II trials, with encouraging results. Other chimeric dengue, tick-borne encephalitis and West Nile virus candidates were developed based on attenuated dengue backbones. To further reduce the impact of flavivirus diseases, vaccination policies and vector control programs in affected countries require revision.

Quality vaccines for all people: Report on the 16th annual general meeting of the Developing Countries Vaccine Manufacturers' Network, 05-07th October 2015, Bangkok, Thailand.

PubMed

Pagliusi, Sonia; Ting, Ching-Chia; Khomvilai, Sumana

2016-06-30

The Developing Countries Vaccine Manufacturers Network (DCVMN) assembled high-profile leaders from global health organisations and vaccine manufactures for its 16th Annual General Meeting to work towards a common goal: providing quality vaccines for all people. Vaccines contribute to a healthy community and robust health system; the Ebola outbreak has raised awareness of the threat and damage one single infectious disease can make, and it is clear that the world was not prepared. However, more research to better understand emerging infectious agents might lead to suitable vaccines which help prevent future outbreaks. DCVMN members presented their progress in developing novel vaccines against Dengue, HPV, Chikungunya, Cholera, cell-based influenza and other vaccines, demonstrating the commitment towards eliminating and eradicating preventable diseases worldwide through global collaboration and technology transfer. The successful introduction of novel Sabin-IPV and Oral Cholera vaccine in China and Korea respectively in 2015 was highlighted. In order to achieve global immunisation, local authorities and community leaders play an important role in the decision-making in vaccine introduction and uptake, based on the ability of vaccines to protect vaccinated people and protect non-vaccinated in the community through herd immunity. Reducing the risk of vaccine shortages can also be achieved by increasing regulatory convergence at regional and international levels. Combatting preventable diseases remains challenging, and collective efforts for improving multi-centre clinical trials, creating regional vaccine security strategies, fostering developing vaccine markets and procurement, and building trust in vaccines were discussed. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Vaccine development for allergen-specific immunotherapy based on recombinant allergens and synthetic allergen peptides: Lessons from the past and novel mechanisms of action for the future

PubMed Central

Valenta, Rudolf; Campana, Raffaela; Focke-Tejkl, Margit; Niederberger, Verena

2016-01-01

In the past, the development of more effective, safe, convenient, broadly applicable, and easy to manufacture vaccines for allergen-specific immunotherapy (AIT) has been limited by the poor quality of natural allergen extracts. Progress made in the field of molecular allergen characterization has now made it possible to produce defined vaccines for AIT and eventually for preventive allergy vaccination based on recombinant DNA technology and synthetic peptide chemistry. Here we review the characteristics of recombinant and synthetic allergy vaccines that have reached clinical evaluation and discuss how molecular vaccine approaches can make AIT more safe and effective and thus more convenient. Furthermore, we discuss how new technologies can facilitate the reproducible manufacturing of vaccines of pharmaceutical grade for inhalant, food, and venom allergens. Allergy vaccines in clinical trials based on recombinant allergens, recombinant allergen derivatives, and synthetic peptides allow us to target selectively different immune mechanisms, and certain of those show features that might make them applicable not only for therapeutic but also for prophylactic vaccination. PMID:26853127

2015 Guidance on cancer immunotherapy development in early-phase clinical studies.

PubMed

2015-12-01

The development of cancer immunotherapies is progressing rapidly with a variety of technological approaches. They consist of "cancer vaccines", which are based on the idea of vaccination, "effector cell therapy", classified as passive immunotherapy, and "inhibition of immunosuppression", which intends to break immunological tolerance to autoantigens or immunosuppressive environments characterizing antitumor immune responses. Recent reports showing clinical evidence of efficacy of immune checkpoint inhibitors and adoptive immunotherapies with tumor-infiltrating lymphocytes and tumor-specific receptor gene-modified T cells indicate the beginning of a new era for cancer immunotherapy. This guidance summarizes ideas that will be helpful to those who plan to develop cancer immunotherapy. The aims of this guidance are to discuss and offer important points in early phase clinical studies of innovative cancer immunotherapy, with future progress in this field, and to contribute to the effective development of cancer immunotherapy aligned with the scope of regulatory science. This guidance covers cancer vaccines, effector cell therapy, and inhibition of immunosuppression, including immune checkpoint inhibitors. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Delayed-Type Hypersensitivity and Hepatitis B Vaccine Responses, in vivo Markers of Cellular and Humoral Immune Function, and the Risk of AIDS or Death

PubMed Central

Patterson, Shane B.; Landrum, Michael L; Okulicz, Jason F.

2014-01-01

Background Delayed-type hypersensitivity (DTH) test responsiveness is associated with HIV disease progression; however it is unknown whether other immune markers, such as hepatitis B virus (HBV) vaccine seroresponse, also predict HIV outcomes. Methods Eligible participants received HBV vaccine after HIV diagnosis, had non-anergic DTH testing at the time of last HBV vaccination, and available post-vaccine HBV antibody responses. The risk of progression to AIDS or death from the time of last HBV vaccination was evaluated. Results Of 369 eligible participants with non-anergic DTH responses, 148 (40%) were HBV vaccine responders. In a multivariate model adjusted for age, CD4 count, viral load, and number of vaccinations, HBV vaccine non-responders had an increased risk of progression to AIDS or death (HR 1.81; 95% CI, 1.03–3.19). Conclusions HBV vaccine seroresponses were independent of DTH responses which suggest that non-response to HBV vaccine is not solely due to cell-mediated immune dysfunction in HIV-infected persons. PMID:24793945

Preclinical development of a vaccine against oligomeric alpha-synuclein based on virus-like particles.

PubMed

Doucet, Marika; El-Turabi, Aadil; Zabel, Franziska; Hunn, Benjamin H M; Bengoa-Vergniory, Nora; Cioroch, Milena; Ramm, Mauricio; Smith, Amy M; Gomes, Ariane Cruz; Cabral de Miranda, Gustavo; Wade-Martins, Richard; Bachmann, Martin F

2017-01-01

Parkinson's disease (PD) is a progressive and currently incurable neurological disorder characterised by the loss of midbrain dopaminergic neurons and the accumulation of aggregated alpha-synuclein (a-syn). Oligomeric a-syn is proposed to play a central role in spreading protein aggregation in the brain with associated cellular toxicity contributing to a progressive neurological decline. For this reason, a-syn oligomers have attracted interest as therapeutic targets for neurodegenerative conditions such as PD and other alpha-synucleinopathies. In addition to strategies using small molecules, neutralisation of the toxic oligomers by antibodies represents an attractive and highly specific strategy for reducing disease progression. Emerging active immunisation approaches using vaccines are already being trialled to induce such antibodies. Here we propose a novel vaccine based on the RNA bacteriophage (Qbeta) virus-like particle conjugated with short peptides of human a-syn. High titres of antibodies were successfully and safely generated in wild-type and human a-syn over-expressing (SNCA-OVX) transgenic mice following vaccination. Antibodies from vaccine candidates targeting the C-terminal regions of a-syn were able to recognise Lewy bodies, the hallmark aggregates in human PD brains. Furthermore, antibodies specifically targeted oligomeric and aggregated a-syn as they exhibited 100 times greater affinity for oligomeric species over monomer a-syn proteins in solution. In the SNCA-OVX transgenic mice used, vaccination was, however, unable to confer significant changes to oligomeric a-syn bioburden. Similarly, there was no discernible effect of vaccine treatment on behavioural phenotype as compared to control groups. Thus, antibodies specific for oligomeric a-syn induced by vaccination were unable to treat symptoms of PD in this particular mouse model.

Preclinical development of a vaccine against oligomeric alpha-synuclein based on virus-like particles

PubMed Central

Zabel, Franziska; Hunn, Benjamin H.M.; Bengoa-Vergniory, Nora; Cioroch, Milena; Ramm, Mauricio; Smith, Amy M.; Gomes, Ariane Cruz; Cabral de Miranda, Gustavo; Wade-Martins, Richard; Bachmann, Martin F.

2017-01-01

Parkinson's disease (PD) is a progressive and currently incurable neurological disorder characterised by the loss of midbrain dopaminergic neurons and the accumulation of aggregated alpha-synuclein (a-syn). Oligomeric a-syn is proposed to play a central role in spreading protein aggregation in the brain with associated cellular toxicity contributing to a progressive neurological decline. For this reason, a-syn oligomers have attracted interest as therapeutic targets for neurodegenerative conditions such as PD and other alpha-synucleinopathies. In addition to strategies using small molecules, neutralisation of the toxic oligomers by antibodies represents an attractive and highly specific strategy for reducing disease progression. Emerging active immunisation approaches using vaccines are already being trialled to induce such antibodies. Here we propose a novel vaccine based on the RNA bacteriophage (Qbeta) virus-like particle conjugated with short peptides of human a-syn. High titres of antibodies were successfully and safely generated in wild-type and human a-syn over-expressing (SNCA-OVX) transgenic mice following vaccination. Antibodies from vaccine candidates targeting the C-terminal regions of a-syn were able to recognise Lewy bodies, the hallmark aggregates in human PD brains. Furthermore, antibodies specifically targeted oligomeric and aggregated a-syn as they exhibited 100 times greater affinity for oligomeric species over monomer a-syn proteins in solution. In the SNCA-OVX transgenic mice used, vaccination was, however, unable to confer significant changes to oligomeric a-syn bioburden. Similarly, there was no discernible effect of vaccine treatment on behavioural phenotype as compared to control groups. Thus, antibodies specific for oligomeric a-syn induced by vaccination were unable to treat symptoms of PD in this particular mouse model. PMID:28797124

Progress toward measles elimination--Eastern Mediterranean Region, 2008-2012.

PubMed

Teleb, Nadia; Lebo, Emmaculate; Ahmed, Hinda; Hossam, Abdel Rahman; El Sayed, El Tayeb; Dabbagh, Alya; Strebel, Peter; Rota, Paul; Alexander, James

2014-06-13

In 1997, the 22 countries in the World Health Organization (WHO) Eastern Mediterranean Region (EMR) adopted a goal of measles elimination by 2010. To achieve this goal, the WHO Regional Office for the Eastern Mediterranean Region (EMRO) developed a four-pronged strategy: 1) achieve ≥ 95% vaccination coverage of children with the first dose of measles-containing vaccine (MCV1) in every district of each country through routine immunization services, 2) achieve ≥ 95% vaccination coverage with the second dose of measles-containing vaccine (MCV2) in every district of each country either through a routine 2-dose vaccination schedule or through supplementary immunization activities (SIAs), 3) conduct high-quality, case-based surveillance in all countries, and 4) provide optimal clinical case management, including supplementing diets with vitamin A. Although significant progress was made toward measles elimination in the EMR during 1997-2007, the measles elimination goal was not reached by the target date of 2010, and the date was revised to 2015. This report updates previous reports and summarizes the progress made toward measles elimination in EMR during 2008-2012. From 2008 to 2012, large outbreaks occurred in countries with a high incidence of measles, and reported annual measles cases in EMR increased from 12,186 to 36,456. To achieve measles elimination in EMR, efforts are needed to increase 2-dose vaccination coverage, especially in countries with high incidence of measles and in conflict-affected countries, and to implement innovative strategies to reach populations at high risk in areas with poor access to vaccination services or with civil strife.

Pneumococcal conjugate vaccine introduction in Latin America and the Caribbean: progress and lessons learned.

PubMed

de Oliveira, Lucia Helena; Trumbo, Silas Pierson; Ruiz Matus, Cuauhtémoc; Sanwogou, N Jennifer; Toscano, Cristiana M

2016-10-01

In Latin America and the Caribbean, pneumococcus has been estimated to cause 12,000-28,000 deaths, 182,000 hospitalizations, and 1.4 million clinic visits annually. Countries in the Americas have been among the first developing nations to introduce pneumococcal conjugate vaccines into their Expanded Programs on Immunization, with 34 countries and territories having introduced these vaccines as of September 2015. Lessons learned for successful vaccine introduction include the importance of coordination between political and technical decision makers, adjustments to the cold chain prior to vaccine introduction, and the need for detailed plans addressing the financial and technical sustainability of introduction. Though many questions on the Pneumococcal Conjugate Vaccine remain unanswered, the experience of the Americas suggests that the vaccines can be introduced quickly and effectively.

Economic and practical challenges to the formulation of vaccines against endemic infectious diseases such as malaria.

PubMed

Plebanski, Magdalena; Lopez, Ester; Proudfoot, Owen; Cooke, Brian M; Itzstein, Mark von; Coppel, Ross L

2006-09-01

Herein, we analyze in general the current vaccine market and identify potential factors driving and modulating supply and demand for vaccines. An emphasis is placed on changes in regulation in the last 20 years which have led to increased indirect costs of production, and which can create a barrier against the timely use of technological advances to reduce direct costs. Other defining industry characteristics, such as firm numbers and sizes, cost and pricing strategies, nature extent and impact of Government involvement and international regulation are noted. These considerations, far from being removed from basic vaccine research, influence its ability to achieve aims that can be then progressed into effective vaccine products. We discuss specifically the development of particulate vaccines against malaria, a major lethal disease and health problem prevalent in Africa, including some key economic and methodological challenges and opportunities. We note some practical issues blocking the development of effective particulate vaccines for the Third World, mainly driven by the regulatory spiral noted above.

Rotavirus epidemiology and vaccine demand: considering Bangladesh chapter through the book of global disease burden.

PubMed

Mahmud-Al-Rafat, Abdullah; Muktadir, Abdul; Muktadir, Hasneen; Karim, Mahbubul; Maheshwari, Arpan; Ahasan, Mohammad Mainul

2018-02-01

Rotavirus is the major cause of gastroenteritis in children throughout the world. Every year, a large number of children aged < 5 years die from rotavirus-related diarrhoeal diseases. Though these infections are vaccine-preventable, the vast majority of children in low-income countries suffer from the infection. The situation leads to severe economic loss and constitutes a major public health problem. We searched electronic databases including PubMed and Google scholar using the following words: "features of rotavirus," "epidemiology of rotavirus," "rotavirus serotypes," "rotavirus in Bangladesh," "disease burden of rotavirus," "rotavirus vaccine," "low efficacy of rotavirus vaccine," "inactivated rotavirus vaccine". Publications until July 2017 have been considered for this work. Currently, two live attenuated vaccines are available throughout the world. Many countries have included rotavirus vaccines in national immunization program to reduce the disease burden. However, due to low efficacy of the available vaccines, satisfactory outcome has not yet been achieved in developing countries such as Bangladesh. Poor economic, public health, treatment, and sanitation status of the low-income countries necessitate the need for the most effective rotavirus vaccines. Therefore, the present scenario demands the development of a highly effective rotavirus vaccine. In this regard, inactivated rotavirus vaccine concept holds much promise for reducing the current disease burden. Recent advancements in developing an inactivated rotavirus vaccine indicate a significant progress towards disease prophylaxis and control.

Correlates of Protection for M Protein-Based Vaccines against Group A Streptococcus

PubMed Central

Smeesters, Pierre R.; Frost, Hannah R. C.; Steer, Andrew C.

2015-01-01

Group A streptococcus (GAS) is known to cause a broad spectrum of illness, from pharyngitis and impetigo, to autoimmune sequelae such as rheumatic heart disease, and invasive diseases. It is a significant cause of infectious disease morbidity and mortality worldwide, but no efficacious vaccine is currently available. Progress in GAS vaccine development has been hindered by a number of obstacles, including a lack of standardization in immunoassays and the need to define human correlates of protection. In this review, we have examined the current immunoassays used in both GAS and other organisms, and explored the various challenges in their implementation in order to propose potential future directions to identify a correlate of protection and facilitate the development of M protein-based vaccines, which are currently the main GAS vaccine candidates. PMID:26101780

What's new in tuberculosis vaccines?

PubMed Central

Ginsberg, Ann M.

2002-01-01

Over the past 10 years, tuberculosis (TB) vaccine development has resurged as an active area of investigation. The renewed interest has been stimulated by the recognition that, although BCG is delivered to approximately 90% of all neonates globally through the Expanded Programme on Immunization, Mycobacterium tuberculosis continues to cause over 8 million new cases of TB and over 2 million deaths annually. Over one hundred TB vaccine candidates have been developed, using different approaches to inducing protective immunity. Candidate vaccines are typically screened in small animal models of primary TB disease for their ability to protect against a virulent strain of M. tuberculosis. The most promising are now beginning to enter human safety trials, marking real progress in this field for the first time in 80 years. PMID:12132007

Vaccine-induced T cells Provide Partial Protection Against High-dose Rectal SIVmac239 Challenge of Rhesus Macaques

PubMed Central

Lasaro, Marcio O; Haut, Larissa H; Zhou, Xiangyang; Xiang, Zhiquan; Zhou, Dongming; Li, Yan; Giles-Davis, Wynetta; Li, Hua; Engram, Jessica C; DiMenna, Lauren J; Bian, Ang; Sazanovich, Marina; Parzych, Elizabeth M; Kurupati, Raj; Small, Juliana C; Wu, Te-Lang; Leskowitz, Rachel M; Klatt, Nicole R; Brenchley, Jason M; Garber, David A; Lewis, Mark; Ratcliffe, Sarah J; Betts, Michael R; Silvestri, Guido; Ertl, Hildegund C

2011-01-01

Despite enormous efforts by the scientific community, an effective HIV vaccine remains elusive. To further address to what degree T cells in absence of antibodies may protect against simian immunodeficiency virus (SIV) disease progression, rhesus macaques were vaccinated intramuscularly with a chimpanzee-derived Ad vector (AdC) serotype 6 and then boosted intramuscularly with a serologically distinct AdC vector of serotype 7 both expressing Gag of SIVmac239. Animals were subsequently boosted intramuscularly with a modified vaccinia Ankara (MVA) virus expressing Gag and Tat of the homologous SIV before mucosal challenge with a high dose of SIVmac239 given rectally. Whereas vaccinated animals showed only a modest reduction of viral loads, their overall survival was improved, in association with a substantial protection from the loss of CD4+ T cells. In addition, the two vaccinated Mamu-A*01+ macaques controlled viral loads to levels below detection within weeks after challenge. These data strongly suggest that T cells, while unable to affect SIV acquisition upon high-dose rectal infection, can reduce disease progression. Induction of potent T-cell responses should thus remain a component of our efforts to develop an efficacious vaccine to HIV-1. PMID:21081905

Vaccine-induced T cells provide partial protection against high-dose rectal SIVmac239 challenge of rhesus macaques.

PubMed

Lasaro, Marcio O; Haut, Larissa H; Zhou, Xiangyang; Xiang, Zhiquan; Zhou, Dongming; Li, Yan; Giles-Davis, Wynetta; Li, Hua; Engram, Jessica C; Dimenna, Lauren J; Bian, Ang; Sazanovich, Marina; Parzych, Elizabeth M; Kurupati, Raj; Small, Juliana C; Wu, Te-Lang; Leskowitz, Rachel M; Klatt, Nicole R; Brenchley, Jason M; Garber, David A; Lewis, Mark; Ratcliffe, Sarah J; Betts, Michael R; Silvestri, Guido; Ertl, Hildegund C

2011-02-01

Despite enormous efforts by the scientific community, an effective HIV vaccine remains elusive. To further address to what degree T cells in absence of antibodies may protect against simian immunodeficiency virus (SIV) disease progression, rhesus macaques were vaccinated intramuscularly with a chimpanzee-derived Ad vector (AdC) serotype 6 and then boosted intramuscularly with a serologically distinct AdC vector of serotype 7 both expressing Gag of SIVmac239. Animals were subsequently boosted intramuscularly with a modified vaccinia Ankara (MVA) virus expressing Gag and Tat of the homologous SIV before mucosal challenge with a high dose of SIVmac239 given rectally. Whereas vaccinated animals showed only a modest reduction of viral loads, their overall survival was improved, in association with a substantial protection from the loss of CD4(+) T cells. In addition, the two vaccinated Mamu-A*01(+) macaques controlled viral loads to levels below detection within weeks after challenge. These data strongly suggest that T cells, while unable to affect SIV acquisition upon high-dose rectal infection, can reduce disease progression. Induction of potent T-cell responses should thus remain a component of our efforts to develop an efficacious vaccine to HIV-1.

New Horizons in the Development of Novel Needle-Free Immunization Strategies to Increase Vaccination Efficacy.

PubMed

Schulze, Kai; Ebensen, Thomas; Riese, Peggy; Prochnow, Blair; Lehr, Claus-Michael; Guzmán, Carlos A

2016-01-01

The young twenty-first century has already brought several medical advances, such as a functional artificial human liver created from stem cells, improved antiviral (e.g., against HIV) and cancer (e.g., against breast cancer) therapies, interventions controlling cardiovascular diseases, and development of new and optimized vaccines (e.g., HPV vaccine). However, despite this substantial progress and the achievements of the last century, humans still suffer considerably from diseases, especially from infectious diseases. Thus, almost one-fourth of all deaths worldwide are caused directly or indirectly by infectious agents. Although vaccination has led to the control of many diseases, including smallpox, diphtheria, and tetanus, emerging diseases are still not completely contained. Furthermore, pathogens such as Bordetella pertussis undergo alterations making adaptation of the respective vaccine necessary. Moreover, insufficient implementation of vaccination campaigns leads to re-emergence of diseases which were believed to be already under control (e.g., poliomyelitis). Therefore, novel vaccination strategies need to be developed in order to meet the current challenges including lack of compliance, safety issues, and logistic constraints. In this context, mucosal and transdermal approaches constitute promising noninvasive vaccination strategies able to match these demands.

Current Status of Rift Valley Fever Vaccine Development

PubMed Central

Faburay, Bonto; LaBeaud, Angelle Desiree; McVey, D. Scott; Wilson, William C.; Richt, Juergen A.

2017-01-01

Rift Valley Fever (RVF) is a mosquito-borne zoonotic disease that presents a substantial threat to human and public health. It is caused by Rift Valley fever phlebovirus (RVFV), which belongs to the genus Phlebovirus and the family Phenuiviridae within the order Bunyavirales. The wide distribution of competent vectors in non-endemic areas coupled with global climate change poses a significant threat of the transboundary spread of RVFV. In the last decade, an improved understanding of the molecular biology of RVFV has facilitated significant progress in the development of novel vaccines, including DIVA (differentiating infected from vaccinated animals) vaccines. Despite these advances, there is no fully licensed vaccine for veterinary or human use available in non-endemic countries, whereas in endemic countries, there is no clear policy or practice of routine/strategic livestock vaccinations as a preventive or mitigating strategy against potential RVF disease outbreaks. The purpose of this review was to provide an update on the status of RVF vaccine development and provide perspectives on the best strategies for disease control. Herein, we argue that the routine or strategic vaccination of livestock could be the best control approach for preventing the outbreak and spread of future disease. PMID:28925970

Recent advances in recombinant protein-based malaria vaccines

PubMed Central

Draper, Simon J.; Angov, Evelina; Horii, Toshihiro; Miller, Louis H.; Srinivasan, Prakash; Theisen, Michael; Biswas, Sumi

2015-01-01

Plasmodium parasites are the causative agent of human malaria, and the development of a highly effective vaccine against infection, disease and transmission remains a key priority. It is widely established that multiple stages of the parasite's complex lifecycle within the human host and mosquito vector are susceptible to vaccine-induced antibodies. The mainstay approach to antibody induction by subunit vaccination has been the delivery of protein antigen formulated in adjuvant. Extensive efforts have been made in this endeavor with respect to malaria vaccine development, especially with regard to target antigen discovery, protein expression platforms, adjuvant testing, and development of soluble and virus-like particle (VLP) delivery platforms. The breadth of approaches to protein-based vaccines is continuing to expand as innovative new concepts in next-generation subunit design are explored, with the prospects for the development of a highly effective multi-component/multi-stage/multi-antigen formulation seeming ever more likely. This review will focus on recent progress in protein vaccine design, development and/or clinical testing for a number of leading malaria antigens from the sporozoite-, merozoite- and sexual-stages of the parasite's lifecycle–including PfCelTOS, PfMSP1, PfAMA1, PfRH5, PfSERA5, PfGLURP, PfMSP3, Pfs48/45 and Pfs25. Future prospects and challenges for the development, production, human delivery and assessment of protein-based malaria vaccines are discussed. PMID:26458807

Vesicular stomatitis virus-based vaccines protect nonhuman primates against aerosol challenge with Ebola and Marburg viruses.

PubMed

Geisbert, Thomas W; Daddario-Dicaprio, Kathleen M; Geisbert, Joan B; Reed, Douglas S; Feldmann, Friederike; Grolla, Allen; Ströher, Ute; Fritz, Elizabeth A; Hensley, Lisa E; Jones, Steven M; Feldmann, Heinz

2008-12-09

Considerable progress has been made over the last decade in developing candidate preventive vaccines that can protect nonhuman primates against Ebola and Marburg viruses. A vaccine based on recombinant vesicular stomatitis virus (VSV) seems to be particularly robust as it can also confer protection when administered as a postexposure treatment. While filoviruses are not thought to be transmitted by aerosol in nature the inhalation route is among the most likely portals of entry in the setting of a bioterrorist event. At present, all candidate filoviral vaccines have been evaluated against parenteral challenges but none have been tested against an aerosol exposure. Here, we evaluated our recombinant VSV-based Zaire ebolavirus (ZEBOV) and Marburg virus (MARV) vaccines against aerosol challenge in cynomolgus macaques. All monkeys vaccinated with a VSV vector expressing the glycoprotein of ZEBOV were completely protected against an aerosol exposure of ZEBOV. Likewise, all monkeys vaccinated with a VSV vector expressing the glycoprotein of MARV were completely protected against an aerosol exposure of MARV. All control animals challenged by the aerosol route with either ZEBOV or MARV succumbed. Interestingly, disease in control animals appeared to progress slower than previously seen in macaques exposed to comparable doses by intramuscular injection.

Advances in the development of enterohemorrhagic Escherichia coli vaccines using murine models of infection

PubMed Central

Garcia-Angulo, Victor A.; Kalita, Anjana; Torres, Alfredo G.

2013-01-01

Enterohemorrhagic Escherichia coli (EHEC) strains are food borne pathogens with importance in public health. EHEC colonizes the large intestine and causes diarrhea, hemorrhagic colitis and in some cases, life-threatening hemolytic-uremic syndrome (HUS) due to the production of Shiga toxins (Stx). The lack of effective clinical treatment, sequelae after infection and mortality rate in humans supports the urgent need of prophylactic approaches, such as development of vaccines. Shedding from cattle, the main EHEC reservoir and considered the principal food contamination source, has prompted the development of licensed vaccines that reduce EHEC colonization in ruminants. Although murine models do not fully recapitulate human infection, they are commonly used to evaluate EHEC vaccines and the immune/protective responses elicited in the host. Mice susceptibility differs depending of the EHEC inoculums; therefore, displaying different mortality rates and Stx-mediated renal damage. Therefore, several experimental protocols have being pursued in this model to develop EHEC-specific vaccines. Recent candidate vaccines evaluated include those composed of virulence factors alone or as fused-subunits, DNA-based, attenuated bacteria and bacterial ghosts. In this review, we summarize progress in the design and testing of EHEC vaccines and the use of different strategies for the evaluation of novel EHEC vaccines in the murine model. PMID:23707170

Development and approval of live attenuated influenza vaccines based on Russian master donor viruses: Process challenges and success stories.

PubMed

Rudenko, Larisa; Yeolekar, Leena; Kiseleva, Irina; Isakova-Sivak, Irina

2016-10-26

Influenza is a viral infection that affects much of the global population each year. Vaccination remains the most effective tool for preventing the disease. Live attenuated influenza vaccine (LAIV) has been used since the 1950s to protect humans against seasonal influenza. LAIVs developed by the Institute of Experimental Medicine (IEM), Saint Petersburg, Russia, have been successfully used in Russia since 1987. In 2006, the World Health Organization (WHO) announced a Global action plan for influenza vaccines (GAP). WHO, recognizing potential advantages of LAIV over the inactivated influenza vaccine in a pandemic situation, included LAIV in the GAP. BioDiem Ltd., a vaccine development company based in Melbourne, Australia which held the rights for the Russian LAIV, licensed this technology to WHO in 2009. WHO was permitted to grant sub-licenses to vaccine manufacturers in newly industrialized and developing countries to use the Russian LAIV for the development, manufacture, use and sale of pandemic and seasonal LAIVs. To date, WHO has granted sub-licenses to vaccine manufacturers in China (Changchun BCHT Biotechnology Co., Ltd.), India (Serum Institute of India Pvt. Ltd.) and Thailand (Government Pharmaceutical Organization). In parallel, in 2009, IEM signed an agreement with WHO, under which IEM committed to supply pandemic and seasonal candidate vaccine viruses to the sub-licensees. This paper describes the progress made by collaborators from China, India, Russia and Thailand in developing preventive measures, including LAIV against pandemic influenza. Copyright © 2016 Elsevier Ltd. All rights reserved.

Neonatal tetanus elimination in Pakistan: progress and challenges.

PubMed

Lambo, Jonathan A; Nagulesapillai, Tharsiya

2012-12-01

Pakistan is one of the 34 countries that have not achieved the neonatal tetanus (NT) global elimination target set by the World Health Organization (WHO). NT, caused by Clostridium tetani, is a highly fatal infection of the neonatal period. It is one of the most underreported diseases and remains a major but preventable cause of neonatal and infant mortality in many developing countries. In 1989, the World Health Assembly called for the elimination of NT by 1995, and since then considerable progress has been made using the following strategies: clean delivery practices, routine tetanus toxoid (TT) immunization of pregnant women, and immunization of all women of childbearing age with three doses of TT vaccine in high-risk areas during supplementary immunization campaigns. This review presents the activities, progress, and challenges in achieving NT elimination in Pakistan. A review of the literature found TT vaccination coverage in Pakistan ranged from 60% to 74% over the last decade. Low vaccination coverage, the main driver for NT in Pakistan, is due to many factors, including demand failure for TT vaccine resulting from inadequate knowledge of TT vaccine among reproductive age females and inadequate information about the benefits of TT provided by health care workers and the media. Other factors linked to low vaccination coverage include residing in rural areas, lack of formal education, poor knowledge about place and time to get vaccinated, and lack of awareness about the importance of vaccination. A disparity exists in TT vaccination coverage and antenatal care between urban and rural areas due to access and utilization of health care services. NT reporting is incomplete, as cases from the private sector and rural areas are underreported. To successfully eliminate NT, women of reproductive age must be made aware of the benefits of TT vaccine, not only to themselves, but also to their families. Effective communication strategies for TT vaccine delivery and health education focusing on increasing awareness of NT are strongly suggested. It is imperative that the private and government sectors work cooperatively to report NT cases and improve routine TT vaccination coverage. Copyright © 2012 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Progress in the development of subunit vaccines for gastrointestinal nematodes of ruminants.

PubMed

Matthews, J B; Geldhof, P; Tzelos, T; Claerebout, E

2016-12-01

The global increase in anthelmintic resistant nematodes of ruminants, together with consumer concerns about chemicals in food, necessitates the development of alternative methods of control for these pathogens. Subunit recombinant vaccines are ideally placed to fill this gap. Indeed, they are probably the only valid option for the long-term control of ruminant parasitic nematodes given the increasing ubiquity of multidrug resistance in a range of worm species across the world. The development of a subunit multicellular parasite vaccine to the point of practical application would be a groundbreaking step in the control of these important endemic infections of livestock. This review summarizes the current status of subunit vaccine development for a number of important gastrointestinal nematodes of cattle and sheep, with a focus on the limitations and problems encountered thus far, and suggestions as to how these hurdles might be overcome. © 2016 John Wiley & Sons Ltd.

Development and pre-clinical evaluation in the swine model of a mucosal vaccine tablet for human influenza viruses: A proof-of-concept study.

PubMed

Busignies, V; Simon, G; Mollereau, G; Bourry, O; Mazel, V; Rosa-Calatrava, M; Tchoreloff, P

2018-03-01

Liquid vaccine formulations present some disadvantages such as stability problems, cold chain requirement or administration by trained personnel. Vaccine formulated as tablets would present a wide range of progress such as an increase stability that would facilitate the administration, the distribution and the storage of vaccine formulations. This work investigates the possibility to develop a mucosal tablet vaccine for human influenza viruses. The tablets were tested in vitro for biological efficacy and stability and in vivo in swine as a model for influenza A virus immunity. First, the ability to produce by compaction a stable vaccine with a preserved antigen was demonstrated. In a second part, vaccine tablets were used to immunize pigs. After positioning the tablets on the buccal mucosa, the animals were challenged by inoculation of the A/H1N1 pandemic virus. The responses were compared to those observed in animals vaccinated intramuscularly with the commercial liquid vaccine. It was observed signs of priming of the pig's immune system with vaccine tablets, even if the immune response stayed lower than vaccination by intramuscular route. Thus, we present attractive results that indicate a promising potential for mucosal vaccine tablets. Copyright © 2018 Elsevier B.V. All rights reserved.

U.S. medical countermeasure development since 2001: a long way yet to go.

PubMed

Russell, Philip K; Gronvall, Gigi Kwik

2012-03-01

The U.S. government has taken significant steps toward developing and acquiring vaccines, drugs, and other medical countermeasures (MCMs) to protect and treat the population after a biological attack. In contrast to 2001, there is now a procedure for the Department of Health and Human Services (HHS) to develop, license, and stockpile MCMs for civilian use. Another major accomplishment is smallpox preparedness: There is now an adequate supply of vaccine for every person in the U.S., and there is an alternative vaccine meant for immunocompromised people and those with close contact with them. In spite of these and other accomplishments, the U.S. government MCM effort has been criticized by federal advisory committees, National Academy of Sciences reports, a congressional commission, and outside analysts who state that the efforts lack central leadership and accountability and that the pace of progress has been slow. A clear operational strategy for using MCMs, which would guide their development and acquisition, is also lacking. In this article, we review key areas of progress made since 2001 to develop and acquire MCMs, and we summarize what we judge to be the most critical and often mentioned areas where improvements are needed.

Malaria vaccines: past, present and future.

PubMed

von Seidlein, Lorenz; Bejon, Philip

2013-12-01

The currently available malaria control tools have allowed malaria elimination in many regions but there remain many regions where malaria control has made little progress. A safe and protective malaria vaccine would be a huge asset for malaria control. Despite the many challenges, efforts continue to design and evaluate malaria vaccine candidates. These candidates target different stages in the life cycle of Plasmodia. The most advanced vaccine candidates target the pre-erythrocytic stages in the life cycle of the parasite and include RTS,S/AS01, which has progressed through clinical development to the stage that it may be licensed in 2015. Attenuated whole-parasite vaccine candidates are highly protective, but there are challenges to manufacture and to administration. Cellular immunity is targeted by the prime-boost approach. Priming vectors trigger only modest responses but these are focused on the recombinant antigen. Boosting vectors trigger strong but broad non-specific responses. The heterologous sequence produces strong immunological responses to the recombinant antigen. Candidates that target the blood stages of the parasite have to result in an immune response that is more effective than the response to an infection to abort or control the infection of merozoites and hence disease. Finally, the sexual stages of the parasite offer another target for vaccine development, which would prevent the transmission of malaria. Today it seems unlikely that any candidate targeting a single antigen will provide complete protection against an organism of the complexity of Plasmodium. A systematic search for vaccine targets and combinations of antigens may be a more promising approach.

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

Accelerating the development of a therapeutic vaccine for human Chagas disease: rationale and prospects

PubMed Central

Zhan, Bin; Heffernan, Michael J; Jones, Kathryn; Valenzuela, Jesus G; Kamhawi, Shaden; Ortega, Jaime; de Leon Rosales, Samuel Ponce; Lee, Bruce Y; Bacon, Kristina M; Fleischer, Bernhard; Slingsby, BT; Cravioto, Miguel Betancourt; Tapia-Conyer, Roberto

2013-01-01

Chagas disease is a leading cause of heart disease affecting approximately 10 million people in Latin America and elsewhere worldwide. The two major drugs available for the treatment of Chagas disease have limited efficacy in Trypanosoma cruzi-infected adults with indeterminate (patients who have seroconverted but do not yet show signs or symptoms) and determinate (patients who have both seroconverted and have clinical disease) status; they require prolonged treatment courses and are poorly tolerated and expensive. As an alternative to chemotherapy, an injectable therapeutic Chagas disease vaccine is under development to prevent or delay Chagasic cardiomyopathy in patients with indeterminate or determinate status. The bivalent vaccine will be comprised of two recombinant T. cruzi antigens, Tc24 and TSA-1, formulated on alum together with the Toll-like receptor 4 agonist, E6020. Proof-of-concept for the efficacy of these antigens was obtained in preclinical testing at the Autonomous University of Yucatan. Here the authors discuss the potential for a therapeutic Chagas vaccine as well as the progress made towards such a vaccine, and the authors articulate a roadmap for the development of the vaccine as planned by the nonprofit Sabin Vaccine Institute Product Development Partnership and Texas Children’s Hospital Center for Vaccine Development in collaboration with an international consortium of academic and industrial partners in Mexico, Germany, Japan, and the USA. PMID:23151163

Accelerating the development of a therapeutic vaccine for human Chagas disease: rationale and prospects.

PubMed

Dumonteil, Eric; Bottazzi, Maria Elena; Zhan, Bin; Heffernan, Michael J; Jones, Kathryn; Valenzuela, Jesus G; Kamhawi, Shaden; Ortega, Jaime; de Leon Rosales, Samuel Ponce; Lee, Bruce Y; Bacon, Kristina M; Fleischer, Bernhard; Slingsby, B T; Cravioto, Miguel Betancourt; Tapia-Conyer, Roberto; Hotez, Peter J

2012-09-01

Chagas disease is a leading cause of heart disease affecting approximately 10 million people in Latin America and elsewhere worldwide. The two major drugs available for the treatment of Chagas disease have limited efficacy in Trypanosoma cruzi-infected adults with indeterminate (patients who have seroconverted but do not yet show signs or symptoms) and determinate (patients who have both seroconverted and have clinical disease) status; they require prolonged treatment courses and are poorly tolerated and expensive. As an alternative to chemotherapy, an injectable therapeutic Chagas disease vaccine is under development to prevent or delay Chagasic cardiomyopathy in patients with indeterminate or determinate status. The bivalent vaccine will be comprised of two recombinant T. cruzi antigens, Tc24 and TSA-1, formulated on alum together with the Toll-like receptor 4 agonist, E6020. Proof-of-concept for the efficacy of these antigens was obtained in preclinical testing at the Autonomous University of Yucatan. Here the authors discuss the potential for a therapeutic Chagas vaccine as well as the progress made towards such a vaccine, and the authors articulate a roadmap for the development of the vaccine as planned by the nonprofit Sabin Vaccine Institute Product Development Partnership and Texas Children's Hospital Center for Vaccine Development in collaboration with an international consortium of academic and industrial partners in Mexico, Germany, Japan, and the USA.

Progress on plague vaccine development.

PubMed

Rosenzweig, Jason A; Jejelowo, Olufisayo; Sha, Jian; Erova, Tatiana E; Brackman, Sheri M; Kirtley, Michelle L; van Lier, Cristina J; Chopra, Ashok K

2011-07-01

Yersinia pestis (YP), the gram-negative plague bacterium, has shaped human history unlike any other pathogen known to mankind. YP (transmitted by the bite of an infected flea) diverged only recently from the related enteric pathogen Yersinia pseudotuberculosis but causes radically different diseases. Three forms of plague exist in humans: bubonic (swollen lymph nodes or bubos), septicemic (spread of YP through the lymphatics or bloodstream from the bubos to other organs), and contagious, pneumonic plague which can be communicated via YP-charged respiratory droplets resulting in person-person transmission and rapid death if left untreated (50-90% mortality). Despite the potential threat of weaponized YP being employed in bioterrorism and YP infections remaining prevalent in endemic regions of the world where rodent populations are high (including the four corner regions of the USA), an efficacious vaccine that confers immunoprotection has yet to be developed. This review article will describe the current vaccine candidates being evaluated in various model systems and provide an overall summary on the progress of this important endeavor.

Structural Insights into the Mechanisms of Antibody-Mediated Neutralization of Flavivirus Infection: Implications for Vaccine Development

PubMed Central

Pierson, Theodore C.; Fremont, Daved H.; Kuhn, Richard J.; Diamond, Michael S.

2009-01-01

Flaviviruses are a group of small RNA viruses that cause severe disease in humans worldwide and are the target of several vaccine development programs. A primary goal of these efforts is to elicit a protective humoral response directed against the envelope proteins arrayed on the surface of the flavivirus virion. Advances in the structural biology of these viruses has catalyzed rapid progress toward understanding the complexity of the flavivirus immunogen and the molecular basis of antibody-mediated neutralization. These insights have identified factors that govern the potency of neutralizing antibodies and will inform the design and evaluation of novel vaccines. PMID:18779049

Potential Vaccines and Post-Exposure Treatments for Filovirus Infections

PubMed Central

Friedrich, Brian M.; Trefry, John C.; Biggins, Julia E.; Hensley, Lisa E.; Honko, Anna N.; Smith, Darci R.; Olinger, Gene G.

2012-01-01

Viruses of the family Filoviridae represent significant health risks as emerging infectious diseases as well as potentially engineered biothreats. While many research efforts have been published offering possibilities toward the mitigation of filoviral infection, there remain no sanctioned therapeutic or vaccine strategies. Current progress in the development of filovirus therapeutics and vaccines is outlined herein with respect to their current level of testing, evaluation, and proximity toward human implementation, specifically with regard to human clinical trials, nonhuman primate studies, small animal studies, and in vitro development. Contemporary methods of supportive care and previous treatment approaches for human patients are also discussed. PMID:23170176

iVAX: An integrated toolkit for the selection and optimization of antigens and the design of epitope-driven vaccines.

PubMed

Moise, Leonard; Gutierrez, Andres; Kibria, Farzana; Martin, Rebecca; Tassone, Ryan; Liu, Rui; Terry, Frances; Martin, Bill; De Groot, Anne S

2015-01-01

Computational vaccine design, also known as computational vaccinology, encompasses epitope mapping, antigen selection and immunogen design using computational tools. The iVAX toolkit is an integrated set of tools that has been in development since 1998 by De Groot and Martin. It comprises a suite of immunoinformatics algorithms for triaging candidate antigens, selecting immunogenic and conserved T cell epitopes, eliminating regulatory T cell epitopes, and optimizing antigens for immunogenicity and protection against disease. iVAX has been applied to vaccine development programs for emerging infectious diseases, cancer antigens and biodefense targets. Several iVAX vaccine design projects have had success in pre-clinical studies in animal models and are progressing toward clinical studies. The toolkit now incorporates a range of immunoinformatics tools for infectious disease and cancer immunotherapy vaccine design. This article will provide a guide to the iVAX approach to computational vaccinology.

Rabbit and Nonhuman Primate Models of Toxin-Targeting Human Anthrax Vaccines

PubMed Central

Phipps, Andrew J.; Premanandan, Christopher; Barnewall, Roy E.; Lairmore, Michael D.

2004-01-01

The intentional use of Bacillus anthracis, the etiological agent of anthrax, as a bioterrorist weapon in late 2001 made our society acutely aware of the importance of developing, testing, and stockpiling adequate countermeasures against biological attacks. Biodefense vaccines are an important component of our arsenal to be used during a biological attack. However, most of the agents considered significant threats either have been eradicated or rarely infect humans alive today. As such, vaccine efficacy cannot be determined in human clinical trials but must be extrapolated from experimental animal models. This article reviews the efficacy and immunogenicity of human anthrax vaccines in well-defined animal models and the progress toward developing a rugged immunologic correlate of protection. The ongoing evaluation of human anthrax vaccines will be dependent on animal efficacy data in the absence of human efficacy data for licensure by the U.S. Food and Drug Administration. PMID:15590776

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.

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

New developments and concepts related to biomarker application to vaccines

PubMed Central

Ahmed, S. Sohail; Black, Steve; Ulmer, Jeffrey

2012-01-01

Summary This minireview will provide a perspective on new developments and concepts related to biomarker applications for vaccines. In the context of preventive vaccines, biomarkers have the potential to predict adverse events in select subjects due to differences in genetic make‐up/underlying medical conditions or to predict effectiveness (good versus poor response). When expanding them to therapeutic vaccines, their utility in identification of patients most likely to respond favourably (or avoid potentially negative effects of treatment) becomes self‐explanatory. Despite the progress made so far on dissection of various pathways of biological significance in humans, there is still plenty to unravel about the mysteries related to the quantitative and qualitative aspects of the human host response. This review will provide a focused overview of new concepts and developments in the field of vaccine biomarkers including (i) vaccine‐dependent signatures predicting subject response and safety, (ii) predicting therapeutic vaccine efficacy in chronic diseases, (iii) exploring the genetic make‐up of the host that may modulate subject‐specific adverse events or affect the quality of immune responses, and (iv) the topic of volunteer stratification as a result of biomarker screening (e.g. for therapeutic vaccines but also potentially for preventive vaccines) or as a reflection of an effort to compare select groups (e.g. vaccinated subjects versus patients recovering from infection) to enable the discovery of clinically relevant biomarkers for preventive vaccines. PMID:21895991

Patent data mining: a tool for accelerating HIV vaccine innovation.

PubMed

Clark, K; Cavicchi, J; Jensen, K; Fitzgerald, R; Bennett, A; Kowalski, S P

2011-05-31

Global access to advanced vaccine technologies is challenged by the interrelated components of intellectual property (IP) management strategies, technology transfer (legal and technical) capabilities and the capacity necessary for accelerating R&D, commercialization and delivery of vaccines. Due to a negative association with the management of IP, patents are often overlooked as a vast resource of freely available, information akin to scientific journals as well as business and technological information and trends fundamental for formulating policies and IP management strategies. Therefore, a fundamental step towards facilitating global vaccine access will be the assembly, organization and analysis of patent landscapes, to identify the amount of patenting, ownership (assignees) and fields of technology covered. This is critical for making informed decisions (e.g., identifying licensees, building research and product development collaborations, and ascertaining freedom to operate). Such information is of particular interest to the HIV vaccine community where the HIV Vaccine Enterprise, have voiced concern that IP rights (particularly patents and trade secrets) may prevent data and materials sharing, delaying progress in research and development of a HIV vaccine. We have compiled and analyzed a representative HIV vaccine patent landscape for a prime-boost, DNA/adenoviral vaccine platform, as an example for identifying obstacles, maximizing opportunities and making informed IP management strategy decisions towards the development and deployment of an efficacious HIV vaccine. Copyright © 2011 Elsevier Ltd. All rights reserved.

Ethical and policy issues in using vaccines to treat and prevent cocaine and nicotine dependence.

PubMed

Hall, Wayne; Gartner, Coral

2011-05-01

To describe the rationale of vaccines against cocaine and nicotine, to review progress in developing and trialing vaccines to treat dependence on these drugs and to discuss some of the ethical issues that may arise from their use in legally coerced addiction treatment or for prevention of addiction in adolescents. Several randomized controlled trials of cocaine and nicotine vaccines for relapse prevention have produced mixed results. The studies demonstrate that it is possible to raise antibodies to cocaine and nicotine in humans. In abstinent patients who show high levels of drug antibodies, the rewarding effects of these drugs are attenuated. Phase 2 trials have not found nicotine vaccines to be superior to placebo because only a third of those vaccinated develop sufficient levels of antibody to block the effects of nicotine. Vaccines are a novel approach to relapse prevention that need to more reliably induce immunity in a larger proportion of vaccinated patients if they are to protect against relapse after achieving abstinence. Vaccines are unlikely to prevent addiction in adolescents. Their use under legal coercion should only be considered after considerable experience with their use in voluntary patients.

DNA vaccine against visceral leishmaniasis: a promising approach for prevention and control.

PubMed

Kumar, A; Samant, M

2016-05-01

The visceral leishmaniasis (VL) caused by Leishmania donovani parasite severely affects large populations in tropical and subtropical regions of the world. The arsenal of drugs available is limited, and resistance is common in clinical field isolates. Therefore, vaccines could be an important alternative for prevention against VL. Recently, some investigators advocated the protective efficacy of DNA vaccines, which induces the T cell-based immunity against VL. The vaccine antigens are selected as conserved in various Leishmania species and provide a viable strategy for DNA vaccine development. Our understanding for DNA vaccine development against VL is not enough and much technological advancement is required. Improved formulations and methods of delivery are required, which increase the uptake of DNA vaccine by cells; optimization of vaccine vectors/encoded antigens to augment and direct the host immune response in VL. Despite the many genes identified as vaccine candidates, the disappointing potency of the DNA vaccines in VL underscores the challenges encountered in the efforts to translate efficacy in preclinical models into clinical realities. This review will provide a brief background of DNA vaccines including the insights gained about the design, strategy, safety issues, varied candidates, progress and challenges that play a role in their ability against VL. © 2016 John Wiley & Sons Ltd.

Vaccination against tuberculosis in badgers and cattle: an overview of the challenges, developments and current research priorities in Great Britain.

PubMed

Chambers, M A; Carter, S P; Wilson, G J; Jones, G; Brown, E; Hewinson, R G; Vordermeier, M

2014-07-26

Bovine tuberculosis (TB) is a significant threat to the cattle industry in England and Wales. It is widely acknowledged that a combination of measures targeting both cattle and wildlife will be required to eradicate bovine TB or reduce its prevalence until European official freedom status is achieved. Vaccination of cattle and/or badgers could contribute to bovine TB control in Great Britain, although there are significant gaps in our knowledge regarding the impact that vaccination would actually have on bovine TB incidence. Laboratory studies have demonstrated that vaccination with BCG can reduce the progression and severity of TB in both badgers and cattle. This is encouraging in terms of the prospect of a sustained vaccination programme achieving reductions in disease prevalence; however, developing vaccines for tackling the problem of bovine TB is challenging, time-consuming and resource-intensive, as this review article sets out to explain. British Veterinary Association.

Update on the current status of cytomegalovirus vaccines

PubMed Central

Sung, Heungsup; Schleiss, Mark R

2013-01-01

Human cytomegalovirus (HCMV) is ubiquitous in all populations, and is the most commonly recognized cause of congenital viral infection in developed countries. On the basis of the economic costs saved and the improvement in quality of life that could potentially be conferred by a successful vaccine for prevention of congenital HCMV infection, the Institute of Medicine has identified HCMV vaccine development as a major public health priority. An effective vaccine could potentially also be beneficial in preventing or ameliorating HCMV disease in immunocompromised individuals. Although there are no licensed HCMV vaccines currently available, enormous progress has been made in the last decade, as evidenced by the recently reported results of a Phase II trial of a glycoprotein B vaccine for the prevention of HCMV infection in seronegative women of childbearing age. HCMV vaccines currently in clinical trials include: glycoprotein B subunit vaccines; alphavirus replicon particle vaccines; DNA vaccines; and live-attenuated vaccines. A variety of vaccine strategies are also being examined in preclinical systems and animal models of infection. These include: recombinant vesicular stomatitis virus vaccines; recombinant modified vaccinia virus Ankara; replication-deficient adenovirus-vectored vaccines; and recombinant live-attenuated virus vaccines generated by mutagenesis of cloned rodent CMV genomes maintained as bacterial artificial chromosomes in Escherichia coli. In this article, we provide an overview of the current state of clinical trials and preclinical development of vaccines against HCMV, with an emphasis on studies that have been conducted in the past 5 years. We also summarize a number of recent advances in the study of the biology of HCMV, particularly with respect to epithelial and endothelial cell entry of the virus, which have implications for future vaccine design. PMID:21087108

Update on the current status of cytomegalovirus vaccines.

PubMed

Sung, Heungsup; Schleiss, Mark R

2010-11-01

Human cytomegalovirus (HCMV) is ubiquitous in all populations, and is the most commonly recognized cause of congenital viral infection in developed countries. On the basis of the economic costs saved and the improvement in quality of life that could potentially be conferred by a successful vaccine for prevention of congenital HCMV infection, the Institute of Medicine has identified HCMV vaccine development as a major public health priority. An effective vaccine could potentially also be beneficial in preventing or ameliorating HCMV disease in immunocompromised individuals. Although there are no licensed HCMV vaccines currently available, enormous progress has been made in the last decade, as evidenced by the recently reported results of a Phase II trial of a glycoprotein B vaccine for the prevention of HCMV infection in seronegative women of childbearing age. HCMV vaccines currently in clinical trials include: glycoprotein B subunit vaccines; alphavirus replicon particle vaccines; DNA vaccines; and live-attenuated vaccines. A variety of vaccine strategies are also being examined in preclinical systems and animal models of infection. These include: recombinant vesicular stomatitis virus vaccines; recombinant modified vaccinia virus Ankara; replication-deficient adenovirus-vectored vaccines; and recombinant live-attenuated virus vaccines generated by mutagenesis of cloned rodent CMV genomes maintained as bacterial artificial chromosomes in Escherichia coli. In this article, we provide an overview of the current state of clinical trials and preclinical development of vaccines against HCMV, with an emphasis on studies that have been conducted in the past 5 years. We also summarize a number of recent advances in the study of the biology of HCMV, particularly with respect to epithelial and endothelial cell entry of the virus, which have implications for future vaccine design.

Virus like particles as a platform for cancer vaccine development.

PubMed

Ong, Hui Kian; Tan, Wen Siang; Ho, Kok Lian

2017-01-01

Cancers have killed millions of people in human history and are still posing a serious health problem worldwide. Therefore, there is an urgent need for developing preventive and therapeutic cancer vaccines. Among various cancer vaccine development platforms, virus-like particles (VLPs) offer several advantages. VLPs are multimeric nanostructures with morphology resembling that of native viruses and are mainly composed of surface structural proteins of viruses but are devoid of viral genetic materials rendering them neither infective nor replicative. In addition, they can be engineered to display multiple, highly ordered heterologous epitopes or peptides in order to optimize the antigenicity and immunogenicity of the displayed entities. Like native viruses, specific epitopes displayed on VLPs can be taken up, processed, and presented by antigen-presenting cells to elicit potent specific humoral and cell-mediated immune responses. Several studies also indicated that VLPs could overcome the immunosuppressive state of the tumor microenvironment and break self-tolerance to elicit strong cytotoxic lymphocyte activity, which is crucial for both virus clearance and destruction of cancerous cells. Collectively, these unique characteristics of VLPs make them optimal cancer vaccine candidates. This review discusses current progress in the development of VLP-based cancer vaccines and some potential drawbacks of VLPs in cancer vaccine development. Extracellular vesicles with close resembling to viral particles are also discussed and compared with VLPs as a platform in cancer vaccine developments.

Vaccines against Ebola virus.

PubMed

Venkatraman, Navin; Silman, Daniel; Folegatti, Pedro M; Hill, Adrian V S

2017-08-02

We have just witnessed the largest and most devastating outbreak of Ebola virus disease, which highlighted the urgent need for development of an efficacious vaccine that could be used to curtail future outbreaks. Prior to 2014, there had been limited impetus worldwide to develop a vaccine since the virus was first discovered in 1976. Though too many lives were lost during this outbreak, it resulted in the significantly accelerated clinical development of a number of candidate vaccines through an extraordinary collaborative global effort coordinated by the World Health Organisation (WHO) and involving a number of companies, trial centres, funders, global stakeholders and agencies. We have acquired substantial safety and immunogenicity data on a number of vaccines in Caucasian and African populations. The rapid pace of events led to the initiation of the landmark efficacy trial testing the rVSV-vectored vaccine, which showed high level efficacy in an outbreak setting when deployed using an innovative ring vaccination strategy. Though the Public Health Emergency of International Concern (PHEIC) declared by the WHO has now been lifted, the global scientific community faces numerous challenges ahead to ensure that there is a licensed, deployable vaccine available for use in future outbreaks for at least the Zaire and Sudan strains of Ebola virus. There remain several unanswered questions on the durability of protection, mechanistic immunological correlates and preferred deployment strategies. This review outlines a brief history of the development of Ebola vaccines, the significant progress made since the scale of the outbreak became apparent, some lessons learnt and how they could shape future development of vaccines and the management of similar outbreaks. Copyright © 2017. Published by Elsevier Ltd.

Recent advances in recombinant protein-based malaria vaccines.

PubMed

Draper, Simon J; Angov, Evelina; Horii, Toshihiro; Miller, Louis H; Srinivasan, Prakash; Theisen, Michael; Biswas, Sumi

2015-12-22

Plasmodium parasites are the causative agent of human malaria, and the development of a highly effective vaccine against infection, disease and transmission remains a key priority. It is widely established that multiple stages of the parasite's complex lifecycle within the human host and mosquito vector are susceptible to vaccine-induced antibodies. The mainstay approach to antibody induction by subunit vaccination has been the delivery of protein antigen formulated in adjuvant. Extensive efforts have been made in this endeavor with respect to malaria vaccine development, especially with regard to target antigen discovery, protein expression platforms, adjuvant testing, and development of soluble and virus-like particle (VLP) delivery platforms. The breadth of approaches to protein-based vaccines is continuing to expand as innovative new concepts in next-generation subunit design are explored, with the prospects for the development of a highly effective multi-component/multi-stage/multi-antigen formulation seeming ever more likely. This review will focus on recent progress in protein vaccine design, development and/or clinical testing for a number of leading malaria antigens from the sporozoite-, merozoite- and sexual-stages of the parasite's lifecycle-including PfCelTOS, PfMSP1, PfAMA1, PfRH5, PfSERA5, PfGLURP, PfMSP3, Pfs48/45 and Pfs25. Future prospects and challenges for the development, production, human delivery and assessment of protein-based malaria vaccines are discussed. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

The biology of Theileria parva and control of East Coast fever - Current status and future trends.

