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Sample records for improving vaccine safety

  1. Vector Design for Improved DNA Vaccine Efficacy, Safety and Production

    PubMed Central

    Williams, James A.

    2013-01-01

    DNA vaccination is a disruptive technology that offers the promise of a new rapidly deployed vaccination platform to treat human and animal disease with gene-based materials. Innovations such as electroporation, needle free jet delivery and lipid-based carriers increase transgene expression and immunogenicity through more effective gene delivery. This review summarizes complementary vector design innovations that, when combined with leading delivery platforms, further enhance DNA vaccine performance. These next generation vectors also address potential safety issues such as antibiotic selection, and increase plasmid manufacturing quality and yield in exemplary fermentation production processes. Application of optimized constructs in combination with improved delivery platforms tangibly improves the prospect of successful application of DNA vaccination as prophylactic vaccines for diverse human infectious disease targets or as therapeutic vaccines for cancer and allergy. PMID:26344110

  2. Vaccine Safety

    MedlinePlus

    ... During Pregnancy Frequently Asked Questions about Vaccine Recalls Historical Vaccine Safety Concerns FAQs about GBS and Menactra ... CISA Resources for Healthcare Professionals Evaluation Current Studies Historical Background 2001-12 Publications Technical Reports Vaccine Safety ...

  3. Live Attenuated S. Typhimurium Vaccine with Improved Safety in Immuno-Compromised Mice

    PubMed Central

    Periaswamy, Balamurugan; Maier, Lisa; Vishwakarma, Vikalp; Slack, Emma; Kremer, Marcus; Andrews-Polymenis, Helene L.; McClelland, Michael; Grant, Andrew J.; Suar, Mrutyunjay; Hardt, Wolf-Dietrich

    2012-01-01

    Live attenuated vaccines are of great value for preventing infectious diseases. They represent a delicate compromise between sufficient colonization-mediated adaptive immunity and minimizing the risk for infection by the vaccine strain itself. Immune defects can predispose to vaccine strain infections. It has remained unclear whether vaccine safety could be improved via mutations attenuating a vaccine in immune-deficient individuals without compromising the vaccine's performance in the normal host. We have addressed this hypothesis using a mouse model for Salmonella diarrhea and a live attenuated Salmonella Typhimurium strain (ssaV). Vaccination with this strain elicited protective immunity in wild type mice, but a fatal systemic infection in immune-deficient cybb−/−nos2−/− animals lacking NADPH oxidase and inducible NO synthase. In cybb−/−nos2−/− mice, we analyzed the attenuation of 35 ssaV strains carrying one additional mutation each. One strain, Z234 (ssaV SL1344_3093), was >1000-fold attenuated in cybb−/−nos2−/− mice and ≈100 fold attenuated in tnfr1−/− animals. However, in wt mice, Z234 was as efficient as ssaV with respect to host colonization and the elicitation of a protective, O-antigen specific mucosal secretory IgA (sIgA) response. These data suggest that it is possible to engineer live attenuated vaccines which are specifically attenuated in immuno-compromised hosts. This might help to improve vaccine safety. PMID:23029007

  4. Vaccine Safety Datalink

    Cancer.gov

    The Vaccine Safety Datalink is part of the National Immunization Program within the Centers for Disease Control and Prevention and was started in recognition of gaps in the scientific knowledge of rare vaccine side effects.