PubMed

Nene, Vishvanath; Kiara, Henry; Lacasta, Anna; Pelle, Roger; Svitek, Nicholas; Steinaa, Lucilla

2016-06-01

Tremendous progress has been made over the last ten years on East Coast fever (ECF) research. Publication of a reference genome sequence of Theileria parva, the causative agent of ECF, has led to a more thorough characterization of the genotypic and antigenic diversity of the pathogen. It also facilitated identification of antigens that are targets of bovine major histocompatibility complex class I restricted cytotoxic T-lymphocytes (CTLs), induced by a live parasite-based infection and treatment method (ITM) vaccine. This has led to improved knowledge of epitope-specific T-cell responses to ITM that most likely contribute to the phenomenon of strain-specific immunity. The Muguga cocktail ITM vaccine, which provides broad-spectrum immunity to ECF is now a registered product in three countries in eastern Africa. Effort is directed at improving and scaling up the production process to make this vaccine more widely available on a commercial basis in the region. Meanwhile, research to develop a subunit vaccine based on parasite neutralizing antibodies and CTLs has been revived through convening of a research consortium to develop proof-of-concept for a next generation vaccine. Many new scientific and technical advances are facilitating this objective. Hence, the next decade promises even more progress toward an improved control of ECF. Copyright © 2016 The Authors. Published by Elsevier GmbH.. All rights reserved.

Toward the development of effective transmission-blocking vaccines for malaria.

PubMed

Nikolaeva, Daria; Draper, Simon J; Biswas, Sumi

2015-05-01

The continued global burden of malaria can in part be attributed to a complex lifecycle, with both human hosts and mosquito vectors serving as transmission reservoirs. In preclinical models of vaccine-induced immunity, antibodies to parasite sexual-stage antigens, ingested in the mosquito blood meal, can inhibit parasite survival in the insect midgut as judged by ex vivo functional studies such as the membrane feeding assay. In an era of renewed political momentum for malaria elimination and eradication campaigns, such observations have fueled support for the development and implementation of so-called transmission-blocking vaccines. While leading candidates are being evaluated using a variety of promising vaccine platforms, the field is also beginning to capitalize on global '-omics' data for the rational genome-based selection and unbiased characterization of parasite and mosquito proteins to expand the candidate list. This review covers the progress and prospects of these recent developments.

A brief history of vaccines: smallpox to the present.

PubMed

Hsu, Jennifer L

2013-01-01

Modern vaccine history began in the late 18th century with the discovery of smallpox immunization by Edward Jenner. This pivotal step led to substantial progress in prevention of infectious diseases with inactivated vaccines for multiple infectious diseases, including typhoid, plague and cholera. Each advance produced significant decreases in infection-associated morbidity and mortality, thus shaping our modem cultures. As knowledge of microbiology and immunology grew through the 20th century, techniques were developed for cell culture of viruses. This allowed for rapid advances in prevention of polio, varicella, influenza and others. Finally, recent research has led to development of alternative vaccine strategies through use of vectored antigens, pathogen subunits (purified proteins or polysaccharides) or genetically engineered antigens. As the science of vaccinology continues to rapidly evolve, knowledge of the past creates added emphasis on the importance of developing safe and effective strategies for infectious disease prevention in the 21st century.

Measles, mumps, rubella vaccine induced subacute sclerosing panencephalitis.

PubMed

Belgamwar, R B; Prasad, S; Appaya, P

1997-11-01

The incidence of subacute sclerosing panencephalitis (SSPE), a progressive and fatal neurodegenerative disease caused by the measles virus, has declined with widespread use of measles vaccine. The risk of SSPE after measles vaccination has been estimated at 0.7/million doses. This paper reports the case of a 15-year-old girl from India who developed SSPE presumably as a result of a delayed effect of measles, mumps, and rubella (MMR) vaccine. She presented with a 2-month history of behavioral disturbances, a deterioration in school performance, forgetfulness, silly smiling, handwriting changes, social withdrawal, and ataxia. The girl had received MMR vaccine at 9 months of age and had no past history of measles. Her measles antibody titre was 1:625 in both serum and cerebrospinal fluid.

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

Burkholderia pseudomallei and Burkholderia mallei vaccines: Are we close to clinical trials?

PubMed

Titball, Richard W; Burtnick, Mary N; Bancroft, Gregory J; Brett, Paul

2017-10-20

B. pseudomallei is the cause of melioidosis, a serious an often fatal disease of humans and animals. The closely related bacterium B. mallei, which cases glanders, is considered to be a clonal derivative of B. pseudomallei. Both B. pseudomallei and B. mallei were evaluated by the United States and the former USSR as potential bioweapons. Much of the effort to devise biodefence vaccines in the past decade has been directed towards the identification and formulation of sub-unit vaccines which could protect against both melioidosis and glanders. A wide range of proteins and polysaccharides have been identified which protective immunity in mice. In this review we highlight the significant progress that has been made in developing glycoconjugates as sub-unit vaccines. We also consider some of the important the criteria for licensing, including the suitability of the "animal rule" for assessing vaccine efficacy, the protection required from a vaccine and the how correlates of protection will be identified. Vaccines developed for biodefence purposes could also be used in regions of the world where naturally occurring disease is endemic. Copyright © 2017 Elsevier Ltd. All rights reserved.

Activation of B Cells by a Dendritic Cell-Targeted Oral Vaccine

PubMed Central

Sahay, Bikash; Owen, Jennifer L.; Yang, Tao; Zadeh, Mojgan; Lightfoot, Yaíma L.; Ge, Jun-Wei; Mohamadzadeh, Mansour

2015-01-01

Production of long-lived, high affinity humoral immunity is an essential characteristic of successful vaccination and requires cognate interactions between T and B cells in germinal centers. Within germinal centers, specialized T follicular helper cells assist B cells and regulate the antibody response by mediating the differentiation of B cells into memory or plasma cells after exposure to T cell-dependent antigens. It is now appreciated that local immune responses are also essential for protection against infectious diseases that gain entry to the host by the mucosal route; therefore, targeting the mucosal compartments is the optimum strategy to induce protective immunity. However, because the gastrointestinal mucosae are exposed to large amounts of environmental and dietary antigens on a daily basis, immune regulatory mechanisms exist to favor tolerance and discourage autoimmunity at these sites. Thus, mucosal vaccination strategies must ensure that the immunogen is efficiently taken up by the antigen presenting cells, and that the vaccine is capable of activating humoral and cellular immunity, while avoiding the induction of tolerance. Despite significant progress in mucosal vaccination, this potent platform for immunotherapy and disease prevention must be further explored and refined. Here we discuss recent progress in the understanding of the role of different phenotypes of B cells in the development of an efficacious mucosal vaccine against infectious disease. PMID:24372255

Case Report: Successful Sporozoite Challenge Model in Human Volunteers with Plasmodium vivax Strain Derived from Human Donors

DTIC Science & Technology

2009-01-01

CBC, reticulocyte count, G-6-PD determination, Duffy phenotype, ABO and Rh group typing, hemoglobin electrophoresis and erythrocyte sedimentation ... rates and APTT† Cardiovascular disease Hepatic or renal abnormalities Cardiovascular function Immunodeficiency Electrocardiogram Autoimmune...malaria vaccine. Progress has been achieved in the development of P. vivax pre- erythrocytic subunit vaccines such as the circumsporo- zoite (CS) and

Laser vaccine adjuvants. History, progress, and potential.

PubMed

Kashiwagi, Satoshi; Brauns, Timothy; Gelfand, Jeffrey; Poznansky, Mark C

2014-01-01

Immunologic adjuvants are essential for current vaccines to maximize their efficacy. Unfortunately, few have been found to be sufficiently effective and safe for regulatory authorities to permit their use in vaccines for humans and none have been approved for use with intradermal vaccines. The development of new adjuvants with the potential to be both efficacious and safe constitutes a significant need in modern vaccine practice. The use of non-damaging laser light represents a markedly different approach to enhancing immune responses to a vaccine antigen, particularly with intradermal vaccination. This approach, which was initially explored in Russia and further developed in the US, appears to significantly improve responses to both prophylactic and therapeutic vaccines administered to the laser-exposed tissue, particularly the skin. Although different types of lasers have been used for this purpose and the precise molecular mechanism(s) of action remain unknown, several approaches appear to modulate dendritic cell trafficking and/or activation at the irradiation site via the release of specific signaling molecules from epithelial cells. The most recent study, performed by the authors of this review, utilized a continuous wave near-infrared laser that may open the path for the development of a safe, effective, low-cost, simple-to-use laser vaccine adjuvant that could be used in lieu of conventional adjuvants, particularly with intradermal vaccines. In this review, we summarize the initial Russian studies that have given rise to this approach and comment upon recent advances in the use of non-tissue damaging lasers as novel physical adjuvants for vaccines.

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.

Immunization of children with secondary immunodeficiency.

PubMed

Esposito, Susanna; Prada, Elisabetta; Lelii, Mara; Castellazzi, Luca

2015-01-01

The main causes of secondary immunodeficiency at a pediatric age include infectious diseases (mainly HIV infection), malignancies, haematopoietic stem cell or solid organ transplantation and autoimmune diseases. Children with secondary immunodeficiency have an increased risk of severe infectious diseases that could be prevented by adequate vaccination coverage, but vaccines administration can be associated with reduced immune response and an increased risk of adverse reactions. The immunogenicity of inactivated and recombinant vaccines is comparable to that of healthy children at the moment of vaccination, but it undergoes a progressive decline over time, and in the absence of a booster, the patients remain at risk of developing vaccine-preventable infections. However, the administration of live attenuated viral vaccines is controversial because of the risk of the activation of vaccine viruses. A specific immunization program should be administered according to the clinical and immunological status of each of these conditions to ensure a sustained immune response without any risks to the patients' health.

WHO initiative to increase global and equitable access to influenza vaccine in the event of a pandemic: supporting developing country production capacity through technology transfer.

PubMed

Friede, Martin; Palkonyay, Laszlo; Alfonso, Claudia; Pervikov, Yuri; Torelli, Guido; Wood, David; Kieny, Marie Paule

2011-07-01

Should a highly pathogenic avian influenza virus, such as the H5N1 virus type currently circulating in birds, become transmissible among humans, an effective vaccine, rapidly available in vast quantities, would be the best tool to prevent high case-fatalities and the breakdown of health and social services. The number of vaccine doses that could be produced on demand has risen sharply over the last few years; however, it is still alarmingly short of the 13 billion doses that would be needed if two doses were required to protect fully the world's population. Most developing countries would be last in the queue to benefit from a pandemic vaccine. The World Health Organization, together with governments, the pharmaceutical industry and other stakeholders, has been implementing the global pandemic influenza action plan to increase vaccine supply since 2006. Building capacity in developing countries to manufacture influenza vaccine is an integral part of this plan, as well as research and development into more efficacious technologies, e.g. those that allow significant dose-sparing. To this end, the influenza vaccine technology transfer initiative was launched in 2007 and, to date, vaccine manufacturers in 11 developing countries have received grants to acquire the capacity to produce inactivated or live attenuated influenza vaccine for their populations. In addition, a centralized 'hub' has been established to facilitate training in the new technologies for scientists and regulators in the countries. This supplement of Vaccine is devoted to showcasing the interim results of the WHO initiative and the impressive progress made by the developing country manufacturers. Copyright © 2011 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

Plasmodium Sporozoite Biology.

PubMed

Frischknecht, Friedrich; Matuschewski, Kai

2017-05-01

Plasmodium sporozoite transmission is a critical population bottleneck in parasite life-cycle progression and, hence, a target for prophylactic drugs and vaccines. The recent progress of a candidate antisporozoite subunit vaccine formulation to licensure highlights the importance of sporozoite transmission intervention in the malaria control portfolio. Sporozoites colonize mosquito salivary glands, migrate through the skin, penetrate blood vessels, breach the liver sinusoid, and invade hepatocytes. Understanding the molecular and cellular mechanisms that mediate the remarkable sporozoite journey in the invertebrate vector and the vertebrate host can inform evidence-based next-generation drug development programs and immune intervention strategies. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

The contribution of vaccination to global health: past, present and future.

PubMed

Greenwood, Brian

2014-01-01

Vaccination has made an enormous contribution to global health. Two major infections, smallpox and rinderpest, have been eradicated. Global coverage of vaccination against many important infectious diseases of childhood has been enhanced dramatically since the creation of WHO's Expanded Programme of Immunization in 1974 and of the Global Alliance for Vaccination and Immunization in 2000. Polio has almost been eradicated and success in controlling measles makes this infection another potential target for eradication. Despite these successes, approximately 6.6 million children still die each year and about a half of these deaths are caused by infections, including pneumonia and diarrhoea, which could be prevented by vaccination. Enhanced deployment of recently developed pneumococcal conjugate and rotavirus vaccines should, therefore, result in a further decline in childhood mortality. Development of vaccines against more complex infections, such as malaria, tuberculosis and HIV, has been challenging and achievements so far have been modest. Final success against these infections may require combination vaccinations, each component stimulating a different arm of the immune system. In the longer term, vaccines are likely to be used to prevent or modulate the course of some non-infectious diseases. Progress has already been made with therapeutic cancer vaccines and future potential targets include addiction, diabetes, hypertension and Alzheimer's disease.

Framework for Optimal Global Vaccine Stockpile Design for Vaccine-Preventable Diseases: Application to Measles and Cholera Vaccines as Contrasting Examples.

PubMed

Thompson, Kimberly M; Duintjer Tebbens, Radboud J

2016-07-01

Managing the dynamics of vaccine supply and demand represents a significant challenge with very high stakes. Insufficient vaccine supplies can necessitate rationing, lead to preventable adverse health outcomes, delay the achievements of elimination or eradication goals, and/or pose reputation risks for public health authorities and/or manufacturers. This article explores the dynamics of global vaccine supply and demand to consider the opportunities to develop and maintain optimal global vaccine stockpiles for universal vaccines, characterized by large global demand (for which we use measles vaccines as an example), and nonuniversal (including new and niche) vaccines (for which we use oral cholera vaccine as an example). We contrast our approach with other vaccine stockpile optimization frameworks previously developed for the United States pediatric vaccine stockpile to address disruptions in supply and global emergency response vaccine stockpiles to provide on-demand vaccines for use in outbreaks. For measles vaccine, we explore the complexity that arises due to different formulations and presentations of vaccines, consideration of rubella, and the context of regional elimination goals. We conclude that global health policy leaders and stakeholders should procure and maintain appropriate global vaccine rotating stocks for measles and rubella vaccine now to support current regional elimination goals, and should probably also do so for other vaccines to help prevent and control endemic or epidemic diseases. This work suggests the need to better model global vaccine supplies to improve efficiency in the vaccine supply chain, ensure adequate supplies to support elimination and eradication initiatives, and support progress toward the goals of the Global Vaccine Action Plan. © 2014 Society for Risk Analysis.

The Twenty-Year Story of a Plant-Based Vaccine Against Hepatitis B: Stagnation or Promising Prospects?

PubMed Central

Pniewski, Tomasz

2013-01-01

Hepatitis B persists as a common human disease despite effective vaccines having been employed for almost 30 years. Plants were considered as alternative sources of vaccines, to be mainly orally administered. Despite 20-year attempts, no real anti-HBV plant-based vaccine has been developed. Immunization trials, based on ingestion of raw plant tissue and conjugated with injection or exclusively oral administration of lyophilized tissue, were either impractical or insufficient due to oral tolerance acquisition. Plant-produced purified HBV antigens were highly immunogenic when injected, but their yields were initially insufficient for practical purposes. However, knowledge and technology have progressed, hence new plant-derived anti-HBV vaccines can be proposed today. All HBV antigens can be efficiently produced in stable or transient expression systems. Processing of injection vaccines has been developed and needs only to be successfully completed. Purified antigens can be used for injection in an equivalent manner to the present commercial vaccines. Although oral vaccines require improvement, plant tissue, lyophilized or extracted and converted into tablets, etc., may serve as a boosting vaccine. Preliminary data indicate also that both vaccines can be combined in an effective parenteral-oral immunization procedure. A partial substitution of injection vaccines with oral formulations still offers good prospects for economically viable and efficacious anti-HBV plant-based vaccines. PMID:23337199

The 5As: A practical taxonomy for the determinants of vaccine uptake.

PubMed

Thomson, Angus; Robinson, Karis; Vallée-Tourangeau, Gaëlle

2016-02-17

Suboptimal vaccine uptake in both childhood and adult immunisation programs limits their full potential impact on global health. A recent progress review of the Global Vaccine Action Plan stated that "countries should urgently identify barriers and bottlenecks and implement targeted approaches to increase and sustain coverage". However, vaccination coverage may be determined by a complex mix of demographic, structural, social and behavioral factors. To develop a practical taxonomy to organise the myriad possible root causes of a gap in vaccination coverage rates, we performed a narrative review of the literature and tested whether all non-socio-demographic determinants of coverage could be organised into 4 dimensions: Access, Affordability, Awareness and Acceptance. Forty-three studies were reviewed, from which we identified 23 primary determinants of vaccination uptake. We identified a fifth domain, Activation, which captured interventions such as SMS reminders which effectively nudge people towards getting vaccinated. The 5As taxonomy captured all identified determinants of vaccine uptake. This intuitive taxonomy has already facilitated mutual understanding of the primary determinants of suboptimal coverage within inter-sectorial working groups, a first step towards them developing targeted and effective solutions. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Progress in Childhood Vaccination Data in Immunization Information Systems - United States, 2013-2016.

PubMed

Murthy, Neil; Rodgers, Loren; Pabst, Laura; Fiebelkorn, Amy Parker; Ng, Terence

2017-11-03

In 2016, 55 jurisdictions in 49 states and six cities in the United States* used immunization information systems (IISs) to collect and manage immunization data and support vaccination providers and immunization programs. To monitor progress toward achieving IIS program goals, CDC surveys jurisdictions through an annual self-administered IIS Annual Report (IISAR). Data from the 2013-2016 IISARs were analyzed to assess progress made in four priority areas: 1) data completeness, 2) bidirectional exchange of data with electronic health record systems, 3) clinical decision support for immunizations, and 4) ability to generate childhood vaccination coverage estimates. IIS participation among children aged 4 months through 5 years increased from 90% in 2013 to 94% in 2016, and 33 jurisdictions reported ≥95% of children aged 4 months through 5 years participating in their IIS in 2016. Bidirectional messaging capacity in IISs increased from 25 jurisdictions in 2013 to 37 in 2016. In 2016, nearly all jurisdictions (52 of 55) could provide automated provider-level coverage reports, and 32 jurisdictions reported that their IISs could send vaccine forecasts to providers via Health Level 7 (HL7) messaging, up from 17 in 2013. Incremental progress was made in each area since 2013, but continued effort is needed to implement these critical functionalities among all IISs. Success in these priority areas, as defined by the IIS Functional Standards (1), bolsters clinicians' and public health practitioners' ability to attain high vaccination coverage in pediatric populations, and prepares IISs to develop more advanced functionalities to support state/local immunization services. Success in these priority areas also supports the achievement of federal immunization objectives, including the use of IISs as supplemental sampling frames for vaccination coverage surveys like the National Immunization Survey (NIS)-Child, reducing data collection costs, and supporting increased precision of state-level estimates.

Vaccines and immunotherapeutics for the prevention and treatment of infections with West Nile virus.

PubMed

Beasley, David W C

2011-02-01

The emergence of West Nile virus (WNV) in North America in 1999 as a cause of severe neurological disease in humans, horses and birds stimulated development of vaccines for human and veterinary use, as well as polyclonal/monoclonal antibodies and other immunomodulating compounds for use as therapeutics. Although disease incidence in North America has declined since the peak epidemics in 2002-2003, the virus has continued to be annually transmitted in the Americas and to cause periodic epidemics in Europe and the Middle East. Continued transmission of the virus with human and animal disease suggests that vaccines and therapeutics for the prevention and treatment of WNV disease could be of great benefit. This article focuses on progress in development and evaluation of vaccines and immunotherapeutics for the prevention and treatment of WNV disease in humans and animals.

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.

The International AIDS Vaccine Initiative's Capacity Building Activities in East Africa

PubMed Central

Cochrane, Gavin; Robin, Enora; Hanlin, Rebecca; Castle-Clarke, Sophie; MacLure, Calum; Parks, Sarah; Chataway, Joanna

2016-01-01

Abstract The International AIDS Vaccine Initiative (IAVI) is one of a number of Product Development Partnerships created to bridge the gap between scientific and technological potential and the needs of low income populations in low and middle income countries. Specifically IAVI is focused on creating a preventative vaccine for HIV/AIDS. Whilst the remit of IAVI is to create new science, technology and products, its work necessarily involves a wide range of stakeholders and different constituencies in industrially developing and developed countries. Its capacity building activities relate to strengthening the ability to conduct clinical trials and are broad based, spanning scientific and technological capacity through to organisational, advocacy and broader development capabilities. The aim of this study was to deepen IAVI's understanding of how it contributes to capacity building activities in East Africa (Uganda, Kenya and Rwanda), spanning scientific and technological capacity through to organisational, advocacy and broader development capabilities. IAVI's mission to develop an HIV vaccine has become increasingly connected to wider health systems strengthening, through its clinical research activities in East Africa. Since it began its operations in the region, IAVI has made a significant contribution to training interventions to support scientific excellence and good clinical practice and invested in infrastructure and laboratories at Clinical Research Centres in East Africa. Although clear challenges still exist with ensuring sustained investment, accessing marginalized populations and demonstrating progress in capacity building, the experiences of IAVI to date suggest that substantial progress is being made towards wider health systems strengthening in the region. PMID:28083400

Salk's HIV immunogen: an immune-based therapy in human trials since 1988.

PubMed

Jonas Salk, the developer of the first polio vaccine, has created a therapeutic vaccine for HIV which helps the immune system fight disease progression. Salk uses inactivated HIV-1 virus combined with Incomplete Freund's Adjuvant (IFA) in the vaccine preparation. The resulting HIV-1 immunogen was first studied in 1987, and since then, 235 seropositive individuals have received inoculations without serious adverse effects. Data from the first 25 subjects indicate that immunization with the HIV-1 immunogen results in improvement of cell-mediated response against the virus, a slower increase in the amount of virus present, and a reduced rate of clinical progression. Subsequent studies also show that higher doses of immunogen may produce stronger cell-mediated responses and high HIV-DTH (delayed-type hypersensitivity responsiveness immunogen) is associated with better outcome. Additional trials of HIV-1 immunogen are awaiting Food and Drug Administration approval.

RECENT ADVANCES IN STRATEGIES FOR IMMUNOTHERAPY OF HUMAN PAPILLOMAVIRUS-INDUCED LESIONS

PubMed Central

Kanodia, Shreya; Da Silva, Diane M.; Kast, W. Martin

2016-01-01

Human papillomavirus (HPV)-induced lesions are distinct in that they have targetable foreign antigens, the expression of which is necessary to maintain the cancerous phenotype. Hence, they pose as a very attractive target for “proof of concept” studies in the development of therapeutic vaccines. This review will focus on the most recent clinical trials for the immunotherapy of mucosal and cutaneous HPV-induced lesions as well as emerging therapeutic strategies that have been tested in pre-clinical models for HPV-induced lesions. Progress in peptide-based vaccines, DNA-based vaccines, viral/bacterial vector-based vaccines, immune response modifiers, photodynamic therapy and T cell receptor based therapy for HPV will be discussed. PMID:17973257

Sequential inflammatory processes define human progression from M. tuberculosis infection to tuberculosis disease.

PubMed

Scriba, Thomas J; Penn-Nicholson, Adam; Shankar, Smitha; Hraha, Tom; Thompson, Ethan G; Sterling, David; Nemes, Elisa; Darboe, Fatoumatta; Suliman, Sara; Amon, Lynn M; Mahomed, Hassan; Erasmus, Mzwandile; Whatney, Wendy; Johnson, John L; Boom, W Henry; Hatherill, Mark; Valvo, Joe; De Groote, Mary Ann; Ochsner, Urs A; Aderem, Alan; Hanekom, Willem A; Zak, Daniel E

2017-11-01

Our understanding of mechanisms underlying progression from Mycobacterium tuberculosis infection to pulmonary tuberculosis disease in humans remains limited. To define such mechanisms, we followed M. tuberculosis-infected adolescents longitudinally. Blood samples from forty-four adolescents who ultimately developed tuberculosis disease (“progressors”) were compared with those from 106 matched controls, who remained healthy during two years of follow up. We performed longitudinal whole blood transcriptomic analyses by RNA sequencing and plasma proteome analyses using multiplexed slow off-rate modified DNA aptamers. Tuberculosis progression was associated with sequential modulation of immunological processes. Type I/II interferon signalling and complement cascade were elevated 18 months before tuberculosis disease diagnosis, while changes in myeloid inflammation, lymphoid, monocyte and neutrophil gene modules occurred more proximally to tuberculosis disease. Analysis of gene expression in purified T cells also revealed early suppression of Th17 responses in progressors, relative to M. tuberculosis-infected controls. This was confirmed in an independent adult cohort who received BCG re-vaccination; transcript expression of interferon response genes in blood prior to BCG administration was associated with suppression of IL-17 expression by BCG-specific CD4 T cells 3 weeks post-vaccination. Our findings provide a timeline to the different immunological stages of disease progression which comprise sequential inflammatory dynamics and immune alterations that precede disease manifestations and diagnosis of tuberculosis disease. These findings have important implications for developing diagnostics, vaccination and host-directed therapies for tuberculosis. Clincialtrials.gov, NCT01119521.

Farming of Plant-Based Veterinary Vaccines and Their Applications for Disease Prevention in Animals

PubMed Central

Liew, Pit Sze; Hair-Bejo, Mohd

2015-01-01

Plants have been studied for the production of pharmaceutical compounds for more than two decades now. Ever since the plant-made poultry vaccine against Newcastle disease virus made a breakthrough and went all the way to obtain regulatory approval, research to use plants for expression and delivery of vaccine proteins for animals was intensified. Indeed, in view of the high production costs of veterinary vaccines, plants represent attractive biofactories and offer many promising advantages in the production of recombinant vaccine proteins. Furthermore, the possibility of conducting immunogenicity and challenge studies in target animals has greatly exaggerated the progress. Although there are no edible plant-produced animal vaccines in the market, plant-based vaccine technology has great potentials. In this review, development, uses, and advantages of plant-based recombinant protein production in various expression platforms are discussed. In addition, examples of plant-based veterinary vaccines showing strong indication in terms of efficacy in animal disease prevention are also described. PMID:26351454

Aspergillus vaccines: Hardly worth studying or worthy of hard study?

PubMed Central

Levitz, Stuart M.

2016-01-01

Vaccines rank among the greatest advances in the history of public health. Yet, despite the need, there are no licensed vaccines to protect humans against fungal diseases, including aspergillosis. In this focused review, some of the major scientific and logistical challenges to developing vaccines to protect at-risk individuals against aspergillosis are discussed. Approaches that have shown promise in animal models include vaccines that protect against multiple fungal genera and those that are specifically directed to Aspergillus. Advances in proteomics and glycomics have facilitated identification of candidate antigens for use in subunit vaccines. Novel adjuvants and delivery systems are becoming available that can skew vaccine responses toward those associated with protection. Immunotherapy consisting of adoptive transfer of Aspergillus-specific T cells to allogeneic hematopoietic transplant recipients has advanced to human testing but is technically difficult and of unproven benefit. While progress has been impressive, much work still needs to be done if vaccines against aspergillosis are to become a reality. PMID:27639242

Subunit vaccines for the prevention of mucosal infection with Chlamydia trachomatis

PubMed Central

Yu, Hong; Karunakaran, Karuna P.; Jiang, Xiaozhou; Brunham, Robert C.

2016-01-01

Chlamydia trachomatis is the most common preventable cause of tubal infertility in women. In high-income countries, despite public health control efforts, C. trachomatis case rates continue to rise. Most medium and low-income countries lack any Chlamydia control program; therefore, a vaccine is essential for the control of Chlamydia infections. A rationally designed Chlamydia vaccine requires understanding of the immunological correlates of protective immunity, pathological responses to this mucosal pathogen, identification of optimal vaccine antigens and selection of suitable adjuvant delivery systems that engender protective immunity. Fortunately, Chlamydia vaccinology is facilitated by genomic knowledge and by murine models that reproduce many of the features of human C. trachomatis infection. This article reviews recent progress in these areas with a focus on subunit vaccine development. PMID:26938202

Immunology and evolvement of the adenovirus prime, MVA boost Ebola virus vaccine.

PubMed

Zhou, Yan; Sullivan, Nancy J

2015-08-01

The 2014 Ebola virus outbreak caused an order of magnitude more deaths in a single outbreak than all previous known outbreaks combined, affecting both local and international public health, and threatening the security and economic stability of the countries in West Africa directly confronting the outbreak. The severity of the epidemic lead to a global response to assist with patient care, outbreak control, and deployment of vaccines. The latter was possible due to the long history of basic and clinical research aimed at identifying a safe and effective vaccine to protect against Ebola virus infection. This review highlights the immunology, development, and progress of vaccines based on replication-defective adenovirus vectors, culminating in the successful launch of the first Phase III trial of an Ebola virus vaccine. Published by Elsevier Ltd.

Success and failure of vaccines against renin-angiotensin system components.

PubMed

Brown, Morris J

2009-10-01

Therapeutic vaccination pre-dated modern drugs as a possible strategy for treating hypertension. This approach is now being rediscovered, through use of modified angiotensins as immunogens together with carriers and adjuvants. Effective blockade of the renin-angiotensin system (RAS) with treatment twice a year might suit patients who dislike taking drugs on a daily basis and would also be an attractive option for those who have blood pressures in the prehypertensive range, if it can prevent hypertension itself from developing. Proof of concept with a vaccine whose efficacy is easy to measure will encourage development of further vaccines directed against targets such as aldosterone or other pathways where alternative treatments are scarce or absent. Two angiotensin-based vaccines are currently in development: PMD3117 comprises modified angiotensin I coupled to keyhole limpet hemocyanin, and Cyt006-AngQb is a conjugate of angiotensin II linked to virus particles. Early phase II studies in patients with hypertension demonstrated some efficacy, but the vaccines are not as effective as existing inhibitors of the RAS. Large studies now in progress will establish whether further modification of the immunogen or adjuvant is required to boost antibody titers.

Vaccine development against Neisseria meningitidis

PubMed Central

Vogel, Ulrich; Claus, Heike

2011-01-01

Summary Meningococcal disease is communicable by close contact or droplet aerosols. Striking features are high case fatality rates and peak incidences of invasive disease in infants, toddlers and adolescents. Vaccine development is hampered by bacterial immune evasion strategies including molecular mimicry. As for Haemophilus influenzae and Streptococcus pneumoniae, no vaccine has therefore been developed that targets all serogroups of Neisseria meningitidis. Polysaccharide vaccines available both in protein conjugated and non‐conjugated form, have been introduced against capsular serogroups A, C, W‐135 and Y, but are ineffective against serogroup B meningococci, which cause a significant burden of disease in many parts of the world. Detoxified outer membrane vesicles are used since decades to elicit protection against epidemic serogroup B disease. Genome mining and biochemical approaches have provided astounding progress recently in the identification of immunogenic, yet reasonably conserved outer membrane proteins. As subcapsular proteins nevertheless are unlikely to immunize against all serogroup B variants, thorough investigation by surrogate assays and molecular epidemiology approaches are needed prior to introduction and post‐licensure of protein vaccines. Research currently addresses the analysis of life vaccines, meningococcus B polysaccharide modifications and mimotopes, as well as the use of N. lactamicaouter membrane vesicles. PMID:21255369

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

Vaccination against herpes zoster in developed countries: state of the evidence.

PubMed

Drolet, Mélanie; Oxman, Michael N; Levin, Myron J; Schmader, Kenneth E; Johnson, Robert W; Patrick, David; Mansi, James A; Brisson, Marc

2013-05-01

Although progress has been made in the treatment of herpes zoster (HZ) and postherpetic neuralgia (PHN), available therapeutic options are only partially effective. Given evidence that a live-attenuated varicella-zoster-virus vaccine is effective at reducing the incidence of HZ, PHN and the burden of illness, policymakers and clinicians are being asked to make recommendations regarding the use of the zoster vaccine. In this report, we summarize the evidence regarding the: (1) burden of illness; (2) vaccine efficacy and safety; and (3) cost-effectiveness of vaccination, to assist evidence-based policy making and guide clinicians in their recommendations. First, there is general agreement that the overall burden of illness associated with HZ and PHN is substantial. Second, the safety and efficacy of the zoster vaccine at reducing the burden of illness due to HZ and the incidence of PHN have been clearly demonstrated in large placebo-controlled trials. However, uncertainty remains about the vaccine's duration of protection. Third, vaccination against HZ is likely to be cost-effective when the vaccine is given at approximately 65 y of age, if vaccine duration is longer than 10 y.

Cost of production of live attenuated dengue vaccines: a case study of the Instituto Butantan, Sao Paulo, Brazil.

PubMed

Mahoney, R T; Francis, D P; Frazatti-Gallina, N M; Precioso, A R; Raw, I; Watler, P; Whitehead, P; Whitehead, S S

2012-07-06

A vaccine to prevent dengue disease is urgently needed. Fortunately, a few tetravalent candidate vaccines are in the later stages of development and show promise. But, if the cost of these candidates is too high, their beneficial potential will not be realized. The price of a vaccine is one of the most important factors affecting its ultimate application in developing countries. In recent years, new vaccines such as those for human papilloma virus and pneumococcal disease (conjugate vaccine) have been introduced with prices in developed countries exceeding $50 per dose. These prices are above the level affordable by developing countries. In contrast, other vaccines such as those against Japanese encephalitis (SA14-14-2 strain vaccine) and meningitis type A have prices in developing countries below one dollar per dose, and it is expected that their introduction and use will proceed more rapidly. Because dengue disease is caused by four related viruses, vaccines must be able to protect against all four. Although there are several live attenuated dengue vaccine candidates under clinical evaluation, there remains uncertainty about the cost of production of these tetravalent vaccines, and this uncertainty is an impediment to rapid progress in planning for the introduction and distribution of dengue vaccines once they are licensed. We have undertaken a detailed economic analysis, using standard industrial methodologies and applying generally accepted accounting practices, of the cost of production of a live attenuated vaccine, originally developed at the US National Institutes of Health (National Institute of Allergy and Infectious Diseases), to be produced at the Instituto Butantan in Sao Paulo, Brazil. We determined direct costs of materials, direct costs of personnel and labor, indirect costs, and depreciation. These were analyzed assuming a steady-state production of 60 million doses per year. Although this study does not seek to compute the price of the final licensed vaccine, the cost of production estimate produced here leads to the conclusion that the vaccine can be made available at a price that most ministries of health in developing countries could afford. This conclusion provides strong encouragement for supporting the development of the vaccine so that, if it proves to be safe and effective, licensure can be achieved soon and the burden of dengue disease can be reduced. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

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.

Sipuleucel-T: Prototype for development of anti-tumor vaccines.

PubMed

Carballido, Estrella; Fishman, Mayer

2011-04-01

Prostate cancer immunotherapy officially debuted with the recent FDA approval of Sipuleucel-T. The novel trend of cancer immunotherapy relies on the identification of particular tumor-associated antigens, like prostatic acid phosphatase (PAP). Sipuleucel-T consists of autologous dendritic cells activated in vitro with recombinant fusion protein PA2024, PAP-linked to granulocyte-macrophage colony-stimulating factor. Sipuleucel-T represents a prototype for the development of cancer vaccines. Preclinical and clinical data as well as landmark studies for the existing narrow chemotherapy alternatives and early immunotherapy trials will be discussed. The pivotal trial demonstrated a 4.1-month difference of median survival, but with no effect on time to progression in asymptomatic or minimally symptomatic metastatic castrate-resistant patients. Several immunologic effects were observed in the treated population, including antibody and T cell-specific activity to P2024 and PAP. With all new therapies the extent of clinical and objective benefits versus encountered limitations should be evaluated. This review highlights the events and decisions in the process of the development of Sipuleucel-T. We discuss how this successful immunotherapy outcome challenges us to use it as a starting point for variations to or try to amplify practical anticancer progress within the antitumor vaccine paradigm.

Strengthening vaccination policies in Latin America: an evidence-based approach.

PubMed

Tapia-Conyer, Roberto; Betancourt-Cravioto, Miguel; Saucedo-Martínez, Rodrigo; Motta-Murguía, Lourdes; Gallardo-Rincón, Héctor

2013-08-20

Despite many successes in the region, Latin American vaccination policies have significant shortcomings, and further work is needed to maintain progress and prepare for the introduction of newly available vaccines. In order to address the challenges facing Latin America, the Commission for the Future of Vaccines in Latin America (COFVAL) has made recommendations for strengthening evidence-based policy-making and reducing regional inequalities in immunisation. We have conducted a comprehensive literature review to assess the feasibility of these recommendations. Standardisation of performance indicators for disease burden, vaccine coverage, epidemiological surveillance and national health resourcing can ensure comparability of the data used to assess vaccination programmes, allowing deeper analysis of how best to provide services. Regional vaccination reference schemes, as used in Europe, can be used to develop best practice models for vaccine introduction and scheduling. Successful models exist for the continuous training of vaccination providers and decision-makers, with a new Latin American diploma aiming to contribute to the successful implementation of vaccination programmes. Permanent, independent vaccine advisory committees, based on the US Advisory Committee on Immunization Practices (ACIP), could facilitate the uptake of new vaccines and support evidence-based decision-making in the administration of national immunisation programmes. Innovative financing mechanisms for the purchase of new vaccines, such as advance market commitments and cost front-loading, have shown potential for improving vaccine coverage. A common regulatory framework for vaccine approval is needed to accelerate delivery and pool human, technological and scientific resources in the region. Finally, public-private partnerships between industry, government, academia and non-profit sectors could provide new investment to stimulate vaccine development in the region, reducing prices in the long term. These reforms are now crucial, particularly as vaccines for previously neglected, developing-world diseases become available. In summary, a regionally-coordinated health policy will reduce vaccination inequality in Latin America. Copyright © 2013 Elsevier Ltd. All rights reserved.

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.

Progress in HIV vaccine development

PubMed Central

Hsu, Denise C.; O'Connell, Robert J.

2017-01-01

ABSTRACT An HIV-1 vaccine is needed to curtail the HIV epidemic. Only one (RV144) out of the 6 HIV-1 vaccine efficacy trials performed showed efficacy. A potential mechanism of protection is the induction of functional antibodies to V1V2 region of HIV envelope. The 2 main current approaches to the generation of protective immunity are through broadly neutralizing antibodies (bnAb) and induction of functional antibodies (non-neutralizing Abs with other potential anti-viral functions). Passive immunization using bnAb has advanced into phase II clinical trials. The induction of bnAb using mimics of the natural Env trimer or B-cell lineage vaccine design is still in pre-clinical phase. An attempt at optimization of protective functional antibodies will be assessed next with the efficacy trial (HVTN702) about to start. With on-going optimization of prime/boost strategies, the development of mosaic immunogens, replication competent vectors, and emergence of new strategies designed to induce bnAb, the prospects for a preventive HIV vaccine have never been more promising. PMID:28281871

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.

Purified coronavirus Spike protein nanoparticles induce coronavirus neutralizing antibodies in mice

PubMed Central

Mu, Haiyan; Taylor, Justin K; Massare, Michael; Flyer, David C

2014-01-01

Development of vaccination strategies for emerging pathogens are particularly challenging because of the sudden nature of the emergence of these viruses and the long process needed for traditional vaccine development. Therefore, there is a need for development of a rapid method of vaccine development that can respond to emerging pathogens in a short time frame. The emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 and Middle East respiratory syndrome (MERS-CoV) in late 2012 demonstrate the importance of coronaviruses as emerging pathogens. The spike glycoproteins of coronaviruses reside on the surface of the virion and are responsible for virus entry. The spike glycoprotein is the major immunodominant antigen of coronaviruses and has proven to be an excellent target for vaccine designs that seek to block coronavirus entry and promote antibody targeting of infected cells. Vaccination strategies for coronaviruses have involved live attenuated virus, recombinant viruses, non-replicative virus-like particles expressing coronavirus proteins or DNA plasmids expressing coronavirus genes. None of these strategies has progressed to an approved human coronavirus vaccine in the ten years since SARS-CoV emerged. Here we describe a novel method for generating MERS-CoV and SARS-CoV full-length spike nanoparticles, which in combination with adjuvants are able to produce high titer antibodies in mice. PMID:24736006

[Dengue, zika, chikungunya and the development of vaccines].

PubMed

Kantor, Isabel N

2018-01-01

Dengue (DENV), zika (ZIKV) and chikungunya (CHIKV), three arbovirosis transmitted by Aedes mosquitoes, have spread in recent decades in humid tropical and subtropical zones. Dengue is epidemic in subtropical areas of Argentina. DENV infection confers lasting immunity against the infecting serotype but increases the risk of serious disease upon reinfection by any of the other three. The recombinant tetravalent vaccine Dengvaxia® prevents severe dengue and hospitalization in seropositive subjects. In 2017, Dengvaxia was approved in Argentina, for ages 9 to 45, but is not included in the national vaccination calendar. Two other vaccines are in Phase III evaluation: one developed by NIAID / Instituto Butantan and the other by Takeda. ZIKV, a virus associated with microcephaly in newborns in Brazil, circulates since 2016 in Argentina. There is still not effective treatment nor vaccine with proven activity against ZIKV. There has been no active circulation of CHIKV in Argentina in 2017. Outbreaks of CHIKV fever have a complication: the development of chronic post-disease rheumatism. There are not approved vaccines for humans nor effective antiviral therapies. The seriousness of these virosis has contributed to a rapid progress in the knowledge of the infection processes and the immune response. For now, Aedes aegypti and A. albopictus vectors continue to expand, suggesting that the vaccine will be the most effective means of controlling these viruses. Here we summarize information about these arbovirosis in Argentina and Brazil and describe advances in the development and evaluation of vaccines.

[The development of therapeutic vaccine for hepatitis C virus].

PubMed

Kimura, Kiminori; Kohara, Michinori

2012-10-01

Chronic hepatitis C caused by infection with the hepatitis C virus(HCV)is a global health problem. HCV causes persistent infection that can lead to chronic liver diseases such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The therapeutic efficacy of antiviral drugs is not optimal in patients with chronic infection; furthermore, an effective vaccine has not yet been developed. To design an effective HCV vaccine, generation of a convenient animal model of HCV infection is necessary. Recently, we used the Cre/loxP switching system to generate an immunocompetent mouse model of HCV expression, thereby enabling the study of host immune responses against HCV proteins. At present vaccine has not yet been shown to be therapeutically effective against chronic HCV infection. We examined the therapeutic effects of a recombinant vaccinia virus(rVV)encoding HCV protein in a mouse model. we generated rVVs for 3 different HCV proteins and found that one of the recombinant viruses encoding a nonstructural protein(rVV-N25)resolved pathological chronic hepatitis C symptoms in the liver. We propose the possibility that rVV-N25 immunization has the potential for development of an effective therapeutic vaccine for HCV induced chronic hepatitis. The utilization of the therapeutic vaccine can protect progress to chronic hepatitis, and as a consequence, leads to eradication of hepatocellular carcinoma. In this paper, we summarized our current study for HCV therapeutic vaccine and review the vaccine development to date.

The protective immune response produced in dogs after primary vaccination with the LiESP/QA-21 vaccine (CaniLeish®) remains effective against an experimental challenge one year later

PubMed Central

2014-01-01

Control of canine leishmaniasis is an important objective for the benefit of dogs living in or visiting endemic areas and for public health because of the zoonotic nature of this disease. Resistance or susceptibility to developing canine leishmaniasis after exposure to Leishmania infantum is primarily determined by the ability of the immune system to develop an appropriate Th1-dominated specific response to the parasite. For this reason there is a need for effective canine vaccines that can decrease the number of dogs developing progressive infections. In this study, we followed the impact of the LiESP/QA-21 canine vaccine (composed of excreted-secreted proteins of L. infantum and the QA-21 saponin adjuvant), recently launched commercially in Europe, on selected humoral and cellular immune parameters following an infectious intravenous challenge with L. infantum promastigotes administered one year after the primary vaccine course. We also followed parasitological parameters to determine the parasitological status of the challenged dogs. In contrast to controls, vaccinated dogs retained significantly stronger cell-mediated immune responses against the parasite despite a virulent challenge and had significantly lower mean parasite burdens at the end of the study, associated with a lower probability of developing active infections. These results confirm that the immune responses generated by vaccination with LiESP/QA-21 are still effective against an intravenous challenge one year after the primary vaccine course. PMID:24964736

Cellular immunotherapy for soft tissue sarcomas

PubMed Central

Finkelstein, Steven Eric; Fishman, Mayer; Conley, Anthony P.; Gabrilovich, Dmitry; Antonia, Scott; Chiappori, Alberto

2015-01-01

SUMMARY Soft tissue sarcomas are rare neoplasms, with approximately 9,000 new cases in the United States every year. Unfortunately, there is little progress in the treatment of metastatic soft tissue sarcomas in the past two decades beyond the standard approaches of surgery, chemotherapy, and radiation. Immunotherapy is a modality complementary to conventional therapy,. It is appealing because functional anti-tumor activity could affect both local-regional and systemic disease and act over a prolonged period of time. In this report, we review immunotherapeutic investigative strategies being developed, including several tumor vaccine, antigen vaccine, and dendritic cell vaccine strategies. PMID:22401634

Plasmodium immunomics.

PubMed

Doolan, Denise L

2011-01-01

The Plasmodium parasite, the causative agent of malaria, is an excellent model for immunomic-based approaches to vaccine development. The Plasmodium parasite has a complex life cycle with multiple stages and stage-specific expression of ∼5300 putative proteins. No malaria vaccine has yet been licensed. Many believe that an effective vaccine will need to target several antigens and multiple stages, and will require the generation of both antibody and cellular immune responses. Vaccine efforts to date have been stage-specific and based on only a very limited number of proteins representing <0.5% of the genome. The recent availability of comprehensive genomic, proteomic and transcriptomic datasets from human and selected non-human primate and rodent malarias provide a foundation to exploit for vaccine development. This information can be mined to identify promising vaccine candidate antigens, by proteome-wide screening of antibody and T cell reactivity using specimens from individuals exposed to malaria and technology platforms such as protein arrays, high throughput protein production and epitope prediction algorithms. Such antigens could be incorporated into a rational vaccine development process that targets specific stages of the Plasmodium parasite life cycle with immune responses implicated in parasite elimination and control. Immunomic approaches which enable the selection of the best possible targets by prioritising antigens according to clinically relevant criteria may overcome the problem of poorly immunogenic, poorly protective vaccines that has plagued malaria vaccine developers for the past 25 years. Herein, current progress and perspectives regarding Plasmodium immunomics are reviewed. Copyright © 2010 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

A third generation vaccine for human visceral leishmaniasis and post kala azar dermal leishmaniasis: First-in-human trial of ChAd63-KH

PubMed Central

Osman, Mohamed; Mistry, Anoop; Keding, Ada; Cook, Elizabeth; Wiggins, Rebecca; Di Marco, Stefania; Colloca, Stefano; Siani, Loredana; Smith, Deborah F.; Aebischer, Toni; Lacey, Charles J.

2017-01-01

Background Visceral leishmaniasis (VL or kala azar) is the most serious form of human leishmaniasis, responsible for over 20,000 deaths annually, and post kala azar dermal leishmaniasis (PKDL) is a stigmatizing skin condition that often occurs in patients after successful treatment for VL. Lack of effective or appropriately targeted cell mediated immunity, including CD8+ T cell responses, underlies the progression of VL and progression to PKDL, and can limit the therapeutic efficacy of anti-leishmanial drugs. Hence, in addition to the need for prophylactic vaccines against leishmaniasis, the development of therapeutic vaccines for use alone or in combined immuno-chemotherapy has been identified as an unmet clinical need. Here, we report the first clinical trial of a third-generation leishmaniasis vaccine, developed intentionally to induce Leishmania-specific CD8+ T cells. Methods We conducted a first-in-human dose escalation Phase I trial in 20 healthy volunteers to assess the safety, tolerability and immunogenicity of a prime-only adenoviral vaccine for human VL and PKDL. ChAd63-KH is a replication defective simian adenovirus expressing a novel synthetic gene (KH) encoding two Leishmania proteins KMP-11 and HASPB. Uniquely, the latter was engineered to reflect repeat domain polymorphisms and arrangements identified from clinical isolates. We monitored innate immune responses by whole blood RNA-Seq and antigen specific CD8+ T cell responses by IFNγ ELISPOT and intracellular flow cytometry. Findings ChAd63-KH was safe at intramuscular doses of 1x1010 and 7.5x1010 vp. Whole blood transcriptomic profiling indicated that ChAd63-KH induced innate immune responses characterized by an interferon signature and the presence of activated dendritic cells. Broad and quantitatively robust CD8+ T cell responses were induced by vaccination in 100% (20/20) of vaccinated subjects. Conclusion The results of this study support the further development of ChAd63-KH as a novel third generation vaccine for VL and PKDL. Trial registration This clinical trial (LEISH1) was registered at EudraCT (2012-005596-14) and ISRCTN (07766359). PMID:28498840

A third generation vaccine for human visceral leishmaniasis and post kala azar dermal leishmaniasis: First-in-human trial of ChAd63-KH.

PubMed

Osman, Mohamed; Mistry, Anoop; Keding, Ada; Gabe, Rhian; Cook, Elizabeth; Forrester, Sarah; Wiggins, Rebecca; Di Marco, Stefania; Colloca, Stefano; Siani, Loredana; Cortese, Riccardo; Smith, Deborah F; Aebischer, Toni; Kaye, Paul M; Lacey, Charles J

2017-05-01

Visceral leishmaniasis (VL or kala azar) is the most serious form of human leishmaniasis, responsible for over 20,000 deaths annually, and post kala azar dermal leishmaniasis (PKDL) is a stigmatizing skin condition that often occurs in patients after successful treatment for VL. Lack of effective or appropriately targeted cell mediated immunity, including CD8+ T cell responses, underlies the progression of VL and progression to PKDL, and can limit the therapeutic efficacy of anti-leishmanial drugs. Hence, in addition to the need for prophylactic vaccines against leishmaniasis, the development of therapeutic vaccines for use alone or in combined immuno-chemotherapy has been identified as an unmet clinical need. Here, we report the first clinical trial of a third-generation leishmaniasis vaccine, developed intentionally to induce Leishmania-specific CD8+ T cells. We conducted a first-in-human dose escalation Phase I trial in 20 healthy volunteers to assess the safety, tolerability and immunogenicity of a prime-only adenoviral vaccine for human VL and PKDL. ChAd63-KH is a replication defective simian adenovirus expressing a novel synthetic gene (KH) encoding two Leishmania proteins KMP-11 and HASPB. Uniquely, the latter was engineered to reflect repeat domain polymorphisms and arrangements identified from clinical isolates. We monitored innate immune responses by whole blood RNA-Seq and antigen specific CD8+ T cell responses by IFNγ ELISPOT and intracellular flow cytometry. ChAd63-KH was safe at intramuscular doses of 1x1010 and 7.5x1010 vp. Whole blood transcriptomic profiling indicated that ChAd63-KH induced innate immune responses characterized by an interferon signature and the presence of activated dendritic cells. Broad and quantitatively robust CD8+ T cell responses were induced by vaccination in 100% (20/20) of vaccinated subjects. The results of this study support the further development of ChAd63-KH as a novel third generation vaccine for VL and PKDL. This clinical trial (LEISH1) was registered at EudraCT (2012-005596-14) and ISRCTN (07766359).

Recent progress in the development of anthrax vaccines.

PubMed

Kaur, Manpreet; Bhatnagar, Rakesh

2011-12-01

Bacillus anthracis is the etiological agent of anthrax. Although anthrax is primarily an epizootic disease; humans are at risk for contracting anthrax. The potential use of B. anthracis spores as biowarfare agent has led to immense attention. Prolonged vaccination schedule of current anthrax vaccine and variable protection conferred; often leading to failure of therapy. This highlights the need for alternative anthrax countermeasures. A number of approaches are being investigated to substitute or supplement the existing anthrax vaccines. These relied on expression of Protective antigen (PA), the key protective immunogen; in bacterial or plant systems; or utilization of attenuated strains of B. anthracis for immunization. Few studies have established potential of domain IV of PA for immunization. Other targets including the spore, capsule, S-layer and anthrax toxin components have been investigated for imparting protective immunity. It has been shown that co-immunization of PA with domain I of lethal factor that binds PA resulted in higher antibody responses. Of the epitope based vaccines, the loop neutralizing determinant, in particular; elicited robust neutralizing antibody response and conferred 97% protection upon challenge. DNA vaccination resulted in varying degree of protection and seems a promising approach. Additionally, the applicability of monoclonal and therapeutic antibodies in the treatment of anthrax has also been demonstrated. The recent progress in the direction of anthrax prophylaxis has been evaluated in this review.

Recovery of antigen-specific T cell responses from dogs infected with Leishmania (L.) infantum by use of vaccine associated TLR-agonist adjuvant.

PubMed

Schaut, Robert G; Grinnage-Pulley, Tara L; Esch, Kevin J; Toepp, Angela J; Duthie, Malcolm S; Howard, Randall F; Reed, Steven G; Petersen, Christine A

2016-10-17

Visceral leishmaniasis (VL), caused by infection with the obligate intracellular protozoan parasite Leishmania infantum, is a fatal disease of dogs and humans. Protection against VL requires a T helper 1 (Th1) skewed CD4 + T response, but despite this knowledge, there are currently no approved-to-market vaccines for humans and only three veterinary-use vaccines globally. As VL progresses from asymptomatic to symptomatic, L. infantum-specific interferon gamma (IFNγ) driven-Th1 responses become dampened and a state of immune exhaustion established. T cell exhaustion and other immunoregulatory processes, starting during asymptomatic disease, are likely to hinder vaccine-induced responses if vaccine is administered to infected, but asymptomatic and seronegative, individuals. In this study we evaluated how immune exhaustion, shown previously by our group to worsen in concert with VL progression, effected the capacity of vaccine candidate antigen/toll-like receptor (TLR) agonist combinations to promote protective CD4 + T cell responses during progressive VL. In conjunction with Th1 responses, we also evaluated concomitant stimulation of immune-balanced IL-10 regulatory cytokine production by these vaccine products in progressive VL canine T cells. Vaccine antigen L111f in combination with TLR agonists significantly recovered CD4 + T cell IFNγ intracellular production in T cells from asymptomatic VL dogs. Vaccine antigen NS with TLR agonists significantly recovered CD4 + T cell production in both endemic control and VL dogs. Combinations of TLR agonists and vaccine antigens overcame L. infantum induced cellular exhaustion, allowing robust Th1 CD4 + T cell responses from symptomatic dogs that previously had dampened responses to antigen alone. Antigen-agonist adjuvants can be utilized to promote more robust vaccine responses from infected hosts in endemic areas where vaccination of asymptomatic, L. infantum-infected animals is likely. Copyright © 2016. Published by Elsevier Ltd.

Development of malaria transmission-blocking vaccines: from concept to product.

PubMed

Wu, Yimin; Sinden, Robert E; Churcher, Thomas S; Tsuboi, Takafumi; Yusibov, Vidadi

2015-06-01

Despite decades of effort battling against malaria, the disease is still a major cause of morbidity and mortality. Transmission-blocking vaccines (TBVs) that target sexual stage parasite development could be an integral part of measures for malaria elimination. In the 1950s, Huff et al. first demonstrated the induction of transmission-blocking immunity in chickens by repeated immunizations with Plasmodium gallinaceum-infected red blood cells. Since then, significant progress has been made in identification of parasite antigens responsible for transmission-blocking activity. Recombinant technologies accelerated evaluation of these antigens as vaccine candidates, and it is possible to induce effective transmission-blocking immunity in humans both by natural infection and now by immunization with recombinant vaccines. This chapter reviews the efforts to produce TBVs, summarizes the current status and advances and discusses the remaining challenges and approaches. Copyright © 2015 Elsevier Ltd. All rights reserved.

Surface antigens of Plasmodium falciparum gametocytes--a new class of transmission-blocking vaccine targets?

PubMed

Sutherland, Colin J

2009-08-01

The re-establishment of elimination and eradication on the malaria control agenda has led to calls for renewed effort in the development of parasite transmission-blocking interventions. Vaccines are ideally suited to this task, but progress towards an anti-gamete transmission-blocking vaccine, designed to act on parasites in blood-fed mosquitoes, has been slow. Recent work has confirmed that the surface of the gametocyte-infected erythrocyte presents antigens to the host immune system, and elicits specific humoral immune responses to these antigens, termed gametocyte surface antigens (GSAs). Likely candidate molecules, including antigens encoded by sub-telomeric multi-gene families, are discussed, and a hypothetical group of parasite molecules involved in spatial and temporal signal transduction in the human host is proposed, the tropins and circadins. The next steps for development of anti-gametocyte transmission-blocking vaccines for P. falciparum and the other human malaria species are considered.

Mechanisms of immunity to Leishmania major infection in mice: the contribution of DNA vaccines coding for two novel sets of histones (H2A-H2B or H3-H4).

PubMed

Carrión, Javier

2011-09-01

The immune phenotype conferred by two different sets of histone genes (H2A-H2B or H3-H4) was assessed. BALB/c mice vaccinated with pcDNA3H2AH2B succumbed to progressive cutaneous leishmaniosis (CL), whereas vaccination with pcDNA3H3H4 resulted in partial resistance to Leishmania major challenge associated with the development of mixed T helper 1 (Th1)/Th2-type response and a reduction in parasite-specific Treg cells number at the site of infection. Therefore, the presence of histones H3 and H4 may be considered essential in the development of vaccine strategies against CL based on the Leishmania histones. Copyright © 2011 Elsevier Ltd. All rights reserved.

[Ten years of human papillomavirus vaccination. From dermatology to oncology via infectology].

PubMed

Moraga-Llop, Fernando A

2018-05-01

Human papillomavirus (HPV) was first identified in dermatology, and it was subsequently demonstrated that is was required for the development of uterine cervical cancer and other tumours, after a persistent infection by any of its oncogenic genotypes. Ten years ago, the most common infections and cancers associated with HPV could be prevented by immunisation with 2vaccines, one bivalent, and another tetravalent, and having just marketed a nonavalent one. During the period 2007-2008, the HPV vaccine was included in the Autonomous Communities vaccination calendar, and it is the second vaccine, after that of Hepatitis B, that prevents cancer. In these 10 years that these vaccines have been available the knowledge has progressed and there have been significant advances in vaccination strategies, as well as in the indications and recommendations. These include, lowering the age in the vaccination schedule, prescribing of 2doses at 9 years and at 13-14 years, systematic vaccination of the male in some countries, immunisation of the woman after adolescence, implementation of vaccination programmes in developed countries, prevention of other cancers, recommendations for vaccinations for populations at high risk of HPV infection, scientific evidence on the impact and effectiveness of vaccination, and confirmation of the safety of these vaccines, with more than 270 million doses administered, as has already been observed in clinical trials. The role of health professionals is essential to achieve and maintain high vaccine coverage. Copyright © 2017 Asociación Española de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

[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.

Vaccination against herpes zoster in developed countries

PubMed Central

Drolet, Mélanie; Oxman, Michael N.; Levin, Myron J.; Schmader, Kenneth E.; Johnson, Robert W.; Patrick, David; Mansi, James A.; Brisson, Marc

2013-01-01

Although progress has been made in the treatment of herpes zoster (HZ) and postherpetic neuralgia (PHN), available therapeutic options are only partially effective. Given evidence that a live-attenuated varicella-zoster-virus vaccine is effective at reducing the incidence of HZ, PHN and the burden of illness, policymakers and clinicians are being asked to make recommendations regarding the use of the zoster vaccine. In this report, we summarize the evidence regarding the: (1) burden of illness; (2) vaccine efficacy and safety; and (3) cost-effectiveness of vaccination, to assist evidence-based policy making and guide clinicians in their recommendations. First, there is general agreement that the overall burden of illness associated with HZ and PHN is substantial. Second, the safety and efficacy of the zoster vaccine at reducing the burden of illness due to HZ and the incidence of PHN have been clearly demonstrated in large placebo-controlled trials. However, uncertainty remains about the vaccine’s duration of protection. Third, vaccination against HZ is likely to be cost-effective when the vaccine is given at approximately 65 y of age, if vaccine duration is longer than 10 y. PMID:23324598

Progress toward measles elimination--European Region, 2005--2008.

PubMed

2009-02-20

In 2002, the World Health Organization (WHO) Regional Committee for the European Region (EUR) revised earlier targets to eliminate indigenous measles and achieve rubella control by resolving to 1) eliminate both diseases in EUR member states by 2010, using a combination of routine and supplementary immunization strategies, and 2) monitor progress toward this goal through improved surveillance. This report summarizes progress toward measles elimination during 2005--2008 and updates a previous report from 2005. In 2005 and 2006, large-scale outbreaks occurred in the eastern EUR member states. However, in 2007 and 2008, overall measles incidence in EUR declined to a historic low of <10 cases per 1 million population, with the majority of cases reported from Western Europe. During 2005-2007, routine vaccination coverage with 1 dose of measles-containing vaccine (MCV) among children aged 12--23 months in EUR reached a high of 93%-94%, up from 90%-91% during 2000-2004. Nevertheless, two major challenges to measles elimination remain: 1) suboptimal vaccination coverage in many countries, which has led to continued outbreaks and the resurgence of indigenous measles in some Western European countries, and 2) setbacks with implementation of supplementary immunization activities (SIAs) in Eastern Europe in 2008. Achieving the measles elimination goal by 2010 will require 1) development of approaches to sustain and increase vaccination coverage, 2) promotion of effective outbreak prevention and control measures, and 3) further strengthening of surveillance.

Yellow fever 17-D vaccine is neurotropic and produces encephalitis in immunosuppressed hamsters.

PubMed

Mateo, Rosa I; Xiao, Shu-Yuan; Travassos da Rosa, Amelia P A; Lei, Hao; Guzman, Hilda; Lu, Liang; Tesh, Robert B

2007-11-01

Immunosuppressed (cyclophosphamide) adult golden hamsters inoculated intraperitoneally (i.p.) with wild-type Asibi yellow fever virus (YFV) developed a rapidly fatal illness. Histopathologic and immunohistochemical studies of tissues from these animals showed typical hepatic changes of severe yellow fever (inflammation, hepatocyte necrosis, and steatosis) without brain involvement. In contrast, 50% of immunosuppressed hamsters receiving the YFV-17D-attenuated vaccine developed a slowly progressive encephalitic-type illness. Brain tissue from these latter animals revealed focal neuronal changes, inflammation, and YFV antigen-positive neurons; however, the liver and spleen appeared normal. YFV was isolated from brain cultures of many of these animals. Immunocompetent (non-immunosuppressed) hamsters inoculated with both viruses developed a subclinical infection. Results of this study indicate that wild-type YFV is hepatotropic in immunosuppressed hamsters, whereas the attenuated YFV-17 is primarily neurotropic. These findings support current recommendations against yellow fever vaccination of immunosuppressed/immunocompromised people and suggest that this hamster model might be useful for monitoring the safety of other live-attenuated YFV vaccines.

Progress and Challenges toward the Development of Vaccines against Avian Infectious Bronchitis

PubMed Central

Bande, Faruku; Arshad, Siti Suri; Hair Bejo, Mohd; Moeini, Hassan; Omar, Abdul Rahman

2015-01-01

Avian infectious bronchitis (IB) is a widely distributed poultry disease that has huge economic impact on poultry industry. The continuous emergence of new IBV genotypes and lack of cross protection among different IBV genotypes have been an important challenge. Although live attenuated IB vaccines remarkably induce potent immune response, the potential risk of reversion to virulence, neutralization by the maternal antibodies, and recombination and mutation events are important concern on their usage. On the other hand, inactivated vaccines induce a weaker immune response and may require multiple dosing and/or the use of adjuvants that probably have potential safety risks and increased economic burdens. Consequently, alternative IB vaccines are widely sought. Recent advances in recombinant DNA technology have resulted in experimental IB vaccines that show promise in antibody and T-cells responses, comparable to live attenuated vaccines. Recombinant DNA vaccines have also been enhanced to target multiple serotypes and their efficacy has been improved using delivery vectors, nanoadjuvants, and in ovo vaccination approaches. Although most recombinant IB DNA vaccines are yet to be licensed, it is expected that these types of vaccines may hold sway as future vaccines for inducing a cross protection against multiple IBV serotypes. PMID:25954763

Leishmania vaccines: progress and problems.

PubMed

Kedzierski, L; Zhu, Y; Handman, E

2006-01-01

Leishmania are protozoan parasites spread by a sandfly insect vector and causing a spectrum of diseases collectively known as leishmaniasis. The disease is a significant health problem in many parts of the world resulting in an estimated 12 million new cases each year. Current treatment is based on chemotherapy, which is difficult to administer, expensive and becoming ineffective due to the emergence of drug resistance. Leishmaniasis is considered one of a few parasitic diseases likely to be controllable by vaccination. The relatively uncomplicated leishmanial life cycle and the fact that recovery from infection renders the host resistant to subsequent infection indicate that a successful vaccine is feasible. Extensive evidence from studies in animal models indicates that solid protection can be achieved by immunisation with protein or DNA vaccines. However, to date no such vaccine is available despite substantial efforts by many laboratories. Advances in our understanding of Leishmania pathogenesis and generation of host protective immunity, together with the completed Leishmania genome sequence open new avenues for vaccine research. The major remaining challenges are the translation of data from animal models to human disease and the transition from the laboratory to the field. This review focuses on advances in anti-leishmania vaccine development over the recent years and examines current problems hampering vaccine development and implementation.

Immunization of children with secondary immunodeficiency

PubMed Central

Esposito, Susanna; Prada, Elisabetta; Lelii, Mara; Castellazzi, Luca

2015-01-01

ABSTRACT The main causes of secondary immunodeficiency at a pediatric age include infectious diseases (mainly HIV infection), malignancies, haematopoietic stem cell or solid organ transplantation and autoimmune diseases. Children with secondary immunodeficiency have an increased risk of severe infectious diseases that could be prevented by adequate vaccination coverage, but vaccines administration can be associated with reduced immune response and an increased risk of adverse reactions. The immunogenicity of inactivated and recombinant vaccines is comparable to that of healthy children at the moment of vaccination, but it undergoes a progressive decline over time, and in the absence of a booster, the patients remain at risk of developing vaccine-preventable infections. However, the administration of live attenuated viral vaccines is controversial because of the risk of the activation of vaccine viruses. A specific immunization program should be administered according to the clinical and immunological status of each of these conditions to ensure a sustained immune response without any risks to the patients' health. PMID:26176360

Immunogenicity and protection efficacy of subunit-based smallpox vaccines using variola major antigens.

PubMed

Sakhatskyy, Pavlo; Wang, Shixia; Zhang, Chuanyou; Chou, Te-Hui; Kishko, Michael; Lu, Shan

2008-02-05

The viral strain responsible for smallpox infection is variola major (VARV). As a result of the successful eradication of smallpox with the vaccinia virus (VACV), the general population is no longer required to receive a smallpox vaccine, and will have no protection against smallpox. This lack of immunity is a concern due to the potential for use of smallpox as a biological weapon. Considerable progress has been made in the development of subunit-based smallpox vaccines resulting from the identification of VACV protective antigens. It also offers the possibility of using antigens from VARV to formulate the next generation subunit-based smallpox vaccines. Here, we show that codon-optimized DNA vaccines expressing three VARV antigens (A30, B7 and F8) and their recombinant protein counterparts elicited high-titer, cross-reactive, VACV neutralizing antibody responses in mice. Vaccinated mice were protected from intraperitoneal and intranasal challenges with VACV. These results suggest the feasibility of a subunit smallpox vaccine based on VARV antigen sequences to induce immunity against poxvirus infection.

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.

Amyotrophic Lateral Sclerosis after Receiving the Human Papilloma Virus Vaccine: A Case Report of a 15-year-old Girl.

PubMed

Hikiami, Ryota; Yamakado, Hodaka; Tatsumi, Shinsui; Ayaki, Takashi; Hashi, Yuichiro; Yamashita, Hirofumi; Sawamoto, Nobukatsu; Tsuji, Teruyuki; Urushitani, Makoto; Takahashi, Ryosuke

2018-02-09

We herein report a 15-year-old girl who developed rapid progressive muscle weakness soon after the third injection of a bivalent human papilloma virus (HPV) vaccine. Although immunotherapies were performed for possible vaccine-related disorders, she died of respiratory failure 14 months after the onset of the disease. A genetic analysis identified a heterozygous p.P525L mutation of the fused in sarcoma (FUS) gene, and a histopathological analysis was also consistent with FUS-associated amyotrophic lateral sclerosis (ALS) without any evidence of neuroinflammation. We concluded the diagnosis to be FUS-ALS, although we cannot completely rule out the possibility that the vaccination worked as a trigger.

Vaccines for viral diseases with dermatologic manifestations.

PubMed

Brentjens, Mathijs H; Yeung-Yue, Kimberly A; Lee, Patricia C; Tyring, Stephen K

2003-04-01

Vaccines against infectious diseases have been available since the 1800s, when an immunization strategy against smallpox developed by Jenner gained wide acceptance. Until recently, the only vaccination strategies available involved the use of protein-based, whole killed, and attenuated live virus vaccines. These strategies have led to the development of effective vaccines against a variety of diseases with primary or prominent cutaneous manifestations. Effective and safe vaccines now used worldwide include those directed against measles and rubella (now commonly used together with a mumps vaccine as the trivalent MMR), chickenpox, and hepatitis B. The eradication of naturally occurring smallpox remains one of the greatest successes in the history of modern medicine, but stockpiles of live smallpox exist in the United States and Russia. Renewed interest in the smallpox vaccine reflects concerns about a possible bioterrorist threat using this virus. Yellow fever is a hemorrhagic virus endemic to tropical areas of South America and Africa. An effective vaccine for this virus has existed since 1937, and it is used widely in endemic areas of South America, and to a lesser extent in Africa. This vaccine is recommended once every 10 years for people who are traveling to endemic areas. Advances in immunology have led to a greater understanding of immune system function in viral diseases. Progress in genetics and molecular biology has allowed researchers to design vaccines with novel mechanisms of action (eg, DNA, vector, and VLP vaccines). Vaccines have also been designed to specifically target particular viral components, allowing for stimulation of various arms of the immune system as desired. Ongoing research shows promise in prophylactic and therapeutic vaccination for viral infections with cutaneous manifestations. Further studies are necessary before vaccines for HSV, HPV, and HIV become commercially available.

A pilot study of peptide vaccines for VEGF receptor 1 and 2 in patients with recurrent/progressive high grade glioma.

PubMed

Shibao, Shunsuke; Ueda, Ryo; Saito, Katsuya; Kikuchi, Ryogo; Nagashima, Hideaki; Kojima, Atsuhiro; Kagami, Hiroshi; Pareira, Eriel Sandika; Sasaki, Hikaru; Noji, Shinobu; Kawakami, Yutaka; Yoshida, Kazunari; Toda, Masahiro

2018-04-20

Early-phase clinical studies of glioma vaccines have shown feasibility and encouraging preliminary clinical activity. A vaccine that targets tumor angiogenesis factors in glioma microenvironment has not been reported. Therefore, we performed a pilot study to evaluate the safety and immunogenicity of a novel vaccination targeting tumor angiogenesis with synthetic peptides for vascular endothelial growth factor (VEGF) receptor epitopes in patients with recurrent/progressive high grade gliomas. Eight patients received intranodal vaccinations weekly at a dose of 2mg/kg bodyweight 8 times. T-lymphocyte responses against VEGF receptor (VEGFR) epitopes were assessed by enzyme linked immunosorbent spot assays. This treatment was well-tolerated in patients. The first four vaccines induced positive immune responses against at least one of the targeted VEGFR epitopes in the peripheral blood mononuclear cells in 87.5% of patients. The median overall survival time in all patients was 15.9 months. Two achieved progression-free status lasting at least 6 months. Two patients with recurrent GBM demonstrated stable disease. Plasma IL-8 level was negatively correlated with overall survival. These data demonstrate the safety and immunogenicity of VEGFR peptide vaccines targeting tumor vasculatures in high grade gliomas.

Ebolavirus Vaccines: Progress in the Fight Against Ebola Virus Disease.

PubMed

Wu, Xiao-Xin; Yao, Hang-Ping; Wu, Nan-Ping; Gao, Hai-Nv; Wu, Hai-Bo; Jin, Chang-Zhong; Lu, Xiang-Yun; Xie, Tian-Shen; Li, Lan-Juan

2015-01-01

Ebolaviruses are highly infectious pathogens that cause lethal Ebola virus disease (EVD) in humans and non-human primates (NHPs). Due to their high pathogenicity and transmissibility, as well as the potential to be misused as a bioterrorism agent, ebolaviruses would threaten the health of global populations if not controlled. In this review, we describe the origin and structure of ebolaviruses and the development of vaccines from the beginning of the 1980s, including conventional ebolavirus vaccines, DNA vaccines, Ebola virus-like particles (VLPs), vaccinia virus-based vaccines, Venezuelan equine encephalitis virus (VEEV)-like replicon particles, Kunjin virus-based vaccine, recombinant Zaire Ebolavirusx2206;VP30, recombinant cytomegalovirus (CMV)-based vaccines, recombinant rabies virus (RABV)-based vaccines, recombinant paramyxovirus-based vaccines, adenovirus-based vaccines and vesicular stomatitis virus (VSV)-based vaccines. No licensed vaccine or specific treatment is currently available to counteract ebolavirus infection, although DNA plasmids and several viral vector approaches have been evaluated as promising vaccine platforms. These vaccine candidates have been confirmed to be successful in protecting NHPs against lethal infection. Moreover, these vaccine candidates were successfully advanced to clinical trials. The present review provides an update of the current research on Ebola vaccines, with the aim of providing an overview on current prospects in the fight against EVD. © 2015 The Author(s) Published by S. Karger AG, Basel.

Vaccine Development against Zoonotic Hepatitis E Virus: Open Questions and Remaining Challenges

PubMed Central

Nan, Yuchen; Wu, Chunyan; Zhao, Qin; Sun, Yani; Zhang, Yan-Jin; Zhou, En-Min

2018-01-01

Hepatitis E virus (HEV) is a fecal-orally transmitted foodborne viral pathogen that causes acute hepatitis in humans and is responsible for hepatitis E outbreaks worldwide. Since the discovery of HEV as a zoonotic agent, this virus has been isolated from a variety of hosts with an ever-expanding host range. Recently, a subunit HEV vaccine developed for the prevention of human disease was approved in China, but is not yet available to the rest of the world. Meanwhile, notable progress and knowledge has been made and revealed in recent years to better understand HEV biology and infection, including discoveries of quasi-enveloped HEV virions and of a new function of the HEV-ORF3 product. However, the impact of these new findings on the development of a protective vaccine against zoonotic HEV infection requires further discussion. In this review, hallmark characteristics of HEV zoonosis, the history of HEV vaccine development, and recent discoveries in HEV virology are described. Moreover, special attention is focused on quasi-enveloped HEV virions and the potential role of the HEV-ORF3 product as antibody-neutralization target on the surface of quasi-enveloped HEV virions to provide new insights for the future development of improved vaccines against zoonotic HEV infection. PMID:29520257

Vaccine Development against Zoonotic Hepatitis E Virus: Open Questions and Remaining Challenges.

PubMed

Nan, Yuchen; Wu, Chunyan; Zhao, Qin; Sun, Yani; Zhang, Yan-Jin; Zhou, En-Min

2018-01-01

Hepatitis E virus (HEV) is a fecal-orally transmitted foodborne viral pathogen that causes acute hepatitis in humans and is responsible for hepatitis E outbreaks worldwide. Since the discovery of HEV as a zoonotic agent, this virus has been isolated from a variety of hosts with an ever-expanding host range. Recently, a subunit HEV vaccine developed for the prevention of human disease was approved in China, but is not yet available to the rest of the world. Meanwhile, notable progress and knowledge has been made and revealed in recent years to better understand HEV biology and infection, including discoveries of quasi-enveloped HEV virions and of a new function of the HEV-ORF3 product. However, the impact of these new findings on the development of a protective vaccine against zoonotic HEV infection requires further discussion. In this review, hallmark characteristics of HEV zoonosis, the history of HEV vaccine development, and recent discoveries in HEV virology are described. Moreover, special attention is focused on quasi-enveloped HEV virions and the potential role of the HEV-ORF3 product as antibody-neutralization target on the surface of quasi-enveloped HEV virions to provide new insights for the future development of improved vaccines against zoonotic HEV infection.

The Effect of Oral Vaccination with Mycobacterium bovis BCG on the Development of Tuberculosis in Captive European Badgers (Meles meles).

PubMed

Chambers, Mark A; Aldwell, Frank; Williams, Gareth A; Palmer, Si; Gowtage, Sonya; Ashford, Roland; Dalley, Deanna J; Davé, Dipesh; Weyer, Ute; Salguero, Francisco J; Nunez, Alejandro; Nadian, Allan K; Crawshaw, Timothy; Corner, Leigh A L; Lesellier, Sandrine

2017-01-01

The European badger ( Meles meles ) is a reservoir host of Mycobacterium bovis and responsible for a proportion of the tuberculosis (TB) cases seen in cattle in the United Kingdom and Republic of Ireland. An injectable preparation of the bacillus Calmette-Guérin (BCG) vaccine is licensed for use in badgers in the UK and its use forms part of the bovine TB eradication plans of England and Wales. However, there are practical limitations to the widespread application of an injectable vaccine for badgers and a research priority is the development of an oral vaccine deliverable to badgers in bait. Previous studies reported the successful vaccination of badgers with oral preparations of 10 8 colony forming units (CFU) of both Pasteur and Danish strains of BCG contained within a lipid matrix composed of triglycerides of fatty acids. Protection against TB in these studies was expressed as a reduction in the number and apparent progression of visible lesions, and reductions in the bacterial load and dissemination of infection. To reduce the cost of an oral vaccine and reduce the potential for environmental contamination with BCG, it is necessary to define the minimal efficacious dose of oral BCG for badgers. The objectives of the two studies reported here were to compare the efficacy of BCG Danish strain in a lipid matrix with unformulated BCG given orally, and to evaluate the efficacy of BCG Danish in a lipid matrix at a 10-fold lower dose than previously evaluated in badgers. In the first study, both BCG unformulated and in a lipid matrix reduced the number and apparent progression of visible lesions and the dissemination of infection from the lung. In the second study, vaccination with BCG in the lipid matrix at a 10-fold lower dose produced a similar outcome, but with greater intra-group variability than seen with the higher dose in the first study. Further research is needed before we are able to recommend a final dose of BCG for oral vaccination of badgers against TB or to know whether oral vaccination of wild badgers with BCG will significantly reduce transmission of the disease.

The Effect of Oral Vaccination with Mycobacterium bovis BCG on the Development of Tuberculosis in Captive European Badgers (Meles meles)

PubMed Central

Chambers, Mark A.; Aldwell, Frank; Williams, Gareth A.; Palmer, Si; Gowtage, Sonya; Ashford, Roland; Dalley, Deanna J.; Davé, Dipesh; Weyer, Ute; Salguero, Francisco J.; Nunez, Alejandro; Nadian, Allan K.; Crawshaw, Timothy; Corner, Leigh A. L.; Lesellier, Sandrine

2017-01-01

The European badger (Meles meles) is a reservoir host of Mycobacterium bovis and responsible for a proportion of the tuberculosis (TB) cases seen in cattle in the United Kingdom and Republic of Ireland. An injectable preparation of the bacillus Calmette-Guérin (BCG) vaccine is licensed for use in badgers in the UK and its use forms part of the bovine TB eradication plans of England and Wales. However, there are practical limitations to the widespread application of an injectable vaccine for badgers and a research priority is the development of an oral vaccine deliverable to badgers in bait. Previous studies reported the successful vaccination of badgers with oral preparations of 108 colony forming units (CFU) of both Pasteur and Danish strains of BCG contained within a lipid matrix composed of triglycerides of fatty acids. Protection against TB in these studies was expressed as a reduction in the number and apparent progression of visible lesions, and reductions in the bacterial load and dissemination of infection. To reduce the cost of an oral vaccine and reduce the potential for environmental contamination with BCG, it is necessary to define the minimal efficacious dose of oral BCG for badgers. The objectives of the two studies reported here were to compare the efficacy of BCG Danish strain in a lipid matrix with unformulated BCG given orally, and to evaluate the efficacy of BCG Danish in a lipid matrix at a 10-fold lower dose than previously evaluated in badgers. In the first study, both BCG unformulated and in a lipid matrix reduced the number and apparent progression of visible lesions and the dissemination of infection from the lung. In the second study, vaccination with BCG in the lipid matrix at a 10-fold lower dose produced a similar outcome, but with greater intra-group variability than seen with the higher dose in the first study. Further research is needed before we are able to recommend a final dose of BCG for oral vaccination of badgers against TB or to know whether oral vaccination of wild badgers with BCG will significantly reduce transmission of the disease. PMID:28174695

Dengue vaccine: come let's fight the menace.

PubMed

Chawla, Sumit; Sahoo, Soumya Swaroop; Singh, Inderjeet; Verma, Madhur; Gupta, Vikas; Kumari, Sneh

2015-01-01

Although dengue has a global distribution, the World Health Organization (WHO) South-East Asia region together with Western Pacific region bears nearly 75% of the current global disease burden. Globally, the societal burden has been estimated to be approximately 528 to 1300 disability-adjusted life years (DALY) per million to populations in endemic regions Dengue is believed to infect 50 to 100 million people worldwide a year with half a million life-threatening infections requiring hospitalization, resulting in approximately 12,500 to 25,000 deaths. Despite being known for decades and nearly half the world's population is at risk for infection with as many as 100 million cases occurring annually, the pitiable state is that we still have no antiviral drugs to treat it and no vaccines to prevent it. In recent years, however, the development of dengue vaccines has accelerated dramatically in tandem with the burgeoning dengue problem with a rejuvenated vigour. However, recent progress in molecular-based vaccine strategies, as well as a renewed commitment by the World Health Organization (WHO) to co-ordinate global efforts on vaccine development, finally provides hope that control of this serious disease may be at hand. Today, several vaccines are in various stages of advanced development, with clinical trials currently underway on 5 candidate vaccines. Trials in the most advanced stages are showing encouraging preliminary data, and the leading candidate could be licensed as early as 2015.

The Hard Way towards an Antibody-Based HIV-1 Env Vaccine: Lessons from Other Viruses

PubMed Central

Ringel, Oliver; Vieillard, Vincent; Debré, Patrice; Eichler, Jutta; Büning, Hildegard

2018-01-01

Although effective antibody-based vaccines have been developed against multiple viruses, such approaches have so far failed for the human immunodeficiency virus type 1 (HIV-1). Despite the success of anti-retroviral therapy (ART) that has turned HIV-1 infection into a chronic disease and has reduced the number of new infections worldwide, a vaccine against HIV-1 is still urgently needed. We discuss here the major reasons for the failure of “classical” vaccine approaches, which are mostly due to the biological properties of the virus itself. HIV-1 has developed multiple mechanisms of immune escape, which also account for vaccine failure. So far, no vaccine candidate has been able to induce broadly neutralizing antibodies (bnAbs) against primary patient viruses from different clades. However, such antibodies were identified in a subset of patients during chronic infection and were shown to protect from infection in animal models and to reduce viremia in first clinical trials. Their detailed characterization has guided structure-based reverse vaccinology approaches to design better HIV-1 envelope (Env) immunogens. Furthermore, conserved Env epitopes have been identified, which are promising candidates in view of clinical applications. Together with new vector-based technologies, considerable progress has been achieved in recent years towards the development of an effective antibody-based HIV-1 vaccine. PMID:29662026

What We Have Learned and What We Have Missed in Tuberculosis Pathophysiology for a New Vaccine Design: Searching for the “Pink Swan”

PubMed Central

Cardona, Pere-Joan

2017-01-01

This is a call to encourage the search for a new vaccine to stop the progression of Mycobacterium tuberculosis infection to tuberculosis (TB) disease. TB is a highly discreet and stigmatized disease, with a massive impact on human health. It has killed 1.2 billion people in the last 200 years and still kills 1.5 million people per year. Over the last 20 years, the TB vaccine field has experienced spectacular developments, and we have learned about (1) the importance of the Th1 response in controlling infection, mainly against RD1 and Ag85 antigens; (2) the stability of the antigenic repertoire; (3) the dynamics of M. tuberculosis granulomas; or (4) the link between typical and atypical pulmonary TB and the immune status of the host. However, we still do not (1) know how to avoid M. tuberculosis infection and reinfection; (2) understand the major role of the increase in lesion size in progression from infection to disease; (3) the role of interlobular septa in encapsulating pulmonary lesions; or (4) the role of neutrophilic infiltration and an exaggerated inflammatory response in the development of TB disease. These are strong reasons to pursue new, imaginative proposals involving both the antibody response and a balanced, tolerant immune response that averts progression toward TB. So far, the scientific mindset has been quite monolithic and has mainly focused on the stimulation of conventional T cells. But this approach has failed. For that reason, we are seeking unconventional perspectives to find a “pink swan,” a more efficacious and safer vaccine candidate. PMID:28555137

What We Have Learned and What We Have Missed in Tuberculosis Pathophysiology for a New Vaccine Design: Searching for the "Pink Swan".

PubMed

Cardona, Pere-Joan

2017-01-01

This is a call to encourage the search for a new vaccine to stop the progression of Mycobacterium tuberculosis infection to tuberculosis (TB) disease. TB is a highly discreet and stigmatized disease, with a massive impact on human health. It has killed 1.2 billion people in the last 200 years and still kills 1.5 million people per year. Over the last 20 years, the TB vaccine field has experienced spectacular developments, and we have learned about (1) the importance of the Th1 response in controlling infection, mainly against RD1 and Ag85 antigens; (2) the stability of the antigenic repertoire; (3) the dynamics of M. tuberculosis granulomas; or (4) the link between typical and atypical pulmonary TB and the immune status of the host. However, we still do not (1) know how to avoid M. tuberculosis infection and reinfection; (2) understand the major role of the increase in lesion size in progression from infection to disease; (3) the role of interlobular septa in encapsulating pulmonary lesions; or (4) the role of neutrophilic infiltration and an exaggerated inflammatory response in the development of TB disease. These are strong reasons to pursue new, imaginative proposals involving both the antibody response and a balanced, tolerant immune response that averts progression toward TB. So far, the scientific mindset has been quite monolithic and has mainly focused on the stimulation of conventional T cells. But this approach has failed. For that reason, we are seeking unconventional perspectives to find a "pink swan," a more efficacious and safer vaccine candidate.

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.

Establishing global policy recommendations: the role of the Strategic Advisory Group of Experts on immunization.

PubMed

Duclos, Philippe; Okwo-Bele, Jean-Marie; Salisbury, David

2011-02-01

The vaccine landscape has changed considerably over the last decade with many new vaccines and technological developments, unprecedented progress in reaching out to children and the development of new financing mechanisms. At the same time, there are more demands and additional expectations of national policy makers, donors and other interested parties for increased protection through immunization. The Global Immunization Vision and Strategy (GIVS), which broadens the previous scope of immunization efforts, sets a number of goals to be met by countries. The WHO has recently reviewed and adjusted both its policy making structure and processes for vaccines and immunization to include an enlarged consultation process to generate evidence-based recommendations, thereby ensuring the transparency of the decision making process and improving communications. This article describes the process of development of immunization policy recommendations at the global level and some of their impacts. It focuses on the roles and modes of operating of the Strategic Advisory Group of Experts on immunization, which is the overarching advisory group involved with the issuance of policy recommendations, monitoring and facilitating the achievement of the GIVS goals. The article also describes the process leading to the publication of WHO vaccine position papers, which provide WHO recommendations on vaccine use. WHO vaccine-related recommendations have become a necessary step in the pathway to the introduction and use of vaccines, especially in developing countries and, consequently, have a clear and significant impact.

Role of nanotechnology in HIV/AIDS vaccine development.

PubMed

Liu, Ying; Chen, Chunying

2016-08-01

HIV/AIDS is one of the worst crises affecting global health and influencing economic development and social stability. Preventing and treating HIV infection is a crucial task. However, there is still no effective HIV vaccine for clinical application. Nanotechnology has the potential to solve the problems associated with traditional HIV vaccines. At present, various nano-architectures and nanomaterials can function as potential HIV vaccine carriers or adjuvants, including inorganic nanomaterials, liposomes, micelles and polymer nanomaterials. In this review, we summarize the current progress in the use of nanotechnology for the development of an HIV/AIDS vaccine and discuss its potential to greatly improve the solubility, permeability, stability and pharmacokinetics of HIV vaccines. Although nanotechnology holds great promise for applications in HIV/AIDS vaccines, there are still many inadequacies that result in a variety of risks and challenges. The potential hazards to the human body and environment associated with some nano-carriers, and their underlying mechanisms require in-depth study. Non-toxic or low-toxic nanomaterials with adjuvant activity have been identified. However, studying the confluence of factors that affect the adjuvant activity of nanomaterials may be more important for the optimization of the dosage and immunization strategy and investigations into the exact mechanism of action. Moreover, there are no uniform standards for investigations of nanomaterials as potential vaccine adjuvants. These limitations make it harder to analyze and deduce rules from the existing data. Developing vaccine nano-carriers or adjuvants with high benefit-cost ratios is important to ensure their broad usage. Despite some shortcomings, nanomaterials have great potential and application prospects in the fields of AIDS treatment and prevention. Copyright © 2016 Elsevier B.V. All rights reserved.

Recent advances towards tuberculosis control: vaccines and biomarkers

PubMed Central

Weiner, J; Kaufmann, S H E

2014-01-01

Weiner 3rd J, Kaufmann SHE (Max Planck Institute for Infection Biology, Berlin, Germany). Recent advances towards tuberculosis control: vaccines and biomarkers. (Review). J Intern Med 2014; 275: 467–480. Of all infectious diseases, tuberculosis (TB) remains one of the most important causes of morbidity and mortality. Recent advances in understanding the biology of Mycobacterium tuberculosis (Mtb) infection and the immune response of the infected host have led to the development of several new vaccines, a number of which are already undergoing clinical trials. These include pre-exposure prime vaccines, which could replace bacille Calmette–Guérin (BCG), and pre-exposure booster vaccines given in addition to BCG. Infants are the target population of these two types of vaccines. In addition, several postexposure vaccines given during adolescence or adult life, in addition to BCG as a priming vaccine during infancy, are undergoing clinical testing. Therapeutic vaccines are currently being assessed for their potential to cure active TB as an adjunct to chemotherapy. BCG replacement vaccines are viable recombinant BCG or double-deletion mutants of Mtb. All booster vaccines are composed of one or several antigens, either expressed by viral vectors or formulated with adjuvants. Therapeutic vaccines are killed mycobacterial preparations. Finally, multivariate biomarkers and biosignatures are being generated from high-throughput data with the aim of providing better diagnostic tools to specifically determine TB progression. Here, we provide a technical overview of these recent developments as well of the relevant computational approaches and highlight the obstacles that still need to be overcome. PMID:24635488

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.

How Influenza Vaccination Policy May affect Vaccine Logistics

PubMed Central

Assi, Tina-Marie; Rookkapan, Korngamon; Rajgopal, Jayant; Sornsrivichai, Vorasith; Brown, Shawn T.; Welling, Joel S.; Norman, Bryan A.; Connor, Diana L.; Chen, Sheng-I; Slayton, Rachel B.; Laosiritaworn, Yongjua; Wateska, Angela R.; Wisniewski, Stephen R.; Lee, Bruce Y.

2012-01-01

Background When policymakers make decision about the target populations and timing of influenza vaccination, they may not consider the impact on the vaccine supply chains, which may in turn affect vaccine availability. Purpose Our goal is to explore the effects on the Thailand vaccine supply chain of introducing influenza vaccines and varying the target populations and immunization time-frames. Methods Utilized our custom-designed software HERMES (Highly Extensible Resource for Modeling Supply Chains), we developed a detailed, computational discrete-event simulation model of the Thailand's National Immunization Program (NIP) supply chain in Trang Province, Thailand., A suite of experiments simulated introducing influenza vaccines for different target populations and over different time-frames prior to and during the annual influenza season. Results Introducing influenza vaccines creates bottlenecks that reduce the availability of both influenza vaccines as well as the other NIP vaccines, with provincial to district transport capacity being the primary constraint. Even covering only 25% of the Advisory Committee on Immunization Practice-recommended population while administering the vaccine over six months hinders overall vaccine availability so that only 62% of arriving patients can receive vaccines. Increasing the target population from 25% to 100% progressively worsens these bottlenecks, while increasing influenza vaccination time - frame from 1 to 6 months decreases these bottlenecks. Conclusion Since the choice of target populations for influenza vaccination and the time-frame to deliver this vaccine can substantially affect the flow of all vaccines, policy-makers may want to consider supply chain effects when choosing target populations for a vaccine. PMID:22537993

Rational development of a protective P. vivax vaccine evaluated with transgenic rodent parasite challenge models

PubMed Central

Salman, Ahmed M.; Montoya-Díaz, Eduardo; West, Heather; Lall, Amar; Atcheson, Erwan; Lopez-Camacho, Cesar; Ramesar, Jai; Bauza, Karolis; Collins, Katharine A.; Brod, Florian; Reis, Fernando; Pappas, Leontios; González-Cerón, Lilia; Janse, Chris J.; Hill, Adrian V. S.; Khan, Shahid M.; Reyes-Sandoval, Arturo

2017-01-01

Development of a protective and broadly-acting vaccine against the most widely distributed human malaria parasite, Plasmodium vivax, will be a major step towards malaria elimination. However, a P. vivax vaccine has remained elusive by the scarcity of pre-clinical models to test protective efficacy and support further clinical trials. In this study, we report the development of a highly protective CSP-based P. vivax vaccine, a virus-like particle (VLP) known as Rv21, able to provide 100% sterile protection against a stringent sporozoite challenge in rodent models to malaria, where IgG2a antibodies were associated with protection in absence of detectable PvCSP-specific T cell responses. Additionally, we generated two novel transgenic rodent P. berghei parasite lines, where the P. berghei csp gene coding sequence has been replaced with either full-length P. vivax VK210 or the allelic VK247 csp that additionally express GFP-Luciferase. Efficacy of Rv21 surpassed viral-vectored vaccination using ChAd63 and MVA. We show for the first time that a chimeric VK210/247 antigen can elicit high level cross-protection against parasites expressing either CSP allele, which provide accessible and affordable models suitable to support the development of P. vivax vaccines candidates. Rv21 is progressing to GMP production and has entered a path towards clinical evaluation. PMID:28417968

Fusions of Breast Carcinoma and Dendritic Cells as a Vaccine for the Treatment of Metatastic Breast Cancer

DTIC Science & Technology

2012-07-01

well tolerated, induced immunologic responses in a majority of patients, and resulted in disease regression in subset. We postulated that...immunity are being obtained at serial time points following vaccination. Time to disease progression and RECIST measurable disease response will be...progressive disease , and one elected to pursue standard of care therapy only. Three participants, BV01, BV04 and BV06, completed vaccinations. Two patients

Seasonal vaccination against malaria: a potential use for an imperfect malaria vaccine.

PubMed

Greenwood, Brian; Dicko, Alassane; Sagara, Issaka; Zongo, Issaka; Tinto, Halidou; Cairns, Matthew; Kuepfer, Irene; Milligan, Paul; Ouedraogo, Jean-Bosco; Doumbo, Ogobara; Chandramohan, Daniel

2017-05-02

In many parts of the African Sahel and sub-Sahel, where malaria remains a major cause of mortality and morbidity, transmission of the infection is highly seasonal. Seasonal malaria chemoprevention (SMC), which involves administration of a full course of malaria treatment to young children at monthly intervals during the high transmission season, is proving to be an effective malaria control measure in these areas. However, SMC does not provide complete protection and it is demanding to deliver for both families and healthcare givers. Furthermore, there is a risk of the emergence in the future of resistance to the drugs, sulfadoxine-pyrimethamine and amodiaquine, that are currently being used for SMC. Substantial progress has been made in the development of malaria vaccines during the past decade and one malaria vaccine, RTS,S/AS01, has received a positive opinion from the European Medicines Authority and will soon be deployed in large-scale, pilot implementation projects in sub-Saharan Africa. A characteristic feature of this vaccine, and potentially of some of the other malaria vaccines under development, is that they provide a high level of efficacy during the period immediately after vaccination, but that this wanes rapidly, perhaps because it is difficult to develop effective immunological memory to malaria antigens in subjects exposed previously to malaria infection. A potentially effective way of using malaria vaccines with high initial efficacy but which provide only a short period of protection could be annual, mass vaccination campaigns shortly before each malaria transmission season in areas where malaria transmission is confined largely to a few months of the year.

Progress toward implementation of human papillomavirus vaccination--the Americas, 2006-2010.

PubMed

2011-10-14

Cervical cancer is a major cause of morbidity and mortality in the Americas, where an estimated 80,574 new cases and 36,058 deaths were reported in 2008, with 85% of this burden occurring in Latin America and the Caribbean. Two oncogenic human papillomavirus (HPV) types (16 and 18) cause approximately 70% of cervical cancers and a substantial proportion of other HPV-related cancers. HPV vaccination provides an opportunity to greatly reduce cervical cancer burden through primary prevention of HPV infection. This report summarizes the progress toward HPV vaccine introduction in the Americas, focusing on countries that have introduced the vaccine in national or regional immunization programs. As of January 2011, four countries in the Americas had introduced HPV vaccine. Overcoming issues related to financing and delivery of HPV vaccine remains a key public health challenge to more widespread implementation of HPV vaccination in the Americas.

Human-animal chimeras for vaccine development: an endangered species or opportunity for the developing world?

PubMed Central

2010-01-01

Background In recent years, the field of vaccines for diseases such as Human Immunodeficiency Virus (HIV) which take a heavy toll in developing countries has faced major failures. This has led to a call for more basic science research, and development as well as evaluation of new vaccine candidates. Human-animal chimeras, developed with a 'humanized' immune system could be useful to study infectious diseases, including many neglected diseases. These would also serve as an important tool for the efficient testing of new vaccine candidates to streamline promising candidates for further trials in humans. However, developing human-animal chimeras has proved to be controversial. Discussion Development of human-animal chimeras for vaccine development has been slowed down because of opposition by some philosophers, ethicists and policy makers in the west-they question the moral status of such animals, and also express discomfort about transgression of species barriers. Such opposition often uses a contemporary western world view as a reference point. Human-animal chimeras are often being created for diseases which cause significantly higher morbidity and mortality in the developing world as compared to the developed world. We argue in our commentary that given this high disease burden, we should look at socio-cultural perspectives on human-animal chimera like beings in the developing world. On examination, it's clear that such beings have been part of mythology and cultural descriptions in many countries in the developing world. Summary To ensure that important research on diseases afflicting millions like malaria, HIV, Hepatitis-C and dengue continues to progress, we recommend supporting human-animal chimera research for vaccine development in developing countries (especially China and India which have growing technical expertise in the area). The negative perceptions in some parts of the west about human-animal chimeras can be used as an opportunity for nurturing important vaccine development research in the developing world. PMID:20482820

Current therapeutic vaccination and immunotherapy strategies for HPV-related diseases.

PubMed

Skeate, Joseph G; Woodham, Andrew W; Einstein, Mark H; Da Silva, Diane M; Kast, W Martin

2016-06-02

Carcinomas of the anogenital tract, in particular cervical cancer, remains one of the most common cancers in women, and represent the most frequent gynecological malignancies and the fourth leading cause of cancer death in women worldwide. Human papillomavirus (HPV)-induced lesions are immunologically distinct in that they express viral antigens, which are necessary to maintain the cancerous phenotype. The causal relationship between HPV infection and anogenital cancer has prompted substantial interest in the development of therapeutic vaccines against high-risk HPV types targeting the viral oncoproteins E6 and E7. This review will focus on the most recent clinical trials for immunotherapies for mucosal HPV-induced lesions as well as emerging therapeutic strategies that have been tested in pre-clinical models for HPV-induced diseases. Progress in peptide- and protein-based vaccines, DNA-based vaccines, viral/bacterial vector-based vaccines, immune checkpoint inhibition, immune response modifiers, and adoptive cell therapy for HPV will be discussed.

The vaccines consistency approach project: an EPAA initiative.

PubMed

De Mattia, F; Hendriksen, C; Buchheit, K H; Chapsal, J M; Halder, M; Lambrigts, D; Redhead, K; Rommel, E; Scharton-Kersten, T; Sesardic, T; Viviani, L; Ragan, I

2015-01-01

The consistency approach for release testing of established vaccines promotes the use of in vitro, analytical, non-animal based systems allowing the monitoring of quality parameters during the whole production process. By using highly sensitive non-animal methods, the consistency approach has the potential to improve the quality of testing and to foster the 3Rs (replacement, refinement and reduction of animal use) for quality control of established vaccines. This concept offers an alternative to the current quality control strategy which often requires large numbers of laboratory animals. In order to facilitate the introduction of the consistency approach for established human and veterinary vaccine quality control, the European Partnership for Alternatives to Animal Testing (EPAA) initiated a project, the "Vaccines Consistency Approach Project", aiming at developing and validating the consistency approach with stakeholders from academia, regulators, OMCLs, EDQM, European Commission and industry. This report summarises progress since the project's inception.

Evolving T-cell vaccine strategies for HIV, the virus with a thousand faces

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

Korber, Bette

HIV's rapid global spread and the human suffering it has left in its wake have made AIDS a global heath priority for the 25 years since its discovery. Yet its capacity to rapidly evolve has made combating this virus a tremendous challenge. The obstacles to creating an effective HIV vaccine are formidable, but there are advances in the field on many fronts, in terms of novel vectors, adjuvants, and antigen design strategies. SIV live attenuated vaccine models are able to confer protection against heterologous challenge, and this continues to provide opportunities to explore the biological underpinnings of a protective effectmore » (9). More indirect, but equally important, is new understanding regarding the biology of acute infection (43), the role of immune response in long-term non-progression (6,62, 81), and defining characteristics of broadly neutralizing antibodies (4). In this review we will focus on summarizing strategies directed towards a single issue, that of contending with HIV variation in terms of designing aT-cell vaccine. The strategies that prove most effective in this area can ultimately be combined with the best strategies under development in other areas, with the hope of ultimately converging on a viable vaccine candidate. Only two large HIV vaccine efficacy trials have been completed and both have failed to prevent infection or confer a benefit to infected individual (23,34), but there is ample reason to continue our efforts. A historic breakthrough came in 1996, when it was realized that although the virus could escape from a single antiretroviral (ARV) therapy, it could be thwarted by a combination of medications that simultaneously targeted different parts of the virus (HAART) (38). This revelation came after 15 years of research, thought, and clinical testing; to enable that vital progress the research and clinical communities had to first define and understand, then develop a strategy to counter, the remarkable evolutionary potential of the virus. HAART, for the first time, provided an effective treatment to help those with living with HIV stay healthy. Nonetheless, the treatment has limitations. People with HIV face a lifetime of expensive daily multi-drug regimens, often with side effects; drug resistance at the individual and population level are issues (56); and universal access, despite substantial progress, is a dream not yet realized for many of the millions of the world's poor who are living with HIV (68). These issues, combined with the growing numbers of people infected globally and impact of HIV on society, make the development of an HIV vaccine or a prophylactic prevention strategy a crucial if elusive goal. In some ways, the history of HIV vaccine deVelopment has paralleled the early stages of designing effective therapy. We had to test the simple strategies first, but meanwhile the story of the impact of diversity from an immunological perspective is still unfolding, and novel ideas countermeasures are being explored.« less

Staphylococcus aureus-dependent septic arthritis in murine knee joints: local immune response and beneficial effects of vaccination

PubMed Central

Corrado, Alessia; Donato, Paolo; Maccari, Silvia; Cecchi, Raffaella; Spadafina, Tiziana; Arcidiacono, Letizia; Tavarini, Simona; Sammicheli, Chiara; Laera, Donatello; Manetti, Andrea Guido Oreste; Ruggiero, Paolo; Galletti, Bruno; Nuti, Sandra; De Gregorio, Ennio; Bertholet, Sylvie; Seubert, Anja; Bagnoli, Fabio; Bensi, Giuliano; Chiarot, Emiliano

2016-01-01

Staphylococcus aureus is the major cause of human septic arthritis and osteomyelitis, which deserve special attention due to their rapid evolution and resistance to treatment. The progression of the disease depends on both bacterial presence in situ and uncontrolled disruptive immune response, which is responsible for chronic disease. Articular and bone infections are often the result of blood bacteremia, with the knees and hips being the most frequently infected joints showing the worst clinical outcome. We report the development of a hematogenous model of septic arthritis in murine knees, which progresses from an acute to a chronic phase, similarly to what occurs in humans. Characterization of the local and systemic inflammatory and immune responses following bacterial infection brought to light specific signatures of disease. Immunization of mice with the vaccine formulation we have recently described (4C-Staph), induced a strong antibody response and specific CD4+ effector memory T cells, and resulted in reduced bacterial load in the knee joints, a milder general inflammatory state and protection against bacterial-mediated cellular toxicity. Possible correlates of protection are finally proposed, which might contribute to the development of an effective vaccine for human use. PMID:27901071

Mesoporous silica nanoparticles as antigen carriers and adjuvants for vaccine delivery

NASA Astrophysics Data System (ADS)

Mody, Karishma T.; Popat, Amirali; Mahony, Donna; Cavallaro, Antonino S.; Yu, Chengzhong; Mitter, Neena

2013-05-01

Vaccines have been at the forefront of improving human health for over two centuries. The challenges faced in developing effective vaccines flow from complexities associated with the immune system and requirement of an efficient and safe adjuvant to induce a strong adaptive immune response. Development of an efficient vaccine formulation requires careful selection of a potent antigen, efficient adjuvant and route of delivery. Adjuvants are immunological agents that activate the antigen presenting cells (APCs) and elicit a strong immune response. In the past decade, the use of mesoporous silica nanoparticles (MSNs) has gained significant attention as potential delivery vehicles for various biomolecules. In this review, we aim to highlight the potential of MSNs as vaccine delivery vehicles and their ability to act as adjuvants. We have provided an overview on the latest progress on synthesis, adsorption and release kinetics and biocompatibility of MSNs as next generation antigen carriers and adjuvants. A comprehensive summary on the ability of MSNs to deliver antigens and elicit both humoral and cellular immune responses is provided. Finally, we give insight on fundamental challenges and some future prospects of these nanoparticles as adjuvants.

VaxCelerate II: Rapid development of a self-assembling vaccine for Lassa fever

PubMed Central

Leblanc, Pierre; Moise, Leonard; Luza, Cybelle; Chantaralawan, Kanawat; Lezeau, Lynchy; Yuan, Jianping; Field, Mary; Richer, Daniel; Boyle, Christine; Martin, William D; Fishman, Jordan B; Berg, Eric A; Baker, David; Zeigler, Brandon; Mais, Dale E; Taylor, William; Coleman, Russell; Warren, H Shaw; Gelfand, Jeffrey A; De Groot, Anne S; Brauns, Timothy; Poznansky, Mark C

2014-01-01

Development of effective vaccines against emerging infectious diseases (EID) can take as much or more than a decade to progress from pathogen isolation/identification to clinical approval. As a result, conventional approaches fail to produce field-ready vaccines before the EID has spread extensively. Lassa is a prototypical emerging infectious disease endemic to West Africa for which no successful vaccine is available. We established the VaxCelerate Consortium to address the need for more rapid vaccine development by creating a platform capable of generating and pre-clinically testing a new vaccine against specific pathogen targets in less than 120 d. A self-assembling vaccine is at the core of the approach. It consists of a fusion protein composed of the immunostimulatory Mycobacterium tuberculosis heat shock protein 70 (MtbHSP70) and the biotin binding protein, avidin. Mixing the resulting protein (MAV) with biotinylated pathogen-specific immunogenic peptides yields a self-assembled vaccine (SAV). To meet the time constraint imposed on this project, we used a distributed R&D model involving experts in the fields of protein engineering and production, bioinformatics, peptide synthesis/design and GMP/GLP manufacturing and testing standards. SAV immunogenicity was first tested using H1N1 influenza specific peptides and the entire VaxCelerate process was then tested in a mock live-fire exercise targeting Lassa fever virus. We demonstrated that the Lassa fever vaccine induced significantly increased class II peptide specific interferon-γ CD4+ T cell responses in HLA-DR3 transgenic mice compared to peptide or MAV alone controls. We thereby demonstrated that our SAV in combination with a distributed development model may facilitate accelerated regulatory review by using an identical design for each vaccine and by applying safety and efficacy assessment tools that are more relevant to human vaccine responses than current animal models. PMID:25483693

Marker vaccines and companion diagnostic tests for classical swine fever.

PubMed

Floegel-Niesmann, G

2003-01-01

For Classical Swine Fever (CSF) a subunit vaccine consisting of the E2 protein is commercially available. The discriminatory ELISAs detect antibodies against another viral protein, the E(rns). As CSF has already been eradicated from many countries the use of a marker vaccine in these regions can only be contemplated as emergency vaccination after a new introduction of virus. Therefore, a Large Scale Marker Vaccine Trial was financed by the EU Commission and organised by the EU Reference Laboratory for CSF in 1999. When tested under the conditions of emergency vaccination, e.g. challenge before full immunity had developed, it was shown, that most CSF challenge infections took a subclinical course with reduced virus shedding. Transplacental transmission in pregnant sows could not be prevented after an application of a single vaccine dose. The most serious deficiencies have been found in the discriminatory ELISAs. Both available tests have shown deficiencies in sensitivity and specificity compared to conventional CSF antibody ELISAs. At the time, when the trial was performed, no confirmatory test was available to verify the results of the discriminatory ELISAs. Currently two new developments of marker vaccines for CSF are in progress. A chimaeric vaccine is based on infectious clones of the conventional live vaccine (C-strain) where a gene is replaced with the corresponding gene of the closely related pestivirus Bovine Viral Diarrhoea (BVD) virus. Conversely, the E2 gene of a BVD virus can be replaced by the E2 of a virulent CSF virus. The other principle is the construction of a DNA vaccine, expressing the E2 gene after entering the host cell. Deletion mutants of the E2 gene have also been constructed and tested for their induction of immunity. Both new developments are based on the same discriminatory tests as mentioned previously and developments of other principles for discrimination are rare.

VaxCelerate II: rapid development of a self-assembling vaccine for Lassa fever.

PubMed

Leblanc, Pierre; Moise, Leonard; Luza, Cybelle; Chantaralawan, Kanawat; Lezeau, Lynchy; Yuan, Jianping; Field, Mary; Richer, Daniel; Boyle, Christine; Martin, William D; Fishman, Jordan B; Berg, Eric A; Baker, David; Zeigler, Brandon; Mais, Dale E; Taylor, William; Coleman, Russell; Warren, H Shaw; Gelfand, Jeffrey A; De Groot, Anne S; Brauns, Timothy; Poznansky, Mark C

2014-01-01

Development of effective vaccines against emerging infectious diseases (EID) can take as much or more than a decade to progress from pathogen isolation/identification to clinical approval. As a result, conventional approaches fail to produce field-ready vaccines before the EID has spread extensively. Lassa is a prototypical emerging infectious disease endemic to West Africa for which no successful vaccine is available. We established the VaxCelerate Consortium to address the need for more rapid vaccine development by creating a platform capable of generating and pre-clinically testing a new vaccine against specific pathogen targets in less than 120 d A self-assembling vaccine is at the core of the approach. It consists of a fusion protein composed of the immunostimulatory Mycobacterium tuberculosis heat shock protein 70 (MtbHSP70) and the biotin binding protein, avidin. Mixing the resulting protein (MAV) with biotinylated pathogen-specific immunogenic peptides yields a self-assembled vaccine (SAV). To meet the time constraint imposed on this project, we used a distributed R&D model involving experts in the fields of protein engineering and production, bioinformatics, peptide synthesis/design and GMP/GLP manufacturing and testing standards. SAV immunogenicity was first tested using H1N1 influenza specific peptides and the entire VaxCelerate process was then tested in a mock live-fire exercise targeting Lassa fever virus. We demonstrated that the Lassa fever vaccine induced significantly increased class II peptide specific interferon-γ CD4(+) T cell responses in HLA-DR3 transgenic mice compared to peptide or MAV alone controls. We thereby demonstrated that our SAV in combination with a distributed development model may facilitate accelerated regulatory review by using an identical design for each vaccine and by applying safety and efficacy assessment tools that are more relevant to human vaccine responses than current animal models.

Developing whole mycobacteria cell vaccines for tuberculosis: Workshop proceedings, Max Planck Institute for Infection Biology, Berlin, Germany, July 9, 2014.