  5. Rabies vaccines: a review of progress towards improved efficacy and safety.

    PubMed

    Tsiang, H

    1998-10-01

    Over the years, the technology for producing human rabies vaccines has undergone many improvements. These improvements consist in the use of tissue cultures for the production of viral antigens, replacing the former nervous tissue substrate vaccines. The low virus yields in tissue cultures led to the development of the concentration and purification of virus supernatants. Another technical improvement was obtained by using microcarriers for virus production in VERO cell suspension cultures. This technique permits commercial-scale production of rabies vaccine, lowering production costs and thus extending the availability of the vaccine to a broader population in developing countries. Besides improvements in rabies vaccine production technology, the use of various vaccination regimens and routes of administration in field trials has resulted in considerable gains in our experience of postexposure treatment (PET) of this disease. The standard WHO recommended regimen for PET using concentrated and purified tissue culture vaccines consists of a 5-dose course of intramuscular injections at days 0, 3, 7, 14 and 28. Reduced vaccination regimens such as the 2-1-1 have been proven to be efficient in raising protective antibody responses. Reduction in the total volume of rabies vaccine is also possible by using the intradermal route of injection, provided the vaccine is administered at several sites. The overall consequence is a progressive shift in the worldwide use of rabies vaccines from those of nervous tissue origin to the contemporary tissue culture vaccines. PMID:18020604

  6. The Vaccine Safety Datalink: successes and challenges monitoring vaccine safety.

    PubMed

    McNeil, Michael M; Gee, Julianne; Weintraub, Eric S; Belongia, Edward A; Lee, Grace M; Glanz, Jason M; Nordin, James D; Klein, Nicola P; Baxter, Roger; Naleway, Allison L; Jackson, Lisa A; Omer, Saad B; Jacobsen, Steven J; DeStefano, Frank

    2014-09-22

    The Vaccine Safety Datalink (VSD) is a collaborative project between the Centers for Disease Control and Prevention (CDC) and 9 health care organizations. Established in 1990, VSD is a vital resource informing policy makers and the public about the safety of vaccines used in the United States. Large linked databases are used to identify and evaluate adverse events in over 9 million individuals annually. VSD generates rapid, important safety assessments for both routine vaccinations and emergency vaccination campaigns. VSD monitors safety of seasonal influenza vaccines in near-real time, and provided essential information on the safety of influenza A (H1N1) 2009 monovalent vaccine during the recent pandemic. VSD investigators have published important studies demonstrating that childhood vaccines are not associated with autism or other developmental disabilities. VSD prioritizes evaluation of new vaccines; searches for possible unusual health events after vaccination; monitors vaccine safety in pregnant women; and has pioneered development of biostatistical research methods. PMID:25108215

  7. Safety of human papillomavirus vaccines: a review

    PubMed Central

    Stillo, Michela; Carrillo Santisteve, Paloma; Lopalco, Pier Luigi

    2015-01-01

    Introduction: Between 2006 and 2009, two different human papillomavirus virus (HPV) vaccines were licensed for use: a quadrivalent (qHPVv) and a bivalent (bHPVv) vaccine. Since 2008, HPV vaccination programmes have been implemented in the majority of the industrialized countries. Since 2013, HPV vaccination has been part of the national programs of 66 countries including almost all countries in North America and Western Europe. Despite all the efforts made by individual countries, coverage rates are lower than expected. Vaccine safety represents one of the main concerns associated with the lack of acceptance of HPV vaccination both in the European Union/European Economic Area and elsewhere. Areas covered: Safety data published on bivalent and quadrivalent HPV vaccines, both in pre-licensure and post-licensure phase, are reviewed. Expert opinion: Based on the latest scientific evidence, both HPV vaccines seem to be safe. Nevertheless, public concern and rumors about adverse events (AE) represent an important barrier to overcome in order to increase vaccine coverage. Passive surveillance of AEs is an important tool for detecting safety signals, but it should be complemented by activities aimed at assessing the real cause of all suspect AEs. Improved vaccine safety surveillance is the first step for effective communication based on scientific evidence. PMID:25689872

  8. Vaccine Safety Resources for Nurses

    PubMed Central

    Shimabukuro, Tom T.; Hibbs, Beth F.; Moro, Pedro L.; Broder, Karen R.; Vellozzi, Claudia

    2015-01-01

    Overview Nurses are on the front lines of health care delivery, and many of them routinely administer immunizations. The authors describe the Centers for Disease Control and Prevention’s (CDC) vaccine safety monitoring systems, explaining how nurses can access inquiry channels and other immunization information resources. Examples of recent vaccine safety inquiries are also provided. PMID:26222474