PubMed

2015-06-12

On July 9, 2014, Aeras and the Max Planck Institute for Infection Biology convened a workshop entitled "Whole Mycobacteria Cell Vaccines for Tuberculosis" at the Max Planck Institute for Infection Biology on the grounds of the Charité Hospital in Berlin, Germany, close to the laboratory where, in 1882, Robert Koch first identified Mycobacterium tuberculosis (Mtb) as the pathogen responsible for tuberculosis (TB). The purpose of the meeting was to discuss progress in the development of TB vaccines based on whole mycobacteria cells. Live whole cell TB vaccines discussed at this meeting were derived from Mtb itself, from Bacille Calmette-Guérin (BCG), the only licensed vaccine against TB, which was genetically modified to reduce pathogenicity and increase immunogenicity, or from commensal non-tuberculous mycobacteria. Inactivated whole cell TB and non-tuberculous mycobacterial vaccines, intended as immunotherapy or as safer immunization alternatives for HIV+ individuals, also were discussed. Workshop participants agreed that TB vaccine development is significantly hampered by imperfect animal models, unknown immune correlates of protection and the absence of a human challenge model. Although a more effective TB vaccine is needed to replace or enhance the limited effectiveness of BCG in all age groups, members of the workshop concurred that an effective vaccine would have the greatest impact on TB control when administered to adolescents and adults, and that use of whole mycobacteria cells as TB vaccine candidates merits greater support, particularly given the limited understanding of the specific Mtb antigens necessary to generate an immune response capable of preventing Mtb infection and/or disease. Copyright © 2015. Published by Elsevier Ltd.. All rights reserved.

Recent advances in the development of vaccines for Ebola virus disease.

PubMed

Ohimain, Elijah Ige

2016-01-04

Ebola virus is one of the most dangerous microorganisms in the world causing hemorrhagic fevers in humans and non-human primates. Ebola virus (EBOV) is a zoonotic infection, which emerges and re-emerges in human populations. The 2014 outbreak was caused by the Zaire strain, which has a kill rate of up to 90%, though 40% was recorded in the current outbreak. The 2014 outbreak is larger than all 20 outbreaks that have occurred since 1976, when the virus was first discovered. It is the first time that the virus was sustained in urban centers and spread beyond Africa into Europe and USA. Thus far, over 22,000 cases have been reported with about 50% mortality in one year. There are currently no approved therapeutics and preventive vaccines against Ebola virus disease (EVD). Responding to the devastating effe1cts of the 2014 outbreak and the potential risk of global spread, has spurred research for the development of therapeutics and vaccines. This review is therefore aimed at presenting the progress of vaccine development. Results showed that conventional inactivated vaccines produced from EBOV by heat, formalin or gamma irradiation appear to be ineffective. However, novel vaccines production techniques have emerged leading to the production of candidate vaccines that have been demonstrated to be effective in preclinical trials using small animal and non-human primates (NHP) models. Some of the promising vaccines have undergone phase 1 clinical trials, which demonstrated their safety and immunogenicity. Many of the candidate vaccines are vector based such as Vesicular Stomatitis Virus (VSV), Rabies Virus (RABV), Adenovirus (Ad), Modified Vaccinia Ankara (MVA), Cytomegalovirus (CMV), human parainfluenza virus type 3 (HPIV3) and Venezuelan Equine Encephalitis Virus (VEEV). Other platforms include virus like particle (VLP), DNA and subunit vaccines. Copyright © 2015 Elsevier B.V. All rights reserved.

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.

Therapeutic Vaccination for HPV Induced Cervical Cancers

PubMed Central

Brinkman, Joeli A.; Hughes, Sarah H.; Stone, Pamela; Caffrey, Angela S.; Muderspach, Laila I.; Roman, Lynda D.; Weber, Jeffrey S.; Kast, W. Martin

2007-01-01

Cervical Cancer is the second leading cause of cancer–related deaths in women worldwide and is associated with Human Papillomavirus (HPV) infection, creating a unique opportunity to treat cervical cancer through anti-viral vaccination. Although a prophylactic vaccine may be available within a year, millions of women, already infected, will continue to suffer from HPV-related disease, emphasizing the need to develop therapeutic vaccination strategies. A majority of clinical trials examining therapeutic vaccination have shown limited efficacy due to examining patients with more advanced-stage cancer who tend to have decreased immune function. Current trends in clinical trials with therapeutic agents examine patients with pre-invasive lesions in order to prevent invasive cervical cancer. However, longer follow-up is necessary to correlate immune responses to lesion regression. Meanwhile, preclinical studies in this field include further exploration of peptide or protein vaccination, and the delivery of HPV antigens in DNA-based vaccines or in viral vectors. As long as pre-clinical studies continue to advance, the prospect of therapeutic vaccination to treat existing lesions seem good in the near future. Positive consequences of therapeutic vaccination would include less disfiguring treatment options and fewer instances of recurrent or progressive lesions leading to a reduction in cervical cancer incidence. PMID:17627067

Vaccine approaches conferring cross-protection against influenza viruses

PubMed Central

Vemula, Sai V.; Sayedahmed, Ekramy E; Sambhara, Suryaprakash; Mittal, Suresh K.

2018-01-01

Introduction Annual vaccination is one of the most efficient and cost-effective strategies to prevent and control influenza epidemics. Most of currently available influenza vaccines are strong inducer of antibody responses against viral surface proteins, hemagglutinin (HA) and neuraminidase (NA), but are poor inducers of cell-mediated immune responses against conserved internal proteins. Moreover, due to the high variability of viral surface proteins because of antigenic drift or antigenic shift, many of the currently licensed vaccines confer little or no protection against drift or shift variants. Areas covered Next generation influenza vaccines that can induce humoral immune responses to receptor-binding epitopes as well as broadly neutralizing conserved epitopes, and cell-mediated immune responses against highly conserved internal proteins would be effective against variant viruses as well as a novel pandemic influenza until circulating strain-specific vaccines become available. Here we discuss vaccine approaches that have potential to provide broad spectrum protection against influenza viruses. Expert opinion Based on current progress in defining cross-protective influenza immunity, it seems that the development of a universal influenza vaccine is feasible. It would revolutionize the strategy for influenza pandemic preparedness, and significantly impact the shelf-life and protection efficacy of seasonal influenza vaccines. PMID:28925296

Measles and rubella elimination in the WHO Region for Europe: progress and challenges.

PubMed

O'Connor, P; Jankovic, D; Muscat, M; Ben-Mamou, M; Reef, S; Papania, M; Singh, S; Kaloumenos, T; Butler, R; Datta, S

2017-08-01

Globally measles remains one of the leading causes of death among young children even though a safe and cost-effective vaccine is available. The World Health Organization (WHO) European Region has seen a decline in measles and rubella cases in recent years. The recent outbreaks have primarily affected adolescents and young adults with no vaccination or an incomplete vaccination history. Eliminating measles and rubella is one of the top immunization priorities of the European Region as outlined in the European Vaccine Action Plan 2015-2020. Following the 2010 decision by the Member States in the Region to initiate the process of verifying elimination, the European Regional Verification Commission for Measles and Rubella Elimination (RVC) was established in 2011. The RVC meets every year to evaluate the status of measles and rubella elimination in the Region based on documentation submitted by each country's National Verification Committees. The verification process was however modified in late 2014 to assess the elimination status at the individual country level instead of at regional level. The WHO European Region has made substantial progress towards measles and rubella elimination over the past 5 years. The RVC's conclusion in 2016 that 70% and 66% of the 53 Member States in the Region had interrupted the endemic transmission of measles and rubella, respectively, by 2015 is a testament to this progress. Nevertheless, where measles and rubella remain endemic, challenges in vaccination service delivery and disease surveillance will need to be addressed through focused technical assistance from WHO and development partners. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

[AIDS: "We will win"].

PubMed

Chabrier, H

1989-11-13

An international colloquium on AIDS held near Paris from October 26-28, 1989, unlike the World Conference on AIDS in Montreal the year before, was able to find reasons for optimism. Significant progress was reported in immunotherapy and in chemotherapy. Successful experiments in vaccinating monkeys against the AIDS virus were reported from the US, France, and Zaire. Time is needed to prove the efficacy of the vaccines because of the slow development in AIDS. A vaccine is being tested by Jonas Salk and collaborators in 75 seropositive volunteers who do not yet show full blown disease but who have very low levels of T4 lymphocytes. Plans are underway for a larger test on 500 seropositive patients at different stages of infection. According to Salk, the new chemical and logical approach toward AIDS will allow combinations of immunotherapy and chemotherapy to destroy the virus. R. Gallo of France listed as accomplishments of the past year a better understanding of the virus, improved case management techniques, increased ability to control Kaposi's sarcoma, considerable progress in the search for a vaccine, and detection of immune proteins that affect the virus. New biological markers permit establishment of correlations between cellular modifications and the progress of the disease as well as the precise effects of treatment. The new immune system drugs immuthiol and DDI are expected to reach the market soon. Patients very soon will be able to receive less toxic alternative treatments, which can be combined for greater efficacy once their toxic interactions are understood.

New Animal Model Could Boost Research on AIDS Drugs and Vaccines | Poster

Cancer.gov

By Frank Blanchard, Staff Writer, and Jeff Lifson, Guest Writer In a research milestone reported in the June 20 issue of the journal Science, scientists have developed a minimally modified version of HIV-1, the virus that causes AIDS in infected humans, that is capable of causing progressive infection and AIDS in monkeys. The advance should help create more authentic animal models of the disease and provide a potentially invaluable approach for faster and better preclinical evaluation of new drugs and vaccines.

A baiting system for the oral rabies vaccination of wild foxes and skunks.

PubMed

Johnston, D H; Voigt, D R

1982-01-01

A bait delivery system has been developed for red foxes and skunks in Ontario, Canada. A biomarker (Tetracycline HCl) is incorporated into a meatball in a plastic bag. Deposits of tetracycline in teeth are detected microscopically with ultra-violet illumination of undecalcified sections. Baits were dropped from aircraft at the rate of 35 per km2 and accepted by 70% of foxes and 60% of skunks in the test area. Trials of various strains of inactivated vaccines are in progress.

The Role of Rearranged Neu Genes in the Progression of Rat Mammary Tumors Induced by N-nitroso N’-methylurea.

DTIC Science & Technology

1997-08-01

anti-neu antibody response of DNA vaccine immunized mice again by indirectly flowcytometry assay, we confirm our previous finding. We also examine the... flowcytometry assay, I have confirmed my previous finding from Elisa assay. 5 I also examined the cellular immunity response of DNA immunized mice by CTL...immunized mice by indirectly flowcytometry assay. I also find mice immunized with neu DNA vaccine did not develop detectable cytotoxic T lymphocyte

A pilot study of peptide vaccines for VEGF receptor 1 and 2 in patients with recurrent/progressive high grade glioma

PubMed Central

Shibao, Shunsuke; Ueda, Ryo; Saito, Katsuya; Kikuchi, Ryogo; Nagashima, Hideaki; Kojima, Atsuhiro; Kagami, Hiroshi; Pareira, Eriel Sandika; Sasaki, Hikaru; Noji, Shinobu; Kawakami, Yutaka; Yoshida, Kazunari; Toda, Masahiro

2018-01-01

Object Early-phase clinical studies of glioma vaccines have shown feasibility and encouraging preliminary clinical activity. A vaccine that targets tumor angiogenesis factors in glioma microenvironment has not been reported. Therefore, we performed a pilot study to evaluate the safety and immunogenicity of a novel vaccination targeting tumor angiogenesis with synthetic peptides for vascular endothelial growth factor (VEGF) receptor epitopes in patients with recurrent/progressive high grade gliomas. Methods Eight patients received intranodal vaccinations weekly at a dose of 2mg/kg bodyweight 8 times. T-lymphocyte responses against VEGF receptor (VEGFR) epitopes were assessed by enzyme linked immunosorbent spot assays. Results This treatment was well-tolerated in patients. The first four vaccines induced positive immune responses against at least one of the targeted VEGFR epitopes in the peripheral blood mononuclear cells in 87.5% of patients. The median overall survival time in all patients was 15.9 months. Two achieved progression-free status lasting at least 6 months. Two patients with recurrent GBM demonstrated stable disease. Plasma IL-8 level was negatively correlated with overall survival. Conclusion These data demonstrate the safety and immunogenicity of VEGFR peptide vaccines targeting tumor vasculatures in high grade gliomas. PMID:29765561

Current progress in the development of a prophylactic vaccine for HIV-1

PubMed Central

Gamble, Lena J; Matthews, Qiana L

2011-01-01

Since its discovery and characterization in the early 1980s as a virus that attacks the immune system, there has been some success for the treatment of human immunodeficiency virus-1 (HIV-1) infection. However, due to the overwhelming public health impact of this virus, a vaccine is needed urgently. Despite the tireless efforts of scientist and clinicians, there is still no safe and effective vaccine that provides sterilizing immunity. A vaccine that provides sterilizing immunity against HIV infection remains elusive in part due to the following reasons: 1) degree of diversity of the virus, 2) ability of the virus to evade the hosts’ immunity, and 3) lack of appropriate animal models in which to test vaccine candidates. There have been several attempts to stimulate the immune system to provide protection against HIV-infection. Here, we will discuss attempts that have been made to induce sterilizing immunity, including traditional vaccination attempts, induction of broadly neutralizing antibody production, DNA vaccines, and use of viral vectors. Some of these attempts show promise pending continued research efforts. PMID:21267356

Immunogenicity and Protection Efficacy of Subunit-based Smallpox Vaccines Using Variola Major Antigens

PubMed Central

Sakhatskyy, Pavlo; Wang, Shixia; Zhang, Chuanyou; Chou, Te-Hui; Kishko, Michael; Lu, Shan

2008-01-01

The viral strain responsible for smallpox infection is variola major (VARV). As a result of the successful eradication of smallpox with the vaccinia virus (VACV), the general population is no longer required to receive a smallpox vaccine, and will have no protection against smallpox. This lack of immunity is a concern due to the potential for use of smallpox as a biological weapon. Considerable progress has been made in the development of subunit-based smallpox vaccines resulting from the identification of VACV protective antigens. It also offers the possibility of using antigens from VARV to formulate the next generation subunit-based smallpox vaccines. Here, we show that codon-optimized DNA vaccines expressing three VARV antigens (A30, B7 and F8) and their recombinant protein counterparts elicited high-titer, cross-reactive, VACV neutralizing antibody responses in mice. Vaccinated mice were protected from intraperitoneal and intranasal challenges with VACV. These results suggest the feasibility of a subunit smallpox vaccine based on the VARV antigen sequences to induce immunity against poxvirus infection. PMID:17950773

[Innovations in vaccinology: challenge and opportunities for Africa].

PubMed

Diop, Doudou; Sanicas, Melvin

2017-01-01

Immunization is undoubtedly one of the most effective and most cost-effective health interventions. Vaccines continue to revolutionize our ability to prevent diseases and improve health. With all the technological advances, we are able to extend the benefits of vaccines to more people and to provide better protection from life-threatening infectious diseases. Nevertheless, thanks to the unceasing implementation of novel microbial strains on a worldwide basis, research in vaccinology must innovate continuously. African countries have made great progress in increasing routine immunization coverage rates and in introducing newly developed vaccines. New types of vaccines associated with vectorization, administration and specific licensing tools as well as with adjuvants designed to finely modulate immune responses are expected to be achieved in the near future. African countries need to work to develop a regional approach to respond effectively to the many challenges. Providing better information, implementing healthcare personnel vaccinology training programs and well targeted research projects are the keys to future achievements in the field.

Regulatory, biosafety and safety challenges for novel cells as substrates for human vaccines.

PubMed

Hess, Ralf D; Weber, Friedemann; Watson, Keith; Schmitt, Siegfried

2012-04-05

In the development of novel substrates used for production of human vaccines there has been significant progress made in recent years. Emerging and re-emerging infectious diseases like the recent porcine Influenza A virus (H1N1) pandemic necessitated the availability of unprecedented amounts of vaccines. In addition, the high demand for vaccines in the industrialised countries has also been paralleled by a steep increase in demand in developing countries. The manufacturing capability for viral vaccines produced in embryonated hen eggs and conventional/classical cell substrates, such as chicken embryo fibroblasts, has now reached its capacity limit. This constraint may be overcome by utilising other recognised cell substrates such as Madin Darby Canine Kidney (MDCK) (dog origin), Chinese Hamster Ovary (CHO) (hamster cells) or Vero cells (monkey origin) or as an alternative, introduce new cell substrates of human or avian origin. Using new cell substrates may prove to be a highly replication-proficient way of producing live viral vaccines such as Influenza A viruses. Despite some advantages, cell substrates may pose a small residual risk to humans since some of them are known to be tumourigenic in immunosuppressed animals. However, this residual risk should be considered acceptable by regulators. Safety testing requirements for cell substrates used in the manufacture of vaccines is mandated by published guidance from organisations such as World Health Organization (WHO), United States Food and Drug Administration (FDA), European Medicines Agency (EMA) and International Conferences on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human use (ICH) as well as requirements laid down in compendial monographs (Ph. Eur. and USP). This paper considers the guidance contained in these regulatory documents. In addition, the safety challenges and almost arbitrary risk-based classification of cell substrates used in the production of human vaccines together with compliance to GCCP (Good Cell Culture Practice) are discussed. Even though there has been tremendous progress in the last few years, reflected mainly by revisions and updates to regulatory guidance documents, there still is still no consensus between regulators nor significant harmonisation of the guidance documents or monographs. Copyright © 2012 Elsevier Ltd. All rights reserved.

A Randomized Phase II Study of Concurrent Docetaxel Plus Vaccine Versus Vaccine Alone in Metastatic Androgen Independent Prostate Cancer

PubMed Central

Arlen, Philip M.; Gulley, James L.; Parker, Catherine; Skarupa, Lisa; Pazdur, Mary; Panicali, Dennis; Beetham, Patricia; Tsang, Kwong Y.; Grosenbach, Douglas W.; Feldman, Jarett; Steinberg, Seth M.; Jones, Elizabeth; Chen, Clara; Marte, Jennifer; Schlom, Jeffrey; Dahut, William

2006-01-01

Purpose: Docetaxel has activity against androgen insensitive prostate cancer (AIPC) and preclinical studies have demonstrated that taxane-based chemotherapy can enhance antitumor response of vaccines. The primary objective of this study was to determine if concurrent docetaxel (with dexamethasone) had any effect on generating an immune response to the vaccine. Secondary endpoints were whether vaccine could be given safely with docetaxel and the clinical outcome of the treatment regimen. Experimental Design: The vaccination regimen was composed of (1) recombinant vaccinia virus (rV) that expresses the prostate-specific antigen gene (rV-PSA) admixed with (2) rV that expresses the B7.1 costimulatory gene (rV-B7.1), and (3) sequential booster vaccinations with recombinant fowlpox virus (rF-) containing the PSA gene (rF- PSA). Patients received GM-CSF with each vaccination. Twenty-eight patients with metastatic AIPC were randomized to receive either vaccine and weekly docetaxel or vaccine alone. Patients on the vaccine alone arm were allowed to cross over to receive docetaxel alone at time of disease progression. The ELISPOT assay was used to monitor immune responses for PSA-specific T cells. Results: The median increase in these T-cell precursors to PSA was 3.33-fold in both arms following 3 months of therapy. In addition, immune responses to other prostate cancer associated tumor antigens were also detected post-vaccination. Eleven patients who progressed on vaccine alone crossed over to receive docetaxel at time of progression. Median PFS on docetaxel was 6.1 months after receiving vaccine compared with 3.7 months with the same regimen in a historical control. Conclusion: This is the first clinical trial to demonstrate that docetaxel can be administered safely with immunotherapy without inhibiting vaccine specific T-cell responses. Furthermore, patients previously vaccinated with an anticancer vaccine may respond longer to docetaxel compared with a historical control of patients receiving docetaxel alone. Larger prospective clinical studies will be required to validate these findings. PMID:16489082

Antigenicity and Immunogenicity in HIV-1 Antibody-Based Vaccine Design

PubMed Central

Kong, Leopold; Sattentau, Quentin J

2012-01-01

Neutralizing antibodies can protect from infection by immunodeficiency viruses. However, the induction by active vaccination of antibodies that can potently neutralize a broad range of circulating virus strains is a goal not yet achieved, despite more than 2 decades of research. Here we review progress made in the field, from early empirical studies to today’s rational structure-based vaccine antigen design. We discuss the existence of broadly neutralizing antibodies, their implications for epitope discovery and recent progress made in antigen design. Finally, we consider the relationship between antigenicity and immunogenicity for B cell recognition and antibody production, a major hurdle for rational vaccine design to overcome. PMID:23227445

Serological Monitoring Is Key To Sustain Progress of the Maternal and Neonatal Tetanus Elimination Initiative.

PubMed

Levine, Myron M; Pasetti, Marcela F

2016-07-01

In this issue of Clinical and Vaccine Immunology, Scobie and colleagues (H. M. Scobie et al., Clin Vaccine Immunol 23:546-554, 2016, http://dx.doi.org/10.1128/CVI.00052-16) report a nationwide serosurvey of tetanus immunity in >2,000 Cambodian women of child-bearing age to monitor progress toward maternal and neonatal tetanus elimination. This commentary discusses vaccines as interventions for disease control, elimination, and eradication and emphasizes the importance of the tools needed to monitor the effectiveness of initiatives that deliver the vaccines programmatically. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Single-cycle replicable Rift Valley fever virus mutants as safe vaccine candidates.

PubMed

Terasaki, Kaori; Tercero, Breanna R; Makino, Shinji

2016-05-02

Rift Valley fever virus (RVFV) is an arbovirus circulating between ruminants and mosquitoes to maintain its enzootic cycle. Humans are infected with RVFV through mosquito bites or direct contact with materials of infected animals. The virus causes Rift Valley fever (RVF), which was first recognized in the Great Rift Valley of Kenya in 1931. RVF is characterized by a febrile illness resulting in a high rate of abortions in ruminants and an acute febrile illness, followed by fatal hemorrhagic fever and encephalitis in humans. Initially, the virus was restricted to the eastern region of Africa, but the disease has now spread to southern and western Africa, as well as outside of the African continent, e.g., Madagascar, Saudi Arabia and Yemen. There is a serious concern that the virus may spread to other areas, such as North America and Europe. As vaccination is an effective tool to control RVFV epidemics, formalin-inactivated vaccines and live-attenuated RVFV vaccines have been used in endemic areas. The formalin-inactivated vaccines require boosters for effective protection, whereas the live-attenuated vaccines enable the induction of protective immunity by a single vaccination. However, the use of live-attenuated RVFV vaccines for large human populations having a varied health status is of concern, because of these vaccines' residual neuro-invasiveness and neurovirulence. Recently, novel vaccine candidates have been developed using replication-defective RVFV that can undergo only a single round of replication in infected cells. The single-cycle replicable RVFV does not cause systemic infection in immunized hosts, but enables the conferring of protective immunity. This review summarizes the properties of various RVFV vaccines and recent progress on the development of the single-cycle replicable RVFV vaccines. Copyright © 2015 Elsevier B.V. All rights reserved.

Vaccines for preventing infection with Pseudomonas aeruginosa in cystic fibrosis.

PubMed

Johansen, Helle Krogh; Gøtzsche, Peter C

2015-08-23

Chronic pulmonary infection in cystic fibrosis results in progressive lung damage. Once colonisation of the lungs with Pseudomonas aeruginosa occurs, it is almost impossible to eradicate. Vaccines, aimed at reducing infection with Pseudomonas aeruginosa, have been developed. This is an update of a previously published review. To assess the effectiveness of vaccination against Pseudomonas aeruginosa in cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register using the terms vaccines AND pseudomonas (last search 30 March 2015). We previously searched PubMed using the terms vaccin* AND cystic fibrosis (last search 30 May 2013). Randomised trials (published or unpublished) comparing Pseudomonas aeruginosa vaccines (oral, parenteral or intranasal) with control vaccines or no intervention in cystic fibrosis. The authors independently selected trials, assessed them and extracted data. Six trials were identified. Two trials were excluded since they were not randomised and one old, small trial because it was not possible to assess whether is was randomised. The three included trials comprised 483, 476 and 37 patients, respectively. No data have been published from one of the large trials, but the company stated in a press release that the trial failed to confirm the results from an earlier study and that further clinical development was suspended. In the other large trial, relative risk for chronic infection was 0.91 (95% confidence interval 0.55 to 1.49), and in the small trial, the risk was also close to one. In the large trial, one patient was reported to have died in the observation period. In that trial, 227 adverse events (4 severe) were registered in the vaccine group and 91 (1 severe) in the control group. In this large trial of a vaccine developed against flagella antigens, antibody titres against the epitopes contained in the vaccine were higher in the vaccine group compared to the placebo group (P < 0.0001). Vaccines against Pseudomonas aeruginosa cannot be recommended.

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 market will be required.

Correlates of adjuvanticity: A review on adjuvants in licensed vaccines.

PubMed

Del Giudice, Giuseppe; Rappuoli, Rino; Didierlaurent, Arnaud M

2018-05-22

After decades of slow progress, the last years have seen a rapid acceleration of the development of adjuvanted vaccines which have lately been approved for human use. These adjuvants consist of different components, e.g. aluminium salts, emulsions such as MF59 and AS03, Toll-like receptor (TLR) agonists (CpG ormonophosphoryl lipid A (MPL) adsorbed on aluminium salts as in AS04) or combination of immunopotentiators (QS-21 and MPL in AS01). Despite their distinctive features, most of these adjuvants share some key characteristics. For example, they induce early activation (although at different levels) of innate immunity which then translates into higher antibody and cellular responses to the vaccine antigens. In addition, most of these adjuvants (e.g. MF59, AS03, AS04) clearly induce a wider breadth of adaptive responses able to confer protection against, for example, heterovariants of the influenza viruses (MF59, AS03) or against human papillomavirus strains not contained in the vaccine (AS04). Finally, the use of some of these adjuvants has contributed to significantly enhance the immune response and the efficacy and effectiveness of vaccines in the elderly who experience a waning of the immune responsiveness to infection and vaccination, as shown for MF59- or AS03-adjuvanted influenza vaccines and AS01-adjuvanted herpes zoster vaccine. These results, together with the track record of acceptable safety profiles of the adjuvanted vaccines, pave the way for the development of novel vaccines at the extremes of age and against infections with a high toll of morbidity and mortality. Here, we review the mechanisms associated with the performance of those adjuvanted vaccines in animal models and in humans through recent advances in systems vaccinology and biomarker discovery. We also provide some perspectives on remaining knowledge gaps but also on opportunities that could accelerate the development of new vaccines. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

[Influenza vaccination. Effectiveness of current vaccines and future challenges].

PubMed

Ortiz de Lejarazu, Raúl; Tamames, Sonia

2015-01-01

Seasonal influenza is an annual challenge for health-care systems, due to factors such as co-circulation of 2 influenza A subtypes jointly with 2 influenza B lineages; the antigenic drift of these virus, which eludes natural immunity, as well as immunity conferred by vaccination; together with influenza impact in terms of morbidity and mortality. Influenza vaccines have been available for more than 70 years and they have progressed in formulation, production and delivery route. Recommendations on vaccination are focused on those with a higher probability of severe disease, and have a progressively wider coverage, and classically based on inactivated vaccines, but with an increasing importance of attenuated live vaccines. More inactivated vaccines are becoming available, from adyuvanted and virosomal vaccines to intradermal delivery, cell-culture or quadrivalent. Overall vaccine effectiveness is about 65%, but varies depending on characteristics of vaccines, virus, population and the outcomes to be prevented, and ranges from less than 10% to almost 90%. Future challenges are formulations that confer more extensive and lasting protection, as well as increased vaccination coverage, especially in groups such as pregnant women and health-care professionals, as well as being extended to paediatrics. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

An update on vaccines for tuberculosis - there is more to it than just waning of BCG efficacy with time.

PubMed

Romano, Marta; Huygen, Kris

2012-12-01

Apart from better diagnostics and new anti-microbial drugs, an effective vaccine for tuberculosis is urgently needed to halt this poverty-related disease, afflicting millions of people worldwide. After a general introduction on the global threat of tuberculosis, the pros and cons of the existing M. bovis BCG vaccine are discussed. As the correlates of protection against tuberculosis remain largely unknown, new findings in biomarker research are described. Next, an update on the ongoing Phase I and Phase II clinical trials is given. Finally, some of the most promising novel pre-clinical developments using live attenuated vaccines, sub-unit vaccines, prime-boost strategies, and new vaccination routes are discussed. The field has made considerable progress and 12 vaccine candidates have now actually entered Phase I or Phase IIa and IIb clinical trials. It is argued that the variable protection conferred by the existing BCG vaccine against reactivation of latent TB is caused not only by waning of its efficacy with time but also by its weak induction of MHC class I restricted responses. Prime-boost strategies based on the actual BCG vaccine may not be sufficient to overcome this hurdle. The use of plasmid DNA vaccination might offer a solution.

Cost-effectiveness of novel vaccines for tuberculosis control: a decision analysis study

PubMed Central

2011-01-01

Background The development of a successful new tuberculosis (TB) vaccine would circumvent many limitations of current diagnostic and treatment practices. However, vaccine development is complex and costly. We aimed to assess the potential cost effectiveness of novel vaccines for TB control in a sub-Saharan African country - Zambia - relative to the existing strategy of directly observed treatment, short course (DOTS) and current level of bacille Calmette-Guérin (BCG) vaccination coverage. Methods We conducted a decision analysis model-based simulation from the societal perspective, with a 3% discount rate and all costs expressed in 2007 US dollars. Health outcomes and costs were projected over a 30-year period, for persons born in Zambia (population 11,478,000 in 2005) in year 1. Initial development costs for single vaccination and prime-boost strategies were prorated to the Zambian share (0.398%) of global BCG vaccine coverage for newborns. Main outcome measures were TB-related morbidity, mortality, and costs over a range of potential scenarios for vaccine efficacy. Results Relative to the status quo strategy, a BCG replacement vaccine administered at birth, with 70% efficacy in preventing rapid progression to TB disease after initial infection, is estimated to avert 932 TB cases and 422 TB-related deaths (prevention of 199 cases/100,000 vaccinated, and 90 deaths/100,000 vaccinated). This would result in estimated net savings of $3.6 million over 30 years for 468,073 Zambians born in year 1 of the simulation. The addition of a booster at age 10 results in estimated savings of $5.6 million compared to the status quo, averting 1,863 TB cases and 1,011 TB-related deaths (prevention of 398 cases/100,000 vaccinated, and of 216 deaths/100,000 vaccinated). With vaccination at birth alone, net savings would be realized within 1 year, whereas the prime-boost strategy would require an additional 5 years to realize savings, reflecting a greater initial development cost. Conclusions Investment in an improved TB vaccine is predicted to result in considerable cost savings, as well as a reduction in TB morbidity and TB-related mortality, when added to existing control strategies. For a vaccine with waning efficacy, a prime-boost strategy is more cost-effective in the long term. PMID:21269503

Structure and Computation in Immunoreagent Design: From Diagnostics to Vaccines.

PubMed

Gourlay, Louise; Peri, Claudio; Bolognesi, Martino; Colombo, Giorgio

2017-12-01

Novel immunological tools for efficient diagnosis and treatment of emerging infections are urgently required. Advances in the diagnostic and vaccine development fields are continuously progressing, with reverse vaccinology and structural vaccinology (SV) methods for antigen identification and structure-based antigen (re)design playing increasingly relevant roles. SV, in particular, is predicted to be the front-runner in the future development of diagnostics and vaccines targeting challenging diseases such as AIDS and cancer. We review state-of-the-art methodologies for structure-based epitope identification and antigen design, with specific applicative examples. We highlight the implications of such methods for the engineering of biomolecules with improved immunological properties, potential diagnostic and/or therapeutic uses, and discuss the perspectives of structure-based rational design for the production of advanced immunoreagents. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nanodelivery Systems as New Tools for Immunostimulant or Vaccine Administration: Targeting the Fish Immune System

PubMed Central

Ji, Jie; Torrealba, Debora; Ruyra, Àngels; Roher, Nerea

2015-01-01

Fish disease treatments have progressed significantly over the last few years and have moved from the massive use of antibiotics to the development of vaccines mainly based on inactivated bacteria. Today, the incorporation of immunostimulants and antigens into nanomaterials provide us with new tools to enhance the performance of immunostimulation. Nanoparticles are dispersions or solid particles designed with specific physical properties (size, surface charge, or loading capacity), which allow controlled delivery and therefore improved targeting and stimulation of the immune system. The use of these nanodelivery platforms in fish is in the initial steps of development. Here we review the advances in the application of nanoparticles to fish disease prevention including: the type of biomaterial, the type of immunostimulant or vaccine loaded into the nanoparticles, and how they target the fish immune system. PMID:26492276

Progress toward the Development of a NEAT Protein Vaccine for Anthrax Disease

PubMed Central

Balderas, Miriam A.; Nguyen, Chinh T. Q.; Terwilliger, Austen; Keitel, Wendy A.; Iniguez, Angelina; Torres, Rodrigo; Palacios, Frederico; Goulding, Celia W.

2016-01-01

Bacillus anthracis is a sporulating Gram-positive bacterium that is the causative agent of anthrax and a potential weapon of bioterrorism. The U.S.-licensed anthrax vaccine is made from an incompletely characterized culture supernatant of a nonencapsulated, toxigenic strain (anthrax vaccine absorbed [AVA]) whose primary protective component is thought to be protective antigen (PA). AVA is effective in protecting animals and elicits toxin-neutralizing antibodies in humans, but enthusiasm is dampened by its undefined composition, multishot regimen, recommended boosters, and potential for adverse reactions. Improving next-generation anthrax vaccines is important to safeguard citizens and the military. Here, we report that vaccination with recombinant forms of a conserved domain (near-iron transporter [NEAT]), common in Gram-positive pathogens, elicits protection in a murine model of B. anthracis infection. Protection was observed with both Freund's and alum adjuvants, given subcutaneously and intramuscularly, respectively, with a mixed composite of NEATs. Protection correlated with an antibody response against the NEAT domains and a decrease in the numbers of bacteria in major organs. Anti-NEAT antibodies promote opsonophagocytosis of bacilli by alveolar macrophages. To guide the development of inactive and safe NEAT antigens, we also report the crystal structure of one of the NEAT domains (Hal) and identify critical residues mediating its heme-binding and acquisition activity. These results indicate that we should consider NEAT proteins in the development of an improved antianthrax vaccine. PMID:27647868

Maternal and neonatal tetanus

PubMed Central

Thwaites, C Louise; Beeching, Nicholas J; Newton, Charles R

2017-01-01

Maternal and neonatal tetanus is still a substantial but preventable cause of mortality in many developing countries. Case fatality from these diseases remains high and treatment is limited by scarcity of resources and effective drug treatments. The Maternal and Neonatal Tetanus Elimination Initiative, launched by WHO and its partners, has made substantial progress in eliminating maternal and neonatal tetanus. Sustained emphasis on improvement of vaccination coverage, birth hygiene, and surveillance, with specific approaches in high-risk areas, has meant that the incidence of the disease continues to fall. Despite this progress, an estimated 58 000 neonates and an unknown number of mothers die every year from tetanus. As of June, 2014, 24 countries are still to eliminate the disease. Maintenance of elimination needs ongoing vaccination programmes and improved public health infrastructure. PMID:25149223

Oral vaccination: where we are?

PubMed

Silin, Dmytro S; Lyubomska, Oksana V; Jirathitikal, Vichai; Bourinbaiar, Aldar S

2007-07-01

As early as 900 years ago, the Bedouins of the Negev desert were reported to kill a rabid dog, roast its liver and feed it to a dog-bitten person for three to five days according to the size and number of bites [1] . In sixteenth century China, physicians routinely prescribed pills made from the fleas collected from sick cows, which purportedly prevented smallpox. One may dismiss the wisdom of the Bedouins or Chinese but the Nobel laureate, Charles Richet, demonstrated in 1900 that feeding raw meat can cure tuberculous dogs - an approach he termed zomotherapy. Despite historical clues indicating the feasibility of oral vaccination, this particular field is notoriously infamous for the abundance of dead-end leads. Today, most commercial vaccines are delivered by injection, which has the principal limitation that recipients do not like needles. In the last few years, there has been a sharp increase in interest in needle-free vaccine delivery; new data emerges almost daily in the literature. So far, there are very few licensed oral vaccines, but many more vaccine candidates are in development. Vaccines delivered orally have the potential to take immunization to a fundamentally new level. In this review, the authors summarize the recent progress in the area of oral vaccines.

Aspergillus vaccines: Hardly worth studying or worthy of hard study?

PubMed

Levitz, Stuart M

2017-01-01

Vaccines rank among the greatest advances in the history of public health. Yet, despite the need, there are no licensed vaccines to protect humans against fungal diseases, including aspergillosis. In this focused review, some of the major scientific and logistical challenges to developing vaccines to protect at-risk individuals against aspergillosis are discussed. Approaches that have shown promise in animal models include vaccines that protect against multiple fungal genera and those that are specifically directed to Aspergillus Advances in proteomics and glycomics have facilitated identification of candidate antigens for use in subunit vaccines. Novel adjuvants and delivery systems are becoming available that can skew vaccine responses toward those associated with protection. Immunotherapy consisting of adoptive transfer of Aspergillus-specific T cells to allogeneic hematopoietic transplant recipients has advanced to human testing but is technically difficult and of unproven benefit. While progress has been impressive, much work still needs to be done if vaccines against aspergillosis are to become a reality. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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.

A novel vaccine targeting Fusobacterium nucleatum against abscesses and halitosis

PubMed Central

Liu, Pei-Feng; Haake, Susan Kinder; Gallo, Richard L.; Huang, Chun-Ming

2011-01-01

An abscess in a gum pocket, resulting from bacterial infection, is a common source of chronic halitosis. Although antibiotics are generally prescribed for abscesses, they require multiple treatments with risks of creating resistant bacterial strains. Here we develop a novel vaccine using ultraviolet-inactivated Fusobacterium nucleatum (F. nucleatum), a representative oral bacterium for halitosis. A gum pocket model, established by continuous inoculation of F. nucleatum, was employed to validate the vaccine potency. Mice immunized with inactivated F. nucleatum effectively minimized the progression of abscesses, measured by swollen tissues of gum pockets. Most notably, the immunized mice were capable of eliciting neutralizing antibodies against the production of volatile sulfur compounds of F. nucleatum. The novel vaccine inducing protective immunity provides an alternative option to conventional antibiotic treatments for chronic halitosis associated with abscesses. PMID:19162109

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.

HPV16 synthetic long peptide (HPV16-SLP) vaccination therapy of patients with advanced or recurrent HPV16-induced gynecological carcinoma, a phase II trial.

PubMed

van Poelgeest, Mariette I E; Welters, Marij J P; van Esch, Edith M G; Stynenbosch, Linda F M; Kerpershoek, Gijs; van Persijn van Meerten, Els L; van den Hende, Muriel; Löwik, Margriet J G; Berends-van der Meer, Dorien M A; Fathers, Lorraine M; Valentijn, A Rob P M; Oostendorp, Jaap; Fleuren, Gert Jan; Melief, Cornelis J M; Kenter, Gemma G; van der Burg, Sjoerd H

2013-04-04

Human papilloma virus type 16 (HPV16)-induced gynecological cancers, in particular cervical cancers, are found in many women worldwide. The HPV16 encoded oncoproteins E6 and E7 are tumor-specific targets for the adaptive immune system permitting the development of an HPV16-synthetic long peptide (SLP) vaccine with an excellent treatment profile in animal models. Here, we determined the toxicity, safety, immunogenicity and efficacy of the HPV16 SLP vaccine in patients with advanced or recurrent HPV16-induced gynecological carcinoma. Patients with HPV16-positive advanced or recurrent gynecological carcinoma (n = 20) were subcutaneously vaccinated with an HPV16-SLP vaccine consisting of a mix of 13 HPV16 E6 and HPV16 E7 overlapping long peptides in Montanide ISA-51 adjuvant. The primary endpoints were safety, toxicity and tumor regression as determined by RECIST. In addition, the vaccine-induced T-cell response was assessed by proliferation and associated cytokine production as well as IFNγ-ELISPOT. No systemic toxicity beyond CTCAE grade II was observed. In a few patients transient flu-like symptoms were observed. In 9 out of 16 tested patients vaccine-induced HPV16-specific proliferative responses were detected which were associated with the production of IFNγ, TNFα, IL-5 and/or IL-10. ELISPOT analysis revealed a vaccine-induced immune response in 11 of the 13 tested patients. The capacity to respond to the vaccine was positively correlated to the patient's immune status as reflected by their response to common recall antigens at the start of the trial. Median survival was 12.6 ± 9.1 months. No regression of tumors was observed among the 12 evaluable patients. Nineteen patients died of progressive disease. The HPV16-SLP vaccine was well tolerated and induced a broad IFNγ-associated T-cell response in patients with advanced or recurrent HPV16-induced gynecological carcinoma but neither induced tumor regression nor prevented progressive disease. We, therefore, plan to use this vaccine in combination with chemotherapy and immunomodulation.

Modeling the public health impact of malaria vaccines for developers and policymakers

PubMed Central

2013-01-01

Background Efforts to develop malaria vaccines show promise. Mathematical model-based estimates of the potential demand, public health impact, and cost and financing requirements can be used to inform investment and adoption decisions by vaccine developers and policymakers on the use of malaria vaccines as complements to existing interventions. However, the complexity of such models may make their outputs inaccessible to non-modeling specialists. This paper describes a Malaria Vaccine Model (MVM) developed to address the specific needs of developers and policymakers, who need to access sophisticated modeling results and to test various scenarios in a user-friendly interface. The model’s functionality is demonstrated through a hypothetical vaccine. Methods The MVM has three modules: supply and demand forecast; public health impact; and implementation cost and financing requirements. These modules include pre-entered reference data and also allow for user-defined inputs. The model includes an integrated sensitivity analysis function. Model functionality was demonstrated by estimating the public health impact of a hypothetical pre-erythrocytic malaria vaccine with 85% efficacy against uncomplicated disease and a vaccine efficacy decay rate of four years, based on internationally-established targets. Demand for this hypothetical vaccine was estimated based on historical vaccine implementation rates for routine infant immunization in 40 African countries over a 10-year period. Assumed purchase price was $5 per dose and injection equipment and delivery costs were $0.40 per dose. Results The model projects the number of doses needed, uncomplicated and severe cases averted, deaths and disability-adjusted life years (DALYs) averted, and cost to avert each. In the demonstration scenario, based on a projected demand of 532 million doses, the MVM estimated that 150 million uncomplicated cases of malaria and 1.1 million deaths would be averted over 10 years. This is equivalent to 943 uncomplicated cases and 7 deaths averted per 1,000 vaccinees. In discounted 2011 US dollars, this represents $11 per uncomplicated case averted and $1,482 per death averted. If vaccine efficacy were reduced to 75%, the estimated uncomplicated cases and deaths averted over 10 years would decrease by 14% and 19%, respectively. Conclusions The MVM can provide valuable information to assist decision-making by vaccine developers and policymakers, information which will be refined and strengthened as field studies progress allowing further validation of modeling assumptions. PMID:23815273

Modeling the public health impact of malaria vaccines for developers and policymakers.

PubMed

Nunes, Julia K; Cárdenas, Vicky; Loucq, Christian; Maire, Nicolas; Smith, Thomas; Shaffer, Craig; Måseide, Kårstein; Brooks, Alan

2013-07-01

Efforts to develop malaria vaccines show promise. Mathematical model-based estimates of the potential demand, public health impact, and cost and financing requirements can be used to inform investment and adoption decisions by vaccine developers and policymakers on the use of malaria vaccines as complements to existing interventions. However, the complexity of such models may make their outputs inaccessible to non-modeling specialists. This paper describes a Malaria Vaccine Model (MVM) developed to address the specific needs of developers and policymakers, who need to access sophisticated modeling results and to test various scenarios in a user-friendly interface. The model's functionality is demonstrated through a hypothetical vaccine. The MVM has three modules: supply and demand forecast; public health impact; and implementation cost and financing requirements. These modules include pre-entered reference data and also allow for user-defined inputs. The model includes an integrated sensitivity analysis function. Model functionality was demonstrated by estimating the public health impact of a hypothetical pre-erythrocytic malaria vaccine with 85% efficacy against uncomplicated disease and a vaccine efficacy decay rate of four years, based on internationally-established targets. Demand for this hypothetical vaccine was estimated based on historical vaccine implementation rates for routine infant immunization in 40 African countries over a 10-year period. Assumed purchase price was $5 per dose and injection equipment and delivery costs were $0.40 per dose. The model projects the number of doses needed, uncomplicated and severe cases averted, deaths and disability-adjusted life years (DALYs) averted, and cost to avert each. In the demonstration scenario, based on a projected demand of 532 million doses, the MVM estimated that 150 million uncomplicated cases of malaria and 1.1 million deaths would be averted over 10 years. This is equivalent to 943 uncomplicated cases and 7 deaths averted per 1,000 vaccinees. In discounted 2011 US dollars, this represents $11 per uncomplicated case averted and $1,482 per death averted. If vaccine efficacy were reduced to 75%, the estimated uncomplicated cases and deaths averted over 10 years would decrease by 14% and 19%, respectively. The MVM can provide valuable information to assist decision-making by vaccine developers and policymakers, information which will be refined and strengthened as field studies progress allowing further validation of modeling assumptions.

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 outcomes of these efforts to establish an alternative framework for vaccine evaluation are a more robust vaccine pipeline, improved appreciation of vaccine value and hence of its relative affordability, and greater public access and acceptance of vaccines. Copyright © 2017.

Seasonal influenza vaccine dose distribution in 195 countries (2004-2013): Little progress in estimated global vaccination coverage.

PubMed

Palache, Abraham; Oriol-Mathieu, Valerie; Fino, Mireli; Xydia-Charmanta, Margarita

2015-10-13

Seasonal influenza is an important disease which results in 250,000-500,000 annual deaths worldwide. Global targets for vaccination coverage rates (VCRs) in high-risk groups are at least 75% in adults ≥65 years and increased coverage in other risk groups. The International Federation of Pharmaceutical Manufacturers and Associations Influenza Vaccine Supply (IFPMA IVS) International Task Force developed a survey methodology in 2008, to assess the global distribution of influenza vaccine doses as a proxy for VCRs. This paper updates the previous survey results on absolute numbers of influenza vaccine doses distributed between 2004 and 2013 inclusive, and dose distribution rates per 1000 population, and provides a qualitative assessment of the principal enablers and barriers to seasonal influenza vaccination. The two main findings from the quantitative portion of the survey are the continued negative trend for dose distribution in the EURO region and the perpetuation of appreciable differences in scale of dose distribution between WHO regions, with no observed convergence in the rates of doses distributed per 1000 population over time. The main findings from the qualitative portion of the survey were that actively managing the vaccination program in real-time and ensuring political commitment to vaccination are important enablers of vaccination, whereas insufficient access to vaccination and lack of political commitment to seasonal influenza vaccination programs are likely contributing to vaccination target failures. In all regions of the world, seasonal influenza vaccination is underutilized as a public health tool. The survey provides evidence of lost opportunity to protect populations against potentially serious influenza-associated disease. We call on the national and international public health communities to re-evaluate their political commitment to the prevention of the annual influenza disease burden and to develop a systematic approach to improve vaccine distribution equitably. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chlamydia vaccines: recent developments and the role of adjuvants in future formulations.

PubMed

Igietseme, Joseph U; Eko, Francis O; Black, Carolyn M

2011-11-01

Bacteria of the genus Chlamydia cause a plethora of ocular, genital and respiratory diseases that continue to pose a considerable public health challenge worldwide. The major diseases are conjunctivitis and blinding trachoma, non-gonococcal urethritis, cervicitis, pelvic inflammatory disease, ectopic pregnancy, tubal factor infertility and interstitial pneumonia. The rampart asymptomatic infections prevent timely and effective antibiotic treatments, and quite often clinical presentation of sequelae is the first evidence of an infection. Besides, significant broad coverage in population screening and treatment is economically and logistically impractical, and mass education for public awareness has been ineffective. The current medical opinion is that an efficacious prophylactic vaccine is the best approach to protect humans from chlamydial infections. Unfortunately, a human vaccine has yet to be realized despite successful veterinary vaccines. Fortunately, recent advances in chlamydial immunobiology, cell biology, molecular pathogenesis, genomics, antigen discovery and animal models of infections are hastening progress toward an efficacious vaccine. Thus, it is established that Chlamydia immunity is mediated by T cells and a complementary antibody response, and several potential vaccine candidates have been identified. However, further advances are needed in effective vaccine delivery systems and safe potent adjuvants to boost and sustain immune responses for long-lasting protective immunity. This article focuses on the current status of human chlamydial vaccine research, specifically how application of new delivery systems and human compatible adjuvants could lead to a timely achievement of efficacious Chlamydia vaccines. The ranking of the candidate vaccine antigens for human vaccine development will await the availability of results from studies in which the antigens are tested by comparable experimental standards, such as antigen-adjuvant combination, route of delivery and possible toxicity.

Single-cycle replicable Rift Valley fever virus mutants as safe vaccine candidates

PubMed Central

Terasaki, Kaori; Tercero, Breanna R.; Makino, Shinji

2015-01-01

Rift Valley fever virus (RVFV) is an arbovirus circulating between ruminants and mosquitoes to maintain its enzootic cycle. Humans are infected with RVFV through mosquito bites or direct contact with materials of infected animals. The virus causes Rift Valley fever, which was first recognized in the Great Rift Valley of Kenya in 1931. RVFV is characterized by a febrile illness resulting in a high rate of abortions in ruminants and an acute febrile illness, followed by fatal hemorrhagic fever and encephalitis in humans. Initially, the virus was restricted to the eastern region of Africa, but the disease has now spread to southern and western Africa, as well as outside of the African continent, e.g., Madagascar, Saudi Arabia and Yemen. There is a serious concern that the virus may spread to other areas, such as North America and Europe. As vaccination is an effective tool to control RVFV epidemics, formalin-inactivated vaccines and live-attenuated RVFV vaccines have been used in endemic areas. The formalin-inactivated vaccines require boosters for effective protection, whereas the live-attenuated vaccines enable the induction of protective immunity by a single vaccination. However, the use of live-attenuated RVFV vaccines for large human populations having a varied health status is of concern, because of these vaccines’ residual neuro-invasiveness and neurovirulence. Recently, novel vaccine candidates have been developed using replication-defective RVFV that can undergo only a single round of replication in infected cells. The single-cycle replicable RVFV does not cause systemic infection in immunized hosts, but enables the conferring of protective immunity. This review summarizes the properties of various RVFV vaccines and recent progress on the development of the single-cycle replicable RVFV vaccines. PMID:26022573

Afriflu2--second international workshop on influenza vaccination in the African continent--8 November 2012, Cape Town (South Africa).

PubMed

Schoub, Barry D; Gessner, Bradford D; Ampofo, William; Cohen, Adam L; Steffen, Christoph A

2013-08-02

The second meeting of the Afriflu conferences took place in Cape Town, South Africa, with over 60 participants from 15 countries in Africa and also outside the continent. Significant progress in surveillance has been made in better understanding the illness burden of influenza on the continent, which limited evidence suggests is greater than that in the developed world. In southern Africa HIV and TB coinfections play a major role in increasing hospitalisation and mortality, while elsewhere in Africa other cofactors still need to be determined. There is currently no indigenous vaccine production in sub-Saharan Africa and only one facility, based in South Africa, capable of filling imported bulk. Innovative vaccine strategies will need to be explored, such as maternal immunisation, and also the possibility of other influenza vaccine options, such as live attenuated influenza vaccine for young children. Sustained indigenous vaccine production is essential for the continent to have vaccine security in the event of a pandemic even though establishing local production faces considerable challenges especially ensuring adequate markets on the continent. There is an urgent need to develop effective communication messages for decision makers as well as healthcare workers addressing the importance of influenza even in the face of the major competing health burdens of the continent. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Cancer vaccines: the challenge of developing an ideal tumor killing system.

PubMed

Mocellin, Simone

2005-09-01

Despite the evidence that the immune system plays a significant role in controlling tumor growth in natural conditions and in response to therapeutic vaccination, cancer cells can survive their attack as the disease progresses and no vaccination regimen should be currently proposed to patients outside experimental clinical trials. Clinical results show that the immune system can be actively polarized against malignant cells by means of a variety of vaccination strategies, and that in some cases this is associated with tumor regression. This implies that under some unique circumstances, the naturally "dormant" immune effectors can actually be put at work and used as endogenous weapons against malignant cells. Consequently, the main challenge of tumor immunologists appears to lie on the ability of reproducing those conditions in a larger set of patients. The complexity of the immune network and the still enigmatic host-tumor interactions make these tasks at the same time challenging and fascinating. Recent tumor immunology findings are giving new impetus to the development of more effective vaccination strategies and might revolutionize the way of designing the next generation of cancer vaccines. In the near future, the implementation of these insights in the clinical setting and the completion/conduction of comparative randomized phase III trials will allow oncologists to define the actual role of cancer vaccines in the fight against malignancy.

Progress in the development of Fasciola hepatica vaccine using recombinant fatty acid binding protein with the adjuvant adaptation system ADAD.

PubMed

López-Abán, J; Casanueva, P; Nogal, J; Arias, M; Morrondo, P; Diez-Baños, P; Hillyer, G V; Martínez-Fernández, A R; Muro, A

2007-04-30

Fatty acid binding proteins (FABP) have been designed as a potential vaccine against fasciolosis. In this work, the immunoprophylaxis of the recombinant Fh15 FABP from F. hepatica (Fh15) in adjuvant/immunomodulator ADAD system was evaluated using mice and sheep challenged with F. hepatica. The ADAD system combines the Fh15 antigen with an immunomodulator (hydroalcoholic extract of Polypodium leucotomos; PAL) and/or an adjuvant (saponins of Quillaja saponaria; Qs) in a water/oil emulsion (30/70) with a non-mineral oil (Montanide). All the infected control mice died by 41-48 days post-infection. The mice vaccinated with ADAD only with PAL+Fh15 present a survival rate of 40-50% and those vaccinated with ADAD containing PAL+Qs+Fh15 had a survival rate of 50-62.5%. IgG1 antibodies were lower in surviving mice in comparison with non-surviving mice. The sheep vaccinated with ADAD PAL+Qs+Fh15 showed lower fluke recovery (43%), less hepatic lesions and higher post-infection daily weight gain than F. hepatica infected control animals. Thus, the ADAD system using recombinant fatty acid binding proteins from F. hepatica could be a good option to develop vaccines against F. hepatica.

Immune systems in developed and developing countries; implications for the design of vaccines that will work where BCG does not.

PubMed

Rook, Graham A W; Dheda, Keertan; Zumla, Alimuddin

2006-01-01

New vaccine candidates for tuberculosis are beginning to enter clinical trials. In this review we discuss issues surrounding the design of these candidates, and the way they were screened in animal models. First, screening vaccines for their ability to attenuate inevitably fatal tuberculosis in immunologically naïve mice might be leading to the selection of inappropriate candidates. We need to screen vaccines for their ability to stop the development of progressive disease, since this is what they must achieve in man. A solution to this problem is proposed. Secondly, we point out that some mouse models of tuberculosis in laboratories in developing countries, where exposure to environmental mycobacteria is large, mimic neglected aspects of human disease more closely than do low-dose infections in hyper-susceptible immunologically naïve mice in the USA or Europe. We need to think more about geographical differences in immunological experience, and these mouse models can help us. Thirdly, we conclude that in developing countries where BCG fails this is not because there is too little Th1 response, but rather because the Th1 response is rendered ineffective and immunopathological by other subversive mechanisms, including IL-4 responses and inappropriate regulatory T cell function. Therefore, we suggest that vaccines that will work in those countries might need to have immunoregulatory properties that can switch off pre-existing subversive mechanisms, and block their development in the future. The development of such vaccines, that might work where BCG does not, will require a greater understanding of the roles of the many types of regulatory T cell in tuberculosis.

Blood Interferon Signatures Putatively Link Lack of Protection Conferred by the RTS,S Recombinant Malaria Vaccine to an Antigen-specific IgE Response

PubMed Central

Rinchai, Darawan; Presnell, Scott; Vidal, Marta; Dutta, Sheetij; Chauhan, Virander; Cavanagh, David; Moncunill, Gemma; Dobaño, Carlota; Chaussabel, Damien

2017-01-01

Malaria remains a major cause of mortality and morbidity worldwide. Progress has been made in recent years with the development of vaccines that could pave the way towards protection of hundreds of millions of exposed individuals. Here we used a modular repertoire approach to re-analyze a publically available microarray blood transcriptome dataset monitoring the response to malaria vaccination. We report the seminal identification of interferon signatures in the blood of subjects on days 1, 3 and 14 following administration of the third dose of the RTS,S recombinant malaria vaccine. These signatures at day 1 correlate with protection, and at days 3 and 14 to susceptibility to subsequent challenge of study subjects with live parasites. In addition we putatively link the decreased abundance of interferon-inducible transcripts observed at days 3 and 14 post-vaccination with the elicitation of an antigen-specific IgE response in a subset of vaccine recipients that failed to be protected by the RTS,S vaccine. Furthermore, profiling of antigen-specific levels of IgE in a Mozambican cohort of malaria-exposed children vaccinated with RTS,S identified an association between elevated baseline IgE levels and subsequent development of naturally acquired malaria infection during follow up. Taken together these findings warrant further investigation of the role of antigen-specific IgE in conferring susceptibility to malaria infection. PMID:28883910

Vaccinating women previously exposed to human papillomavirus: a cost-effectiveness analysis of the bivalent vaccine.

PubMed

Turner, Hugo C; Baussano, Iacopo; Garnett, Geoff P

2013-01-01

Recent trials have indicated that women with prior exposure to Human papillomavirus (HPV) subtypes 16/18 receive protection against reinfection from the HPV vaccines. However, many of the original models investigating the cost effectiveness of different vaccination strategies for the protection of cervical cancer assumed, based on the trial results at that time, that these women received no protection. We developed a deterministic, dynamic transmission model that incorporates the vaccine-induced protection of women with prior exposure to HPV. The model was used to estimate the cost effectiveness of progressively extending a vaccination programme using the bivalent vaccine to older age groups both with and without protection of women with prior exposure. We did this under a range of assumptions on the level of natural immunity. Our modelling projections indicate that including the protection of women with prior HPV exposure can have a profound effect on the cost effectiveness of vaccinating adults. The impact of this protection is inversely related to the level of natural immunity. Our results indicate that adult vaccination strategies should potentially be reassessed, and that it is important to include the protection of non-naive women previously infected with HPV in future studies. Furthermore, they also highlight the need for a more thorough investigation of this protection.

Epidemiology of HPV 16 and Cervical Cancer in Finland and the Potential Impact of Vaccination: Mathematical Modelling Analyses

PubMed Central

Barnabas, Ruanne V; Laukkanen, Päivi; Koskela, Pentti; Kontula, Osmo; Lehtinen, Matti; Garnett, Geoff P

2006-01-01

Background Candidate human papillomavirus (HPV) vaccines have demonstrated almost 90%-100% efficacy in preventing persistent, type-specific HPV infection over 18 mo in clinical trials. If these vaccines go on to demonstrate prevention of precancerous lesions in phase III clinical trials, they will be licensed for public use in the near future. How these vaccines will be used in countries with national cervical cancer screening programmes is an important question. Methods and Findings We developed a transmission model of HPV 16 infection and progression to cervical cancer and calibrated it to Finnish HPV 16 seroprevalence over time. The model was used to estimate the transmission probability of the virus, to look at the effect of changes in patterns of sexual behaviour and smoking on age-specific trends in cancer incidence, and to explore the impact of HPV 16 vaccination. We estimated a high per-partnership transmission probability of HPV 16, of 0.6. The modelling analyses showed that changes in sexual behaviour and smoking accounted, in part, for the increase seen in cervical cancer incidence in 35- to 39-y-old women from 1990 to 1999. At both low (10% in opportunistic immunisation) and high (90% in a national immunisation programme) coverage of the adolescent population, vaccinating women and men had little benefit over vaccinating women alone. We estimate that vaccinating 90% of young women before sexual debut has the potential to decrease HPV type-specific (e.g., type 16) cervical cancer incidence by 91%. If older women are more likely to have persistent infections and progress to cancer, then vaccination with a duration of protection of less than 15 y could result in an older susceptible cohort and no decrease in cancer incidence. While vaccination has the potential to significantly reduce type-specific cancer incidence, its combination with screening further improves cancer prevention. Conclusions HPV vaccination has the potential to significantly decrease HPV type-specific cervical cancer incidence. High vaccine coverage of women alone, sustained over many decades, with a long duration of vaccine-conferred protection, would have the greatest impact on type-specific cancer incidence. This level of coverage could be achieved through national coordinated programmes, with surveillance to detect cancers caused by nonvaccine oncogenic HPV types. PMID:16573364

Therapeutic cancer vaccines: are we there yet?

PubMed Central

Klebanoff, Christopher A.; Acquavella, Nicholas; Yu, Zhiya; Restifo, Nicholas P.

2011-01-01

Summary Enthusiasm for therapeutic cancer vaccines has been rejuvenated with the recent completion of several large, randomized phase III clinical trials that in some cases have reported an improvement in progression free or overall survival. However, an honest appraisal of their efficacy reveals modest clinical benefit and a frequent requirement for patients with relatively indolent cancers and minimal or no measurable disease. Experience with adoptive cell transfer-based immunotherapies unequivocally establishes that T cells can mediate durable complete responses, even in the setting of advanced metastatic disease. Further, these findings reveal that the successful vaccines of the future must confront (i) a corrupted tumor microenvironment containing regulatory T cells and aberrantly matured myeloid cells, (ii) a tumor-specific T-cell repertoire that is prone to immunologic exhaustion and senescence, and (iii) highly mutable tumor targets capable of antigen loss and immune evasion. Future progress may come from innovations in the development of selective preparative regimens that eliminate or neutralize suppressive cellular populations, more effective immunologic adjuvants, and further refinement of agents capable of antagonizing immune check-point blockade pathways. PMID:21198663

Deconstructing the Antiviral Neutralizing-Antibody Response: Implications for Vaccine Development and Immunity

PubMed Central

VanBlargan, Laura A.

2016-01-01

SUMMARY The antibody response plays a key role in protection against viral infections. While antiviral antibodies may reduce the viral burden via several mechanisms, the ability to directly inhibit (neutralize) infection of cells has been extensively studied. Eliciting a neutralizing-antibody response is a goal of many vaccine development programs and commonly correlates with protection from disease. Considerable insights into the mechanisms of neutralization have been gained from studies of monoclonal antibodies, yet the individual contributions and dynamics of the repertoire of circulating antibody specificities elicited by infection and vaccination are poorly understood on the functional and molecular levels. Neutralizing antibodies with the most protective functionalities may be a rare component of a polyclonal, pathogen-specific antibody response, further complicating efforts to identify the elements of a protective immune response. This review discusses advances in deconstructing polyclonal antibody responses to flavivirus infection or vaccination. Our discussions draw comparisons to HIV-1, a virus with a distinct structure and replication cycle for which the antibody response has been extensively investigated. Progress toward deconstructing and understanding the components of polyclonal antibody responses identifies new targets and challenges for vaccination strategies. PMID:27784796

Novel immunotherapy vaccine development.

PubMed

Jutel, Marek; Akdis, Cezmi A

2014-12-01

Allergen-specific immunotherapy is the only curative treatment for allergic diseases. In spite of the great progress in both vaccine development and the methods of allergen immunotherapy (AIT) in recent years, several key problems related to limited efficacy, side-effects, low patient adherence and the relatively high costs due to the long duration (3-5 years) remain to be solved. The current approaches aiming at optimization of AIT are reviewed, including both conceptual studies in experimental models and proof-of-concept - as well as large, multicenter clinical studies. The most promising approaches to improve efficacy and safety of vaccine-based AIT include bypassing IgE binding and targeting allergen-specific T cells using hypoallergenic recombinant allergen derivatives and immunogenic peptides, the use of new adjuvants and stimulators of the innate immune response, the fusion of allergens to immune modifiers and peptide carrier proteins and new routes of vaccine administration. The cloning of allergen proteins and genetic engineering enabled the production of vaccines that have well defined molecular, immunologic and biologic characteristics as well as modified molecular structure. These new compounds along with new immunization protocols can bring us closer to the ultimate goal of AIT, that is, complete cure of a large number of allergic patients.

An overview of travel-associated central nervous system infectious diseases: risk assessment, general considerations and future directions.

PubMed

Izadi, Morteza; Is'haqi, Arman; Is'haqi, Mohammad Ali; Jonaidi Jafari, Nematollah; Rahamaty, Fatemeh; Banki, Abdolali

2014-08-01

Nervous system infections are among the most important diseases in travellers. Healthy travellers might be exposed to infectious agents of central nervous system, which may require in-patient care. Progressive course is not uncommon in this family of disorders and requires swift diagnosis. An overview of the available evidence in the field is, therefore, urgent to pave the way to increase the awareness of travel-medicine practitioners and highlights dark areas for future research. In November 2013, data were collected from PubMed, Scopus, and Web of Knowledge (1980 to 2013) including books, reviews, and peer-reviewed literature. Works pertained to pre-travel care, interventions, vaccinations related neurological infections were retrieved. Here we provide information on pre-travel care, vaccination, chronic nervous system disorders, and post-travel complications. Recommendations with regard to knowledge gaps, and state-of-the-art research are made. Given an increasing number of international travellers, novel dynamic ways are available for physicians to monitor spread of central nervous system infections. Newer research has made great progresses in developing newer medications, detecting the spread of infections and the public awareness. Despite an ongoing scientific discussion in the field of travel medicine, further research is required for vaccine development, state-of-the-art laboratory tests, and genetic engineering of vectors.

[Towards a new vaccine economy?].

PubMed

Poirot, P; Martin, J F

1994-01-01

When Jonas Salk announced in the mid-50s the availability of a new vaccine against poliomyelitis, the world had the impression that it was now controlling infectious diseases. In fact, the success of this vaccine has been considerable and although some innovations lead to the launch of vaccines against flu, measles, rubella or mumps, the world vaccine market remained remarkably stable till the mid-80s. However, since 1984 (launch of the hepatitis B vaccine) there have been very substantial changes and further change is expected in the next ten years in the world market. Today, big companies are making a concentrated supply: Pasteur Mérieux with its subsidiary Connaught, SmithKline Beecham who acquired the Belgian company RIT, and Merck & Co. who is joining its forces with Pasteur Mérieux. Medium sized and small companies remain and reflect the situation of the past, but must work hard to secure their long term existence eventhough the world demand is going to double before the year 2000. Very substantial technological innovations explain to a large extent the development of the supply: progress in molecular biology, and particularly genetic engineering, lead to recombinant vaccines of which hepatitis B is the best example with worldwide sales in the range of $600 million a year. Similarly, conjugation technologies have allowed the development of new vaccines against meningitis, particularly Haemophilus influenzae type b. More recently, an efficacious vaccine against hepatitis A has been launched and many new products will be marketed in the next years against herpes, Lyme disease, and agents of other meningitis, etc.(ABSTRACT TRUNCATED AT 250 WORDS)

Plant-based oral vaccines against zoonotic and non-zoonotic diseases.

PubMed

Shahid, Naila; Daniell, Henry

2016-11-01

The shared diseases between animals and humans are known as zoonotic diseases and spread infectious diseases among humans. Zoonotic diseases are not only a major burden to livestock industry but also threaten humans accounting for >60% cases of human illness. About 75% of emerging infectious diseases in humans have been reported to originate from zoonotic pathogens. Because antibiotics are frequently used to protect livestock from bacterial diseases, the development of antibiotic-resistant strains of epidemic and zoonotic pathogens is now a major concern. Live attenuated and killed vaccines are the only option to control these infectious diseases and this approach has been used since 1890. However, major problems with this approach include high cost and injectable vaccines is impractical for >20 billion poultry animals or fish in aquaculture. Plants offer an attractive and affordable platform for vaccines against animal diseases because of their low cost, and they are free of attenuated pathogens and cold chain requirement. Therefore, several plant-based vaccines against human and animals diseases have been developed recently that undergo clinical and regulatory approval. Plant-based vaccines serve as ideal booster vaccines that could eliminate multiple boosters of attenuated bacteria or viruses, but requirement of injectable priming with adjuvant is a current limitation. So, new approaches like oral vaccines are needed to overcome this challenge. In this review, we discuss the progress made in plant-based vaccines against zoonotic or other animal diseases and future challenges in advancing this field. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Controlling Dengue with Vaccines in Thailand

PubMed Central

Chao, Dennis L.; Halstead, Scott B.; Halloran, M. Elizabeth; Longini, Ira M.

2012-01-01

Background Dengue is a mosquito-borne infectious disease that constitutes a growing global threat with the habitat expansion of its vectors Aedes aegyti and A. albopictus and increasing urbanization. With no effective treatment and limited success of vector control, dengue vaccines constitute the best control measure for the foreseeable future. With four interacting dengue serotypes, the development of an effective vaccine has been a challenge. Several dengue vaccine candidates are currently being tested in clinical trials. Before the widespread introduction of a new dengue vaccine, one needs to consider how best to use limited supplies of vaccine given the complex dengue transmission dynamics and the immunological interaction among the four dengue serotypes. Methodology/Principal Findings We developed an individual-level (including both humans and mosquitoes), stochastic simulation model for dengue transmission and control in a semi-rural area in Thailand. We calibrated the model to dengue serotype-specific infection, illness and hospitalization data from Thailand. Our simulations show that a realistic roll-out plan, starting with young children then covering progressively older individuals in following seasons, could reduce local transmission of dengue to low levels. Simulations indicate that this strategy could avert about 7,700 uncomplicated dengue fever cases and 220 dengue hospitalizations per 100,000 people at risk over a ten-year period. Conclusions/Significance Vaccination will have an important role in controlling dengue. According to our modeling results, children should be prioritized to receive vaccine, but adults will also need to be vaccinated if one wants to reduce community-wide dengue transmission to low levels. PMID:23145197

Ebola Virus Vaccines – reality or fiction?

PubMed Central

Mire, Chad E.; Geisbert, Thomas W.; Feldmann, Heinz

2016-01-01

For 40 years ebolaviruses have been responsible for sporadic outbreaks of severe and often fatal hemorrhagic fever in humans and nonhuman primates. In December 2013 an unprecedented Zaire ebolavirus epidemic began in West Africa. Although “patient zero” has finally been reached after 2 years, the virus is again causing disease in the region. Currently there are no licensed vaccines or therapeutic countermeasures against ebolaviruses; however, the epidemic in West Africa has focused attention on the potential vaccine platforms developed over the past 15 years. There has been remarkable progress using a variety of platforms including DNA, subunit, and several viral vector approaches, replicating and non-replicating, which have shown varying degrees of protective efficacy in the “gold-standard” nonhuman primate models for Ebolavirus infections. A number of these vaccine platforms have moved into clinical trials over the past year with the hope of finding an efficacious vaccine to prevent future outbreaks/epidemics of Ebola hemorrhagic fever on the scale of the West African epidemic. PMID:27078187

Progress in Vaccine-Preventable and Respiratory Infectious Diseases-First 10 Years of the CDC National Center for Immunization and Respiratory Diseases, 2006-2015.

PubMed

Schuchat, Anne; Anderson, Larry J; Rodewald, Lance E; Cox, Nancy J; Hajjeh, Rana; Pallansch, Mark A; Messonnier, Nancy E; Jernigan, Daniel B; Wharton, Melinda

2018-07-01

The need for closer linkages between scientific and programmatic areas focused on addressing vaccine-preventable and acute respiratory infections led to establishment of the National Center for Immunization and Respiratory Diseases (NCIRD) at the Centers for Disease Control and Prevention. During its first 10 years (2006-2015), NCIRD worked with partners to improve preparedness and response to pandemic influenza and other emergent respiratory infections, provide an evidence base for addition of 7 newly recommended vaccines, and modernize vaccine distribution. Clinical tools were developed for improved conversations with parents, which helped sustain childhood immunization as a social norm. Coverage increased for vaccines to protect adolescents against pertussis, meningococcal meningitis, and human papillomavirus-associated cancers. NCIRD programs supported outbreak response for new respiratory pathogens and oversaw response of the Centers for Disease Control and Prevention to the 2009 influenza A(H1N1) pandemic. Other national public health institutes might also find closer linkages between epidemiology, laboratory, and immunization programs useful.

Current therapeutic vaccination and immunotherapy strategies for HPV-related diseases

PubMed Central

Skeate, Joseph G.; Woodham, Andrew W.; Einstein, Mark H.; Da Silva, Diane M.; Kast, W. Martin

2016-01-01

ABSTRACT Carcinomas of the anogenital tract, in particular cervical cancer, remains one of the most common cancers in women, and represent the most frequent gynecological malignancies and the fourth leading cause of cancer death in women worldwide. Human papillomavirus (HPV)-induced lesions are immunologically distinct in that they express viral antigens, which are necessary to maintain the cancerous phenotype. The causal relationship between HPV infection and anogenital cancer has prompted substantial interest in the development of therapeutic vaccines against high-risk HPV types targeting the viral oncoproteins E6 and E7. This review will focus on the most recent clinical trials for immunotherapies for mucosal HPV-induced lesions as well as emerging therapeutic strategies that have been tested in pre-clinical models for HPV-induced diseases. Progress in peptide- and protein-based vaccines, DNA-based vaccines, viral/bacterial vector-based vaccines, immune checkpoint inhibition, immune response modifiers, and adoptive cell therapy for HPV will be discussed. PMID:26835746

Prospects for immunisation against Marburg and Ebola viruses.

PubMed

Geisbert, Thomas W; Bausch, Daniel G; Feldmann, Heinz

2010-11-01

For more than 30 years the filoviruses, Marburg virus and Ebola virus, have been associated with periodic outbreaks of hemorrhagic fever that produce severe and often fatal disease. The filoviruses are endemic primarily in resource-poor regions in Central Africa and are also potential agents of bioterrorism. Although no vaccines or antiviral drugs for Marburg or Ebola are currently available, remarkable progress has been made over the last decade in developing candidate preventive vaccines against filoviruses in nonhuman primate models. Due to the generally remote locations of filovirus outbreaks, a single-injection vaccine is desirable. Among the prospective vaccines that have shown efficacy in nonhuman primate models of filoviral hemorrhagic fever, two candidates, one based on a replication-defective adenovirus serotype 5 and the other on a recombinant VSV (rVSV), were shown to provide complete protection to nonhuman primates when administered as a single injection. The rVSV-based vaccine has also shown utility when administered for postexposure prophylaxis against filovirus infections. A VSV-based Ebola vaccine was recently used to manage a potential laboratory exposure. 2010 John Wiley & Sons, Ltd.

Influenza vaccines based on virus-like particles

PubMed Central

Kang, Sang-Moo; Song, Jae-Min; Quan, Fu-Shi; Compans, Richard W.

2009-01-01

The simultaneous expression of structural proteins of virus can produce virus-like particles (VLPs) by a self-assembly process in a viral life cycle even in the absence of genomic material. Taking an advantage of structural and morphological similarities of VLPs to native virions, VLPs have been suggested as a promising platform for new viral vaccines. In the light of a pandemic threat, influenza VLPs have been recently developed as a new generation of non-egg based cell culture-derived vaccine candidates against influenza infection. Animals vaccinated with VLPs containing hemagglutinin (HA) or HA and neuraminidase (NA) were protected from morbidity and mortality resulting from lethal influenza infections. Influenza VLPs serve as an excellent model system of an enveloped virus for understanding the properties of VLPs in inducing protective immunity. In this review, we briefly describe the characteristics of influenza VLPs assembled with a lipid bilayer containing glycoproteins, and summarize the current progress on influenza VLPs as an alternative vaccine candidate against seasonal as well as pandemic influenza viruses. In addition, the protective immune correlates induced by vaccination with influenza VLPs are discussed. PMID:19374929

Candidiasis: a fungal infection--current challenges and progress in prevention and treatment.

PubMed

Hani, Umme; Shivakumar, Hosakote G; Vaghela, Rudra; Osmani, Riyaz Ali M; Shrivastava, Atul

2015-01-01

Despite therapeutic advances candidiasis remains a common fungal infection most frequently caused by C. albicans and may occur as vulvovaginal candidiasis or thrush, a mucocutaneous candidiasis. Candidiasis frequently occurs in newborns, in immune-deficient people like AIDS patients, and in people being treated with broad spectrum antibiotics. It is mainly due to C. albicans while other species such as C. tropicalis, C. glabrata, C. parapsilosis and C. krusei are increasingly isolated. OTC antifungal dosage forms such as creams and gels can be used for effective treatment of local candidiasis. Whereas, for preventing spread of the disease to deeper vital organs, candidiasis antifungal chemotherapy is preferred. Use of probiotics and development of novel vaccines is an advanced approach for the prevention of candidiasis. Present review summarizes the diagnosis, current status and challenges in the treatment and prevention of candidiasis with prime focus on host defense against candidiasis, advancements in diagnosis, probiotics role and recent progress in the development of vaccines against candidiasis.

Expression of beta defensin 2 in experimental pulmonary tuberculosis: tentative approach for vaccine development.

PubMed

Rivas-Santiago, Bruno; Cervantes-Villagrana, Alberto; Sada, Eduardo; Hernández-Pando, Rogelio

2012-05-01

Defensins are low molecular weight antimicrobial and immunomodulatory peptides. Their participation against Mycobacterium tuberculosis (MTb) infection has been scarcely studied. We describe the kinetics of murine β-defensin 2 (mBD-2) expression by quantitative real-time PCR and cellular location by immunohistochemistry in murine models of progressive pulmonary tuberculosis and latent infection. During progressive disease, mBD2 gene expression raised its peak at 14 days postinfection, whereas in latent infection it was at 90 days. In both models, mBD-2 immunostaining was essentially located in cells with dendritic morphology located near mediastinal lymph nodes, which correlated with the previous reported highest expression of cell-mediated protected immunity in both models. These results suggest that mBD-2 may play a role in the control of bacilli growth by contributing to establish a Th1 response, being a link between innate and adaptative immunity. These data may be used for the development of new vaccine approaches. Copyright © 2012 IMSS. Published by Elsevier Inc. All rights reserved.

MEFA (multiepitope fusion antigen)-Novel Technology for Structural Vaccinology, Proof from Computational and Empirical Immunogenicity Characterization of an Enterotoxigenic Escherichia coli (ETEC) Adhesin MEFA

PubMed Central

Duan, Qiangde; Lee, Kuo Hao; Nandre, Rahul M; Garcia, Carolina; Chen, Jianhan; Zhang, Weiping

2017-01-01

Vaccine development often encounters the challenge of virulence heterogeneity. Enterotoxigenic Escherichia coli (ETEC) bacteria producing immunologically heterogeneous virulence factors are a leading cause of children’s diarrhea and travelers’ diarrhea. Currently, we do not have licensed vaccines against ETEC bacteria. While conventional methods continue to make progress but encounter challenge, new computational and structure-based approaches are explored to accelerate ETEC vaccine development. In this study, we applied a structural vaccinology concept to construct a structure-based multiepitope fusion antigen (MEFA) to carry representing epitopes of the seven most important ETEC adhesins [CFA/I, CFA/II (CS1–CS3), CFA/IV (CS4–CS6)], simulated antigenic structure of the CFA/I/II/IV MEFA with computational atomistic modeling and simulation, characterized immunogenicity in mouse immunization, and examined the potential of structure-informed vaccine design for ETEC vaccine development. A tag-less recombinant MEFA protein (CFA/I/II/IV MEFA) was effectively expressed and extracted. Molecular dynamics simulations indicated that this MEFA immunogen maintained a stable secondary structure and presented epitopes on the protein surface. Empirical data showed that mice immunized with the tagless CFA/I/II/IV MEFA developed strong antigen-specific antibody responses, and mouse serum antibodies significantly inhibited in vitro adherence of bacteria expressing these seven adhesins. These results revealed congruence of antigen immunogenicity between computational simulation and empirical mouse immunization and indicated this tag-less CFA/I/II/IV MEFA potentially an antigen for a broadly protective ETEC vaccine, suggesting a potential application of MEFA-based structural vaccinology for vaccine design against ETEC and likely other pathogens. PMID:28944092

Lessons in AIDS Vaccine Development Learned from Studies of Equine Infectious, Anemia Virus Infection and Immunity

PubMed Central

Craigo, Jodi K.; Montelaro, Ronald C.

2013-01-01

Equine infectious anemia (EIA), identified in 1843 [1] as an infectious disease of horses and as a viral infection in 1904, remains a concern in veterinary medicine today. Equine infectious anemia virus (EIAV) has served as an animal model of HIV-1/AIDS research since the original identification of HIV. Similar to other lentiviruses, EIAV has a high propensity for genomic sequence and antigenic variation, principally in its envelope (Env) proteins. However, EIAV possesses a unique and dynamic disease presentation that has facilitated comprehensive analyses of the interactions between the evolving virus population, progressive host immune responses, and the definition of viral and host correlates of immune control and vaccine efficacy. Summarized here are key findings in EIAV that have provided important lessons toward understanding long term immune control of lentivirus infections and the parameters for development of an enduring broadly protective AIDS vaccine. PMID:24316675

Progress and future opportunities in the development of vaccines against atherosclerosis.

PubMed

Govea-Alonso, Dania O; Beltrán-López, Josué; Salazar-González, Jorge A; Vargas-Morales, Juan; Rosales-Mendoza, Sergio

2017-04-01

Atherosclerosis represents a serious global health problem that demands new therapeutic and prophylactic interventions. Considering that atherosclerosis has autoimmune and inflammatory components, immunotherapy is a possible focus to treat this disease. Areas covered: Based on the analysis of the current biomedical literature, this review describes the status on the development of vaccines against atherosclerosis. Several targets have been identified including sequences of apolipoprotein B100 (ApoB100), cholesteryl ester transfer protein (CETP), heat shock proteins (HSP), extracellular matrix proteins, T cell receptor β chain variable region 31 (TRBV31), the major outer membrane protein (MOMP), and the outer membrane protein 5 (Pomp5) from Chlamydia pneumoniae. Humoral and cellular immunities to these targets have been associated with therapeutic effects in murine models and humans. The evaluation of some candidates in clinical trials is ongoing. Expert commentary: New research paths based on the use of next generation vaccine production platforms are envisioned.

Evaluation of a Novel Non-Penetrating Electrode for Use in DNA Vaccination

PubMed Central

Donate, Amy; Coppola, Domenico; Cruz, Yolmari; Heller, Richard

2011-01-01

Current progress in the development of vaccines has decreased the incidence of fatal and non-fatal infections and increased longevity. However, new technologies need to be developed to combat an emerging generation of infectious diseases. DNA vaccination has been demonstrated to have great potential for use with a wide variety of diseases. Alone, this technology does not generate a significant immune response for vaccination, but combined with delivery by electroporation (EP), can enhance plasmid expression and immunity. Most EP systems, while effective, can be invasive and painful making them less desirable for use in vaccination. Our lab recently developed a non-invasive electrode known as the multi-electrode array (MEA), which lies flat on the surface of the skin without penetrating the tissue. In this study we evaluated the MEA for its use in DNA vaccination using Hepatitis B virus as the infectious model. We utilized the guinea pig model because their skin is similar in thickness and morphology to humans. The plasmid encoding Hepatitis B surface antigen (HBsAg) was delivered intradermally with the MEA to guinea pig skin. The results show increased protein expression resulting from plasmid delivery using the MEA as compared to injection alone. Within 48 hours of treatment, there was an influx of cellular infiltrate in experimental groups. Humoral responses were also increased significantly in both duration and intensity as compared to injection only groups. While this electrode requires further study, our results suggest that the MEA has potential for use in electrically mediated intradermal DNA vaccination. PMID:21559474

Recent progress in GM-CSF-based cancer immunotherapy.

PubMed

Yan, Wan-Lun; Shen, Kuan-Yin; Tien, Chun-Yuan; Chen, Yu-An; Liu, Shih-Jen

2017-03-01

Cancer immunotherapy is a growing field. GM-CSF, a potent cytokine promoting the differentiation of myeloid cells, can also be used as an immunostimulatory adjuvant to elicit antitumor immunity. Additionally, GM-CSF is essential for the differentiation of dendritic cells, which are responsible for processing and presenting tumor antigens for the priming of antitumor cytotoxic T lymphocytes. Some strategies have been developed for GM-CSF-based cancer immunotherapy in clinical practice: GM-CSF monotherapy, GM-CSF-secreting cancer cell vaccines, GM-CSF-fused tumor-associated antigen protein-based vaccines, GM-CSF-based DNA vaccines and GM-CSF combination therapy. GM-CSF also contributes to the regulation of immunosuppression in the tumor microenvironment. This review provides recommendations regarding GM-CSF-based cancer immunotherapy.

Treatment of Chlamydia-associated ocular disease via a recombinant protein based vaccine in the koala (Phascolarctos cinereus).

PubMed

Waugh, Courtney; Austin, Ray; Polkinghorne, Adam; Timms, Peter

2016-11-01

Koalas (Phascolarctos cinereus) are affected by debilitating chlamydial disease that can lead to blindness, infertility, and death. The causative agent is the intracellular bacterium Chlamydia pecorum. While antibiotics can be used to treat koala chlamydial infection, they are often ineffective or cause severe dysbiosis to the animal's unique gut flora. Recent work has progressed on the development of a protective vaccine for Chlamydia in the koala. This study demonstrates that the use of a vaccine can have a positive effect in koalas already with clinical signs of ocular disease, suggesting a possible therapeutic effect and an alternative to antibiotic therapy. Copyright © 2016 International Alliance for Biological Standardization. All rights reserved.

Potential future impact of a partially effective HIV vaccine in a southern African setting.

PubMed

Phillips, Andrew N; Cambiano, Valentina; Nakagawa, Fumiyo; Ford, Deborah; Lundgren, Jens D; Roset-Bahmanyar, Edith; Roman, François; Van Effelterre, Thierry

2014-01-01

It is important for public health and within the HIV vaccine development field to understand the potential population level impact of an HIV vaccine of partial efficacy--both in preventing infection and in reducing viral load in vaccinated individuals who become infected--in the context of a realistic future implementation scenario in resource limited settings. An individual level model of HIV transmission, progression and the effect of antiretroviral therapy was used to predict the outcome to 2060 of introduction in 2025 of a partially effective vaccine with various combinations of efficacy characteristics, in the context of continued ART roll-out in southern Africa. In the context of our base case epidemic (in 2015 HIV prevalence 28% and incidence 1.7 per 100 person years), a vaccine with only 30% preventative efficacy could make a substantial difference in the rate with which HIV incidence declines; the impact on incidence in relative terms is projected to increase over time, with a projected 67% lower HIV incidence in 2060 compared with no vaccine introduction. The projected mean decline in the general adult population death rate 2040-2060 is 11%. A vaccine with no prevention efficacy but which reduces viral load by 1 log is predicted to result in a modest (14%) reduction in HIV incidence and an 8% reduction in death rate in the general adult population (mean 2040-2060). These effects were broadly similar in multivariable uncertainty analysis. Introduction of a partially effective preventive HIV vaccine would make a substantial long-term impact on HIV epidemics in southern Africa, in addition to the effects of ART. Development of an HIV vaccine, even of relatively low apparent efficacy at the individual level, remains a critical global public health goal.

Vaccination against Salmonella Infection: the Mucosal Way.

PubMed

Gayet, Rémi; Bioley, Gilles; Rochereau, Nicolas; Paul, Stéphane; Corthésy, Blaise

2017-09-01

Salmonella enterica subspecies enterica includes several serovars infecting both humans and other animals and leading to typhoid fever or gastroenteritis. The high prevalence of associated morbidity and mortality, together with an increased emergence of multidrug-resistant strains, is a current global health issue that has prompted the development of vaccination strategies that confer protection against most serovars. Currently available systemic vaccine approaches have major limitations, including a reduced effectiveness in young children and a lack of cross-protection among different strains. Having studied host-pathogen interactions, microbiologists and immunologists argue in favor of topical gastrointestinal administration for improvement in vaccine efficacy. Here, recent advances in this field are summarized, including mechanisms of bacterial uptake at the intestinal epithelium, the assessment of protective host immunity, and improved animal models that closely mimic infection in humans. The pros and cons of existing vaccines are presented, along with recent progress made with novel formulations. Finally, new candidate antigens and their relevance in the refined design of anti- Salmonella vaccines are discussed, along with antigen vectorization strategies such as nanoparticles or secretory immunoglobulins, with a focus on potentiating mucosal vaccine efficacy. Copyright © 2017 American Society for Microbiology.

Highlights of the 8th International Conference on Vaccines for Enteric Diseases: the Scottish Encounter To Defeat Diarrheal Diseases

PubMed Central

Tennant, Sharon M.; Steele, A. Duncan

2016-01-01

Infectious diarrhea is a leading cause of morbidity and of mortality; the burden of disease affects individuals of all ages but particularly young children, especially those living in poor regions where the disease is endemic. It is also a health concern for international travelers to these areas. Experts on vaccines and enteric infections and advocates for global health improvement gathered in Scotland from 8 to 10 July 2015 to discuss recent advances in the assessment and understanding of the burden of enteric diseases and progress in the development and implementation of strategies to prevent these infections. Highlights of the meeting included description of advances in molecular assays to estimate pathogen-specific prevalence, methods to model epidemiologic trends, novel approaches to generate broad-spectrum vaccines, new initiatives to evaluate vaccine performance where they are most needed, renewed interest in human challenge models, immunological readouts as predictors of vaccine efficacy, maternal immunization to prevent enteric infections, and the impact of maternal immunity on the vaccine take of infants. A follow-up scientific gathering to advance Shigella and enterotoxigenic Escherichia coli (ETEC) vaccine efforts will be held from 28 to 30 June 2016 in Washington, DC. PMID:26936100

Gene therapy with autologous, interleukin 2-secreting tumor cells in patients with malignant melanoma.

PubMed

Palmer, K; Moore, J; Everard, M; Harris, J D; Rodgers, S; Rees, R C; Murray, A K; Mascari, R; Kirkwood, J; Riches, P G; Fisher, C; Thomas, J M; Harries, M; Johnston, S R; Collins, M K; Gore, M E

1999-05-20

We vaccinated metastatic melanoma patients with irradiated, autologous melanoma cells genetically engineered to secrete interleukin 2 (IL-2) to investigate whether an anti-tumor immune response would be induced. Melanoma cell cultures were established from surgical specimens and were engineered to secrete IL-2 by infection with recombinant retrovirus. Twelve patients were vaccinated subcutaneously one, two, or three times with approximately 10(7) irradiated, autologous, IL-2-secreting tumor cells. Treatment was well tolerated, with local reactions at 11 of 24 injection sites and minor systemic symptoms of fever and headache after 6 injections. One patient developed anti-tumor DTH after the first vaccination and showed an increased response after the second vaccination. Anti-autologous tumor CTLs could be detected prevaccination in the peripheral blood of seven patients and their activity increased after vaccination in four patients. No UICC-defined clinical responses were seen, but three patients had stable disease for 7-15 months, one of whom has not yet progressed (15+ months). Thus, patient vaccination with autologous, genetically engineered tumor cells is feasible and safe. Anti-tumor DTH and CTLs can be induced in some patients with such a vaccine.

Lessons from HIV-1 vaccine efficacy trials.

PubMed

Excler, Jean-Louis; Michael, Nelson L

2016-11-01

Only four HIV-1 vaccine concepts have been tested in six efficacy trials with no product licensed to date. Several scientific and programmatic lessons can be learned from these studies generating new hypotheses and guiding future steps. RV144 [ALVAC-HIV (canarypox vector) and AIDSVAX B/E (bivalent gp120 HIV-1 subtype B and CRF01_AE)] remains the only efficacy trial that demonstrated a modest vaccine efficacy, which led to the identification of immune correlates of risk. Progress on subtype-specific, ALVAC (canarypox vector) and gp120 vaccine prime-boost approaches has been slow, but we are finally close to the launch of an efficacy study in Africa in 2016. The quest of a globally effective HIV-1 vaccine has led to the development of new approaches. Efficacy studies of combinations of Adenovirus type 26 (Ad26)/Modified Vaccinia Ankara (MVA)/gp140 vaccines with mosaic designs will enter efficacy studies mid-2017 and cytomegalovirus (CMV)-vectored vaccines begin Phase I studies at the same time. Future HIV-1 vaccine efficacy trials face practical challenges as effective nonvaccine prevention programs are projected to decrease HIV-1 incidence. An HIV-1 vaccine is urgently needed. Increased industry involvement, mobilization of resources, expansion of a robust pipeline of new concepts, and robust preclinical challenge studies will be essential to accelerate efficacy testing of next generation HIV-1 vaccine candidates.

Vaccines to Accelerate Malaria Elimination and Eventual Eradication.

PubMed

Healer, Julie; Cowman, Alan F; Kaslow, David C; Birkett, Ashley J

2017-09-01

Remarkable progress has been made in coordinated malaria control efforts with substantial reductions in malaria-associated deaths and morbidity achieved through mass administration of drugs and vector control measures including distribution of long-lasting insecticide-impregnated bednets and indoor residual spraying. However, emerging resistance poses a significant threat to the sustainability of these interventions. In this light, the malaria research community has been charged with the development of a highly efficacious vaccine to complement existing malaria elimination measures. As the past 40 years of investment in this goal attests, this is no small feat. The malaria parasite is a highly complex organism, exquisitely adapted for survival under hostile conditions within human and mosquito hosts. Here we review current vaccine strategies to accelerate elimination and the potential for novel and innovative approaches to vaccine design through a better understanding of the host-parasite interaction. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

Control of viremia and maintenance of intestinal CD4+ memory T cells in SHIV162P3 infected macaques after pathogenic SIVMAC251 challenge

PubMed Central

Pahar, Bapi; Lackner, Andrew A.; Piatak, Michael; Lifson, Jeffrey D.; Wang, Xiaolei; Das, Arpita; Ling, Binhua; Montefiori, David C.; Veazey, Ronald S.

2009-01-01

Recent HIV vaccine failures have prompted calls for more preclinical vaccine testing in nonhuman primates. However, similar to HIV infection of humans, developing a vaccine that protects macaques from infection following pathogenic SIVMAC251 challenge has proven difficult, and current vaccine candidates at best, only reduce viral loads after infection. Here we demonstrate that prior infection with a chimeric simian-human immunodeficiency virus (SHIV) containing an HIV envelope gene confers protection against intravenous infection with the heterologous, highly pathogenic SIVMAC251 in rhesus macaques. Although definitive immune correlates of protection were not identified, preservation and/or restoration of intestinal CD4+ memory T cells were associated with protection from challenge and control of viremia. These results suggest that protection against pathogenic lentiviral infection or disease progression is indeed possible, and may correlate with preservation of mucosal CD4+ T cells. PMID:19298994

Current Progress in Developing Subunit Vaccines against Enterotoxigenic Escherichia coli-Associated Diarrhea

PubMed Central

Sack, David A.

2015-01-01

Diarrhea continues to be a leading cause of death in children <5 years of age, and enterotoxigenic Escherichia coli (ETEC) is the most common bacterial cause of children's diarrhea. Currently, there are no available vaccines against ETEC-associated diarrhea. Whole-cell vaccine candidates have been under development but require further improvements because they provide inadequate protection and produce unwanted adverse effects. Meanwhile, a newer approach using polypeptide or subunit vaccine candidates focusing on ETEC colonization factor antigens (CFAs) and enterotoxins, the major virulence determinants of ETEC diarrhea, shows substantial promise. A conservative CFA/I adhesin tip antigen and a CFA MEFA (multiepitope fusion antigen) were shown to induce cross-reactive antiadhesin antibodies that protected against adherence by multiple important CFAs. Genetic fusion of toxoids derived from ETEC heat-labile toxin (LT) and heat-stable toxin (STa) induced antibodies neutralizing both enterotoxins. Moreover, CFA-toxoid MEFA polypeptides, generated by fusing CFA MEFA to an STa-LT toxoid fusion, induced antiadhesin antibodies that broadly inhibited adherence of the seven most important ETEC CFAs associated with about 80% of the diarrhea cases caused by ETEC strains with known CFAs. This same antigen preparation also induced antitoxin antibodies that neutralized both toxins that are associated with all cases of ETEC diarrhea. Results from these studies suggest that polypeptide or subunit vaccines have the potential to effectively protect against ETEC diarrhea. In addition, novel adhesins and mucin proteases have been investigated as potential alternatives or, more likely, additional antigens for ETEC subunit vaccine development. PMID:26135975

Progress toward the Development of a NEAT Protein Vaccine for Anthrax Disease.

PubMed

Balderas, Miriam A; Nguyen, Chinh T Q; Terwilliger, Austen; Keitel, Wendy A; Iniguez, Angelina; Torres, Rodrigo; Palacios, Frederico; Goulding, Celia W; Maresso, Anthony W

2016-12-01

Bacillus anthracis is a sporulating Gram-positive bacterium that is the causative agent of anthrax and a potential weapon of bioterrorism. The U.S.-licensed anthrax vaccine is made from an incompletely characterized culture supernatant of a nonencapsulated, toxigenic strain (anthrax vaccine absorbed [AVA]) whose primary protective component is thought to be protective antigen (PA). AVA is effective in protecting animals and elicits toxin-neutralizing antibodies in humans, but enthusiasm is dampened by its undefined composition, multishot regimen, recommended boosters, and potential for adverse reactions. Improving next-generation anthrax vaccines is important to safeguard citizens and the military. Here, we report that vaccination with recombinant forms of a conserved domain (near-iron transporter [NEAT]), common in Gram-positive pathogens, elicits protection in a murine model of B. anthracis infection. Protection was observed with both Freund's and alum adjuvants, given subcutaneously and intramuscularly, respectively, with a mixed composite of NEATs. Protection correlated with an antibody response against the NEAT domains and a decrease in the numbers of bacteria in major organs. Anti-NEAT antibodies promote opsonophagocytosis of bacilli by alveolar macrophages. To guide the development of inactive and safe NEAT antigens, we also report the crystal structure of one of the NEAT domains (Hal) and identify critical residues mediating its heme-binding and acquisition activity. These results indicate that we should consider NEAT proteins in the development of an improved antianthrax vaccine. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Influence of residual moisture and sealing atmosphere on viability of two freeze-dried viral vaccines.

PubMed

Precausta, P M; Simatos, D; Le Pemp, M; Devaux, B; Kato, F

1980-10-01

This study demonstrated the complexity of the factors leading to changes in the infectivity titers of freeze-dried canine distemper and poultry infectious bronchitis viral vaccines. The change in moisture content during the storage period was an additional parameter which may influence the infectivity titer. The results emphasized the difficulty of predetermining variations in infectivity titers from the initial residual moisture. The analysis of the variations in infectivity titers during the storage of two vaccines led to the formulation of a hypothesis of the presence of two components of different thermostability. Moreover, the temporary increase in the infectivity titer of infectious bronchitis vaccine stored progressively dissociating during storage concurrent with a progressive inactivation of infectious particles.

Inactivated poliovirus type 2 vaccine delivered to rat skin via high density microprojection array elicits potent neutralising antibody responses.

PubMed

Muller, David A; Pearson, Frances E; Fernando, Germain J P; Agyei-Yeboah, Christiana; Owens, Nick S; Corrie, Simon R; Crichton, Michael L; Wei, Jonathan C J; Weldon, William C; Oberste, M Steven; Young, Paul R; Kendall, Mark A F

2016-02-25

Polio eradication is progressing rapidly, and the live attenuated Sabin strains in the oral poliovirus vaccine (OPV) are being removed sequentially, starting with type 2 in April 2016. For risk mitigation, countries are introducing inactivated poliovirus vaccine (IPV) into routine vaccination programs. After April 2016, monovalent type 2 OPV will be available for type 2 outbreak control. Because the current IPV is not suitable for house-to-house vaccination campaigns (the intramuscular injections require health professionals), we developed a high-density microprojection array, the Nanopatch, delivered monovalent type 2 IPV (IPV2) vaccine to the skin. To assess the immunogenicity of the Nanopatch, we performed a dose-matched study in rats, comparing the immunogenicity of IPV2 delivered by intramuscular injection or Nanopatch immunisation. A single dose of 0.2 D-antigen units of IPV2 elicited protective levels of poliovirus antibodies in 100% of animals. However, animals receiving IPV2 by IM required at least 3 immunisations to reach the same neutralising antibody titres. This level of dose reduction (1/40th of a full dose) is unprecedented for poliovirus vaccine delivery. The ease of administration coupled with the dose reduction observed in this study points to the Nanopatch as a potential tool for facilitating inexpensive IPV for mass vaccination campaigns.

Severe acute respiratory syndrome vaccine efficacy in ferrets: whole killed virus and adenovirus-vectored vaccines.

PubMed

See, Raymond H; Petric, Martin; Lawrence, David J; Mok, Catherine P Y; Rowe, Thomas; Zitzow, Lois A; Karunakaran, Karuna P; Voss, Thomas G; Brunham, Robert C; Gauldie, Jack; Finlay, B Brett; Roper, Rachel L

2008-09-01

Although the 2003 severe acute respiratory syndrome (SARS) outbreak was controlled, repeated transmission of SARS coronavirus (CoV) over several years makes the development of a SARS vaccine desirable. We performed a comparative evaluation of two SARS vaccines for their ability to protect against live SARS-CoV intranasal challenge in ferrets. Both the whole killed SARS-CoV vaccine (with and without alum) and adenovirus-based vectors encoding the nucleocapsid (N) and spike (S) protein induced neutralizing antibody responses and reduced viral replication and shedding in the upper respiratory tract and progression of virus to the lower respiratory tract. The vaccines also diminished haemorrhage in the thymus and reduced the severity and extent of pneumonia and damage to lung epithelium. However, despite high neutralizing antibody titres, protection was incomplete for all vaccine preparations and administration routes. Our data suggest that a combination of vaccine strategies may be required for effective protection from this pathogen. The ferret may be a good model for SARS-CoV infection because it is the only model that replicates the fever seen in human patients, as well as replicating other SARS disease features including infection by the respiratory route, clinical signs, viral replication in upper and lower respiratory tract and lung damage.

Vaccine-induced, simian immunodeficiency virus-specific CD8+ T cells reduce virus replication but do not protect from simian immunodeficiency virus disease progression.

PubMed

Engram, Jessica C; Dunham, Richard M; Makedonas, George; Vanderford, Thomas H; Sumpter, Beth; Klatt, Nichole R; Ratcliffe, Sarah J; Garg, Seema; Paiardini, Mirko; McQuoid, Monica; Altman, John D; Staprans, Silvija I; Betts, Michael R; Garber, David A; Feinberg, Mark B; Silvestri, Guido

2009-07-01

Our limited understanding of the interaction between primate lentiviruses and the host immune system complicates the design of an effective HIV/AIDS vaccine. To identify immunological correlates of protection from SIV disease progression, we immunized two groups of five rhesus macaques (RMs) with either modified vaccinia Ankara (MVA) or MVADeltaudg vectors that expressed SIVmac239 Gag and Tat. Both vectors raised a SIV-specific CD8(+) T cell response, with a magnitude that was greater in mucosal tissues than in peripheral blood. After challenge with SIVmac239, all vaccinated RMs showed mucosal and systemic CD8(+) T cell recall responses that appeared faster and were of greater magnitude than those in five unvaccinated control animals. All vaccinated RMs showed a approximately 1-log lower peak and early set-point SIV viral load than the unvaccinated animals, and then, by 8 wk postchallenge, exhibited levels of viremia similar to the controls. We observed a significant direct correlation between the magnitude of postchallenge SIV-specific CD8(+) T cell responses and SIV viral load. However, vaccinated RMs showed no protection from either systemic or mucosal CD4(+) T cell depletion and no improved survival. The observation that vaccine-induced, SIV-specific CD8(+) T cells that partially control SIVmac239 virus replication fail to protect from immunological or clinical progression of SIV infection underscores both the complexity of AIDS pathogenesis and the challenges of properly assessing the efficacy of candidate AIDS vaccines.

Teleosts Genomics: Progress and Prospects in Disease Prevention and Control.

PubMed

Munang'andu, Hetron Mweemba; Galindo-Villegas, Jorge; David, Lior

2018-04-04

Genome wide studies based on conventional molecular tools and upcoming omics technologies are beginning to gain functional applications in the control and prevention of diseases in teleosts fish. Herein, we provide insights into current progress and prospects in the use genomics studies for the control and prevention of fish diseases. Metagenomics has emerged to be an important tool used to identify emerging infectious diseases for the timely design of rational disease control strategies, determining microbial compositions in different aquatic environments used for fish farming and the use of host microbiota to monitor the health status of fish. Expounding the use of antimicrobial peptides (AMPs) as therapeutic agents against different pathogens as well as elucidating their role in tissue regeneration is another vital aspect of genomics studies that had taken precedent in recent years. In vaccine development, prospects made include the identification of highly immunogenic proteins for use in recombinant vaccine designs as well as identifying gene signatures that correlate with protective immunity for use as benchmarks in optimizing vaccine efficacy. Progress in quantitative trait loci (QTL) mapping is beginning to yield considerable success in identifying resistant traits against some of the highly infectious diseases that have previously ravaged the aquaculture industry. Altogether, the synopsis put forth shows that genomics studies are beginning to yield positive contribution in the prevention and control of fish diseases in aquaculture.

Progress in immunization information systems--United States, 2011.

PubMed

2013-01-25

Immunization information systems (IIS) are confidential, computerized, population-based systems that collect and consolidate vaccination data from vaccination providers and provide important tools for designing and sustaining effective immunization strategies. A Healthy People 2020 objective (IID-18) is to increase to 95% the proportion of children aged <6 years whose immunization records are in fully operational, population-based IIS. The National Vaccine Advisory Committee (NVAC) has published goals for IIS, including required and optional core data elements for which IIS should collect information. Two of the required core data elements are vaccine manufacturer and vaccine lot number. To monitor progress toward achieving these and other program goals, CDC annually surveys 56 immunization program grantees using the IIS Annual Report (IISAR). Results from the 2011 IISAR (completed by 54 grantees) indicate that 84% (19.2 million) of U.S. children aged <6 years participated in IIS, as defined by having at least two recorded vaccinations, an increase from 82% (18.8 million) in 2010. Grantees reported that an average of 63% of vaccination records for these children contained data in the field for vaccine manufacturer and 60% contained data in the field for lot number. A new project under way to capture vaccine product information, expiration date, and lot number on two-dimensional (2D) barcodes on vaccine vials might increase completeness, accuracy, and availability of these data elements in patient medical records and IIS, which in turn might enhance vaccine safety and support vaccine inventory management.

Progress Toward Regional Measles Elimination - Worldwide, 2000-2016.

PubMed

Dabbagh, Alya; Patel, Minal K; Dumolard, Laure; Gacic-Dobo, Marta; Mulders, Mick N; Okwo-Bele, Jean-Marie; Kretsinger, Katrina; Papania, Mark J; Rota, Paul A; Goodson, James L

2017-10-27

The fourth United Nations Millennium Development Goal, adopted in 2000, set a target to reduce child mortality by two thirds by 2015. One indicator of progress toward this target was measles vaccination coverage (1). In 2010, the World Health Assembly (WHA) set three milestones for measles control by 2015: 1) increase routine coverage with the first dose of a measles-containing vaccine (MCV1) among children aged 1 year to ≥90% at the national level and to ≥80% in every district; 2) reduce global annual measles incidence to <5 cases per million population; and 3) reduce global measles mortality by 95% from the 2000 estimate (2).* In 2012, WHA endorsed the Global Vaccine Action Plan, † with the objective of eliminating measles in four World Health Organization (WHO) regions by 2015 and in five regions by 2020. Countries in all six WHO regions have adopted goals for measles elimination by or before 2020. Measles elimination is defined as the absence of endemic measles virus transmission in a region or other defined geographic area for ≥12 months, in the presence of a high quality surveillance system that meets targets of key performance indicators. This report updates a previous report (3) and describes progress toward global measles control milestones and regional measles elimination goals during 2000-2016. During this period, annual reported measles incidence decreased 87%, from 145 to 19 cases per million persons, and annual estimated measles deaths decreased 84%, from 550,100 to 89,780; measles vaccination prevented an estimated 20.4 million deaths. However, the 2015 milestones have not yet been met; only one WHO region has been verified as having eliminated measles. Improved implementation of elimination strategies by countries and their partners is needed, with focus on increasing vaccination coverage through substantial and sustained additional investments in health systems, strengthening surveillance systems, using surveillance data to drive programmatic actions, securing political commitment, and raising the visibility of measles elimination goals.

Guide to active vaccine safety surveillance: Report of CIOMS working group on vaccine safety - executive summary.

PubMed

Heininger, U; Holm, K; Caplanusi, I; Bailey, S R

2017-07-13

In 2013, the Council for International Organizations of Medical Sciences (CIOMS) created a Working Group on Vaccine Safety (WG) to address unmet needs in the area of vaccine pharmacovigilance. Generating reliable data about specific vaccine safety concerns is becoming a priority due to recent progress in the development and deployment of new vaccines of global importance, as well as novel vaccines targeting diseases specifically endemic to many resource-limited countries (RLCs), e.g. malaria, dengue. The WG created a Guide to Active Vaccine Safety Surveillance (AVSS) to assist national regulatory authorities and national immunization program officers in RLCs in determining the best course of action with regards to non-routine pharmacovigilance activities, when confronted with a launch of a new vaccine or a vaccine that is new to their country. Here we summarize the results of the WG, further detailed in the Guide, which for the first time provides a structured approach to identifying and analyzing specific vaccines safety knowledge gaps, while considering all available sources of information, in order to determine whether AVSS is an appropriate solution. If AVSS is confirmed as being the appropriate tool, the Guide provides additional essential information on AVSS, a detailed overview of common types of AVSS and practical implementation considerations. It also provides a framework for a well-constructed and informative AVSS when needed, thus aiming to ensure the best possible safety of immunization in this new landscape. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Herpes simplex virus vaccine studies: from past to present].

PubMed

Us, Dürdal

2006-10-01

The dramatical increase in the prevalence of Herpes simplex virus (HSV) infections and the significant physical and psychosocial morbidity of HSV type 2 infections, generate the need for an efficacious HSV vaccine. The most important properties of HSVs that should be targeted for a successful vaccine are neuronal invasion, latency and reactivation in spite of specific host immune responses. The major expectation for an ideal HSV vaccine candidate is to induce sterilizing immunity, which must be effective at all portals of HSV entry; to prevent or reduce the symptomatic disease and to eliminate or at least to limit the asymptomatic viral shedding. The first vaccine studies have began in the 1920s and in the intervening eight decades there have been many attempts to develop an effective one. Although encouraging findings came from experiments in various animal models, human studies have been disappointing, unfortunately. The vaccine strategies that have undergone clinical evaluation until today included autoinoculation of live HSV, whole inactivated vaccines, attenuated live virus vaccines, modified live virus subunit vaccines, cell culture-derived subunit vaccines, recombinant subunit (glycoprotein) vaccines, DISC (Disabled Infectious Single Cycle) virus vaccines, viral vectors and naked DNA vaccines. In most of the clinical studies the failure of HSV vaccines in spite of inducing very high levels of specific neutralizing antibodies have emphasized that cell-mediated immune response, especially Thl type immunity is important in preventing both primary disease and recurrences with HSV, rather than humoral response. The most hopeful result was obtained with HSV-2 gD and alum/MPL vaccine in clinical studies. This vaccine was found 74% effective in preventing genital disease in HSV seronegative women but was not effective in men or seropositive women. In recent years it is possible to genetically engineer HSV to produce a vaccine strain that is protective without causing human disease. An example for this strategy was the development of a live attenuated vaccine from which neurovirulence gene (gamma1 34.5) has been removed. Another promising one was the replication-defective DISC virus HSV vaccine which is derived from a virus with an essential gene (e.g. gH gene) deleted, so the replication has been limited only to a single cycle. As a result, intensive HSV vaccine trials are currently underway, although all the previous attempts to produce an effective vaccine for the prophylaxis and immunotherapy against HSV have been largely unsuccessful. In this review the history of HSV vaccine development together with the preclinical and clinical studies from past to present has been summarized and recent progress for an effective HSV vaccine together with the further improvements required for an immunogenic vaccine have been discussed.

Recent developments in Helicobacter pylori vaccination.

PubMed

Kusters, J G

2001-01-01

This reviews discusses the recent progress in the development of a vaccine against Helicobacter pylori. To date, this gram-negative, spiral-shaped bacterium is one of the most common infections of mankind. Infection usually occurs during childhood, and when left untreated results in lifelong colonization of the stomach. Helicobacter pylori infection is a chronic gastritis that can lead to peptic ulcer disease, gastric adenocarcinoma and gastric B-cell lymphoma. Antimicrobial therapy is currently the method of choice for curing H. pylori infection, but complex dosing, inconsistent efficiency, development of antibiotic resistance, costs and various side effects compromise widespread use. As a consequence, new strategies for the prevention and eradication of H. pylori infections are being explored. Vaccines are an attractive option, because they are both effective and economic in use. Natural infection with H. pylori usually results in a strong inflammatory Th1-type CD4(+)T-cell response that does not seem to have any protective effects. Successful vaccination studies indicate that a Th2-type response is required for protection, but the exact mechanisms involved in protective immunization are still poorly understood. Although commercial development of products for clinical trial is underway, many important issues, such as lack of a suitable mucosal adjuvant, and prevention of potential side effects, such as postimmunization gastritis, need to be resolved.