  9. A public-professional web-bridge for vaccines and vaccination: user concerns about vaccine safety.

    PubMed

    García-Basteiro, Alberto L; Alvarez-Pasquín, María-José; Mena, Guillermo; Llupià, Anna; Aldea, Marta; Sequera, Victor-Guillermo; Sanz, Sergi; Tuells, Jose; Navarro-Alonso, José-Antonio; de Arísteguí, Javier; Bayas, José-María

    2012-05-28

    Vacunas.org (http://www.vacunas.org), a website founded by the Spanish Association of Vaccinology offers a personalized service called Ask the Expert, which answers any questions posed by the public or health professionals about vaccines and vaccination. The aim of this study was to analyze the factors associated with questions on vaccination safety and determine the characteristics of questioners and the type of question asked during the period 2008-2010. A total of 1341 questions were finally included in the analysis. Of those, 30% were related to vaccine safety. Questions about pregnant women had 5.01 higher odds of asking about safety (95% CI 2.82-8.93) than people not belonging to any risk group. Older questioners (>50 years) were less likely to ask about vaccine safety compared to younger questioners (OR: 0.44, 95% CI 0.25-0.76). Questions made after vaccination or related to influenza (including H1N1) or travel vaccines were also associated with a higher likelihood of asking about vaccine safety. These results identify risk groups (pregnant women), population groups (older people) and some vaccines (travel and influenza vaccines, including H1N1) where greater efforts to provide improved, more-tailored vaccine information in general and on the Internet are required. PMID:22027485

  10. Synthetic virus seeds for improved vaccine safety: Genetic reconstruction of poliovirus seeds for a PER.C6 cell based inactivated poliovirus vaccine.

    PubMed

    Sanders, Barbara P; Edo-Matas, Diana; Papic, Natasa; Schuitemaker, Hanneke; Custers, Jerome H H V

    2015-10-13

    Safety of vaccines can be compromised by contamination with adventitious agents. One potential source of adventitious agents is a vaccine seed, typically derived from historic clinical isolates with poorly defined origins. Here we generated synthetic poliovirus seeds derived from chemically synthesized DNA plasmids encoding the sequence of wild-type poliovirus strains used in marketed inactivated poliovirus vaccines. The synthetic strains were phenotypically identical to wild-type polioviruses as shown by equivalent infectious titers in culture supernatant and antigenic content, even when infection cultures are scaled up to 10-25L bioreactors. Moreover, the synthetic seeds were genetically stable upon extended passaging on the PER.C6 cell culture platform. Use of synthetic seeds produced on the serum-free PER.C6 cell platform ensures a perfectly documented seed history and maximum control over starting materials. It provides an opportunity to maximize vaccine safety which increases the prospect of a vaccine end product that is free from adventitious agents. PMID:26362098

  11. Enhancing vaccine safety capacity globally: a lifecycle perspective

    PubMed Central

    Chen, Robert T.; Shimabukuro, Tom T.; Martin, David B.; Zuber, Patrick L.F.; Weibel, Daniel M.; Sturkenboom, Miriam

    2015-01-01

    Major vaccine safety controversies have arisen in several countries beginning in the last decades of 20th Century. Such periodic vaccine safety controversies are unlikely to go away in the near future as more national immunization programs mature with near elimination of target vaccine-preventable diseases that result in relative greater prominence of adverse events following immunizations, both true reactions and temporally coincidental events. There are several ways in which vaccine safety capacity can be improved in the future to potentially mitigate the impact of future vaccine safety controversies. This paper aims to take a “lifecycle” approach, examining some potential pre- and post-licensure opportunities to improve vaccine safety, in both developed (specifically U.S. and Europe) and low- and middle- income countries. PMID:26433922

  12. Enhancing vaccine safety capacity globally: A lifecycle perspective.

    PubMed

    Chen, Robert T; Shimabukuro, Tom T; Martin, David B; Zuber, Patrick L F; Weibel, Daniel M; Sturkenboom, Miriam

    2015-11-27

    Major vaccine safety controversies have arisen in several countries beginning in the last decades of 20th century. Such periodic vaccine safety controversies are unlikely to go away in the near future as more national immunization programs mature with near elimination of target vaccine-preventable diseases that result in relative greater prominence of adverse events following immunizations, both true reactions and temporally coincidental events. There are several ways in which vaccine safety capacity can be improved to potentially mitigate the impact of future vaccine safety controversies. This paper aims to take a "lifecycle" approach, examining some potential pre- and post-licensure opportunities to improve vaccine safety, in both developed (specifically U.S. and Europe) and low- and middle-income countries. PMID:26433922

  13. Enhancing Vaccine Safety Capacity Globally: A Lifecycle Perspective.

    PubMed

    Chen, Robert T; Shimabukuro, Tom T; Martin, David B; Zuber, Patrick L F; Weibel, Daniel M; Sturkenboom, Miriam

    2015-12-01

    Major vaccine safety controversies have arisen in several countries beginning in the last decades of 20th century. Such periodic vaccine safety controversies are unlikely to go away in the near future as more national immunization programs mature with near elimination of target vaccine-preventable diseases that result in relative greater prominence of adverse events following immunizations, both true reactions and temporally coincidental events. There are several ways in which vaccine safety capacity can be improved to potentially mitigate the impact of future vaccine safety controversies. This paper aims to take a "lifecycle" approach, examining some potential pre- and post-licensure opportunities to improve vaccine safety, in both developed (specifically U.S. and Europe) and low- and middle-income countries. PMID:26590436

  14. An Epitope-Substituted DNA Vaccine Improves Safety and Immunogenicity against Dengue Virus Type 2

    PubMed Central

    Tang, Chung-Tao; Li, Pi-Chun; Liu, I-Ju; Liao, Mei-Ying; Chiu, Chiung-Yi; Chao, Day-Yu; Wu, Han-Chung

    2015-01-01

    Dengue virus (DENV), a global disease, is divided into four serotypes (DENV1-4). Cross-reactive and non-neutralizing antibodies against envelope (E) protein of DENV bind to the Fcγ receptors (FcγR) of cells, and thereby exacerbate viral infection by heterologous serotypes via antibody-dependent enhancement (ADE). Identification and modification of enhancing epitopes may mitigate enhancement of DENV infection. In this study, we characterized the cross-reactive DB21-6 and DB39-2 monoclonal antibodies (mAbs) against domain I-II of DENV; these antibodies poorly neutralized and potently enhanced DENV infection both in vitro and in vivo. In addition, two enhancing mAbs, DB21-6 and DB39-2, were observed to compete with sera antibodies from patients infected with dengue. The epitopes of these enhancing mAbs were identified using phage display, structural prediction, and mapping of virus-like particle (VLP) mutants. N8, R9, V12, and E13 are the reactive residues of DB21-6, while N8, R9, and E13 are the reactive residues of DB39-2. N8 substitution tends to maintain VLP secretion, and decreases the binding activity of DB21-6 and DB39-2. The immunized sera from N8 substitution (N8R) DNA vaccine exerted greater neutralizing and protective activity than wild-type (WT)-immunized sera, both in vitro and in vivo. Furthermore, treatment with N8R-immunized sera reduced the enhancement of mortality in AG129 mice. These results support identification and substitution of enhancing epitope as a novel strategy for developing safe dengue vaccines. PMID:26135599

  15. Conflicts of interest in vaccine safety research.

    PubMed

    DeLong, Gayle

    2012-01-01

    Conflicts of interest (COIs) cloud vaccine safety research. Sponsors of research have competing interests that may impede the objective study of vaccine side effects. Vaccine manufacturers, health officials, and medical journals may have financial and bureaucratic reasons for not wanting to acknowledge the risks of vaccines. Conversely, some advocacy groups may have legislative and financial reasons to sponsor research that finds risks in vaccines. Using the vaccine-autism debate as an illustration, this article details the conflicts of interest each of these groups faces, outlines the current state of vaccine safety research, and suggests remedies to address COIs. Minimizing COIs in vaccine safety research could reduce research bias and restore greater trust in the vaccine program. PMID:22375842