An evaluation of the emerging vaccines against influenza in children

PubMed Central

2013-01-01

Background Influenza is an under-appreciated cause of acute lower respiratory infections (ALRI) in children. It is estimated to cause approximately 20 million new episodes of ALRI in children annually, 97% of these occurring in developing countries. It is also estimated to result in 28000 to 112000 deaths annually in young children. Apart from hospitalisations and deaths, influenza has significant economic consequences. The current egg-based inactivated influenza vaccines have several limitations: annual vaccination, high production costs, and cannot respond adequately to meet the demand during pandemics. Methods We used a modified CHNRI methodology for setting priorities in health research investments. This was done in two stages. In Stage I, we systematically reviewed the literature related to emerging cross-protective vaccines against influenza relevant to several criteria of interest: answerability; cost of development, production and implementation; efficacy and effectiveness; deliverability, affordability and sustainability; maximum potential impact on disease burden reduction; acceptability to the end users and health workers; and effect on equity. In Stage II, we conducted an expert opinion exercise by inviting 20 experts (leading basic scientists, international public health researchers, international policy makers and representatives of pharmaceutical companies). They answered questions from the CHNRI framework and their “collective optimism” towards each criterion was documented on a scale from 0 to 100%. Results The experts expressed very high level of optimism for deliverability, impact on equity, and acceptability to health workers and end users. However, they expressed concerns over the criteria of answerability, low development cost, low product cost, low implementation cost, affordability and, to a lesser extent sustainability. In addition they felt that the vaccine would have higher efficacy and impact on disease burden reduction on overall influenza-associated disease rather than specifically influenza-associated pneumonia. Conclusion Although the landscape of emerging influenza vaccines shows several promising candidates, it is unlikely that the advancements in the newer vaccine technologies will be able to progress through to large scale production in the near future. The combined effects of continued investments in researching new vaccines and improvements of available vaccines will hopefully shorten the time needed to the development of an effective seasonal and pandemic influenza vaccine suitable for large scale production. PMID:24564565

An evaluation of the emerging vaccines against influenza in children.

PubMed

Nair, Harish; Lau, Eva; Brooks, W; Seong, Ang; Theodoratou, Evropi; Zgaga, Lina; Huda, Tanvir; Jadhav, Suresh S; Rudan, Igor; Campbell, Harry

2013-01-01

Influenza is an under-appreciated cause of acute lower respiratory infections (ALRI) in children. It is estimated to cause approximately 20 million new episodes of ALRI in children annually, 97% of these occurring in developing countries. It is also estimated to result in 28000 to 112000 deaths annually in young children. Apart from hospitalisations and deaths, influenza has significant economic consequences. The current egg-based inactivated influenza vaccines have several limitations: annual vaccination, high production costs, and cannot respond adequately to meet the demand during pandemics. We used a modified CHNRI methodology for setting priorities in health research investments. This was done in two stages. In Stage I, we systematically reviewed the literature related to emerging cross-protective vaccines against influenza relevant to several criteria of interest: answerability; cost of development, production and implementation; efficacy and effectiveness; deliverability, affordability and sustainability; maximum potential impact on disease burden reduction; acceptability to the end users and health workers; and effect on equity. In Stage II, we conducted an expert opinion exercise by inviting 20 experts (leading basic scientists, international public health researchers, international policy makers and representatives of pharmaceutical companies). They answered questions from the CHNRI framework and their "collective optimism" towards each criterion was documented on a scale from 0 to 100%. The experts expressed very high level of optimism for deliverability, impact on equity, and acceptability to health workers and end users. However, they expressed concerns over the criteria of answerability, low development cost, low product cost, low implementation cost, affordability and, to a lesser extent sustainability. In addition they felt that the vaccine would have higher efficacy and impact on disease burden reduction on overall influenza-associated disease rather than specifically influenza-associated pneumonia. Although the landscape of emerging influenza vaccines shows several promising candidates, it is unlikely that the advancements in the newer vaccine technologies will be able to progress through to large scale production in the near future. The combined effects of continued investments in researching new vaccines and improvements of available vaccines will hopefully shorten the time needed to the development of an effective seasonal and pandemic influenza vaccine suitable for large scale production.

Vaccines and companion diagnostic tests for foot-and-mouth disease virus. An overview of the experience in South America.

PubMed

Bergmann, I E; Malirat, V; Neitzert, E; Correa Melo, E

2003-01-01

Vaccination constitutes an important control policy for foot-and-mouth disease (FMD) in affected areas with advanced eradication programmes, as well as in free regions that decide to use immunization as a control measure after a recent introduction of the disease. However, considering that vaccinated animals exposed to FMD virus can establish sub-clinical infection and eventually remain persistently infected, availability of tools to identify sub-clinical infection and its silent transmission within and between herds, regardless of their vaccination state, is of utmost importance. In response to the need for new diagnostic tools to support the eradication campaigns implemented in 1988 in South America, during the past decade we have developed, validated and applied a highly sensitive and specific immuno-enzymatic system for recognition of persistence at a herd level. The system is based on the detection of antibodies against non-capsid proteins required for viral replication. These proteins, in principle, are removed from the viral suspensions destined for production of BEI inactivated vaccines. Within the validation steps, evaluation of potential induction of antibodies to non-capsid proteins caused by traces of these proteins eventually remaining in the vaccines was a major concern. This report presents a review on the experience gathered through the application of the system to various experimental and field immunization conditions. It was concluded that vaccination is not expected to induce antibody responses to non-capsid proteins that could lead to misinterpretation of serological investigations. Progress on the development of approaches towards vaccine certification to guarantee absence of interference will be discussed.

A developing country perspective on vaccine-associated paralytic poliomyelitis.

PubMed

John, T Jacob

2004-01-01

When the Expanded Programme on Immunization was established and oral poliovirus vaccine (OPV) was introduced for developing countries to use exclusively, national leaders of public health had no opportunity to make an informed choice between OPV and the inactivated poliovirus vaccine (IPV). Today, as progress is made towards the goal of global eradication of poliomyelitis attributable to wild polioviruses, all developing countries where OPV is used face the risk of vaccine-associated paralytic poliomyelitis (VAPP). Until recently, awareness of VAPP has been poor and quantitative risk analysis scanty but it is now well known that the continued use of OPV perpetuates the risk of VAPP. Discontinuation or declining immunization coverage of OPV will increase the risk of emergence of circulating vaccine-derived polioviruses (cVDPV) that re-acquire wild virus-like properties and may cause outbreaks of polio. To eliminate the risk of cVDPV, either very high immunization coverage must be maintained as long as OPV is in use, or IPV should replace OPV. Stopping OPV without first achieving high immunization coverage with IPV is unwise on account of the possibility of emergence of cVDPV. Increasing numbers of developed nations prefer IPV, and manufacturing capacities have not been scaled up, so its price remains prohibitively high and unaffordable by developing countries, where, in addition, large-scale field experience with IPV is lacking. Under these circumstances, a policy shift to increase the use of IPV in national immunization programmes in developing countries is a necessary first step; once IPV coverage reaches high levels (over 85%), the withdrawal of OPV may begin.

Ses proteins as possible targets for vaccine development against Staphylococcus epidermidis infections.

PubMed

Hofmans, Dorien; Khodaparast, Laleh; Khodaparast, Ladan; Vanstreels, Els; Shahrooei, Mohammad; Van Eldere, Johan; Van Mellaert, Lieve

2018-05-09

The opportunistic pathogen Staphylococcus epidermidis is progressively involved in device-related infections. Since these infections involve biofilm formation, antibiotics are not effective. Conversely, a vaccine can be advantageous to prevent these infections. In view of vaccine development, predicted surface proteins were evaluated on their potential as a vaccine target. Immunoglobulins directed against S. epidermidis surface proteins SesB, M, O, Q and R, were used to firstly affirm their surface location. Further, inhibitory effects of these IgGs on biofilm formation were determined in vitro on polystyrene and polyurethane surfaces and in vivo using a subcutaneous catheter mouse model. We also examined the opsonophagocytic capacity of these IgGs. Surface localization of the five Ses proteins was demonstrated both for planktonic and sessile cells, though to a variable extent. Ses-specific IgGs added to planktonic cells had a variable inhibitory effect on cell adhesion to polystyrene, while only anti-SesO IgGs decreased cell attachment to polyurethane catheters. Although phagocytic killing was only obtained after opsonisation with SesB-specific IgGs, a significant reduction of in vivo formed biofilms was observed after administration of SesB-, SesM- and SesO-specific IgGs. Regardless of their characterization or function, S. epidermidis surface proteins can be adequate targets for vaccine development aiming the prevention of device-related infections caused by invasive S. epidermidis strains. Copyright © 2018 Elsevier Ltd. All rights reserved.

Clinical outcomes of a novel therapeutic vaccine with Tax peptide-pulsed dendritic cells for adult T cell leukaemia/lymphoma in a pilot study.

PubMed

Suehiro, Youko; Hasegawa, Atsuhiko; Iino, Tadafumi; Sasada, Amane; Watanabe, Nobukazu; Matsuoka, Masao; Takamori, Ayako; Tanosaki, Ryuji; Utsunomiya, Atae; Choi, Ilseung; Fukuda, Tetsuya; Miura, Osamu; Takaishi, Shigeo; Teshima, Takanori; Akashi, Koichi; Kannagi, Mari; Uike, Naokuni; Okamura, Jun

2015-05-01

Adult T cell leukaemia/lymphoma (ATL) is a human T cell leukaemia virus type-I (HTLV-I)-infected T cell malignancy with poor prognosis. We herein developed a novel therapeutic vaccine designed to augment an HTLV-I Tax-specific cytotoxic T lymphocyte (CTL) response that has been implicated in anti-ATL effects, and conducted a pilot study to investigate its safety and efficacy. Three previously treated ATL patients, classified as intermediate- to high-risk, were subcutaneously administered with the vaccine, consisting of autologous dendritic cells (DCs) pulsed with Tax peptides corresponding to the CTL epitopes. In all patients, the performance status improved after vaccination without severe adverse events, and Tax-specific CTL responses were observed with peaks at 16-20 weeks. Two patients achieved partial remission in the first 8 weeks, one of whom later achieved complete remission, maintaining their remission status without any additional chemotherapy 24 and 19 months after vaccination, respectively. The third patient, whose tumour cells lacked the ability to express Tax at biopsy, obtained stable disease in the first 8 weeks and later developed slowly progressive disease although additional therapy was not required for 14 months. The clinical outcomes of this pilot study indicate that the Tax peptide-pulsed DC vaccine is a safe and promising immunotherapy for ATL. © 2015 John Wiley & Sons Ltd.

Newcastle Disease: Progress and gaps in the development of vaccines and diagnostic tools

USDA-ARS?s Scientific Manuscript database

Newcastle disease (ND) is a contagious disease of birds that can have severe economic consequences for any poultry producer, including a serious impact on the international trade of poultry and eggs. Newcastle disease virus (NDV) isolates are also called avian paramyxovirus serotype-1 isolates, but ...

Mutation-induced changes of transmembrane pore size revealed by combined ion-channel conductance and single vesicle permeabilization analyses

USDA-ARS?s Scientific Manuscript database

Permeabilization of the endomembrane system by viroporins is instrumental in the progression of host-cell infection by many viral pathogens. Thus, blocking/attenuation of viroporin activity provides a generic methodology for antiviral and vaccine development. We have described that permeabilization ...

Survey of distribution of seasonal influenza vaccine doses in 201 countries (2004-2015): The 2003 World Health Assembly resolution on seasonal influenza vaccination coverage and the 2009 influenza pandemic have had very little impact on improving influenza control and pandemic preparedness.

PubMed

Palache, A; Abelin, A; Hollingsworth, R; Cracknell, W; Jacobs, C; Tsai, T; Barbosa, P

2017-08-24

There is no global monitoring system for influenza vaccination coverage, making it difficult to assess progress towards the 2003 World Health Assembly (WHA) vaccination coverage target. In 2008, the IFPMA Influenza Vaccine Supply International Task Force (IVS) developed a survey method to assess the global distribution of influenza vaccine doses as a proxy for vaccination coverage rates. The latest dose distribution data for 2014 and 2015 was used to update previous analyses. Data were confidentially collected and aggregated by the IFPMA Secretariat, and combined with previous IFPMA IVS survey data (2004-2013). Data were available from 201 countries over the 2004-2015 period. A "hurdle" rate was defined as the number of doses required to reach 15.9% of the population in 2008. Overall, the number of distributed doses progressively increased between 2004 and 2011, driven by a 150% increase in AMRO, then plateaued. One percent fewer doses were distributed in 2015 than in 2011. Twenty-three countries were above the hurdle rate in 2015, compared to 15 in 2004, but distribution was highly uneven in and across all WHO regions. Three WHO regions (AMRO, EURO and WPRO) accounted for about 95% of doses distributed. But in EURO and WPRO, distribution rates in 2015 were only marginally higher than in 2004, and in EURO there was an overall downward trend in dose distribution. The vast majority of countries cannot meet the 2003WHA coverage targets and are inadequately prepared for a global influenza pandemic. With only 5% of influenza vaccine doses being distributed to 50% of the world's population, there is urgency to redress the gross inequities in disease prevention and in pandemic preparedness. The 2003WHA resolution must be reviewed and revised and a call issued for the renewed commitment of Member States to influenza vaccination coverage targets. Copyright © 2017. Published by Elsevier Ltd.

Proteomics-driven Antigen Discovery for Development of Vaccines Against Gonorrhea*

PubMed Central

Zielke, Ryszard A.; Wierzbicki, Igor H.; Baarda, Benjamin I.; Gafken, Philip R.; Soge, Olusegun O.; Holmes, King K.; Jerse, Ann E.; Unemo, Magnus

2016-01-01

Expanding efforts to develop preventive gonorrhea vaccines is critical because of the dire possibility of untreatable gonococcal infections. Reverse vaccinology, which includes genome and proteome mining, has proven very successful in the discovery of vaccine candidates against many pathogenic bacteria. However, progress with this approach for a gonorrhea vaccine remains in its infancy. Accordingly, we applied a comprehensive proteomic platform—isobaric tagging for absolute quantification coupled with two-dimensional liquid chromatography and mass spectrometry—to identify potential gonococcal vaccine antigens. Our previous analyses focused on cell envelopes and naturally released membrane vesicles derived from four different Neisseria gonorrhoeae strains. Here, we extended these studies to identify cell envelope proteins of N. gonorrhoeae that are ubiquitously expressed and specifically induced by physiologically relevant environmental stimuli: oxygen availability, iron deprivation, and the presence of human serum. Together, these studies enabled the identification of numerous potential gonorrhea vaccine targets. Initial characterization of five novel vaccine candidate antigens that were ubiquitously expressed under these different growth conditions demonstrated that homologs of BamA (NGO1801), LptD (NGO1715), and TamA (NGO1956), and two uncharacterized proteins, NGO2054 and NGO2139, were surface exposed, secreted via naturally released membrane vesicles, and elicited bactericidal antibodies that cross-reacted with a panel of temporally and geographically diverse isolates. In addition, analysis of polymorphisms at the nucleotide and amino acid levels showed that these vaccine candidates are highly conserved among N. gonorrhoeae strains. Finally, depletion of BamA caused a loss of N. gonorrhoeae viability, suggesting it may be an essential target. Together, our data strongly support the use of proteomics-driven discovery of potential vaccine targets as a sound approach for identifying promising gonococcal antigens. PMID:27141096

Serologic response in eight alpacas vaccinated by extralabel use of a large animal rabies vaccine during a public health response to a rabid alpaca in South Carolina.

PubMed

Wallace, Ryan M; Niezgoda, Michael; Waggoner, Emily A; Blanton, Jesse Dean; Radcliffe, Rachel A

2016-09-15

CASE DESCRIPTION A female alpaca, kept at pasture with 12 other female alpacas, 2 crias, and 5 goats, was evaluated because of clinical signs of aggression. CLINICAL FINDINGS The clinical signs of aggression progressed to include biting at other animals as well as disorientation. Three days later, the alpaca was euthanized because of suspicion of rabies virus infection. TREATMENT AND OUTCOME No physical injuries were found at necropsy. Brain tissue specimens were confirmed positive for rabies on the basis of direct fluorescent antibody test results. Molecular typing identified the rabies virus variant as one that is enzootic in raccoons. The farm was placed under quarantine, restricting movement of animals on and off the property for 6 months. To prevent further rabies cases, 14 alpacas (12 adults and 2 crias) were vaccinated by extralabel use of a large animal rabies vaccine. Of the 14 vaccinated alpacas, 8 had paired serum samples obtained immediately before and 21 days after vaccination; all 8 alpacas had adequate serum antirabies antibody production in response to rabies vaccination. As a result of an adequate serologic response, the quarantine was reduced to 3 months. In the year after the index rabies case, no other animals on the farm developed rabies. CLINICAL RELEVANCE Extralabel use of rabies vaccines in camelids was used in the face of a public health investigation. This report provides an example of handling of a rabies case for future public health investigations, which will undoubtedly need to develop ad-hoc rabies vaccination recommendations on the basis of the unique characteristics of the event.

World Health Organization perspectives on the contribution of the Global Alliance for Vaccines and Immunization on reducing child mortality.

PubMed

Bustreo, F; Okwo-Bele, J-M; Kamara, L

2015-02-01

Child mortality has decreased substantially globally-from 12.6 million in 1990 to 6.3 million in 2013-due, in large part to of governments' and organisations' work, to prevent pneumonia, diarrhoea and malaria, the main causes of death in the postneonatal period. In 2012, the World Health Assembly adopted the Decade of Vaccines Global Vaccine Action Plan 2011-2020 as the current framework aimed at preventing millions of deaths through more equitable access to existing vaccines for people in all communities. The Global Alliance for Vaccines and Immunization (GAVI) plays a critical role in this effort by financing and facilitating delivery platforms for vaccines, with focused support for the achievements of improved vaccination coverage and acceleration of the uptake of WHO-recommended lifesaving new vaccines in 73 low-income countries. The GAVI Alliance has contributed substantially towards the progress of Millennium Development Goal 4 and to improving women's lives. By 2013, the GAVI Alliance had immunised 440 million additional children and averted six million future deaths from vaccine-preventable diseases in the world's poorest countries. The GAVI Alliance is on track to reducing child mortality to 68 per 1000 live births by 2015 in supported countries. This paper discusses the GAVI Alliance achievements related to Millennium Development Goal 4 and its broader contribution to improving women's lives and health systems, as well as challenges and obstacles it has faced. Additionally, it looks at challenges for the future and how it will continue its work related to reducing child mortality and improving women's health. 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.

The Current Status of the Disease Caused by Enterovirus 71 Infections: Epidemiology, Pathogenesis, Molecular Epidemiology, and Vaccine Development.

PubMed

Chang, Ping-Chin; Chen, Shou-Chien; Chen, Kow-Tong

2016-09-09

Enterovirus 71 (EV71) infections have a major public health impact in the Asia-Pacific region. We reviewed the epidemiology, pathogenesis, and molecular epidemiology of EV71 infection as well as EV71 vaccine development. Previous studies were found using the search terms "enterovirus 71" and "epidemiology" or "pathogenesis" or "molecular epidemiology" or "vaccine" in Medline and PubMed. Articles that were not published in the English language, manuscripts without an abstract, and opinion articles were excluded from the review. The reported epidemiology of cases caused by EV71 infection varied from country to country; seasonal variations in incidence were observed. Most cases of EV71 infection that resulted in hospitalization for complications occurred in children less than five years old. The brainstem was the most likely major target of EV71 infection. The emergence of the EV71 epidemic in the Asia-Pacific region has been associated with the circulation of different genetic lineages (genotypes B3, B4, C1, C2, and C4) that appear to be undergoing rapid evolutionary changes. The relationship between the gene structure of the EV71 virus and the factors that ensure its survival, circulation, and evasion of immunity is still unknown. EV71 infection has emerged as an important global public health problem. Vaccine development, including the development of inactivated whole-virus live attenuated, subviral particles, and DNA vaccines, has been progressing.

Novel multi-peptide vaccination in Hla-A2+ hormone sensitive patients with biochemical relapse of prostate cancer.

PubMed

Feyerabend, Susan; Stevanovic, Stefan; Gouttefangeas, Cécile; Wernet, Dorothee; Hennenlotter, Jörg; Bedke, Jens; Dietz, Klaus; Pascolo, Steve; Kuczyk, Markus; Rammensee, Hans-Georg; Stenzl, Arnulf

2009-06-15

A phase I/II trial was conducted to assess feasibility and tolerability of tumor associated antigen peptide vaccination in hormone sensitive prostate carcinoma (PC) patients with biochemical recurrence after primary surgical treatment. Nineteen HLA-A2 positive patients with rising PSA without detectable metastatic disease or local recurrence received 11 HLA-A*0201-restricted and two HLA class II synthetic peptides derived from PC tumor antigens subcutaneously for 18 months or until PSA progression. The vaccine was emulgated in montanide ISA51 and combined with imiquimod, GM-CSF, mucin-1-mRNA/protamine complex, local hyperthermia or no adjuvant. PSA was assessed, geometric mean doubling times (DT) calculated and clinical performance monitored. PSA DT of 4 out of 19 patients (21%) increased from 4.9 to 25.8 months during vaccination. Out of these, two patients (11%) exhibited PSA stability for 28 and 31 months which were still continuing at data cut-off. One patient showed no change of PSA DT during vaccination but decline after the therapy. Three patients had an interim PSA decline or DT increase followed by DT decrease compared to baseline PSA DT. Three of the responding patients received imiquimod and one the mucin-1-mRNA/protamine complex as adjuvant; both are Toll-like receptor-7 agonists. Eleven (58%) patients had progressive PSA values. The vaccine was well tolerated, and no grade III or IV toxicity occurred. Multi-peptide vaccination stabilized or slowed down PSA progress in four of 19 cases. The vaccination approach is promising with moderate adverse events. Long-term stability delayed androgen deprivation up to 31 months. TLR-7 co-activation seems to be beneficial.

Plague Vaccines: Status and Future.

PubMed

Sun, Wei

2016-01-01

Three major plague pandemics caused by the gram-negative bacterium Yersinia pestis have killed nearly 200 million people in human history. Due to its extreme virulence and the ease of its transmission, Y. pestis has been used purposefully for biowarfare in the past. Currently, plague epidemics are still breaking out sporadically in most of parts of the world, including the United States. Approximately 2000 cases of plague are reported each year to the World Health Organization. However, the potential use of the bacteria in modern times as an agent of bioterrorism and the emergence of a Y. pestis strain resistant to eight antibiotics bring out severe public health concerns. Therefore, prophylactic vaccination against this disease holds the brightest prospect for its long-term prevention. Here, we summarize the progress of the current vaccine development for counteracting plague.

A continuing high incidence of subacute sclerosing panencephalitis (SSPE) in the Eastern Highlands of Papua New Guinea.

PubMed Central

Takasu, T.; Mgone, J. M.; Mgone, C. S.; Miki, K.; Komase, K.; Namae, H.; Saito, Y.; Kokubun, Y.; Nishimura, T.; Kawanishi, R.; Mizutani, T.; Markus, T. J.; Kono, J.; Asuo, P. G.; Alpers, M. P.

2003-01-01

The aims of this descriptive study were to confirm the high incidence of subacute sclerosing panencephalitis (SSPE) previously reported from Papua New Guinea (PNG) and to relate SSPE to previous measles vaccination and measles illness. From February 1997 to April 1999 we diagnosed a total of 55 patients with SSPE at Goroka Base General Hospital in Eastern Highlands Province (EHP) of PNG. The diagnosis was based on high cerebrospinal fluid and serum measles virus antibody titres with progressive neurological disorder and myoclonic jerks. Of these 55 patients 42 were from EHP, including 32 whose onset was in the 2-year period 1997-1998. The annual incidence of SSPE in EHP in these 2 years was 98 per million population under 20 years of age, the highest ever reported. This incidence was more than ten times higher than the highest incidence in the prevaccine era reported from elsewhere. The mean age of onset of SSPE was 7.7 years (range 2.8-14.8 years) and the interval between measles and the onset of SSPE, where known, had a mean of 5.9 years and a range of 2.5-11.1 years. Among the SSPE patients 19 had a documented history of measles vaccination. Eight of these 19 also had documentation of previous measles illness; of these, seven were vaccinated after the development of measles and one was vaccinated 20 days before measles illness. Two non-SSPE children received vaccination twice which was documented and subsequently developed measles which was also substantiated by documentation. Two patients with SSPE yielded amplified nucleotide sequences of measles virus that were different from any of the vaccine strains. We found no evidence to implicate measles vaccination in the development of SSPE. PMID:14596530

Swimming against the current: genetic vaccination against Trypanosoma cruzi infection in mice.

PubMed

Rodrigues, Mauricio M; de Alencar, Bruna C; Claser, Carla; Tzelepis, Fanny; Silveira, Eduardo L; Haolla, Filipe A; Dominguez, Mariana R; Vasconcelos, José Ronnie

2009-07-01

Vaccines have had an unquestionable impact on public health during the last century. The most likely reason for the success of vaccines is the robust protective properties of specific antibodies. However, antibodies exert a strong selective pressure and many microorganisms, such as the obligatory intracellular parasite Trypanosoma cruzi, have been selected to survive in their presence. Although the host develops a strong immune response to T. cruzi, they do not clear the infection and instead progress to the chronic phase of the disease. Parasite persistence during the chronic phase of infection is now considered the main factor contributing to the chronic symptoms of the disease. Based on this finding, containment of parasite growth and survival may be one method to avoid the immunopathology of the chronic phase. In this context, vaccinologists have looked over the past 20 years for other immune effector mechanisms that could eliminate these antibody-resistant pathogens. We and others have tested the hypothesis that non-antibody-mediated cellular immune responses (CD4+ Th1 and CD8+ Tc1 cells) to specific parasite antigens/genes expressed by T. cruzi could indeed be used for the purpose of vaccination. This hypothesis was confirmed in different mouse models, indicating a possible path for vaccine development.

Prevention and Control Strategies to Counter Dengue Virus Infection

PubMed Central

Rather, Irfan A.; Parray, Hilal A.; Lone, Jameel B.; Paek, Woon K.; Lim, Jeongheui; Bajpai, Vivek K.; Park, Yong-Ha

2017-01-01

Dengue is currently the highest and rapidly spreading vector-borne viral disease, which can lead to mortality in its severe form. The globally endemic dengue poses as a public health and economic challenge that has been attempted to suppress though application of various prevention and control techniques. Therefore, broad spectrum techniques, that are efficient, cost-effective, and environmentally sustainable, are proposed and practiced in dengue-endemic regions. The development of vaccines and immunotherapies have introduced a new dimension for effective dengue control and prevention. Thus, the present study focuses on the preventive and control strategies that are currently employed to counter dengue. While traditional control strategies bring temporary sustainability alone, implementation of novel biotechnological interventions, such as sterile insect technique, paratransgenesis, and production of genetically modified vectors, has improved the efficacy of the traditional strategies. Although a large-scale vector control strategy can be limited, innovative vaccine candidates have provided evidence for promising dengue prevention measures. The use of tetravalent dengue vaccine (CYD-TDV) has been the most effective so far in treating dengue infections. Nonetheless, challenges and limitation hinder the progress of developing integrated intervention methods and vaccines; while the improvement in the latest techniques and vaccine formulation continues, one can hope for a future without the threat of dengue virus. PMID:28791258

Prevention and Control Strategies to Counter Dengue Virus Infection.

PubMed

Rather, Irfan A; Parray, Hilal A; Lone, Jameel B; Paek, Woon K; Lim, Jeongheui; Bajpai, Vivek K; Park, Yong-Ha

2017-01-01

Dengue is currently the highest and rapidly spreading vector-borne viral disease, which can lead to mortality in its severe form. The globally endemic dengue poses as a public health and economic challenge that has been attempted to suppress though application of various prevention and control techniques. Therefore, broad spectrum techniques, that are efficient, cost-effective, and environmentally sustainable, are proposed and practiced in dengue-endemic regions. The development of vaccines and immunotherapies have introduced a new dimension for effective dengue control and prevention. Thus, the present study focuses on the preventive and control strategies that are currently employed to counter dengue. While traditional control strategies bring temporary sustainability alone, implementation of novel biotechnological interventions, such as sterile insect technique, paratransgenesis, and production of genetically modified vectors, has improved the efficacy of the traditional strategies. Although a large-scale vector control strategy can be limited, innovative vaccine candidates have provided evidence for promising dengue prevention measures. The use of tetravalent dengue vaccine (CYD-TDV) has been the most effective so far in treating dengue infections. Nonetheless, challenges and limitation hinder the progress of developing integrated intervention methods and vaccines; while the improvement in the latest techniques and vaccine formulation continues, one can hope for a future without the threat of dengue virus.

Understanding HIV infection for the design of a therapeutic vaccine. Part II: Vaccination strategies for HIV.

PubMed

de Goede, A L; Vulto, A G; Osterhaus, A D M E; Gruters, R A

2015-05-01

HIV infection leads to a gradual loss CD4(+) T lymphocytes comprising immune competence and progression to AIDS. Effective treatment with combined antiretroviral drugs (cART) decreases viral load below detectable levels but is not able to eliminate the virus from the body. The success of cART is frustrated by the requirement of expensive lifelong adherence, accumulating drug toxicities and chronic immune activation resulting in increased risk of several non-AIDS disorders, even when viral replication is suppressed. Therefore, there is a strong need for therapeutic strategies as an alternative to cART. Immunotherapy, or therapeutic vaccination, aims to increase existing immune responses against HIV or induce de novo immune responses. These immune responses should provide a functional cure by controlling viral replication and preventing disease progression in the absence of cART. The key difficulty in the development of an HIV vaccine is our ignorance of the immune responses that control of viral replication, and thus how these responses can be elicited and how they can be monitored. Part one of this review provides an extensive overview of the (patho-) physiology of HIV infection. It describes the structure and replication cycle of HIV, the epidemiology and pathogenesis of HIV infection and the innate and adaptive immune responses against HIV. Part two of this review discusses therapeutic options for HIV. Prevention modalities and antiretroviral therapy are briefly touched upon, after which an extensive overview on vaccination strategies for HIV is provided, including the choice of immunogens and delivery strategies. Copyright © 2014. Published by Elsevier Masson SAS.

Longitudinal myelitis associated with yellow fever vaccination.

PubMed

Chaves, M; Riccio, P; Patrucco, L; Rojas, J I; Cristiano, E

2009-07-01

Severe adverse reaction to yellow fever (YF) vaccine includes the yellow fever vaccine-associated neurotropic disease. This terminology includes postvaccinal encephalitis, acute disseminated encephalomyelitis, and Guillain-Barré syndrome. The objective of this communication is to report a patient who received a YF vaccine in Argentina and subsequently developed longitudinal myelitis with a symptom that had previously gone unreported in the literature. A 56-year-old man began with progressive paraparesia, urinary retention, and constipation 48 h previous to admission. The patient received YF vaccine 45 days prior to the onset of the symptoms. There was no history of other immunization or relevant condition. MR of the spine showed longitudinal intramedullary hyperintense signal (D5-12) without gadolinium enhancement. A high concentration of YFV-specific IgM vaccine antibody was found in the cerebrospinal fluid (CSF). Serological tests for other flavivirus were negative. A diagnosis of longitudinal myelitis without encephalitis associated with YF vaccine was performed and symptoms improved 5 days later. This is the first report dealing with longitudinal myelitis as a serious adverse event associated with YF vaccination in which confirmation of the presence of antibodies in CSF was found. To date, it is also the first report with serological confirmation in Argentina and in South America. We consider that the present investigation will raise awareness in the region in the reporting of adverse events related to YF vaccine and improve our knowledge of adverse reactions to the vaccine.

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

Recent progress in chemical and chemoenzymatic synthesis of carbohydrates.

PubMed

Muthana, Saddam; Cao, Hongzhi; Chen, Xi

2009-12-01

The important roles that carbohydrates play in biological processes and their potential application in diagnosis, therapeutics, and vaccine development have made them attractive synthetic targets. Despite ongoing challenges, tremendous progresses have been made in recent years for the synthesis of carbohydrates. The chemical glycosylation methods have become more sophisticated and the synthesis of oligosaccharides has become more predictable. Simplified one-pot glycosylation strategy and automated synthesis are increasingly used to obtain biologically important glycans. On the other hand, chemoenzymatic synthesis continues to be a powerful alternative for obtaining complex carbohydrates. This review highlights recent progress in chemical and chemoenzymatic synthesis of carbohydrates with a particular focus on the methods developed for the synthesis of oligosaccharides, polysaccharides, glycolipids, and glycosylated natural products.

Recent Progress in Chemical and Chemoenzymatic Synthesis of Carbohydrates

PubMed Central

Muthana, Saddam; Cao, Hongzhi; Chen, Xi

2011-01-01

Summary The important roles that carbohydrates play in biological processes and their potential application in diagnosis, therapeutics, and vaccine development have made them attractive synthetic targets. Despite ongoing challenges, tremendous progresses have been made in recent years for the synthesis of carbohydrates. The chemical glycosylation methods have become more sophisticated and the synthesis of oligosaccharides has become more predictable. Simplified one-pot glycosylation strategy and automated synthesis are increasingly used to obtain biologically important glycans. On the other hand, chemoenzymatic synthesis continues to be a powerful alternative for obtaining complex carbohydrates. This review highlights recent progress in chemical and chemoenzymatic synthesis of carbohydrates with a particular focus on the methods developed for the synthesis of oligosaccharides, polysaccharides, glycolipids, and glycosylated natural products. PMID:19833544

Hemorrhagic fever of bunyavirus etiology: disease models and progress towards new therapies.

PubMed

Gowen, Brian B; Hickerson, Brady T

2017-03-01

A growing number of bunyaviruses are known to cause viral hemorrhagic fever (VHF), a severe febrile illness which can progress to hypovolemic shock and multi-organ failure and is characterized by hematologic abnormalities and vascular leak. At present, there are no approved vaccines or antiviral therapies to effectively prevent or treat VHF caused by pathogenic bunyaviruses. Advances in the modeling of bunyaviral infections have facilitated efforts towards the development of novel post-exposure prophylactic and therapeutic countermeasures, several of which may some day be approved for human use. Here, we review recent progress in animal models of severe bunyaviral infections essential to this mission, as well as promising antivirals and biologicals that are at various stages of the development process.

Progress Toward Measles Elimination - South-East Asia Region, 2003-2013.

PubMed

Thapa, Arun; Khanal, Sudhir; Sharapov, Umid; Swezy, Virginia; Sedai, Tika; Dabbagh, Alya; Rota, Paul; Goodson, James L; McFarland, Jeffrey

2015-06-12

In 2013, the 66th session of the Regional Committee of the World Health Organization (WHO) South-East Asia Region adopted the goal of measles elimination and rubella and congenital rubella syndrome control by 2020 after rigorous prior consultations. The recommended strategies include 1) achieving and maintaining ≥95% coverage with 2 doses of measles- and rubella-containing vaccine in every district through routine or supplementary immunization activities (SIAs); 2) developing and sustaining a sensitive and timely case-based measles surveillance system that meets recommended performance indicators; 3) developing and maintaining an accredited measles laboratory network; and 4) achieving timely identification, investigation, and response to measles outbreaks. This report updates previous reports and summarizes progress toward measles elimination in the South-East Asia Region during 2003-2013. Within the region, coverage with the first dose of a measles-containing vaccine (MCV1) increased from 67% to 78%; an estimated 286 million children (95% of the target population) were vaccinated in SIAs; measles incidence decreased 73%, from 59 to 16 cases per million population; and estimated measles deaths decreased 63%. To achieve measles elimination in the region, additional efforts are needed in countries with <95% 2-dose routine MCV coverage, particularly in India and Indonesia, to strengthen routine immunization services, conduct periodic high-quality SIAs, and strengthen measles case-based surveillance and laboratory diagnosis of measles.

Immunology of scorpion toxins and perspectives for generation of anti-venom vaccines.

PubMed

Gazarian, Karlen G; Gazarian, Tatiana; Hernández, Ricardo; Possani, Lourival D

2005-05-16

Scorpions and other venomous animals contain concentrates of biologically active substances developed to block vital physiological and biochemical functions of the victims. These have contrasting human health concerns, provide important pharmacological raw material and pose a serious threat to human life and health in tropical and subtropical regions. Because only occasional and minor quantities of venom are introduced into the human organism with a scorpion sting and their mortal effect is an acute phenomenon these substances are unknown to the immune defense system and thus no immunity has appeared against them during evolution. Antidotes prepared from animal anti-sera are effective against some species of scorpions but depend on the manufacturer and the availability of product to the medical community. Although significant progress has been made in immunological studies of certain groups of toxins, few centers are dedicated to this research. Information is still insufficient to generate a comprehensive picture of the subject and to propose vaccines against venoms. A novel approach based on mimotopes selected from phage-displayed random peptide libraries show potential to impel further progress of toxin immunological studies and to provide putative vaccine resources. In this report we revise the "state of the art" in the field.

Progress with Plasmodium falciparum sporozoite (PfSPZ)-based malaria vaccines.

PubMed

Richie, Thomas L; Billingsley, Peter F; Sim, B Kim Lee; James, Eric R; Chakravarty, Sumana; Epstein, Judith E; Lyke, Kirsten E; Mordmüller, Benjamin; Alonso, Pedro; Duffy, Patrick E; Doumbo, Ogobara K; Sauerwein, Robert W; Tanner, Marcel; Abdulla, Salim; Kremsner, Peter G; Seder, Robert A; Hoffman, Stephen L

2015-12-22

Sanaria Inc. has developed methods to manufacture, purify and cryopreserve aseptic Plasmodium falciparum (Pf) sporozoites (SPZ), and is using this platform technology to develop an injectable PfSPZ-based vaccine that provides high-grade, durable protection against infection with Pf malaria. Several candidate vaccines are being developed and tested, including PfSPZ Vaccine, in which the PfSPZ are attenuated by irradiation, PfSPZ-CVac, in which fully infectious PfSPZ are attenuated in vivo by concomitant administration of an anti-malarial drug, and PfSPZ-GA1, in which the PfSPZ are attenuated by gene knockout. Forty-three research groups in 15 countries, organized as the International PfSPZ Consortium (I-PfSPZ-C), are collaborating to advance this program by providing intellectual, clinical, and financial support. Fourteen clinical trials of these products have been completed in the USA, Europe and Africa, two are underway and at least 12 more are planned for 2015-2016 in the US (four trials), Germany (2 trials), Tanzania, Kenya, Mali, Burkina Faso, Ghana and Equatorial Guinea. Sanaria anticipates application to license a first generation product as early as late 2017, initially to protect adults, and a year later to protect all persons >6 months of age for at least six months. Improved vaccine candidates will be advanced as needed until the following requirements have been met: long-term protection against natural transmission, excellent safety and tolerability, and operational feasibility for population-wide administration. Here we describe the three most developed whole PfSPZ vaccine candidates, associated clinical trials, initial plans for licensure and deployment, and long-term objectives for a final product suitable for mass administration to achieve regional malaria elimination and eventual global eradication. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Progress with Plasmodium falciparum sporozoite (PfSPZ)-based malaria vaccines

PubMed Central

Richie, Thomas L.; Billingsley, Peter F.; Sim, B. Kim Lee; James, Eric R.; Chakravarty, Sumana; Epstein, Judith E.; Lyke, Kirsten E.; Mordmüller, Benjamin; Alonso, Pedro; Duffy, Patrick E.; Doumbo, Ogobara K.; Sauerwein, Robert W.; Tanner, Marcel; Abdulla, Salim; Kremsner, Peter G.; Seder, Robert A.; Hoffman, Stephen L.

2016-01-01

Sanaria Inc. has developed methods to manufacture, purify and cryopreserve aseptic Plasmodium falciparum (Pf) sporozoites (SPZ), and is using this platform technology to develop an injectable PfSPZ-based vaccine that provides high-grade, durable protection against infection with Pf malaria. Several candidate vaccines are being developed and tested, including PfSPZ Vaccine, in which the PfSPZ are attenuated by irradiation, PfSPZ-CVac, in which fully infectious PfSPZ are attenuated in vivo by concomitant administration of an anti-malarial drug, and PfSPZ-GA1, in which the PfSPZ are attenuated by gene knockout. Forty-three research groups in 15 countries, organized as the International PfSPZ Consortium (I-PfSPZ-C), are collaborating to advance this program by providing intellectual, clinical, and financial support. Fourteen clinical trials of these products have been completed in the USA, Europe and Africa, two are underway and at least 12 more are planned for 2015–2016 in the US (four trials), Germany (2 trials), Tanzania, Kenya, Mali, Burkina Faso, Ghana and Equatorial Guinea. Sanaria anticipates application to license a first generation product as early as late 2017, initially to protect adults, and a year later to protect all persons >6 months of age for at least six months. Improved vaccine candidates will be advanced as needed until the following requirements have been met: long-term protection against natural transmission, excellent safety and tolerability, and operational feasibility for population-wide administration. Here we describe the three most developed whole PfSPZ vaccine candidates, associated clinical trials, initial plans for licensure and deployment, and long-term objectives for a final product suitable for mass administration to achieve regional malaria elimination and eventual global eradication. PMID:26469720

Vaccination in Southeast Asia--reducing meningitis, sepsis and pneumonia with new and existing vaccines.

PubMed

Richardson, Alice; Morris, Denise E; Clarke, Stuart C

2014-07-16

Streptococcus pneumoniae, Haemophilus influenzae type b and Neisseria meningitidis are leading causes of vaccine-preventable diseases such as meningitis, sepsis and pneumonia. Although there has been much progress in the introduction of vaccines against these pathogens, access to vaccines remains elusive in some countries. This review highlights the current S. pneumoniae, H. influenzae type b, and N. meningitidis immunization schedules in the 10 countries belonging to the Association of Southeast Asian Nations (ASEAN). Epidemiologic studies may be useful for informing vaccine policy in these countries, particularly when determining the cost-effectiveness of introducing new vaccines. Copyright © 2014 Elsevier Ltd. All rights reserved.

Pharmacological intervention for dengue virus infection.

PubMed

Lai, Jenn-Haung; Lin, Yi-Ling; Hsieh, Shie-Liang

2017-04-01

Dengue virus (DENV) infection has a considerable health impact in tropical and subtropical countries worldwide. Escalation of infection rates greatly increases morbidity and mortality, most commonly from deaths due to dengue hemorrhagic fever and dengue shock syndrome. Although the development of an effective, long-lasting vaccine has been a major aim for control and prevention of DENV infection, the currently licensed vaccine has limitations and is less than satisfactory. Thus, there remains an important need to identify effective and tolerable medications for treatment of DENV-infected patients both in the early phase, to prevent progression to fatal outcomes, and to minimize deaths after patients develop severe complications. This review will address several specific points, including (1) approaches to identify anti-DENV medications, (2) recent advances in the development of potential compounds targeting DENV infection, (3) experience with clinical trials of regimens for DENV infection, (4) some available medications of potential for clinical trials against DENV infection, (5) reasons for unsuccessful outcomes and challenges of anti-DENV treatments, and (6) directions for developing or selecting better anti-DENV strategies. This review provides useful guidance for clinicians selecting drugs for DENV-infected patients with severe manifestations or potential fatal disease progression, and for basic researchers seeking to develop effective anti-DENV regimens. Copyright © 2017 Elsevier Inc. All rights reserved.

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.

Social vaccines to resist and change unhealthy social and economic structures: a useful metaphor for health promotion.

PubMed

Baum, Fran; Narayan, Ravi; Sanders, David; Patel, Vikram; Quizhpe, Arturo

2009-12-01

The term 'social vaccine' is designed to encourage the biomedically orientated health sector to recognize the legitimacy of action on the distal social and economic determinants of health. It is proposed as a term to assist the health promotion movement in arguing for a social view of health which is so often counter to medical and popular conceptions of health. The idea of a social vaccine builds on a long tradition in social medicine as well as on a biomedical tradition of preventing illness through vaccines that protect against disease. Social vaccines would be promoted as a means to encourage popular mobilization and advocacy to change the social and economic structural conditions that render people and communities vulnerable to disease. They would facilitate social and political processes that develop popular and political will to protect and promote health through action (especially governments prepared to intervene and regulate to protect community health) on the social and economic determinants. Examples provided for the effects of social vaccines are: restoring land ownership to Indigenous peoples, regulating the advertising of harmful products and progressive taxation for universal social protection. Social vaccines require more research to improve understanding of social and political processes that are likely to improve health equity worldwide. The vaccine metaphor should be helpful in arguing for increased action on the social determinants of health.

Inactivated poliovirus type 2 vaccine delivered to rat skin via high density microprojection array elicits potent neutralising antibody responses

PubMed Central

Muller, David A.; Pearson, Frances E.; Fernando, Germain J.P.; Agyei-Yeboah, Christiana; Owens, Nick S.; Corrie, Simon R.; Crichton, Michael L.; Wei, Jonathan C.J.; Weldon, William C.; Oberste, M. Steven; Young, Paul R.; Kendall, Mark A. F.

2016-01-01

Polio eradication is progressing rapidly, and the live attenuated Sabin strains in the oral poliovirus vaccine (OPV) are being removed sequentially, starting with type 2 in April 2016. For risk mitigation, countries are introducing inactivated poliovirus vaccine (IPV) into routine vaccination programs. After April 2016, monovalent type 2 OPV will be available for type 2 outbreak control. Because the current IPV is not suitable for house-to-house vaccination campaigns (the intramuscular injections require health professionals), we developed a high-density microprojection array, the Nanopatch, delivered monovalent type 2 IPV (IPV2) vaccine to the skin. To assess the immunogenicity of the Nanopatch, we performed a dose-matched study in rats, comparing the immunogenicity of IPV2 delivered by intramuscular injection or Nanopatch immunisation. A single dose of 0.2 D-antigen units of IPV2 elicited protective levels of poliovirus antibodies in 100% of animals. However, animals receiving IPV2 by IM required at least 3 immunisations to reach the same neutralising antibody titres. This level of dose reduction (1/40th of a full dose) is unprecedented for poliovirus vaccine delivery. The ease of administration coupled with the dose reduction observed in this study points to the Nanopatch as a potential tool for facilitating inexpensive IPV for mass vaccination campaigns. PMID:26911254

Progress in vaccination towards hepatitis B control and elimination in the Region of the Americas.

PubMed

Ropero Álvarez, Alba Maria; Pérez-Vilar, Silvia; Pacis-Tirso, Carmelita; Contreras, Marcela; El Omeiri, Nathalie; Ruiz-Matus, Cuauhtémoc; Velandia-González, Martha

2017-04-17

Over recent decades, the Region of the Americas has made significant progress towards hepatitis B elimination. We summarize the countries/territories' efforts in introducing and implementing hepatitis B (HB) vaccination and in evaluating its impact on HB virus seroprevalence. We collected information about HB vaccination schedules, coverage estimates, and year of vaccine introduction from countries/territories reporting to the Pan American Health Organization/World Health Organization (PAHO/WHO) through the WHO/UNICEF Joint Reporting Form on Immunization. We obtained additional information regarding countries/territories vaccination recommendations and strategies through communications with Expanded Program on Immunization (EPI) managers and national immunization survey reports. We identified vaccine impact studies conducted and published in the Americas. As of October 2016, all 51 countries/territories have included infant HB vaccination in their official immunization schedule. Twenty countries, whose populations represent over 90% of the Region's births, have included nationwide newborn HB vaccination. We estimated at 89% and 75%, the regional three-dose series and the birth dose HB vaccination coverage, respectively, for 2015. The impact evaluations of infant HB immunization programs in the Region have shown substantial reductions in HB surface antigen (HBsAg) seroprevalence. The achievements of vaccination programs in the Americas suggest that the elimination of perinatal and early childhood HB transmission could be feasible in the short-term. Moreover, the data gathered indicate that the Region may have already achieved the 2020 WHO goal for HB control.

New Animal Model Could Boost Research on AIDS Drugs and Vaccines | Frederick National Laboratory for Cancer Research

Cancer.gov

In a research milestone reported in the June 20 issue of the journal Science, scientists have developed a minimally modified version of HIV-1, the virus that causes AIDS in infected humans, that is capable of causing progressive infection and AIDS i

Development of InCVAX as a novel in situ autologous vaccine for metastatic cancers (Conference Presentation)

NASA Astrophysics Data System (ADS)

Hode, Tomas; Alleruzzo, Luciano; Raker, Joseph; Lam, Samuel Siu Kit; Nordquist, Robert E.; Chen, Wei R.

2016-03-01

A novel method, an in situ autologous whole-cell cancer vaccine (inCVAX), is being developed by Immunophotonics, Inc., for the treatment of metastatic cancers. inCVAX combines phototherapy and immunotherapy to potentially induce a systemic anti-tumor immune response in the hosts. Immunophotonics and its academic partners have spent years conducting nonclinical research, developing CMC techniques and conducting clinical research. In 2015 the company initiated a late-stage (II/III) clinical trial in South America for advanced breast cancer patients. The process of developing the inCVAX approach from a laboratory setting into clinical trials requires significant efforts from a group of dedicated engineers, scientists, and physicians. The growth of the company and its business advances demonstrated the determination of a group of visionary investors, entrepreneurs, and business leaders. This talk will chronicle the milestones of the scientific achievement, medical progress, and business development of Immunophotonics.

Recent insights into cutaneous immunization: How to vaccinate via the skin.

PubMed

Engelke, Laura; Winter, Gerhard; Hook, Sarah; Engert, Julia

2015-09-08

Technologies and strategies for cutaneous vaccination have been evolving significantly during the past decades. Today, there is evidence for increased efficacy of cutaneously delivered vaccines allowing for dose reduction and providing a minimally invasive alternative to traditional vaccination. Considerable progress has been made within the field of well-established cutaneous vaccination strategies: Jet and powder injection technologies, microneedles, microporation technologies, electroporation, sonoporation, and also transdermal and transfollicular vaccine delivery. Due to recent advances, the use of cutaneous vaccination can be expanded from prophylactic vaccination for infectious diseases into therapeutic vaccination for both infectious and non-infectious chronic conditions. This review will provide an insight into immunological processes occurring in the skin and introduce the key innovations of cutaneous vaccination technologies. Copyright © 2015 Elsevier Ltd. All rights reserved.

From genomes to vaccines: Leishmania as a model.

PubMed Central

Almeida, Renata; Norrish, Alan; Levick, Mark; Vetrie, David; Freeman, Tom; Vilo, Jaak; Ivens, Alasdair; Lange, Uta; Stober, Carmel; McCann, Sharon; Blackwell, Jenefer M

2002-01-01

The 35 Mb genome of Leishmania should be sequenced by late 2002. It contains approximately 8500 genes that will probably translate into more than 10 000 proteins. In the laboratory we have been piloting strategies to try to harness the power of the genome-proteome for rapid screening of new vaccine candidate. To this end, microarray analysis of 1094 unique genes identified using an EST analysis of 2091 cDNA clones from spliced leader libraries prepared from different developmental stages of Leishmania has been employed. The plan was to identify amastigote-expressed genes that could be used in high-throughput DNA-vaccine screens to identify potential new vaccine candidates. Despite the lack of transcriptional regulation that polycistronic transcription in Leishmania dictates, the data provide evidence for a high level of post-transcriptional regulation of RNA abundance during the developmental cycle of promastigotes in culture and in lesion-derived amastigotes of Leishmania major. This has provided 147 candidates from the 1094 unique genes that are specifically upregulated in amastigotes and are being used in vaccine studies. Using DNA vaccination, it was demonstrated that pooling strategies can work to identify protective vaccines, but it was found that some potentially protective antigens are masked by other disease-exacerbatory antigens in the pool. A total of 100 new vaccine candidates are currently being tested separately and in pools to extend this analysis, and to facilitate retrospective bioinformatic analysis to develop predictive algorithms for sequences that constitute potentially protective antigens. We are also working with other members of the Leishmania Genome Network to determine whether RNA expression determined by microarray analyses parallels expression at the protein level. We believe we are making good progress in developing strategies that will allow rapid translation of the sequence of Leishmania into potential interventions for disease control in humans. PMID:11839176

Progress in HPV vaccination in low- and lower-middle-income countries.

PubMed

LaMontagne, D Scott; Bloem, Paul J N; Brotherton, Julia M L; Gallagher, Katherine E; Badiane, Ousseynou; Ndiaye, Cathy

2017-07-01

The past 10 years have seen remarkable progress in the global scale-up of human papillomavirus (HPV) vaccinations. Forty-three low- and lower-middle-income countries (LLMICs) have gained experience in delivering this vaccine to young adolescent girls through pilot programs, demonstration programs, and national introductions and most of these have occurred in the last 4 years. The experience of Senegal is summarized as an illustrative country case study. Publication of numerous delivery experiences and lessons learned has demonstrated the acceptability and feasibility of HPV vaccinations in LLMICs. Four areas require dedicated action to overcome remaining challenges to national scaling-up: maintaining momentum politically, planning successfully, securing financing, and fostering sustainability. Advances in policy, programming, and science may help accelerate reaching 30 million girls in LLMICs with HPV vaccine by 2020. © 2017 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.

Technology Resource, Distribution, and Development Characteristics of Global Influenza Virus Vaccine: A Patent Bibliometric Analysis.

PubMed

Chen, Ning; Liu, Yun; Cheng, Yijie; Liu, Long; Yan, Zhe; Tao, Lixin; Guo, Xiuhua; Luo, Yanxia; Yan, Aoshuang

2015-01-01

Influenza virus vaccine (IVV) is a promising research domain that is closely related to global health matters, which has been acknowledged not only by scientists and technology developers, but also by policy-makers. Meanwhile, patents encompass valuable technological information and reflect the latest technological inventions as well as the innovative capability of a nation. However, little research has examined this up-and-coming research field using patent bibliometric method. Thus, this paper (a) designs the technology classification system and search strategy for the identification of IVV; and (b) presents a longitudinal analysis of the global IVV development based on the European Patent Office (EPO) patents. Bibliometric analysis is used to rank countries, institutions, inventors and technology subfields contributing to IVV technical progress. The results show that the global trends of IVV are a multi-developing feature of variety but an uneven technical resource distribution. Although the synthetic peptide vaccine is a comparatively young field, it already demonstrates the powerful vitality and the enormous development space. With the worldwide competition increasing, all nations especially China should be looking to increase devotion, enhance capability and regard effectiveness of technological innovation.

Systemic Immunization with Papillomavirus L1 Protein Completely Prevents the Development of Viral Mucosal Papillomas

NASA Astrophysics Data System (ADS)

Suzich, Joann A.; Ghim, Shin-Je; Palmer-Hill, Frances J.; White, Wendy I.; Tamura, James K.; Bell, Judith A.; Newsome, Joseph A.; Bennett Jenson, A.; Schlegel, Richard

1995-12-01

Infection of mucosal epithelium by papillomaviruses is responsible for the induction of genital and oral warts and plays a critical role in the development of human cervical and oropharyngeal cancer. We have employed a canine model to develop a systemic vaccine that completely protects against experimentally induced oral mucosal papillomas. The major capsid protein, L1, of canine oral papillomavirus (COPV) was expressed in Sf9 insect cells in native conformation. L1 protein, which self-assembled into virus-like particles, was purified on CsCl gradients and injected intradermally into the foot pad of beagles. Vaccinated animals developed circulating antibodies against COPV and became completely resistant to experimental challenge with COPV. Successful immunization was strictly dependent upon native L1 protein conformation and L1 type. Partial protection was achieved with as little as 0.125 ng of L1 protein, and adjuvants appeared useful for prolonging the host immune response. Serum immunoglobulins passively transferred from COPV L1-immunized beagles to naive beagles conferred protection from experimental infection with COPV. Our results indicate the feasibility of developing a human vaccine to prevent mucosal papillomas, which can progress to malignancy.

Technology Resource, Distribution, and Development Characteristics of Global Influenza Virus Vaccine: A Patent Bibliometric Analysis

PubMed Central

Liu, Long; Yan, Zhe; Tao, Lixin; Guo, Xiuhua; Luo, Yanxia; Yan, Aoshuang

2015-01-01

Influenza virus vaccine (IVV) is a promising research domain that is closely related to global health matters, which has been acknowledged not only by scientists and technology developers, but also by policy-makers. Meanwhile, patents encompass valuable technological information and reflect the latest technological inventions as well as the innovative capability of a nation. However, little research has examined this up-and-coming research field using patent bibliometric method. Thus, this paper (a) designs the technology classification system and search strategy for the identification of IVV; and (b) presents a longitudinal analysis of the global IVV development based on the European Patent Office (EPO) patents. Bibliometric analysis is used to rank countries, institutions, inventors and technology subfields contributing to IVV technical progress. The results show that the global trends of IVV are a multi-developing feature of variety but an uneven technical resource distribution. Although the synthetic peptide vaccine is a comparatively young field, it already demonstrates the powerful vitality and the enormous development space. With the worldwide competition increasing, all nations especially China should be looking to increase devotion, enhance capability and regard effectiveness of technological innovation. PMID:26372160

Engineering Dendritic Cells to Enhance Cancer Immunotherapy

PubMed Central

Boudreau, Jeanette E; Bonehill, Aude; Thielemans, Kris; Wan, Yonghong

2011-01-01

Cancer immunotherapy aims to establish immune-mediated control of tumor growth by priming T-cell responses to target tumor-associated antigens. Three signals are required for T-cell activation: (i) presentation of cognate antigen in self MHC molecules; (ii) costimulation by membrane-bound receptor-ligand pairs; and (iii) soluble factors to direct polarization of the ensuing immune response. The ability of dendritic cells (DCs) to provide all three signals required for T-cell activation makes them an ideal cancer vaccine platform. Several strategies have been developed to enhance and control antigen presentation, costimulation, and cytokine production. In this review, we discuss progress toward developing DC-based cancer vaccines by genetic modification using RNA, DNA, and recombinant viruses. Furthermore, the ability of DC-based vaccines to activate natural killer (NK) and B-cells, and the impact of gene modification strategies on these populations is described. Clinical trials using gene-modified DCs have shown modest results, therefore, further considerations for DC manipulation to enhance their clinical efficacy are also discussed. PMID:21468005

Control of viremia and maintenance of intestinal CD4(+) memory T cells in SHIV(162P3) infected macaques after pathogenic SIV(MAC251) challenge.

PubMed

Pahar, Bapi; Lackner, Andrew A; Piatak, Michael; Lifson, Jeffrey D; Wang, Xiaolei; Das, Arpita; Ling, Binhua; Montefiori, David C; Veazey, Ronald S

2009-05-10

Recent HIV vaccine failures have prompted calls for more preclinical vaccine testing in non-human primates. However, similar to HIV infection of humans, developing a vaccine that protects macaques from infection following pathogenic SIV(MAC251) challenge has proven difficult, and current vaccine candidates at best, only reduce viral loads after infection. Here we demonstrate that prior infection with a chimeric simian-human immunodeficiency virus (SHIV) containing an HIV envelope gene confers protection against intravenous infection with the heterologous, highly pathogenic SIV(MAC251) in rhesus macaques. Although definitive immune correlates of protection were not identified, preservation and/or restoration of intestinal CD4(+) memory T cells were associated with protection from challenge and control of viremia. These results suggest that protection against pathogenic lentiviral infection or disease progression is indeed possible, and may correlate with preservation of mucosal CD4(+) T cells.

African swine fever virus serotype-specific proteins are significant protective antigens for African swine fever.

PubMed

Burmakina, G; Malogolovkin, A; Tulman, E R; Zsak, L; Delhon, G; Diel, D G; Shobogorov, N M; Morgunov, Yu P; Morgunov, S Yu; Kutish, G F; Kolbasov, D; Rock, D L

2016-07-01

African swine fever (ASF) is an emerging disease threat for the swine industry worldwide. No ASF vaccine is available and progress is hindered by lack of knowledge concerning the extent of ASFV strain diversity and the viral antigens conferring type-specific protective immunity in pigs. Available data from vaccination/challenge experiments in pigs indicate that ASF protective immunity may be haemadsorption inhibition (HAI) serotype-specific. Recently, we have shown that two ASFV proteins, CD2v (EP402R) and C-type lectin (EP153R), are necessary and sufficient for mediating HAI serological specificity (Malogolovkin et al., 2015).. Here, using ASFV inter-serotypic chimeric viruses and vaccination/challenge experiments in pigs, we demonstrate that serotype-specific CD2v and/or C-type lectin proteins are important for protection against homologous ASFV infection. Thus, these viral proteins represent significant protective antigens for ASFV that should be targeted in future vaccine design and development. Additionally, these data support the concept of HAI serotype-specific protective immunity.

Misinformation lingers in memory: Failure of three pro-vaccination strategies.

PubMed

Pluviano, Sara; Watt, Caroline; Della Sala, Sergio

2017-01-01

People's inability to update their memories in light of corrective information may have important public health consequences, as in the case of vaccination choice. In the present study, we compare three potentially effective strategies in vaccine promotion: one contrasting myths vs. facts, one employing fact and icon boxes, and one showing images of non-vaccinated sick children. Beliefs in the autism/vaccines link and in vaccines side effects, along with intention to vaccinate a future child, were evaluated both immediately after the correction intervention and after a 7-day delay to reveal possible backfire effects. Results show that existing strategies to correct vaccine misinformation are ineffective and often backfire, resulting in the unintended opposite effect, reinforcing ill-founded beliefs about vaccination and reducing intentions to vaccinate. The implications for research on vaccines misinformation and recommendations for progress are discussed.

Antigenic determinants of hepatitis E virus and vaccine-induced immunogenicity and efficacy.

PubMed

Zhao, Qinjian; Zhang, Jun; Wu, Ting; Li, Shao-Wei; Ng, Mun-Hon; Xia, Ning-Shao; Shih, James Wai-Kuo

2013-02-01

There is emerging evidence for an under-recognized hepatitis E virus (HEV) as a human pathogen. Among different reasons for this neglect are the unsatisfactory performance and under-utilization of commercial HEV diagnostic kits; for instance, the number of anti-HEV IgM kits marketed in China is about one-fifth of that of hepatitis A kits. Over the last two decades, substantial progress has been achieved in furthering our knowledge on the HEV-specific immune responses, antigenic features of HEV virions, and development of serological assays and more recently prophylactic vaccines. This review will focus on presenting the evidence of the importance of HEV infection for certain cohorts such as pregnant women, the key antigenic determinants of the virus, and immunogenicity and clinical efficacy conferred by a newly developed prophylactic vaccine. Robust immunogenicity, greater than 195-fold and approximately 50-fold increase of anti-HEV IgG level in seronegative and seropositive vaccinees, respectively, as well as impressive clinical efficacy of this vaccine was demonstrated. The protection rate against the hepatitis E disease and the virus infection was shown to be 100% (95% CI 75-100) and 78% (95% CI 66-86), respectively.

Immune-Based Approaches to the Prevention of Mother-to-child-Transmission of HIV-1: Active and Passive Immunization

PubMed Central

Lohman-Payne, Barb; Slyker, Jennifer; Rowland-Jones, Sarah L.

2010-01-01

Synopsis Despite more than two decades of research, an effective vaccine that can prevent HIV-1 infection in populations exposed to the virus remains elusive. In the pursuit of an HIV-1 vaccine, does prevention of exposure to maternal HIV-1 in utero, at birth or in early life through breast-milk require special consideration? In this article we will review what is known about the immune mechanisms of susceptibility and resistance to mother-to-child transmission (MTCT) of HIV-1 and will summarise studies that have used passive or active immunisation strategies to interrupt -MTCT of HIV-1. We will also describe potentially modifiable infectious co-factors that may enhance transmission and/or disease progression (especially in the developing world). Ultimately an effective prophylactic vaccine against HIV-1 infection will need to be deployed as part of the Extended Programme of Immunisation (EPI) recommended by the World Health Organisation (WHO) for use in developing countries, so it is important to understand how the infant immune system responds to HIV-1 antigens, both in natural infection and presented by candidate vaccines. PMID:21078451

Developmental biology of the innate immune response: implications for neonatal and infant vaccine development.

PubMed

Philbin, Victoria Jane; Levy, Ofer

2009-05-01

Molecular characterization of mechanisms by which human pattern recognition receptors (PRRs) detect danger signals has greatly expanded our understanding of the innate immune system. PRRs include Toll-like receptors, nucleotide oligomerization domain-like receptors, retinoic acid inducible gene-like receptors, and C-type lectin receptors. Characterization of the developmental expression of these systems in the fetus, newborn, and infant is incomplete but has yielded important insights into neonatal susceptibility to infection. Activation of PRRs on antigen-presenting cells enhances costimulatory function, and thus PRR agonists are potential vaccine adjuvants, some of which are already in clinical use. Thus, study of PRRs has also revealed how previously mysterious immunomodulators are able to mediate their actions, including the vaccine adjuvant aluminum hydroxide that activates a cytosolic protein complex known as the Nacht domain leucine-rich repeat and pyrin domain-containing protein 3 inflammasome leading to interleukin-1beta production. Progress in characterizing PRRs is thus informing and expanding the design of improved adjuvants. This review summarizes recent developments in the field of innate immunity emphasizing developmental expression in the fetus, newborn, and infant and its implications for the design of more effective neonatal and infant vaccines.

Vaccinia immune globulin: current policies, preparedness, and product safety and efficacy.

PubMed

Wittek, Riccardo

2006-05-01

In 1980 the World Health Organization declared that smallpox was eradicated from the world, and routine smallpox vaccination was discontinued. Nevertheless, samples of the smallpox virus (variola virus) were retained for research purposes, not least because of fears that terrorist groups or rogue states might also have kept samples in order to develop a bioweapon. Variola virus represents an effective bioweapon because it is associated with high morbidity and mortality and is highly contagious. Since September 11, 2001, countries around the world have begun to develop policies and preparedness programs to deal with a bioterror attack, including stockpiling of smallpox vaccine. Smallpox vaccine itself may be associated with a number of serious adverse events, which can often be managed with vaccinia immune globulin (VIG). VIG may also be needed as prophylaxis in patients for whom pre-exposure smallpox vaccine is contraindicated (such as those with eczema or pregnant women), although it is currently not licensed in these cases. Two intravenous formulations of VIG (VIGIV Cangene and VIGIV Dynport) have been licensed by the FDA for the management of patients with progressive vaccinia, eczema vaccinatum, severe generalized vaccinia, and extensive body surface involvement or periocular implantation following inadvertent inoculation.

[Development of Markov models for economics evaluation of strategies on hepatitis B vaccination and population-based antiviral treatment in China].

PubMed

Yang, P C; Zhang, S X; Sun, P P; Cai, Y L; Lin, Y; Zou, Y H

2017-07-10

Objective: To construct the Markov models to reflect the reality of prevention and treatment interventions against hepatitis B virus (HBV) infection, simulate the natural history of HBV infection in different age groups and provide evidence for the economics evaluations of hepatitis B vaccination and population-based antiviral treatment in China. Methods: According to the theory and techniques of Markov chain, the Markov models of Chinese HBV epidemic were developed based on the national data and related literature both at home and abroad, including the settings of Markov model states, allowable transitions and initial and transition probabilities. The model construction, operation and verification were conducted by using software TreeAge Pro 2015. Results: Several types of Markov models were constructed to describe the disease progression of HBV infection in neonatal period, perinatal period or adulthood, the progression of chronic hepatitis B after antiviral therapy, hepatitis B prevention and control in adults, chronic hepatitis B antiviral treatment and the natural progression of chronic hepatitis B in general population. The model for the newborn was fundamental which included ten states, i.e . susceptiblity to HBV, HBsAg clearance, immune tolerance, immune clearance, low replication, HBeAg negative CHB, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma (HCC) and death. The susceptible state to HBV was excluded in the perinatal period model, and the immune tolerance state was excluded in the adulthood model. The model for general population only included two states, survive and death. Among the 5 types of models, there were 9 initial states assigned with initial probabilities, and 27 states for transition probabilities. The results of model verifications showed that the probability curves were basically consistent with the situation of HBV epidemic in China. Conclusion: The Markov models developed can be used in economics evaluation of hepatitis B vaccination and treatment for the elimination of HBV infection in China though the structures and parameters in the model have uncertainty with dynamic natures.

Therapeutic vaccines in HBV: lessons from HCV.

PubMed

Barnes, Eleanor

2015-02-01

Currently, millions of people infected with hepatitis B virus (HBV) are committed to decades of treatment with anti-viral therapy to control viral replication. However, new tools for immunotherapy that include both viral vectors and molecular checkpoint inhibitors are now available. This has led to a resurgence of interest in new strategies to develop immunotherapeutic strategies with the aim of inducing HBeAg seroconversion--an end-point that has been associated with a decrease in the rates of disease progression. Ultimately, a true cure will involve the elimination of covalently closed circular DNA which presents a greater challenge for immunotherapy. In this manuscript, I describe the development of immunotherapeutic strategies for HBV that are approaching or currently in clinical studies, and draw on observations of T cell function in natural infection supported by recent animal studies that may lead to additional rational vaccine strategies using checkpoint inhibitors. I also draw on our recent experience in developing potent vaccines for HCV prophylaxis based on simian adenoviral and MVA vectors used in prime-boost strategies in both healthy volunteers and HCV infected patients. I have shown that the induction of T cell immune responses is markedly attenuated when administered to people with persistent HCV viremia. These studies and recently published animal studies using the woodchuck model suggest that potent vaccines based on DNA or adenoviral vectored vaccination represent a rational way forward. However, combining these with drugs to suppress viral replication, alongside checkpoint inhibitors may be required to induce long-term immune control.

Virulence determinants of Moraxella catarrhalis: distribution and considerations for vaccine development.

PubMed

Blakeway, Luke V; Tan, Aimee; Peak, Ian R A; Seib, Kate L

2017-10-01

Moraxella catarrhalis is a human-restricted opportunistic bacterial pathogen of the respiratory mucosa. It frequently colonizes the nasopharynx asymptomatically, but is also an important causative agent of otitis media (OM) in children, and plays a significant role in acute exacerbations of chronic obstructive pulmonary disease (COPD) in adults. As the current treatment options for M. catarrhalis infection in OM and exacerbations of COPD are often ineffective, the development of an efficacious vaccine is warranted. However, no vaccine candidates for M. catarrhalis have progressed to clinical trials, and information regarding the distribution of M. catarrhalis virulence factors and vaccine candidates is inconsistent in the literature. It is largely unknown if virulence is associated with particular strains or subpopulations of M. catarrhalis, or if differences in clinical manifestation can be attributed to the heterogeneous expression of specific M. catarrhalis virulence factors in the circulating population. Further investigation of the distribution of M. catarrhalis virulence factors in the context of carriage and disease is required so that vaccine development may be targeted at relevant antigens that are conserved among disease-causing strains. The challenge of determining which of the proposed M. catarrhalis virulence factors are relevant to human disease is amplified by the lack of a standardized M. catarrhalis typing system to facilitate direct comparisons of worldwide isolates. Here we summarize and evaluate proposed relationships between M. catarrhalis subpopulations and specific virulence factors in the context of colonization and disease, as well as the current methods used to infer these associations.

Vaccination coverage among children in kindergarten--United States, 2009-10 school year.

PubMed

2011-06-03

Healthy People 2020 objectives include maintaining vaccination coverage among children in kindergarten (IID-10) (1). The target is ≥95% vaccination coverage for the following vaccines: poliovirus; diphtheria and tetanus toxoids and acellular pertussis (DTP/DTaP/DT); measles, mumps, and rubella (MMR); hepatitis B (HepB); and varicella (1). Data from school assessment surveys are used to monitor vaccination coverage and vaccination exemption levels among children enrolled in kindergarten. This report summarizes data from school assessment surveys submitted to CDC by 48 federal immunization program grantees (including 47 states and the District of Columbia) for the 2009-10 school year to describe vaccination coverage and exemption rates (2). For that period, 17 grantees reported coverage of ?95% for four vaccines (poliovirus, DTP/DTaP/DT, MMR, and HepB) and four grantees reported coverage of ≥95% for 2 doses of varicella vaccine. Total exemption rates, including medical, religious, and philosophical exemptions, ranged from <1% to 6.2% across grantees, and 15 grantees reported exemption rates<1%. Survey methods for vaccination coverage and exemption rates varied among grantees, making comparisons difficult and limiting the use of school assessment surveys to report aggregate national rates. Further standardization of school assessment survey methods will generate comparable data between grantees to monitor and track progress in reaching national objectives, and allow development of best practice guidelines for grantees to more effectively use and report school coverage and exemption data. CDC will continue to monitor vaccination coverage and exemption levels and assist grantees in identification of local areas with low vaccination coverage or high exemption rates for further evaluation or intervention.

Streptococcus pneumoniae triggers progression of pulmonary fibrosis through pneumolysin.

PubMed

Knippenberg, Sarah; Ueberberg, Bianca; Maus, Regina; Bohling, Jennifer; Ding, Nadine; Tort Tarres, Meritxell; Hoymann, Heinz-Gerd; Jonigk, Danny; Izykowski, Nicole; Paton, James C; Ogunniyi, Abiodun D; Lindig, Sandro; Bauer, Michael; Welte, Tobias; Seeger, Werner; Guenther, Andreas; Sisson, Thomas H; Gauldie, Jack; Kolb, Martin; Maus, Ulrich A

2015-07-01

Respiratory tract infections are common in patients suffering from pulmonary fibrosis. The interplay between bacterial infection and fibrosis is characterised poorly. To assess the effect of Gram-positive bacterial infection on fibrosis exacerbation in mice. Fibrosis progression in response to Streptococcus pneumoniae was examined in two different mouse models of pulmonary fibrosis. We demonstrate that wild-type mice exposed to adenoviral vector delivery of active transforming growth factor-β1 (TGFß1) or diphteria toxin (DT) treatment of transgenic mice expressing the DT receptor (DTR) under control of the surfactant protein C (SPC) promoter (SPC-DTR) to induce pulmonary fibrosis developed progressive fibrosis following infection with Spn, without exhibiting impaired lung protective immunity against Spn. Antibiotic treatment abolished infection-induced fibrosis progression. The cytotoxin pneumolysin (Ply) of Spn caused this phenomenon in a TLR4-independent manner, as Spn lacking Ply (SpnΔply) failed to trigger progressive fibrogenesis, whereas purified recombinant Ply did. Progressive fibrogenesis was also observed in AdTGFβ1-exposed Ply-challenged TLR4 KO mice. Increased apoptotic cell death of alveolar epithelial cells along with an attenuated intrapulmonary release of antifibrogenic prostaglandin E2 was found to underlie progressive fibrogenesis in Ply-challenged AdTGFβ1-exposed mice. Importantly, vaccination of mice with the non-cytotoxic Ply derivative B (PdB) substantially attenuated Ply-induced progression of lung fibrosis in AdTGFβ1-exposed mice. Our data unravel a novel mechanism by which infection with Spn through Ply release induces progression of established lung fibrosis, which can be attenuated by protein-based vaccination of mice. 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.

Pathogenesis and Current Approaches to Control of Varicella-Zoster Virus Infections

PubMed Central

Gershon, Michael D.

2013-01-01

SUMMARY Varicella-zoster virus (VZV) was once thought to be a fairly innocuous pathogen. That view is no longer tenable. The morbidity and mortality due to the primary and secondary diseases that VZV causes, varicella and herpes zoster (HZ), are significant. Fortunately, modern advances, including an available vaccine to prevent varicella, a therapeutic vaccine to diminish the incidence and ameliorate sequelae of HZ, effective antiviral drugs, a better understanding of VZV pathogenesis, and advances in diagnostic virology have made it possible to control VZV in the United States. Occult forms of VZV-induced disease have been recognized, including zoster sine herpete and enteric zoster, which have expanded the field. Future progress should include development of more effective vaccines to prevent HZ and a more complete understanding of the consequences of VZV latency in the enteric nervous system. PMID:24092852

A Prototype Recombinant-Protein Based Chlamydia pecorum Vaccine Results in Reduced Chlamydial Burden and Less Clinical Disease in Free-Ranging Koalas (Phascolarctos cinereus).

PubMed

Waugh, Courtney; Khan, Shahneaz Ali; Carver, Scott; Hanger, Jonathan; Loader, Joanne; Polkinghorne, Adam; Beagley, Kenneth; Timms, Peter

2016-01-01

Diseases associated with Chlamydia pecorum infection are a major cause of decline in koala populations in Australia. While koalas in care can generally be treated, a vaccine is considered the only option to effectively reduce the threat of infection and disease at the population level. In the current study, we vaccinated 30 free-ranging koalas with a prototype Chlamydia pecorum vaccine consisting of a recombinant chlamydial MOMP adjuvanted with an immune stimulating complex. An additional cohort of 30 animals did not receive any vaccine and acted as comparison controls. Animals accepted into this study were either uninfected (Chlamydia PCR negative) at time of initial vaccination, or infected (C. pecorum positive) at either urogenital (UGT) and/or ocular sites (Oc), but with no clinical signs of chlamydial disease. All koalas were vaccinated/sampled and then re-released into their natural habitat before re-capturing and re-sampling at 6 and 12 months. All vaccinated koalas produced a strong immune response to the vaccine, as indicated by high titres of specific plasma antibodies. The incidence of new infections in vaccinated koalas over the 12-month period post-vaccination was slightly less than koalas in the control group, however, this was not statistically significant. Importantly though, the vaccine was able to significantly reduce the infectious load in animals that were Chlamydia positive at the time of vaccination. This effect was evident at both the Oc and UGT sites and was stronger at 6 months than at 12 months post-vaccination. Finally, the vaccine was also able to reduce the number of animals that progressed to disease during the 12-month period. While the sample sizes were small (statistically speaking), results were nonetheless striking. This study highlights the potential for successful development of a Chlamydia vaccine for koalas in a wild setting.

Rotavirus Vaccines: a story of success with challenges ahead

PubMed Central

O’Ryan, Miguel

2017-01-01

Approximately 40 years have passed since the discovery of the rotavirus and 10 years since the introduction and progressive dissemination of rotavirus vaccines worldwide. Currently, 92 countries have introduced rotavirus vaccines into national or subnational programs with evident impact in disease reduction. Two vaccines have been widely used, and four additional vaccines have been licensed and are being used in defined regions. In this context, one main issue that remains unsolved is the lower vaccine efficacy/effectiveness in low-income countries. An additional partially answered issue relates to rotavirus strain circulation in vaccinated populations. These issues are discussed in this review. The most imperative challenge ahead is to fulfill the WHO’s recommendation to introduce rotavirus vaccines in all countries. PMID:28928954

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.

AIDS vaccines that allow HIV-1 to infect and escape immunologic control: a mathematic analysis of mass vaccination.

PubMed

van Ballegooijen, Marijn; Bogaards, Johannes A; Weverling, Gerrit-Jan; Boerlijst, Maarten C; Goudsmit, Jaap

2003-10-01

Cytotoxic T lymphocyte (CTL)-based HIV vaccine concepts shown to reduce viremia and postpone disease but not to prevent infection in monkeys are currently in human phase 1 trials. To evaluate the potential efficacy of vaccines that cannot prevent HIV-1 to infect and escape immunologic control, we designed a mathematic model that correlates the level of viremia to both infectiousness and disease progression. We speculate that vaccinees will have a virologic set point and disease progression rates comparable to untreated HIV-1-infected individuals with the best prognosis. Our model (illustrated with R0 = 3) shows that a sexually active population can ultimately be reduced to 26% of its initial size as a result of AIDS-related mortality in the absence of treatment or vaccination. Start of vaccination when HIV-1 prevalence is still low might postpone the peak incidence of infection and the dramatic decline in population size by up to 22 years. In conclusion, CTL-based vaccines that do not prevent HIV-1 infection but do postpone the time to onset of AIDS have considerable potential to curb the spread of HIV-1 and to postpone high AIDS-related mortality on a population level. The number of long-term survivors is substantially increased only when vaccination is initiated early in an AIDS epidemic, however.

Interrupting the transmission of wild polioviruses with vaccines: immunological considerations.

PubMed Central

Ghendon, Y.; Robertson, S. E.

1994-01-01

In 1988 the World Health Assembly set the goal of global poliomyelitis eradication by the year 2000. Substantial progress has been made, and 143 countries reported no poliomyelitis cases associated with the wild virus in 1993. This article reviews the immunological considerations relevant to interrupting the transmission of wild polioviruses with vaccines. Although serum immunity prevents poliomyelitis in the individual, it is local immunity that is important in preventing the transmission of polioviruses in the community. Natural infection and vaccination with oral polioviruses vaccine (OPV) produce local immunity in the intestine and the nasopharynx in about 70-80% of individuals. In contrast, inactivated poliovirus vaccine (IPV) produces local intestinal immunity in only 20-30% of the individuals. With either vaccine, however, a substantial proportion of the immunized population can transmit the wild virus. Moreover, although serum immunity is long-lasting, limited data suggest that local immunity may not be as persistent. To interrupt the transmission of wild polioviruses efforts should be made to achieve and sustain high levels of poliovirus vaccine coverage. Recent outbreaks show that wild poliovirus poses a risk for unimmunized individuals, even when overall coverage levels are high. Delivery of poliovirus vaccine to hard-to-reach populations will be of increasing importance as countries progress toward the final stages of poliomyelitis eradication. The immunization status of persons from poliomyelitis-free countries should be updated prior to travel to poliomyelitis-endemic areas. PMID:7867144

Development of a Vaccine against Escherichia coli Urinary Tract Infections

PubMed Central

Mobley, Harry L. T.; Alteri, Christopher J.

2015-01-01

Urinary tract infection (UTI) is the second most common infection in humans after those involving the respiratory tract. This results not only in huge annual economic costs, but in decreased workforce productivity and high patient morbidity. Most infections are caused by uropathogenic Escherichia coli (UPEC). Antibiotic treatment is generally effective for eradication of the infecting strain; however, documentation of increasing antibiotic resistance, allergic reaction to certain pharmaceuticals, alteration of normal gut flora, and failure to prevent recurrent infections represent significant barriers to treatment. As a result, approaches to prevent UTI such as vaccination represent a gap that must be addressed. Our laboratory has made progress toward development of a preventive vaccine against UPEC. The long-term research goal is to prevent UTIs in women with recurrent UTIs. Our objective has been to identify the optimal combination of protective antigens for inclusion in an effective UTI vaccine, optimal adjuvant, optimal dose, and optimal route of delivery. We hypothesized that a multi-subunit vaccine elicits antibody that protects against experimental challenge with UPEC strains. We have systematically identified four antigens that can individually protect experimentally infected mice from colonization of the bladder and/or kidneys by UPEC when administered intranasally with cholera toxin (CT) as an adjuvant. To advance the vaccine for utility in humans, we will group the individual antigens, all associated with iron acquisition (IreA, Hma, IutA, FyuA), into an effective combination to establish a multi-subunit vaccine. We demonstrated for all four vaccine antigens that antigen-specific serum IgG represents a strong correlate of protection in vaccinated mice. High antibody titers correlate with low colony forming units (CFUs) of UPEC following transurethral challenge of vaccinated mice. However, the contribution of cell-mediated immunity cannot be ruled out and must be investigated experimentally. We have demonstrated that antibodies bind to the surface of UPEC expressing the antigens. Sera from women with and without histories of UTI have been tested for antibody levels to vaccine antigens. Our results validate iron acquisition as a target for vaccination against UTI. PMID:26729174

Misinformation lingers in memory: Failure of three pro-vaccination strategies

PubMed Central

Pluviano, Sara

2017-01-01

People’s inability to update their memories in light of corrective information may have important public health consequences, as in the case of vaccination choice. In the present study, we compare three potentially effective strategies in vaccine promotion: one contrasting myths vs. facts, one employing fact and icon boxes, and one showing images of non-vaccinated sick children. Beliefs in the autism/vaccines link and in vaccines side effects, along with intention to vaccinate a future child, were evaluated both immediately after the correction intervention and after a 7-day delay to reveal possible backfire effects. Results show that existing strategies to correct vaccine misinformation are ineffective and often backfire, resulting in the unintended opposite effect, reinforcing ill-founded beliefs about vaccination and reducing intentions to vaccinate. The implications for research on vaccines misinformation and recommendations for progress are discussed. PMID:28749996

Gamma-interferon exerts a critical early restriction on replication and dissemination of yellow fever virus vaccine strain 17D-204.

PubMed

Lam, L K Metthew; Watson, Alan M; Ryman, Kate D; Klimstra, William B

2018-01-01

Live attenuated viruses are historically among the most effective viral vaccines. Development of a safe vaccine requires the virus to be less virulent, a phenotype that is historically arrived by empirical evaluation often leaving the mechanisms of attenuation unknown. The yellow fever virus 17D live attenuated vaccine strain has been developed as a delivery vector for heterologous antigens; however, the mechanisms of attenuation remain elusive. The successful and safe progress of 17D as a vaccine vector and the development of live attenuated vaccines (LAVs) to related flaviviruses requires an understanding of the molecular mechanisms leading to attenuation. Using subcutaneous infection of interferon-deficient mouse models of wild type yellow fever virus (WT YFV) pathogenesis and 17D-mediated immunity, we found that, in the absence of type I IFN (IFN-α/β), type II interferon (IFN-γ) restricted 17D replication, but not that of WT YFV, by 1-2 days post-infection. In this context, IFN-γ responses protected 17D-infected animals from mortality, largely restricted the virus to lymphoid organs, and eliminated viscerotropic disease signs such as steatosis in the liver and inflammatory cell infiltration into the spleen. However, WT YFV caused a disseminated infection, gross liver pathology, and rapid death of the animals. In vitro, IFN-γ treatment of myeloid cells suppressed the replication of 17D significantly more than that of WT YFV, suggesting a direct differential effect on 17D virus replication. Together these data indicate that an important mechanism of 17D attenuation in vivo is increased sensitivity to IFN-γ stimulated responses elicited early after infection.

Clustering of mutations within the inverted repeat regions of a serially-passaged attenuated gallid herpesvirus type 2 strain.

USDA-ARS?s Scientific Manuscript database

Marek’s disease (MD) is the leading cause of losses in chicken production in the world. Over the past 40 years significant progress has been made in the control of MD through the use of vaccines which reduce or delay tumor formation in vaccinated flocks. However, these vaccines fail to induce an imm...

Progress on Identifying Specific Genetic Changes in the Marek's Disease Virus Genome Associated With Attenuation Induced by Repeated In Vitro Passages

USDA-ARS?s Scientific Manuscript database

Marek’s disease (MD) vaccines have been successfully used for decades to control tumor formation induced by Marek’s disease virus (MDV), the causative agent and an oncogenic alphaherpesvirus. However, there is still a need for improved MD vaccines as none are sterilizing, and unpredictable vaccine b...

Advances in viral hepatitis: 50 years of Australian gastroenterology.

PubMed

McCaughan, Geoff

2009-10-01

Viral hepatitis classification, treatments and pathogenesis has been increasingly defined over the past 50 years. Australian researchers have made significant contributions in the areas of viral hepatitis A vaccine development, treatment outcomes for chronic hepatitis B and C, the role of liver transplantation and the pathogenesis of injury and disease progression. This review outlines some of these contributions.

Co-administration of plasmid-encoded granulocyte-macrophage colony-stimulating factor increases human immunodeficiency virus-1 DNA vaccine-induced polyfunctional CD4+ T-cell responses

PubMed Central

Santana, Vinicius Canato; Almeida, Rafael Ribeiro; Ribeiro, Susan Pereira; Ferreira, Luís Carlos de Souza; Kalil, Jorge; Rosa, Daniela Santoro; Cunha-Neto, Edecio

2015-01-01

T-cell based vaccines against human immunodeficiency virus (HIV) generate specific responses that may limit both transmission and disease progression by controlling viral load. Broad, polyfunctional, and cytotoxic CD4+T-cell responses have been associated with control of simian immunodeficiency virus/HIV-1 replication, supporting the inclusion of CD4+ T-cell epitopes in vaccine formulations. Plasmid-encoded granulocyte-macrophage colony-stimulating factor (pGM-CSF) co-administration has been shown to induce potent CD4+ T-cell responses and to promote accelerated priming and increased migration of antigen-specific CD4+ T-cells. However, no study has shown whether co-immunisation with pGM-CSF enhances the number of vaccine-induced polyfunctional CD4+ T-cells. Our group has previously developed a DNA vaccine encoding conserved, multiple human leukocyte antigen (HLA)-DR binding HIV-1 subtype B peptides, which elicited broad, polyfunctional and long-lived CD4+ T-cell responses. Here, we show that pGM-CSF co-immunisation improved both magnitude and quality of vaccine-induced T-cell responses, particularly by increasing proliferating CD4+ T-cells that produce simultaneously interferon-γ, tumour necrosis factor-α and interleukin-2. Thus, we believe that the use of pGM-CSF may be helpful for vaccine strategies focused on the activation of anti-HIV CD4+ T-cell immunity. PMID:26602876

Rational design of HIV vaccines and microbicides: report of the EUROPRISE annual conference 2011

PubMed Central

2012-01-01

Europrise is a Network of Excellence supported by the European Commission within the 6th Framework programme from 2007 to 2012. The Network has involved over 50 institutions from 13 European countries together with 3 industrial partners and 6 African countries. The Network encompasses an integrated program of research, training, dissemination and advocacy within the field of HIV vaccines and microbicides. A central and timely theme of the Network is the development of the unique concept of co-usage of vaccines and microbicides. Training of PhD students has been a major task, and some of these post-graduate students have here summarized novel ideas emanating from presentations at the last annual Europrise meeting in Prague. The latest data and ideas concerning HIV vaccine and microbicide studies are included in this review; these studies are so recent that the majority have yet to be published. Data were presented and discussed concerning novel immunisation strategies; microbicides and PrEP (alone and in combination with vaccines); mucosal transmission of HIV/SIV; mucosal vaccination; novel adjuvants; neutralizing antibodies; innate immune responses; HIV/SIV pathogenesis and disease progression; new methods and reagents. These – necessarily overlapping topics - are comprehensively summarised by the Europrise students in the context of other recent exciting data. PMID:22784600

Rational design of HIV vaccines and microbicides: report of the EUROPRISE annual conference 2011.

PubMed

Ruffin, Nicolas; Borggren, Marie; Euler, Zelda; Fiorino, Fabio; Grupping, Katrijn; Hallengärd, David; Javed, Aneele; Mendonca, Kevin; Pollard, Charlotte; Reinhart, David; Saba, Elisa; Sheik-Khalil, Enas; Sköld, Annette; Ziglio, Serena; Scarlatti, Gabriella; Gotch, Frances; Wahren, Britta; Shattock, Robin J

2012-07-11

Europrise is a Network of Excellence supported by the European Commission within the 6th Framework programme from 2007 to 2012. The Network has involved over 50 institutions from 13 European countries together with 3 industrial partners and 6 African countries. The Network encompasses an integrated program of research, training, dissemination and advocacy within the field of HIV vaccines and microbicides. A central and timely theme of the Network is the development of the unique concept of co-usage of vaccines and microbicides. Training of PhD students has been a major task, and some of these post-graduate students have here summarized novel ideas emanating from presentations at the last annual Europrise meeting in Prague. The latest data and ideas concerning HIV vaccine and microbicide studies are included in this review; these studies are so recent that the majority have yet to be published. Data were presented and discussed concerning novel immunisation strategies; microbicides and PrEP (alone and in combination with vaccines); mucosal transmission of HIV/SIV; mucosal vaccination; novel adjuvants; neutralizing antibodies; innate immune responses; HIV/SIV pathogenesis and disease progression; new methods and reagents. These - necessarily overlapping topics - are comprehensively summarised by the Europrise students in the context of other recent exciting data.

Immunogenicity of DNA- and recombinant protein-based Alzheimer disease epitope vaccines.

PubMed

Davtyan, Hayk; Bacon, Andrew; Petrushina, Irina; Zagorski, Karen; Cribbs, David H; Ghochikyan, Anahit; Agadjanyan, Michael G

2014-01-01

Alzheimer disease (AD) process involves the accumulation of amyloid plaques and tau tangles in the brain, nevertheless the attempts at targeting the main culprits, neurotoxic β-amyloid (Aβ) peptides, have thus far proven unsuccessful for improving cognitive function. Important lessons about anti-Aβ immunotherapeutic strategies were learned from the first active vaccination clinical trials. AD progression could be safely prevented or delayed if the vaccine (1) induces high titers of antibodies specific to toxic forms of Aβ; (2) does not activate the harmful autoreactive T cells that may induce inflammation; (3) is initiated before or at least at the early stages of the accumulation of toxic forms of Aβ. Data from the recent passive vaccination trials with bapineuzumab and solanezumab also indicated that anti-Aβ immunotherapy might be effective in reduction of the AD pathology and even improvement of cognitive and/or functional performance in patients when administered early in the course of the disease. For the prevention of AD the active immunization strategy may be more desirable than passive immunotherapy protocol and it can offer the potential for sustainable clinical and commercial advantages. Here we discuss the active vaccine approaches, which are still in preclinical development and vaccines that are already in clinical trials.

A brief history of hepatitis milestones.

PubMed

Trepo, Christian

2014-02-01

Hepatitis has been a major plague of mankind. The history of the discovery of causative viruses is one of the most fascinating scientific adventures of this half century. Individualization of several types of hepatitis only emerged after world war two. Their identification has been associated with milestones which revolutionized medicine and public health. The discovery of HBV brought the first ever vaccine not prepared by tissue culture but initially directly from plasma and soon the first vaccine produced by genetic engineering. HBV vaccine proved to be the first "anti-cancer" vaccine by preventing hepatocellular carcinoma and practically eradicating it from childhood in Taiwan. Successful vaccines became also available for HAV and more recently HEV. The discovery of HCV in 1989 opened a new era since it was the first virus was identified by a direct molecular approach. Two billion people are infected with HBV and 350 million are chronic carriers of the virus. The extraordinary effectiveness of HBV vaccination was best illustrated in Taiwan and Singapore where in less than 2 decades HBs Ag carriers dropped from 9,1% to 2,7% and HCC from 27% to 17%. Successful development of nucleos(t)ides analogs make it now possible to fully control disease progression with a daily pill long term therapy. The progress in HCV therapy has been even more spectacular and successful treatment jumped from 6 % with interferon alone in 1986 to more than 80% in 2013 with triple combination therapies. Remarkably chronic hepatitis C is the only chronic disease which is curable. It will be soon possible to eradicate HCV infection with, an all oral, daily single pill (containing several molecules) for 3 to 6 months which will cure over 90% of patients. This unprecedented therapeutic victory benefiting hundred millions of people matches the triumphs over small pox, polio and tuberculosis. The next 10 years should undoubtedly witness cure or full control over all forms of acute and chronic hepatitis. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Recent Developments in Synthetic Carbohydrate-Based Diagnostics, Vaccines, and Therapeutics.

PubMed

Fernández-Tejada, Alberto; Cañada, F Javier; Jiménez-Barbero, Jesús

2015-07-20

Glycans are everywhere in biological systems, being involved in many cellular events with important implications for medical purposes. Building upon a detailed understanding of the functional roles of carbohydrates in molecular recognition processes and disease states, glycans are increasingly being considered as key players in pharmacological research. On the basis of the important progress recently made in glycochemistry, glycobiology, and glycomedicine, we provide a complete overview of successful applications and future perspectives of carbohydrates in the biopharmaceutical and medical fields. This review highlights the development of carbohydrate-based diagnostics, exemplified by glycan imaging techniques and microarray platforms, synthetic oligosaccharide vaccines against infectious diseases (e.g., HIV) and cancer, and finally carbohydrate-derived therapeutics, including glycomimetic drugs and glycoproteins. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Plague.

PubMed

Williamson, E D

2009-11-05

Killed whole cell vaccines for plague were first produced as long ago as the late 1890s and modified versions of these are still used, with evidence that they are efficacious against bubonic plague. Renewed efforts with modern technology have yielded new candidate vaccines which are less reactogenic, can be produced in a conventional pharmaceutical manufacturing plant and are protective against the life-threatening pneumonic form of the disease. This paper reviews the progress towards an improved vaccine for plague and assesses the likely impact of a prophylactic vaccine for bubonic and pneumonic plague.

Controlled human infection with RSV: The opportunities of experimental challenge.

PubMed

Habibi, Maximillian S; Chiu, Christopher

2017-01-11

Despite the recent explosion in RSV vaccine development, there remain substantial hurdles to overcome before licensing of effective vaccines will allow widespread use, particularly in high-risk populations. Incomplete understanding of mechanisms and correlates of protection against RSV mean that, for the time being, successful RSV vaccines must directly demonstrate efficacy, which necessitates large and costly clinical trials in naturally infected patients. To mitigate the risks inherent in progressing to these late-stage trials, experimental human RSV infection studies have recently been re-established, representing the interface between pre-clinical models and observational studies of patients. Not only can they be used for early proof-of-concept clinical trials to test vaccine efficacy, but human challenge studies also offer the potential to better understand protective immunity against RSV infection to improve vaccine design and delivery. In the past, controlled human infection studies with RSV have been instrumental in elucidating the influence of factors such as route of infection and type of inoculum on the course of disease. Recently, efficacy trials of novel RSV antiviral drugs have also been successfully undertaken. Now, with advances in technology, detailed investigations of human mucosal immunity in the RSV-infected airway are possible. These have indicated defects in RSV-induced humoral and CD8+ T cell immunity that may contribute to the recurrent symptomatic infection that occurs throughout life and should be circumvented by optimal vaccines. Here, we discuss the insights derived from RSV human challenge models; the major impediments to their more widespread uptake; and their potential benefit in accelerating vaccine development, including future directions to further enhance the relevance of these models to at-risk patient populations. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Use of a LiESP/QA-21 Vaccine (CaniLeish) Stimulates an Appropriate Th1-Dominated Cell-Mediated Immune Response in Dogs

PubMed Central

Moreno, Javier; Vouldoukis, Ioannis; Martin, Virginie; McGahie, David; Cuisinier, Anne-Marie; Gueguen, Sylvie

2012-01-01

Canine leishmaniasis is an important zoonotic disease of dogs. The clinical outcome of infection is variable, with the efficiency of the immune response being the key determining factor. There is now a general consensus that a predominant Th1 immune profile in an overall mixed Th1/Th2 response is associated with resistance in dogs, and the absence of a strong Th1 influence is associated with a progression to clinical disease. As a result, there has been a growing demand for vaccines that can induce a specific, strong Th1 response. In this study, we measured the impact of a primary course of a newly available LiESP/QA-21 vaccine on selected humoral and cellular markers of the canine immune response during the onset of immunity. All vaccinated dogs developed a humoral response characterised by IgG2 production. More importantly, vaccinated dogs developed significantly stronger cell-mediated immunity responses than did control dogs. Vaccination induced specific cellular reactivity to soluble Leishmania antigens, with a Leishmania-specific lymphoproliferation (p = 0.0072), characterised by an increased population of T lymphocytes producing IFN-γ (p = 0.0021) and a significant ability of macrophages to reduce intracellular parasite burdens in vitro after co-culture with autologous lymphocytes (p = 0.0014). These responses were correlated with induction of the NOS pathway and production of NO derivatives, which has been shown to be an important leishmanicidal mechanism. These results confirm that vaccination with LiESP/QA-21 induces an appropriate Th1-profile cell-mediated response within three weeks of completing the primary course, and that this response effectively reduces the parasite load in pre-infected macrophages in vitro. PMID:22724031

The Human Papillomavirus Vaccine: Current Perspective and Future Role in Prevention and Treatment of Anal Intraepithelial Neoplasia and Anal Cancer

PubMed Central

Mehta, Mudresh R.; Lewis, James S.; Lockhart, A. Craig

2016-01-01

The incidences of human papillomavirus (HPV)-related anal cancer and its precursor lesion, anal intraepithelial neoplasia, are rising in the U.S. and globally. Five-year survival rates with current modalities of treatment for anal cancer are generally favorable for localized and regional disease. For metastatic disease, the relative survival rate is poor. Major contributing factors for the increase in anal cancer incidence include increasing receptive anal intercourse (hetero- and homosexual), increasing HPV infections, and longer life expectancy of treated people who are seropositive for human immunodeficiency virus. Because treatment outcomes with systemic therapy in patients with advanced disease are so poor, prevention may be the best approach for reducing disease burden. The association of a major causative agent with anal cancer provides an excellent opportunity for prevention and treatment. The advent of the HPV vaccine for anal cancer prevention and treatment is a significant milestone and has the potential to greatly impact these cancers. The data regarding potential use of the HPV vaccine in anal cancer prevention and treatment are reviewed. Implications for Practice: The incidences of human papillomavirus (HPV)-related anal cancer and its precursor lesion, anal intraepithelial neoplasia, are on the rise in the U.S. and globally. Based on recent studies, the HPV vaccine is approved for prevention of the infection and development of HPV-related anal cancer. In addition, several small studies have shown that the vaccine may be useful as adjuvant therapy for anal cancer. There is a need for public health strategies aimed at education of both patients and practitioners to improve the use of the vaccine for prevention of HPV-related anal cancer. The development of a therapeutic vaccine is a work in progress. PMID:26961923

Evaluation of cross-protection by immunization with an experimental trivalent companion animal periodontitis vaccine in the mouse periodontitis model.

PubMed

Hardham, John; Sfintescu, Cornelia; Evans, Richard T

2008-03-01

Companion animal periodontal disease is one of the most prevalent diseases seen by veterinarians. The goal of this study was to evaluate the vaccine performance of a trivalent canine periodontitis vaccine in the mouse oral challenge model of periodontitis. Mice vaccinated subcutaneously with an inactivated, whole-cell vaccine preparation of Porphyromonas denticanis, Porphyromonas gulae, and Porphyromonas salivosa displayed significantly reduced alveolar bone loss in response to heterologous and cross-species challenges as compared to sham vaccinated animals. Based on the results of these studies, a periodontitis vaccine may be a useful tool in preventing the initiation and progression of periodontitis caused by the most commonly isolated pigmenting anaerobic bacteria in animals.

[Research progress on fascioliasis].

PubMed

Liu, Qian; Cheng, Na; Zhou, Yan; Xu, Xue-Nian

2013-06-01

Fascioliasis is an important zoonosis caused by Fasciola spp. It can cause pathological damages to human liver and gallbladder, as well as economic loss in animal husbandry. Fascioliasis can be easily misdiagnosed with other hepatobiliary diseases. The appearance of resistance to triclabendazole is an issue problem for fascioliasis control. Therefore, research for better diagnostic methods, effective drugs and vaccines become to the focus of fascioliasis control. This article summarizes the progress on epidemiological status, diagnostic method, therapy, drug resistance, vaccine and omics of fascioliasis.

Elimination of Dog-Mediated Human Rabies Deaths by 2030: Needs Assessment and Alternatives for Progress Based on Dog Vaccination.

PubMed

Wallace, Ryan M; Undurraga, Eduardo A; Blanton, Jesse D; Cleaton, Julie; Franka, Richard

2017-01-01

Rabies imposes a substantial burden to about half of the world population. The World Health Organization (WHO), World Organization for Animal Health, and the Food and Agriculture Organization have set the goal of eliminating dog-mediated human rabies deaths by 2030. This could be achieved largely by massive administration of post-exposure prophylaxis-in perpetuity-, through elimination of dog rabies, or combining both. Here, we focused on the resources needed for the elimination of dog rabies virus by 2030. Drawing from multiple datasets, including national dog vaccination campaigns, rabies literature, and expert opinion, we developed a model considering country-specific current dog vaccination capacity to estimate the years and resources required to achieve dog rabies elimination by 2030. Resources were determined based on four factors: (a) country development status, (b) dog vaccination costs, (c) dog rabies vaccine availability, and (d) existing animal health workers. Our calculations were based on the WHO's estimate that vaccinating 70% of the dog population for seven consecutive years would eliminate rabies. If dog rabies vaccine production remains at 2015 levels, we estimate that there will be a cumulative shortage of about 7.5 billion doses to meet expected demand to achieve dog rabies elimination. We estimated a present cost of $6,300 million to eliminate dog rabies in all endemic countries, equivalent to a $3,900 million gap compared to current spending. To eliminate dog rabies, the vaccination workforce may suffice if all public health veterinarians in endemic countries were to dedicate 3 months each year to dog rabies vaccination. We discuss implications of potential technology improvements, including population management, vaccine price reduction, and increases in dog-vaccinating capacities. Our results highlight the resources needed to achieve elimination of dog-mediated human rabies deaths by 2030. As exemplified by multiple successful disease elimination efforts, one size does not fit all. We suggest pragmatic and feasible options toward global dog rabies elimination by 2030, while identifying several benefits and drawbacks of specific approaches. We hope that these results help stimulate and inform a necessary discussion on global and regional strategic planning, resource mobilization, and continuous execution of rabies virus elimination.

Modeling Combinations of Pre-erythrocytic Plasmodium falciparum Malaria Vaccines.

PubMed

Walker, Andrew S; Lourenço, José; Hill, Adrian V S; Gupta, Sunetra

2015-12-01

Despite substantial progress in the control of Plasmodium falciparum infection due to the widespread deployment of insecticide-treated bed nets and artemisinin combination therapies, malaria remains a prolific killer, with over half a million deaths estimated to have occurred in 2013 alone. Recent evidence of the development of resistance to treatments in both parasites and their mosquito vectors has underscored the need for a vaccine. Here, we use a mathematical model of the within-host dynamics of P. falciparum infection, fit to data from controlled human malaria infection clinical trials, to predict the efficacy of co-administering the two most promising subunit vaccines, RTS,S/AS01 and ChAd63-MVA ME-TRAP. We conclude that currently available technologies could be combined to induce very high levels of sterile efficacy, even in immune-naive individuals. © The American Society of Tropical Medicine and Hygiene.

[Origin and development of RUTI, a new therapeutic vaccine against Mycobacterium tuberculosis infection].

PubMed

Cardona, P J; Amat, I

2006-01-01

This article reviews the pathophysiology of the latent form of Mycobacterium tuberculosis along with its natural history and progression in infected tissues. The proposed hypotheses regarding the relationship between M tuberculosis and the associated immune response, the cause of granuloma necrosis, the tolerance of a certain concentration of the bacillus in host tissues, the constant turnover of cells in the lung, and the effect of chemotherapy form the basis for the design of the therapeutic vaccine RUTI against latent M tuberculosis infection. This vaccine is generated from detoxified M tuberculosis cell fragments that facilitate a balanced T helper (Th) 1/Th2/Th3 response to a wide range of antigens along with intense antibody production. Treatment with RUTI following chemotherapy has been demonstrated to be effective in experimental models in mice and guinea pigs and does not exhibit toxicity.

Genital Human Papillomavirus Infection Progression to External Genital Lesions: The HIM Study.

PubMed

Sudenga, Staci L; Ingles, Donna J; Pierce Campbell, Christine M; Lin, Hui-Yi; Fulp, William J; Messina, Jane L; Stoler, Mark H; Abrahamsen, Martha; Villa, Luisa L; Lazcano-Ponce, Eduardo; Giuliano, Anna R

2016-01-01

Human papillomavirus (HPV) causes two types of external genital lesions (EGLs) in men: genital warts (condyloma) and penile intraepithelial neoplasia (PeIN). The purpose of this study was to describe genital HPV progression to a histopathologically confirmed HPV-related EGL. A prospective analysis nested within the HPV Infection in Men (HIM) study was conducted among 3033 men. At each visit, visually distinct EGLs were biopsied; the biopsy specimens were subjected to pathologic evaluation and categorized by pathologic diagnoses. Genital swabs and biopsies were used to identify HPV types using the Linear Array genotyping method for swabs and INNO-LiPA for biopsy specimens. EGL incidence was determined among 1788 HPV-positive men, and cumulative incidence rates at 6, 12, and 24 mo were estimated. The proportion of HPV infections that progressed to EGL was also calculated, along with median time to EGL development. Among 1788 HPV-positive men, 92 developed an incident EGL during follow-up (9 PeIN and 86 condyloma). During the first 12 mo of follow-up, 16% of men with a genital HPV 6 infection developed an HPV 6-positive condyloma, and 22% of genital HPV 11 infections progressed to an HPV 11-positive condyloma. During the first 12 mo of follow-up, 0.5% of men with a genital HPV 16 infection developed an HPV 16-positive PeIN. Although we expected PeIN to be a rare event, the sample size for PeIN (n=10) limited the types of analyses that could be performed. Most EGLs develop following infection with HPV 6, 11, or 16, all of which could be prevented with the 4-valent HPV vaccine. In this study, we looked at genital human papillomavirus (HPV) infections that can cause lesions in men. The HPV that we detected within the lesions could be prevented by a vaccine. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Self-reported Adverse Health Events Following Smallpox Vaccination in a Large Prospective Study of US Military Service Members

DTIC Science & Technology

2007-08-27

bullous erythema multiforme (Stevens‑Johnson syndrome), eczema vaccinatum, generalized vaccinia, progressive vaccinia, and postvac‑ cinal...reported health outcomes, including mental and physical functioning , cardiovascular diseases, and auto- immune disorders, were found. These findings...words: smallpox vaccine, questionnaires, military medicine , longitudinal studies, chronic disease, quality of life [Human Vaccines 4:2, 127‑133; March

Knowledge, attitudes and practices on adolescent vaccination among adolescents, parents and teachers in Africa: A systematic review.

PubMed

Abdullahi, Leila H; Kagina, Benjamin M; Cassidy, Tali; Adebayo, Esther F; Wiysonge, Charles S; Hussey, Gregory D

2016-07-25

Vaccines are the most successful and cost-effective public health interventions available to avert vaccine-preventable diseases and deaths. Despite global progress in adolescent health, many adolescents in Africa still get sick and die from vaccine-preventable diseases due to lack of vaccination. Adolescents, parents and teachers are key players in the development and implementation of adolescent vaccination policies. Optimal knowledge, attitudes and practices towards adolescent vaccination among these key players may improve vaccine uptake among adolescents. We conducted a qualitative and quantitative systematic review on knowledge, attitudes and practices of adolescent vaccination among adolescents, parents and teachers in Africa. We searched PubMed, Cochrane Central Register of Controlled Trials, Scopus, Web of Science, WHOLIS, Africa Wide and CINAHL for eligible quantitative and qualitative primary studies with no time limits. We also checked reference lists of included studies for eligible studies and searched grey literature. Two authors independently screened the search outputs, selected studies and extracted data; resolving discrepancies by consensus and discussion. Qualitative data were analysed using thematic analyses where applicable, while analyses from quantitative studies used different methods based on the type of outcomes. We included 18 cross-sectional studies in this review. The included studies were conducted in 10 out of the 54 countries in Africa. The 18 studies focused on a wide range of adolescent vaccines. Thirteen studies evaluated vaccines against Human Papilloma Virus, while each of the remaining 5 studies, evaluated vaccines against rabies, HIV, tetanus toxoid, tuberculosis and adolescent vaccines in general. Among the key players, we found low to moderate levels of knowledge about adolescent vaccination. Positive attitudes and practices towards adolescent vaccination, especially against Human Papilloma Virus were reported. Despite the low knowledge, our results showed high levels of acceptability to adolescent vaccination among adolescents, parents and teachers. It was evident in our review that all key demographics (parents, adolescents and teachers) were receptive towards adolescent vaccines. We propose relevant policy makers in Africa to consider continuous education programs such as those aimed to inform the parents, adolescents and teachers on adolescent vaccination. Copyright © 2016 Elsevier Ltd. All rights reserved.

Plague history: Yersin's discovery of the causative bacterium in 1894 enabled, in the subsequent century, scientific progress in understanding the disease and the development of treatments and vaccines.

PubMed

Butler, T

2014-03-01

The causative bacterium of plague was described and cultured by Alexandre Yersin in Hong Kong in 1894, after which transmission of bacteria from rodents by flea bites was discovered by Jean-Paul Simond in 1898. Effective treatment with antiserum was initiated in 1896, but this therapy was supplanted by sulphonamides in the 1930s and by streptomycin starting in 1947. India suffered an estimated 6 million deaths in 1900-1909, and Vietnam, during its war in 1965-1975, accounted for approximately 80% of the world's cases; since then, African countries have dominated, with >90% of the world's cases in the 1990s and early 21st century. Serological diagnosis with fraction 1 antigen to detect anti-plague antibodies was developed in the 1950s. Vaccine development started in 1897 with killed whole bacterial cells, and this was followed by a live attenuated bacterial vaccine, leading to millions of persons receiving injections, but the benefits of these vaccines remain clouded by controversy. Plasmid-mediated virulence was established in 1981, and this was followed by specific DNA methods that have allowed detection of plague genes in skeletal specimens from European graves of the sixth to 17th centuries. © 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

'Poisonous, filthy, loathsome, damnable stuff': the rhetorical ecology of vaccination concern.

PubMed

Hausman, Bernice L; Ghebremichael, Mecal; Hayek, Philip; Mack, Erin

2014-12-01

In this article, we analyze newspaper articles and advertisements mentioning vaccination from 1915 to 1922 and refer to historical studies of vaccination practices and attitudes in the early 20th century in order to assess historical continuities and discontinuities in vaccination concern. In the Progressive Era period, there were a number of themes or features that resonated with contemporary issues and circumstances: 1) fears of vaccine contamination; 2) distrust of medical professionals; 3) resistance to compulsory vaccination; and 4) the local nature of vaccination concern. Such observations help scholars and practitioners understand vaccine skepticism as longstanding, locally situated, and linked to the sociocultural contexts in which vaccination occurs and is mandated for particular segments of the population. A rhetorical approach offers a way to understand how discourses are engaged and mobilized for particular purposes in historical contexts. Historically situating vaccine hesitancy and addressing its articulation with a particular rhetorical ecology offers scholars and practitioners a robust understanding of vaccination concerns that can, and should, influence current approaches to vaccination skepticism.

Oral vaccination of wildlife against rabies: opportunities and challenges in prevention and control.

PubMed

Rupprecht, C E; Hanlon, C A; Slate, D

2004-01-01

Rabies is an acute, progressive, fatal encephalitis caused by viruses in the Family Rhabdoviridae, Genus Lyssavirus. Rabies virus is the representative member of the group. Warm-blooded vertebrates are susceptible to experimental infection, but major primary hosts for disease perpetuation encompass bats and mammalian carnivores. The dog is the global reservoir, and important wild carnivores include foxes, raccoons, skunks, and mongoose, among others. Traditionally, reliance upon long-term, widespread, government-supported programmes aimed at population reduction of animals at risk has been unsuccessful as the sole means of rabies control, based in part upon economical, ecological and ethical grounds. In contrast, immunization of domestic dogs with traditional veterinary vaccines by the parenteral route led to the virtual extinction of canine-transmitted rabies in developed countries. Taken from this basic concept of applied herd immunity, the idea of wildlife vaccination was conceived during the 1960s, and modified-live rabies viruses were used for the experimental oral vaccination of carnivores by the 1970s. The development of safe and effective rabies virus vaccines applied in attractive baits resulted in the first field trials in Switzerland in 1978. Thereafter, technical improvements occurred in vaccine quality and production, including the design of recombinant viruses, as well as in the ease of mass distribution of millions of edible baits over large geographical areas. Over the past few decades, extensive oral vaccination programmes focusing upon the red fox, using hand and aerial distribution of vaccine-laden baits, have resulted in the virtual disappearance of rabies in Western Europe. The same dramatic observation held true for southern Ontario. During the 1990s in the United States, oral vaccination programmes concentrated upon raccoons, grey foxes, and coyotes, with similar success. For example, raccoon rabies has not spread west of the current focus in the eastern states, grey fox rabies is contained in west central Texas, and no recent cases of rabies have been reported from coyotes away from the Mexican border for several years. Despite the progress observed and the absence of substantive adverse environmental or health effects, oral vaccination is not a panacea, and should be viewed as an important adjunct to traditional prevention and control techniques in human and veterinary medicine. Local outbreak suppression of rabies among free-ranging wildlife is documented, and regional elimination of particular virus variants among specific, targeted carnivore hosts is demonstrable, but true disease eradication is not achievable at the present time by current techniques. For example, no practical vaccination methods have been designed for bats. Although lyssaviruses appear in relative compartmentalization between the Chiroptera and Carnivora, major spillover events have been detected from bats to carnivores, and phylogenetic analyses suggest a historical basis for extant viral origins due to interactions between these taxa. Thus, bio-political considerations aside, the possibility for pathogen emergence resulting from transmission by rabid bats with subsequent perpetuation among other animals cannot be discounted easily on any continent, with the possible exception of Antarctica. Clearly, given their biodiversity, distribution, and abundance, novel methods would be necessary to consider meaningful control of rabies in these unique volant mammals. Newer approaches in biotechnology may be envisaged some day for eventual extension to bats, as well as more widespread application to global canine rabies remediation in developing countries.

Bringing DNA vaccines closer to commercial use.

PubMed

Carvalho, Joana A; Prazeres, Duarte M F; Monteiro, Gabriel A

2009-10-01

Progress in the application of DNA vaccines as an immunization protocol is evident from the increasing number of such vaccines under evaluation in clinical trials and by the recent approval of several DNA vaccine products for veterinary applications. DNA vaccine technology offers important therapeutic and commercial advantages compared with conventional approaches, including the opportunity to target pathogens characterized by significant genetic diversity using a safe immunization platform, and the ability to use a simple, rapid and well-characterized production method. However, further optimization of DNA vaccine technology through the use of improved constructs, delivery systems and immunization protocols is necessary to clinically achieve the promising results that have been demonstrated in preclinical models.

Immunologic treatments for precancerous lesions and uterine cervical cancer

PubMed Central

2014-01-01

Development of HPV-associated cancers not only depends on efficient negative regulation of cell cycle control that supports the accumulation of genetic damage, but also relies on immune evasion that enable the virus to go undetected for long periods of time. In this way, HPV-related tumors usually present MHC class I down-regulation, impaired antigen-processing ability, avoidance of T-cell mediated killing, increased immunosuppression due to Treg infiltration and secrete immunosuppressive cytokines. Thus, these are the main obstacles that immunotherapy has to face in the treatment of HPV-related pathologies where a number of different strategies have been developed to overcome them including new adjuvants. Although antigen-specific immunotherapy induced by therapeutic HPV vaccines was proved extremely efficacious in pre-clinical models, its progression through clinical trials suffered poor responses in the initial trials. Later attempts seem to have been more promising, particularly against the well-defined precursors of cervical, anal or vulvar cancer, where the local immunosuppressive milieu is less active. This review focuses on the advances made in these fields, highlighting several new technologies (such as mRNA vaccine, plant-derived vaccine). The most promising immunotherapies used in clinical trials are also summarized, along with integrated strategies, particularly promising in controlling tumor metastasis and in eliminating cancer cells altogether. After the early promising clinical results, the development of therapeutic HPV vaccines need to be implemented and applied to the users in order to eradicate HPV-associated malignancies, eradicating existing perception (after the effectiveness of commercial preventive vaccines) that we have already solved the problem. PMID:24667138

"The Impact of Mycobacterium tuberculosis Immune Evasion on Protective Immunity: Implications for TB Vaccine Design" - Meeting report.

PubMed

Boggiano, Cesar; Eichelberg, Katrin; Ramachandra, Lakshmi; Shea, Jaqueline; Ramakrishnan, Lalita; Behar, Samuel; Ernst, Joel D; Porcelli, Steven A; Maeurer, Markus; Kornfeld, Hardy

2017-06-14

Tuberculosis (TB) is the major cause of death from infectious diseases around the world, particularly in HIV infected individuals. TB vaccine design and development have been focused on improving Bacille Calmette-Guérin (BCG) and evaluating recombinant and viral vector expressed Mycobacterium tuberculosis (Mtb) proteins, for boosting BCG-primed immunity, but these approaches have not yet yielded significant improvements over the modest effects of BCG in protecting against infection or disease. On March 7-8, 2016, the National Institute of Allergy and Infectious Diseases (NIAID) convened a workshop on "The Impact of Mtb Immune Evasion on Protective Immunity: Implications for TB Vaccine Design" with the goal of defining immune mechanisms that could be targeted through novel research approaches, to inform vaccine design and immune therapeutic interventions for prevention of TB. The workshop addressed early infection events, the impact of Mtb evolution on the development and maintenance of an adaptive immune response, and the factors that influence protection against and progression to active disease. Scientific gaps and areas of study to revitalize and accelerate TB vaccine design were discussed and prioritized. These included a comprehensive evaluation of innate and Mtb-specific adaptive immune responses in the lung at different stages of disease; determining the role of B cells and antibodies (Abs) during Mtb infection; development of better assays to measure Mtb burden following exposure, infection, during latency and after treatment, and approaches to improving current animal models to study Mtb immunogenicity, TB disease and transmission. Copyright © 2017.

Human papilloma virus vaccines: Current scenario

PubMed Central

Pandhi, Deepika; Sonthalia, Sidharth

2011-01-01

Genital human papillomavirus (HPV) infection is the most common sexually transmitted infection with an estimated worldwide prevalence of 9–13% and approximately 6 million people being infected each year. Mostly acquired during adolescence or young adulthood, HPV presents clinically as anogenital warts and may progress to precancerous lesions and cancers of the cervix, vagina, vulva, penis and anus, and oropharynx. HPV infection is considered to contribute to almost 100% cervical cancers and at least 80% of anal and 40–60% of vulvar, vaginal, and penile cancers. At present, two prophylactic HPV vaccines are commercially available and both are prepared from purified L1 structural proteins. These proteins self-assemble to form virus-like particles that induce a protective immunity. Gardasil® is a quadrivalent vaccine against HPV types 6, 11, 16, and 18 and is recommended for use in females 9–26 years of age, for the prevention of cervical, vulvar, and vaginal cancers and intraepithelial neoplasia and condyloma acuminata and recently for vaccination in boys and men 9–26 years of age for the prevention of genital warts. Cervarix™ is a bivalent vaccine approved for the prevention of cervical cancer and precancerous lesions caused by HPV 16 and 18, in females 10–25 years. HPV vaccines are safe and efficacious against type-specific HPV-induced anogenital warts, precancerous lesions, and cervical cancer. The vaccines are most effective when given before the onset of sexual activity and provide long-term protection. Effective vaccination coverage in young adolescent females will substantially reduce the incidence of these anogenital malignancy-related morbidity and mortality. There is need to generate India-specific data on HPV epidemiology and HPV vaccination efficacy as well as continue worldwide surveillance and development of newer vaccines. PMID:22021967

Tools and Strategies for Malaria Control and Elimination: What Do We Need to Achieve a Grand Convergence in Malaria?

PubMed Central

Hemingway, Janet; Shretta, Rima; Wells, Timothy N. C.; Bell, David; Djimdé, Abdoulaye A.; Achee, Nicole; Qi, Gao

2016-01-01

Progress made in malaria control during the past decade has prompted increasing global dialogue on malaria elimination and eradication. The product development pipeline for malaria has never been stronger, with promising new tools to detect, treat, and prevent malaria, including innovative diagnostics, medicines, vaccines, vector control products, and improved mechanisms for surveillance and response. There are at least 25 projects in the global malaria vaccine pipeline, as well as 47 medicines and 13 vector control products. In addition, there are several next-generation diagnostic tools and reference methods currently in development, with many expected to be introduced in the next decade. The development and adoption of these tools, bolstered by strategies that ensure rapid uptake in target populations, intensified mechanisms for information management, surveillance, and response, and continued financial and political commitment are all essential to achieving global eradication. PMID:26934361

Tools and Strategies for Malaria Control and Elimination: What Do We Need to Achieve a Grand Convergence in Malaria?

PubMed

Hemingway, Janet; Shretta, Rima; Wells, Timothy N C; Bell, David; Djimdé, Abdoulaye A; Achee, Nicole; Qi, Gao

2016-03-01

Progress made in malaria control during the past decade has prompted increasing global dialogue on malaria elimination and eradication. The product development pipeline for malaria has never been stronger, with promising new tools to detect, treat, and prevent malaria, including innovative diagnostics, medicines, vaccines, vector control products, and improved mechanisms for surveillance and response. There are at least 25 projects in the global malaria vaccine pipeline, as well as 47 medicines and 13 vector control products. In addition, there are several next-generation diagnostic tools and reference methods currently in development, with many expected to be introduced in the next decade. The development and adoption of these tools, bolstered by strategies that ensure rapid uptake in target populations, intensified mechanisms for information management, surveillance, and response, and continued financial and political commitment are all essential to achieving global eradication.

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

The Current Status of the Disease Caused by Enterovirus 71 Infections: Epidemiology, Pathogenesis, Molecular Epidemiology, and Vaccine Development

PubMed Central

Chang, Ping-Chin; Chen, Shou-Chien; Chen, Kow-Tong

2016-01-01

Enterovirus 71 (EV71) infections have a major public health impact in the Asia-Pacific region. We reviewed the epidemiology, pathogenesis, and molecular epidemiology of EV71 infection as well as EV71 vaccine development. Previous studies were found using the search terms “enterovirus 71” and “epidemiology” or “pathogenesis” or “molecular epidemiology” or “vaccine” in Medline and PubMed. Articles that were not published in the English language, manuscripts without an abstract, and opinion articles were excluded from the review. The reported epidemiology of cases caused by EV71 infection varied from country to country; seasonal variations in incidence were observed. Most cases of EV71 infection that resulted in hospitalization for complications occurred in children less than five years old. The brainstem was the most likely major target of EV71 infection. The emergence of the EV71 epidemic in the Asia-Pacific region has been associated with the circulation of different genetic lineages (genotypes B3, B4, C1, C2, and C4) that appear to be undergoing rapid evolutionary changes. The relationship between the gene structure of the EV71 virus and the factors that ensure its survival, circulation, and evasion of immunity is still unknown. EV71 infection has emerged as an important global public health problem. Vaccine development, including the development of inactivated whole-virus live attenuated, subviral particles, and DNA vaccines, has been progressing. PMID:27618078

Evidence that antibodies against recombinant SnSAG1 of Sarcocystis neurona merozoites are involved in infection and immunity in equine protozoal myeloencephalitis.

PubMed

Ellison, Siobhan; Witonsky, Sharon

2009-07-01

Sarcocystis neurona is the principal etiologic agent of equine protozoal myeloencephalitis (EPM). An immunodominant protein of S. neurona, SnSAG-1, is expressed by the majority of S. neurona merozoites isolated from spinal tissues of horses diagnosed with EPM and may be a candidate for diagnostic tests and prophylaxis for EPM. Five horses were vaccinated with adjuvanted recombinant SnSAG1 (rSnSAG1) and 5 control (sham vaccinated) horses were vaccinated with adjuvant only. Serum was evaluated pre- and post-vaccination, prior to challenge, for antibodies against rSnSAG1 and inhibitory effects on the infectivity of S. neurona by an in vitro serum neutralization assay. The effect of vaccination with rSnSAG1 on in vivo infection by S. neurona was evaluated by challenging all the horses with S. neurona merozoites. Blinded daily examinations and 4 blinded neurological examinations were used to evaluate the presence of clinical signs of EPM. The 5 vaccinated horses developed serum and cerebrospinal fluid (CSF) titers of SnSAG1, detected by enzyme-linked immunosorbent assay (ELISA), post-vaccination. Post-vaccination serum from vaccinated horses was found to have an inhibitory effect on merozoites, demonstrated by in vitro bioassay. Following the challenge, the 5 control horses displayed clinical signs of EPM, including ataxia. While 4 of the 5 vaccinated horses did not become ataxic. One rSnSAG-1 vaccinated horse showed paresis in 1 limb with muscle atrophy. All horses showed mild, transient, cranial nerve deficits; however, disease did not progress to ataxia in rSnSAG-1 vaccinated horses. The study showed that vaccination with rSnSAG-1 produced antibodies in horses that neutralized merozoites when tested by in vitro culture and significantly reduced clinical signs demonstrated by in vivo challenge.

Evidence that antibodies against recombinant SnSAG1 of Sarcocystis neurona merozoites are involved in infection and immunity in equine protozoal myeloencephalitis

PubMed Central

Ellison, Siobhan; Witonsky, Sharon

2009-01-01

Sarcocystis neurona is the principal etiologic agent of equine protozoal myeloencephalitis (EPM). An immunodominant protein of S. neurona, SnSAG-1, is expressed by the majority of S. neurona merozoites isolated from spinal tissues of horses diagnosed with EPM and may be a candidate for diagnostic tests and prophylaxis for EPM. Five horses were vaccinated with adjuvanted recombinant SnSAG1 (rSnSAG1) and 5 control (sham vaccinated) horses were vaccinated with adjuvant only. Serum was evaluated pre- and post-vaccination, prior to challenge, for antibodies against rSnSAG1 and inhibitory effects on the infectivity of S. neurona by an in vitro serum neutralization assay. The effect of vaccination with rSnSAG1 on in vivo infection by S. neurona was evaluated by challenging all the horses with S. neurona merozoites. Blinded daily examinations and 4 blinded neurological examinations were used to evaluate the presence of clinical signs of EPM. The 5 vaccinated horses developed serum and cerebrospinal fluid (CSF) titers of SnSAG1, detected by enzyme-linked immunosorbent assay (ELISA), post-vaccination. Post-vaccination serum from vaccinated horses was found to have an inhibitory effect on merozoites, demonstrated by in vitro bioassay. Following the challenge, the 5 control horses displayed clinical signs of EPM, including ataxia. While 4 of the 5 vaccinated horses did not become ataxic. One rSnSAG-1 vaccinated horse showed paresis in 1 limb with muscle atrophy. All horses showed mild, transient, cranial nerve deficits; however, disease did not progress to ataxia in rSnSAG-1 vaccinated horses. The study showed that vaccination with rSnSAG-1 produced antibodies in horses that neutralized merozoites when tested by in vitro culture and significantly reduced clinical signs demonstrated by in vivo challenge. PMID:19794889

Mode-of-action, efficacy, and safety of a homologous multi-epitope vaccine in a murine model for adjuvant treatment of renal cell carcinoma.

PubMed

Doehn, Christian; Esser, Norbert; Pauels, Hans-Gerd; Kiessig, Stephan T; Stelljes, Matthias; Grossmann, Armin; Jocham, Dieter; Drevs, Joachim

2009-07-01

In a phase-III trial it was recently shown that an adjuvant renal cell carcinoma (RCC) vaccine (Reniale) reduces the risk of tumour progression following nephrectomy. This clinical trial focused on efficacy and did not investigate end-points relating to mode-of-action of the vaccine. In a murine model we investigated mode-of-action, efficacy, and safety of a homologous RENCA cell-based vaccine. Six groups with 12 BALB/c mice per group received five vaccinations (lysate of 1x10(6)-1x10(7) RENCA cells, manufactured with or without prior IFN-gamma incubation) at 3-wk intervals before tumour transplantation and one vaccination 14 d afterwards. Controls (12 mice) received only solvent. All mice were sacrificed 21 d after tumour transplantation. Animal welfare, tumour growth, number of metastases, and the presence of cytotoxic T-lymphocytes as determined by a (51)chromium-release assay. Adoptive immune transfer experiments (vaccination of nine mice with the RENCA vaccine or saline and transfer of serum, spleen cells, and CD4 and/or CD8 depleted spleen cells into five recipient mice each) were carried out to demonstrate involvement of different immune mechanisms. All controls developed a renal tumour, compared to 7/72 animals (9.7%) in the vaccine groups. The mean number of lung metastases was 100 (range 3-750) in controls and 4 (range 0-196) in the vaccine groups, respectively. Tumour uptake and number of metastases were not related to the vaccine dose. The (51)chromium-release assay confirmed a significant tumour-specific cytolytic activity and marginally increased NK activity of splenocytes from vaccinated mice against RENCA cells compared to controls. Adoptive immune transfer experiments showed that the antitumoural effective immune mechanisms are cell-based. We could demonstrate the mode-of-action, efficacy, and safety of a homologous tumour vaccine in a RENCA model. These findings support the positive results from a phase-III trial with Reniale.

History of veterinary public health in Australasia.

PubMed

Hughes, K L

1991-12-01

The geographic isolation of Australasia has played a significant role in preventing the introduction of exotic diseases or in limiting the spread of many diseases which entered after settlement. Some infections such as psoroptic mange, tuberculosis and brucellosis became widely dispersed and some were ultimately to require novel methods to curtail them, e.g. greater use of rail and road transportation to convey stock, improved methods to locate and muster livestock in bush terrain (helicopters), improved diagnostic tests and the introduction of effective methods for tracing diseases found at abattoirs to the farms of origin. From the 1860s to the 1880s, there were such high mortalities from anthrax in Australia that a business syndicate associated with the Pasteur Institute established a laboratory in Sydney to produce anthrax vaccine from 1890 to 1898. The two-dose vaccine developed by Pasteur was unable to compete with a single dose spore vaccine later pioneered locally by Gunn and McGarvie-Smith. The most important achievements in veterinary public health in Australasia have been the successful eradication of brucellosis, the virtual eradication of hydatid disease in New Zealand and Tasmania, the substantial progress made in the eradication of tuberculosis from all but small regions of Australasia, and the development of a commercial vaccine to prevent Q fever in humans.

Immunisation registers in Italy: a patchwork of computerisation.

PubMed

Alfonsi, V; D'Ancona, F; Rota, M C; Giambi, C; Ranghiasci, A; Iannazzo, S

2012-04-26

In Italy, the 21 regional health authorities are in charge of organising and implementing their own vaccination strategy, based on the national vaccine plan. Immunisation coverage varies greatly among the regions for certain vaccines. Efforts to increase childhood immunisation coverage have included initiatives to develop and implement computerised immunisation registers in as many regions as possible. We undertook a cross-sectional online survey in July 2011 to provide an updated picture of the use, heterogeneity and main functions of different computerised immunisation registers used in the Italian regions and to understand the flow of information from local health units to the regional authorities and to the Ministry of Health. Comparing current data with those obtained in 2007, a substantial improvement is evident. A total of 15 regions are fully computerised (previously nine), with 83% of local health units equipped with a computerised register (previously 70%). Eight of the 15 fully computerised regions use the same software, simplifying data sharing. Only four regions are able to obtain data in real time from local health units. Despite the progress made, the capacity to monitor vaccination coverage and to exchange data appears still limited.

New Approaches to Immunotherapy for HPV Associated Cancers

PubMed Central

Bergot, Anne-Sophie; Kassianos, Andrew; Frazer, Ian H; Mittal, Deepak

2011-01-01

Cervical cancer is the second most common cancer of women worldwide and is the first cancer shown to be entirely induced by a virus, the human papillomavirus (HPV, major oncogenic genotypes HPV-16 and -18). Two recently developed prophylactic cervical cancer vaccines, using virus-like particles (VLP) technology, have the potential to prevent a large proportion of cervical cancer associated with HPV infection and to ensure long-term protection. However, prophylactic HPV vaccines do not have therapeutic effects against pre-existing HPV infections and do not prevent their progression to HPV-associated malignancy. In animal models, therapeutic vaccines for persisting HPV infection can eliminate transplantable tumors expressing HPV antigens, but are of limited efficacy in inducing rejection of skin grafts expressing the same antigens. In humans, clinical trials have reported successful immunotherapy of HPV lesions, providing hope and further interest. This review discusses possible new approaches to immunotherapy for HPV associated cancer, based on recent advances in our knowledge of the immunobiology of HPV infection, of epithelial immunology and of immunoregulation, with a brief overview on previous and current HPV vaccine clinical trials. PMID:24212964

Progress toward measles control - African region, 2001-2008.

PubMed

2009-09-25

In 2001, the countries of the World Health Organization (WHO) African Region (AFR) became part of a global initiative with a goal of reducing the number of measles deaths by 50% by 2005, compared with 1999. Recommended strategies for measles mortality reduction included 1) increasing routine coverage for the first dose of measles-containing vaccine (MCV1) for all children, 2) providing a second opportunity for measles vaccination through supplemental immunization activities (SIAs), 3) improving measles case management, and 4) establishing case-based surveillance with laboratory confirmation of all suspected measles cases. Before introduction of MCV throughout AFR, approximately 1 million measles cases had been reported each year in the early 1980s. After strengthening measles-control activities, annual reported cases declined to an estimated 300,000- -580,000 during the 1990s. This report summarizes the progress made during 2001- -2008 toward improving measles control in AFR. During 2001- -2008 estimated MCV1 coverage increased from 57% to 73%, SIAs vaccinated approximately 398 million children, and reported measles cases decreased by 93%, from 492,116 in 2001 to 32,278 in 2008. By 2005, global measles deaths had decreased by 60%, and the AFR goal had been achieved; AFR adopted a new goal to reduce deaths by 90%, compared with 2000, and that goal was achieved in 2006. However, inaccuracies in reported vaccination coverage exist, surveillance is suboptimal, and measles outbreaks continue to occur in AFR countries. Further progress in measles control will require full implementation of recommended strategies, including validation of vaccination coverage.

Rift Valley fever virus vaccine lacking the NSs and NSm genes is safe, nonteratogenic, and confers protection from viremia, pyrexia, and abortion following challenge in adult and pregnant sheep.

PubMed

Bird, Brian H; Maartens, Louis H; Campbell, Shelley; Erasmus, Baltus J; Erickson, Bobbie R; Dodd, Kimberly A; Spiropoulou, Christina F; Cannon, Deborah; Drew, Clifton P; Knust, Barbara; McElroy, Anita K; Khristova, Marina L; Albariño, César G; Nichol, Stuart T

2011-12-01

Rift Valley fever virus (RVFV) is a mosquito-borne human and veterinary pathogen causing large outbreaks of severe disease throughout Africa and the Arabian Peninsula. Safe and effective vaccines are critically needed, especially those that can be used in a targeted one-health approach to prevent both livestock and human disease. We report here on the safety, immunogenicity, and efficacy of the ΔNSs-ΔNSm recombinant RVFV (rRVFV) vaccine (which lacks the NSs and NSm virulence factors) in a total of 41 sheep, including 29 timed-pregnant ewes. This vaccine was proven safe and immunogenic for adult animals at doses ranging from 1.0 × 10(3) to 1.0 × 10(5) PFU administered subcutaneously (s.c.). Pregnant animals were vaccinated with 1.0 × 10(4) PFU s.c. at day 42 of gestation, when fetal sensitivity to RVFV vaccine-induced teratogenesis is highest. No febrile reactions, clinical illness, or pregnancy loss was observed following vaccination. Vaccination resulted in a rapid increase in anti-RVFV IgM (day 4) and IgG (day 7) titers. No seroconversion occurred in cohoused control animals. A subset of 20 ewes progressed to full-term delivery after vaccination. All lambs were born without musculoskeletal, neurological, or histological birth defects. Vaccine efficacy was assessed in 9 pregnant animals challenged at day 122 of gestation with virulent RVFV (1.0 × 10(6) PFU intravenously). Following challenge, 100% (9/9) of the animals were protected, progressed to full term, and delivered healthy lambs. As expected, all 3 sham-vaccinated controls experienced viremia, fetal death, and abortion postchallenge. These results demonstrate that the ΔNSs-ΔNSm rRVFV vaccine is safe and nonteratogenic and confers high-level protection in sheep.

Update on autism spectrum disorder: vaccines, genomes, and social skills training.

PubMed

McGuinness, Teena M

2015-04-01

Despite making significant progress in understanding autism spectrum disorder (ASD) and its genetic underpinnings, controversy remains regarding ASD and its historical, erroneous association with vaccines. This controversy includes the latest anti-vaccine movement that caused a recurrence of the almost vanquished measles and mumps diseases. The history of ASD, complexities of research involving ASD genetics, and benefits of social skills training are explored. Copyright 2015, SLACK Incorporated.

Novel approaches in cancer immunotherapy.

PubMed

Subramaniam, Deepa S; Liu, Stephen V; Giaccone, Giuseppe

2016-04-01

Our understanding of tumor immunology has exploded in the past 3 decades. The complex relationships between tumor cells, the tumor microenvironment and the immune system cells, especially the cytotoxic and helper T cells and the regulatory T cells are beginning to be elucidated. In this review, we will attempt to provide a brief primer of tumor immunology. Cytokine therapy has historically been the mainstay of immunotherapy in cancers such as melanoma and kidney cancer. We will review some of the advances made with cancer vaccines, with a focus on peptide vaccines, tumor cell vaccines and immune cell vaccines. The pros and cons of nucleic acid-based vaccines including DNA and RNA vaccines will be discussed. Adoptive cell therapy has made significant progress utilizing chimeric antigen-receptor transduced T cells, especially in hematologic malignancies. We will also consider the key targets in checkpoint inhibition, and summarize some of the preclinical and clinical data with respect to checkpoint inhibition. Progress made in the novel immunotherapeutic approach of oncolytic viral therapy will be analyzed. PDL-1 expression by tumor cells and tumor infiltrating lymphocytes has been looked at as a biomarker in clinical trials. Limitations to such an approach and potential candidates for future predictive biomarkers of response to immunotherapy and biomarkers of autoimmunity and adverse reactions will be considered.

Cellular immunity for prevention and clearance of HIV infection.

PubMed

Kalams, Spyros A

2003-05-01

Despite the major strides that have been made in HIV therapy with the advent of potent anti-retroviral drugs, these medications are quite expensive and are still not readily available for the vast majority of infected individuals worldwide. Even when available, the long-term toxicities associated with anti-retroviral medications and the frequent emergence of drug-resistance mutations can complicate therapy, making the formulation of effective vaccines imperative. This chapter will review the current state of understanding regarding cell-mediated immune responses that are associated with control of HIV replication. This knowledge has generated sound hypotheses regarding the prospects for augmenting cell-mediated immunity through immune-based therapies. With regard to prophylactic vaccines, it is presently unclear which vaccine-induced immune responses will protect against infection. While much progress has been made in formulating vaccine constructs designed to elicit cell-mediated immune responses, sterilizing immunity is unlikely to be achieved with the current vaccines. However, the ability to control viremia and prevent disease progression in animal infection models looks promising. The ability to measure immune responses has also advanced markedly over the past few years and will allow investigators to more accurately measure the immunogenicity of vaccine constructs, and correlate the magnitude and breadth of these responses with protection.

Understanding HIV infection for the design of a therapeutic vaccine. Part I: Epidemiology and pathogenesis of HIV infection.

PubMed

de Goede, A L; Vulto, A G; Osterhaus, A D M E; Gruters, R A

2015-03-01

HIV infection leads to a gradual loss CD4+ T lymphocytes comprising immune competence and progression to AIDS. Effective treatment with combined antiretroviral drugs (cART) decreases viral load below detectable levels but is not able to eliminate the virus from the body. The success of cART is frustrated by the requirement of expensive life-long adherence, accumulating drug toxicities and chronic immune activation resulting in increased risk of several non-AIDS disorders, even when viral replication is suppressed. Therefore there is a strong need for therapeutic strategies as an alternative to cART. Immunotherapy, or therapeutic vaccination, aims to increase existing immune responses against HIV or induce de novo immune responses. These immune responses should provide a functional cure by controlling viral replication and preventing disease progression in the absence of cART. The key difficulty in the development of an HIV vaccine is our ignorance of the immune responses that control of viral replication, and thus how these responses can be elicited and how they can be monitored. Part one of this review provides an extensive overview of the (patho-) physiology of HIV infection. It describes the structure and replication cycle of HIV, the epidemiology and pathogenesis of HIV infection and the innate and adaptive immune responses against HIV. Part two of this review discusses therapeutic options for HIV. Prevention modalities and antiretroviral therapy are briefly touched upon, after which an extensive overview on vaccination strategies for HIV is provided, including the choice of immunogens and delivery strategies. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

A phased approach to clinical testing: criteria for progressing from Phase I to Phase II to Phase III studies.

PubMed

André, F E; Foulkes, M A

1998-01-01

The overall intent of clinical testing is to establish, in a series of phased studies, the clinical tolerance and acceptable "safety" of the candidate vaccine, as well as the type, level and persistence of the immune response after its inoculation, to a representative target population, according to a convenient administration schedule. The final stages involve the direct or indirect demonstration of protective efficacy, if possible in the population(s) for which the vaccine is intended. In addition, consistency of production must be demonstrated. At all these stages, the amount of prior information from preclinical and other studies affects and informs the objectives and design of subsequent studies. Progression from one testing phase to the next is dependent upon attaining the pre-set objectives of each series of studies. The precise objectives to be met will be decided on a case-by-case basis. The earliest assessments in humans (Phase I) involve evaluation of short-term clinical tolerance as measured by local and general reactogenicity, and gross assessments of immunogenicity, in a small number of highly selected individuals in an idealised situation. The selection of "optimal" dose and schedule are the result of further dose-ranging investigations (Phase II), involving more volunteers, with longer, more detailed follow-up assessments. It is at this stage that the accumulated evidence on its immunogenicity profile should be sufficient to assess whether or not the vaccine is worthy of further development. The next level of investigation (Phase III) aims to measure with greater precision the vaccine protective efficacy in the intended target population(s) by comparison of infection and/or disease attack rates in vaccine and placebo recipients. In consistency studies different production lots, manufactured at commercial scale, are tested to demonstrate consistency of manufacture. Additional bridging studies to establish similarity of lots at different production scales, or studies of the duration of the immunity conferred, are conducted in parallel with the progression of the studies in the different phases mentioned above. These latter types of studies are usually carried out concurrently with Phase III studies. This progression continues into the post-marketing period (Phase IV) with surveillance of long term efficacy and observational studies of possible rare adverse events to establish "safety" with more confidence. This paper examines, in general, the aims and designs of studies in each phase as an introduction to the more specific publications that follow.

Demographic transition and the dynamics of measles in six provinces in China: A modeling study

PubMed Central

Su, Qiru; An, Zhijie; Ma, Fubao; Xie, Shuyun; Xu, Aiqiang; Zhang, Yanyang; Ding, Zhengrong; Li, Hui; Wang, Huaqing; Luo, Huiming; Wang, Ning; Li, Li; Ferrari, Matthew J.

2017-01-01

Background Industrialization and demographic transition generate nonstationary dynamics in human populations that can affect the transmission and persistence of infectious diseases. Decades of increasing vaccination and development have led to dramatic declines in the global burden of measles, but the virus remains persistent in much of the world. Here we show that a combination of demographic transition, as a result of declining birth rates, and reduced measles prevalence, due to improved vaccination, has shifted the age distribution of susceptibility to measles throughout China. Methods and findings We fit a novel time-varying catalytic model to three decades of age-specific measles case reporting in six provinces in China to quantify the change in the age-specific force of infection for measles virus over time. We further quantified the impact of supplemental vaccination campaigns on the reduction of susceptible individuals. The force of infection of measles has declined dramatically (90%–97% reduction in transmission rate) in three industrialized eastern provinces during the last decade, driving a concomitant increase in both the relative proportion and absolute number of adult cases, while three central and western provinces exhibited dynamics consistent with endemic persistence (24%–73% reduction in transmission rate). The reduction in susceptible individuals due to supplemental vaccination campaigns is frequently below the nominal campaign coverage, likely because campaigns necessarily vaccinate those who may already be immune. The impact of these campaigns has significantly improved over time: campaigns prior to 2005 were estimated to have achieved less than 50% reductions in the proportion susceptible in the target age classes, but campaigns from 2005 onwards reduced the susceptible proportion by 32%–87%. A limitation of this study is that it relies on case surveillance, and thus inference may be biased by age-specific variation in measles reporting. Conclusions The age distribution of measles cases changes in response to both demographic and vaccination processes. Combining both processes in a novel catalytic model, we illustrate that age-specific incidence patterns reveal regional differences in the progress to measles elimination and the impact of vaccination controls in China. The shift in the age distribution of measles susceptibility in response to demographic and vaccination processes emphasizes the importance of progressive control strategies and measures to evaluate program success that anticipate and react to this transition in observed incidence. PMID:28376084

Senescent cells re-engineered to express soluble programmed death receptor-1 for inhibiting programmed death receptor-1/programmed death ligand-1 as a vaccination approach against breast cancer.

PubMed

Chen, Zehong; Hu, Kang; Feng, Lieting; Su, Ruxiong; Lai, Nan; Yang, Zike; Kang, Shijun

2018-06-01

Various types of vaccines have been proposed as approaches for prevention or delay of the onset of cancer by boosting the endogenous immune system. We previously developed a senescent-cell-based vaccine, induced by radiation and veliparib, as a preventive and therapeutic tool against triple-negative breast cancer. However, the programmed death receptor-1/programmed death ligand-1 (PD-1/PD-L1) pathway was found to play an important role in vaccine failure. Hence, we further developed soluble programmed death receptor-1 (sPD1)-expressing senescent cells to overcome PD-L1/PD-1-mediated immune suppression while vaccinating to promote dendritic cell (DC) maturity, thereby amplifying T-cell activation. In the present study, sPD1-expressing senescent cells showed a particularly active status characterized by growth arrest and modified immunostimulatory cytokine secretion in vitro. As expected, sPD1-expressing senescent tumor cell vaccine (STCV/sPD-1) treatment attracted more mature DC and fewer exhausted-PD1 + T cells in vivo. During the course of the vaccine studies, we observed greater safety and efficacy for STCV/sPD-1 than for control treatments. STCV/sPD-1 pre-injections provided complete protection from 4T1 tumor challenge in mice. Additionally, the in vivo therapeutic study of mice with s.c. 4T1 tumor showed that STCV/sPD-1 vaccination delayed tumorigenesis and suppressed tumor progression at early stages. These results showed that STCV/sPD-1 effectively induced a strong antitumor immune response against cancer and suggested that it might be a potential strategy for TNBC prevention. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

[Vaccines: producers in countries of the Southern hemisphere].

PubMed

Bertrand, J J

2007-08-01

Vaccine producers in southern hemisphere countries now contribute significantly to global output. In 2006 southern hemisphere countries accounted for more than 10% of the total worldwide production with a progression approximately 70% greater than all producers combined in the two-year period between 2004 and 2006. Though difficult to measure, production in volume is higher due to lower prices practiced in most of these countries. For many years before the 1980s, production was scattered among numerous limited-scale companies. Most were founded at the initiative of governments striving to cover the needs of the population for essential vaccines. A number of institutions and private structures such as Institut Pasteur Production, Connaught Laboratories, and Institut Merieux have also set up production facilities. Today's producers can be divided into two categories, i.e., local producers that produce mainly monovalent vaccines and worldwide producers with strong R&D investment programs. Local producers are located mainly in large southern hemisphere countries such as China, India, Brazil, and Indonesia as well as in eastern countries. For the most dynamic companies, international development is focused on southern hemisphere countries excluding North America and Europe. With the support international organization such as WHO, UNICEF and GAVI, alliances are now being formed and networks are being organized in an effort to ensure reliable supplies of high quality vaccines at affordable prices in developing countries. The contribution of these producers will increase for the greater benefit of the people living in the southern hemisphere.

Development of an opsonophagocytic killing assay for group a streptococcus.

PubMed

Jones, Scott; Moreland, Nicole J; Zancolli, Marta; Raynes, Jeremy; Loh, Jacelyn M S; Smeesters, Pierre R; Sriskandan, Shiranee; Carapetis, Jonathan R; Fraser, John D; Goldblatt, David

2018-05-15

Group A Streptococcus (GAS) or Streptococcus pyogenes is responsible for an estimated 500,000 deaths worldwide each year. Protection against GAS infection is thought to be mediated by phagocytosis, enhanced by bacteria-specific antibody. There are no licenced GAS vaccines, despite many promising candidates in preclinical and early stage clinical development, the most advanced of which are based on the GAS M-protein. Vaccine progress has been hindered, in part, by the lack of a standardised functional assay suitable for vaccine evaluation. Current assays, developed over 50 years ago, rely on non-immune human whole blood as a source of neutrophils and complement. Variations in complement and neutrophil activity between donors result in variable data that is difficult to interpret. We have developed an opsonophagocytic killing assay (OPKA) for GAS that utilises dimethylformamide (DMF)-differentiated human promyelocytic leukemia cells (HL-60) as a source of neutrophils and baby rabbit complement, thus removing the major sources of variation in current assays. We have standardised the OPKA for several clinically relevant GAS strain types (emm1, emm6 and emm12) and have shown antibody-specific killing for each emm-type using M-protein specific rabbit antisera. Specificity was demonstrated by pre-incubation of the antisera with homologous M-protein antigens that blocked antibody-specific killing. Additional qualifications of the GAS OPKA, including the assessment of the accuracy, precision, linearity and the lower limit of quantification, were also performed. This GAS OPKA assay has the potential to provide a robust and reproducible platform to accelerate GAS vaccine development. Copyright © 2018 Elsevier Ltd. All rights reserved.

Bacillus Calmette-Guérin vaccination reduces the severity and progression of tuberculosis in badgers

PubMed Central

Chambers, Mark A.; Rogers, Fiona; Delahay, Richard J.; Lesellier, Sandrine; Ashford, Roland; Dalley, Deanna; Gowtage, Sonya; Davé, Dipesh; Palmer, Si; Brewer, Jacky; Crawshaw, Timothy; Clifton-Hadley, Richard; Carter, Steve; Cheeseman, Chris; Hanks, Chris; Murray, Alistair; Palphramand, Kate; Pietravalle, Stéphane; Smith, Graham C.; Tomlinson, Alexandra; Walker, Neil J.; Wilson, Gavin J.; Corner, Leigh A. L.; Rushton, Stephen P.; Shirley, Mark D. F.; Gettinby, George; McDonald, Robbie A.; Hewinson, R. Glyn

2011-01-01

Control of bovine tuberculosis (TB) in cattle has proven particularly challenging where reservoirs of infection exist in wildlife populations. In Britain and Ireland, control is hampered by a reservoir of infection in Eurasian badgers (Meles meles). Badger culling has positive and negative effects on bovine TB in cattle and is difficult, costly and controversial. Here we show that Bacillus Calmette-Guérin (BCG) vaccination of captive badgers reduced the progression, severity and excretion of Mycobacterium bovis infection after experimental challenge. In a clinical field study, BCG vaccination of free-living badgers reduced the incidence of positive serological test results by 73.8 per cent. In common with other species, BCG did not appear to prevent infection of badgers subjected to experimental challenge, but did significantly reduce the overall disease burden. BCG vaccination of badgers could comprise an important component of a comprehensive programme of measures to control bovine TB in cattle. PMID:21123260

Breaking Hepatitis B Virus Tolerance and Inducing Protective Immunity Based on Mimicking T Cell-Independent Antigen.

PubMed

Li, Xiaoyan; Ni, Runzhou

2016-11-01

There are over 350 million chronic carriers of hepatitis B virus (HBV) in the world, of whom about a third eventually develop severe HBV-related complications. HBV contributes to liver cirrhosis and hepatocellular carcinoma development. Remarkable progress has been made in selective inhibition of HBV replication by nucleoside analogs. However, how to generate protective antibody of HBsAb in HBV-infected patients after HBV-DNA becomes negative still remains a challenge for scientists. In this study, we show that OmpC-HBsAg 'a' epitope chimeric protein vaccine can break HBV tolerance and induce protective immunity in HBV transgenic mice based on mimicking T cell-independent antigen to bypass T cells from the adaptive immune system. The antibodies induced by the vaccine have the ability to prevent HBV virion infection of human hepatocytes.

Human Immunodeficiency Virus Vaccine Trials

PubMed Central

O’Connell, Robert J.; Kim, Jerome H.; Corey, Lawrence; Michael, Nelson L.

2012-01-01

More than 2 million AIDS-related deaths occurred globally in 2008, and more than 33 million people are living with HIV/AIDS. Despite promising advances in prevention, an estimated 2.7 million new HIV infections occurred in that year, so that for every two patients placed on combination antiretroviral treatment, five people became infected. The pandemic poses a formidable challenge to the development, progress, and stability of global society 30 years after it was recognized. Experimental preventive HIV-1 vaccines have been administered to more than 44,000 human volunteers in more than 187 separate trials since 1987. Only five candidate vaccine strategies have been advanced to efficacy testing. The recombinant glycoprotein (rgp)120 subunit vaccines, AIDSVAX B/B and AIDSVAX B/E, and the Merck Adenovirus serotype (Ad)5 viral-vector expressing HIV-1 Gag, Pol, and Nef failed to show a reduction in infection rate or lowering of postinfection viral set point. Most recently, a phase III trial that tested a heterologous prime-boost vaccine combination of ALVAC-HIV vCP1521 and bivalent rgp120 (AIDSVAX B/E) showed 31% efficacy in protection from infection among community-risk Thai participants. A fifth efficacy trial testing a DNA/recombinant(r) Ad5 prime-boost combination is currently under way. We review the clinical trials of HIV vaccines that have provided insight into human immunogenicity or efficacy in preventing HIV-1 infection. PMID:23209178

Inhalational anthrax (Ames aerosol) in naïve and vaccinated New Zealand rabbits: characterizing the spread of bacteria from lung deposition to bacteremia

PubMed Central

Gutting, Bradford W.; Nichols, Tonya L.; Channel, Stephen R.; Gearhart, Jeffery M.; Andrews, George A.; Berger, Alan E.; Mackie, Ryan S.; Watson, Brent J.; Taft, Sarah C.; Overheim, Katie A.; Sherwood, Robert L.

2012-01-01

There is a need to better understand inhalational anthrax in relevant animal models. This understanding could aid risk assessment, help define therapeutic windows, and provide a better understanding of disease. The aim here was to characterize and quantify bacterial deposition and dissemination in rabbits following exposure to single high aerosol dose (> 100 LD50) of Bacillus anthracis (Ames) spores immediately following exposure through 36 h. The primary goal of collecting the data was to support investigators in developing computational models of inhalational anthrax disease. Rabbits were vaccinated prior to exposure with the human vaccine (Anthrax Vaccine Adsorbed, AVA) or were sham-vaccinated, and were then exposed in pairs (one sham and one AVA) so disease kinetics could be characterized in equally-dosed hosts where one group is fully protected and is able to clear the infection (AVA-vaccinated), while the other is susceptible to disease, in which case the bacteria are able to escape containment and replicate uncontrolled (sham-vaccinated rabbits). Between 4–5% of the presented aerosol dose was retained in the lung of sham- and AVA-vaccinated rabbits as measured by dilution plate analysis of homogenized lung tissue or bronchoalveolar lavage (BAL) fluid. After 6 and 36 h, >80% and >96%, respectively, of the deposited spores were no longer detected in BAL, with no detectable difference between sham- or AVA-vaccinated rabbits. Thereafter, differences between the two groups became noticeable. In sham-vaccinated rabbits the bacteria were detected in the tracheobronchial lymph nodes (TBLN) 12 h post-exposure and in the circulation at 24 h, a time point which was also associated with dramatic increases in vegetative CFU in the lung tissue of some animals. In all sham-vaccinated rabbits, bacteria increased in both TBLN and blood through 36 h at which point in time some rabbits succumbed to disease. In contrast, AVA-vaccinated rabbits showed small numbers of CFU in TBLN between 24 and 36 h post-exposure with small numbers of bacteria in the circulation only at 24 h post-exposure. These results characterize and quantify disease progression in naïve rabbits following aerosol administration of Ames spores which may be useful in a number of different research applications, including developing quantitative models of infection for use in human inhalational anthrax risk assessment. PMID:22919678

[HPV Vaccination Program - The History and Recent Progress].

PubMed

Yoshikawa, Hiroyuki

2017-09-01

Four years have passed since HPV vaccination "crisis" occurred in June 2013. In Japan,a publicly funded HPV vaccination program for adolescent females aged 12-16 years began in December 2010. However,the Japanese government withdrew its recommendation for HPV vaccination in June, 2013 because news reports on potential adverse effects of HPV vaccines without any medical evidence appeared repeatedly. The vaccination coverage among adolescent females decreased quickly from around 70%in females born between 1994 and 1999 to only 1%in females born since 2001 over the country. The suspension of recommendation for vaccination has continued to the present,though there is no scientific or epidemiologic evidence to demonstrate the causal linkage between post-vaccination symptoms and the HPV vaccines. Very recently,an ecological investigation reported that similar symptoms also occur in unvaccinated adolescents in Japan. Medical organizations in Japan are also calling for a resumption of the HPV vaccination program. Now,the resumption of the recommendation needs a political judgment.

Role of word-of-mouth for programs of voluntary vaccination: A game-theoretic approach.

PubMed

Bhattacharyya, Samit; Bauch, Chris T; Breban, Romulus

2015-11-01

We propose a model describing the synergetic feedback between word-of-mouth (WoM) and epidemic dynamics controlled by voluntary vaccination. The key feature consists in combining a game-theoretic model for the spread of WoM and a compartmental model describing VSIR disease dynamics in the presence of a program of voluntary vaccination. We evaluate and compare two scenarios for determinants of behavior, depending on what WoM disseminates: (1) vaccine advertising, which may occur whether or not an epidemic is ongoing and (2) epidemic status, notably disease prevalence. Understanding the synergy between the two strategies could be particularly important for designing voluntary vaccination campaigns. We find that, in the initial phase of an epidemic, vaccination uptake is determined more by vaccine advertising than the epidemic status. As the epidemic progresses, epidemic status becomes increasingly important for vaccination uptake, considerably accelerating vaccination uptake toward a stable vaccination coverage. Copyright © 2015 Elsevier Inc. All rights reserved.

Information Curation among Vaccine Cautious Parents: Web 2.0, Pinterest Thinking, and Pediatric Vaccination Choice.

PubMed

Sobo, Elisa J; Huhn, Arianna; Sannwald, Autumn; Thurman, Lori

2016-01-01

To learn about pediatric vaccine decision-making, we surveyed and interviewed US parents with at least one child kindergarten age or younger (N = 53). Through an anthropologically informed content analysis, we found that fully vaccinating parents (n = 33) mostly saw vaccination as routine. In contrast, selective and nonvaccinating parents (n = 20) exhibited the type of self-informed engagement that the health care system recommends. Selective vaccinators also expressed multiple, sometimes contradictory positions on vaccination that were keyed to individual children's biologies, child size, environmental hazards, specific diseases, and discrete vaccines. Rather than logical progressions, viewpoints were presented as assembled collections, reflecting contemporary information filtering and curation practices and the prevalence of collectively experienced and constructed digital "hive" narratives. Findings confirm the need for a noncategorical approach to intervention that accommodates the fluid, polyvalent nature of vaccine reasoning and the curatorial view selectively vaccinating parents take toward information while honoring their efforts at engaged healthcare consumption.

Tissue- and Serum-Associated Biomarkers of Hepatocellular Carcinoma

PubMed Central

Chauhan, Ranjit; Lahiri, Nivedita

2016-01-01

Hepatocellular carcinoma (HCC), one of the leading causes of cancer deaths in the world, is offering a challenge to human beings, with the current modes of treatment being a palliative approach. Lack of proper curative or preventive treatment methods encouraged extensive research around the world with an aim to detect a vaccine or therapeutic target biomolecule that could lead to development of a drug or vaccine against HCC. Biomarkers or biological disease markers have emerged as a potential tool as drug/vaccine targets, as they can accurately diagnose, predict, and even prevent the diseases. Biomarker expression in tissue, serum, plasma, or urine can detect tumor in very early stages of its development and monitor the cancer progression and also the effect of therapeutic interventions. Biomarker discoveries are driven by advanced techniques, such as proteomics, transcriptomics, whole genome sequencing, micro- and micro-RNA arrays, and translational clinics. In this review, an overview of the potential of tissue- and serum-associated HCC biomarkers as diagnostic, prognostic, and therapeutic targets for drug development is presented. In addition, we highlight recently developed micro-RNA, long noncoding RNA biomarkers, and single-nucleotide changes, which may be used independently or as complementary biomarkers. These active investigations going on around the world aimed at conquering HCC might show a bright light in the near future. PMID:27398029

Crimean-Congo hemorrhagic fever: current and future prospects of vaccines and therapies.

PubMed

Keshtkar-Jahromi, Maryam; Kuhn, Jens H; Christova, Iva; Bradfute, Steven B; Jahrling, Peter B; Bavari, Sina

2011-05-01

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne disease caused by CCHF virus (CCHFV), a nairovirus in the family Bunyaviridae. CCHF occurs sporadically in a number of countries in Asia, the Middle East, southeastern Europe and Africa. Patients may develop subclinical to severe hemorrhagic disease, with fatal outcomes in a substantial percentage of cases. Transmission usually occurs through contact with viremic livestock or patients or bites by infected ticks. The number of reported cases has increased in recent years, possibly due to global climatic change and human perturbations of biocenoses that may have led to the migration of tick vectors. There is currently no FDA-approved vaccine or specific antiviral therapy for CCHF. The classification of CCHFV as a WHO Risk Group IV pathogen and the lack of suitable animal models has caused progress in developing new prophylactic and therapeutic measures to be slow. Ribavirin is active against CCHFV in vitro, but its efficacy for human therapy has not been definitively demonstrated by clinical studies. CCHF-immunoglobulin is also in use, but without clear evidence of efficacy. In this article, we review the development of prophylaxis and therapy for CCHF and discuss future prospects for vaccine and drug development. Copyright © 2011. Published by Elsevier B.V.

Vi Capsular Polysaccharide Produced by Recombinant Salmonella enterica Serovar Paratyphi A Confers Immunoprotection against Infection by Salmonella enterica Serovar Typhi

PubMed Central

Xiong, Kun; Zhu, Chunyue; Chen, Zhijin; Zheng, Chunping; Tan, Yong; Rao, Xiancai; Cong, Yanguang

2017-01-01

Enteric fever is predominantly caused by Salmonella enterica serovar Typhi and Salmonella enterica serovar Paratyphi A, and accounts for an annual global incidence of 26.9 millions. In recent years, the rate of S. Paratyphi A infection has progressively increased. Currently licensed vaccines for typhoid fever, live Ty21a vaccine, Vi subunit vaccine, and Vi-conjugate vaccine, confer inadequate cross immunoprotection against enteric fever caused by S. Paratyphi A. Therefore, development of bivalent vaccines against enteric fever is urgently required. The immunogenic Vi capsular polysaccharide is characteristically produced in S. Typhi, but it is absent in S. Paratyphi A. We propose that engineering synthesis of Vi in S. Paratyphi A live-attenuated vaccine may expand its protection range to cover S. Typhi. In this study, we cloned the viaB locus, which contains 10 genes responsible for Vi biosynthesis, and integrated into the chromosome of S. Paratyphi A CMCC 50093. Two virulence loci, htrA and phoPQ, were subsequently deleted to achieve a Vi-producing attenuated vaccine candidate. Our data showed that, despite more than 200 passages, the viaB locus was stably maintained in the chromosome of S. Paratyphi A and produced the Vi polysaccharide. Nasal immunization of the vaccine candidate stimulated high levels of Vi-specific and S. Paratyphi A-specific antibodies in mice sera as well as total sIgA in intestinal contents, and showed significant protection against wild-type challenge of S. Paratyphi A or S. Typhi. Our study show that the Vi-producing attenuated S. Paratyphi A is a promising bivalent vaccine candidate for the prevention of enteric fever. PMID:28484685

Drug Treatment Combined with BCG Vaccination Reduces Disease Reactivation in Guinea Pigs Infected with Mycobacterium tuberculosis

PubMed Central

Shang, Shaobin; Shanley, Crystal A.; Caraway, Megan L.; Orme, Eileen A.; Henao-Tamayo, Marcela; Hascall-Dove, Laurel; Ackart, David; Orme, Ian M.; Ordway, Diane J.; Basaraba, Randall J.

2012-01-01

Bacillus-Calmette-Guerin (BCG), the only human tuberculosis vaccine, primes a partially protective immune response against M. tuberculosis infection in humans and animals. In guinea pigs, BCG vaccination slows the progression of disease and reduces the severity of necrotic granulomas, which harbor a population of drug-tolerant bacilli. The objective of this study was to determine if reducing disease severity by BCG vaccination of guinea pigs prior to M. tuberculosis challenge enhanced the efficacy of combination drug therapy. At 20 days of infection, treatment of vaccinated and non-vaccinated animals with rifampin, isoniazid, and pyrizinamide (RHZ) was initiated for 4 or 8 weeks. On days 50, 80 and 190 of infection (10 weeks after drug were withdrawn), treatment efficacy was evaluated by quantifying clinical condition, bacterial loads, lesion severity, and dynamic changes in peripheral blood and lung leukocyte numbers by flow cytometry. In a separate, long-term survival study, treatment efficacy was evaluated by determining disease reactivation frequency post-mortem. BCG vaccination alone delayed pulmonary and extra-pulmonary disease progression, but failed to prevent dissemination of bacilli and the formation of necrotic granulomas. Drug therapy either alone or in combination with BCG, was more effective at lessening clinical disease and lesion severity compared to control animals or those receiving BCG alone. Fewer residual lesions in BCG vaccinated and drug treated animals, equated to a reduced frequency of reactivation disease and improvement in survival even out to 500 days of infection. The combining of BCG vaccination and drug therapy was more effective at resolving granulomas such that fewer animals had evidence of residual infection and thus less reactivation disease. PMID:22244979

Phase I trial of RV3-BB rotavirus vaccine: a human neonatal rotavirus vaccine.

PubMed

Danchin, M; Kirkwood, C D; Lee, K J; Bishop, R F; Watts, E; Justice, F A; Clifford, V; Cowley, D; Buttery, J P; Bines, J E

2013-05-28

RV3 is a human neonatal rotavirus strain (G3P[6]) that has been associated with asymptomatic neonatal infection and replicates well in the infant gut. RV3-BB rotavirus vaccine has been developed as a rotavirus vaccine candidate for administration at birth. A single-centre, double-blind, randomised placebo-controlled Phase I study evaluated the safety and tolerability of a single oral dose of the second generation RV3-BB rotavirus vaccine (8.3×10(6)FFU/mL) in 20 adults, 20 children and 20 infants (10 vaccine and 10 placebo per age cohort). Vaccine take was defined as seroconversion (a 3-fold increase in serum anti-rotavirus IgA or serum neutralising antibody (SNA) from baseline at day 28 post-dose) or evidence of RV3-BB viral replication in the faeces by RT-PCR analysis 3-6 days post-vaccination. RV3-BB presence was confirmed by sequence analysis. The RV3-BB vaccine was well tolerated in all participants, with no pattern of adverse events shown to be associated with the study vaccine. In the infant cohort, vaccine take was demonstrated in 8/9 infants following a single dose of vaccine compared with 2/7 placebo recipients. In the infant vaccine group, 5/9 infants exhibited either IgA or SNA seroconversion and 7/9 infants had evidence of RV3-BB replication on days 3-6, compared with 2/7 infants who seroconverted and 0/10 infants with evidence of replication in the placebo group. Two infants in the placebo group had serological evidence of a rotavirus infection within the 28-day study period: one demonstrated an IgA and the other an SNA response, with wild-type virus replication detected in another infant. A single dose of RV3-BB rotavirus vaccine was well tolerated in adults, children and infants. Most infants (8/9) who received RV3-BB demonstrated vaccine take following a single dose. These data support progression of RV3-BB to Phase II immunogenicity and efficacy trials. Copyright © 2013 Elsevier Ltd. All rights reserved.