  16. Safety and efficacy of DNA vaccines

    PubMed Central

    Stenler, Sofia; Blomberg, Pontus; Smith, CI Edvard

    2014-01-01

    While DNA vaccination using plasmid vectors is highly attractive, there is a need for further vector optimization regarding safety, stability, and efficiency. In this commentary, we review the minicircle vector (MC), which is an entity devoid of plasmid bacterial sequences, as an alternative to the traditional plasmid construct. The commentary highlights the recent discovery by Stenler et al. (2014) that the small size of an MC enables improved resistance to the shearing forces associated with e.g. pneumatic delivery methods. This observation may have implications for the regulatory agencies’ requirement of plasmid integrity and quality. PMID:24553064

  17. [Human papillomavirus vaccine. Efficacy and safety].

    PubMed

    Bruni, Laia; Serrano, Beatriz; Bosch, Xavier; Castellsagué, Xavier

    2015-05-01

    Human papillomavirus (HPV) related disease remains a major cause of morbidity and mortality worldwide. Prophylactic vaccines have been recognized as the most effective intervention to control for HPV-related diseases. This article reviews the major phaseii/iii trials of the bivalent (HPVs16/18), quadrivalent (HPVs6/11/16/18), and the recently approved 9-valent vaccine (HPVs6/11/16/18/31/33/45/52/58). Large trials have been conducted showing the safety, immunogenicity and high efficacy of the bivalent and quadrivalent vaccines in the prevention of pre-invasive lesions and infection, especially when administered at young ages before exposure to HPV. Trials of the 9-valent vaccine have also demonstrated the safety, immunogenicity and efficacy of the vaccine in the prevention of infection and disease associated with the vaccine types, and its potential to substantially increase the overall prevention of HPV-related diseases. Post-licensure country reports have shown the recent and early impact of these vaccines at population level after the implementation of established HPV vaccination programs, including decreases in the prevalence of vaccine HPV types, the incidence of genital warts, and the incidence of high-grade cervical abnormalities. If widely implemented, current HPV vaccines may drastically reduce the incidence of cervical cancer and other HPV-related cancers and diseases. PMID:25937455

  18. Safety considerations for new vaccine development.

    PubMed

    Ellenberg, S S

    2001-01-01

    Vaccines are highly effective and extremely safe. Although most known vaccine reactions are minor (e.g. fever, injection site pain or swelling), rare but serious reactions such as vaccine-associated paralytic polio do occur. When large populations are vaccinated, some adverse health events may occur by chance shortly after vaccination. It is difficult to determine whether these are truly coincidental or attributable to the vaccine. The most reliable way to assess causality is in a controlled study, but clinical trials of new vaccines are typically too small to detect rare but serious effects. If the size of these trials were increased, much more could be learned about the safety of a vaccine prior to its exposure to entire populations. This information would increase confidence in the safety of vaccines, would be a valuable resource for assessing spontaneous reports of adverse events after licensure, and would reduce the risk of licensing a new vaccine that had the potential to cause severe injury to a small proportion of vaccinees. PMID:11802587

  19. The safety of influenza vaccines in children: An Institute for Vaccine Safety white paper.

    PubMed

    Halsey, Neal A; Talaat, Kawsar R; Greenbaum, Adena; Mensah, Eric; Dudley, Matthew Z; Proveaux, Tina; Salmon, Daniel A

    2015-12-30

    Most influenza vaccines are generally safe, but influenza vaccines can cause rare serious adverse events. Some adverse events, such as fever and febrile seizures, are more common in children than adults. There can be differences in the safety of vaccines in different populations due to underlying differences in genetic predisposition to the adverse event. Live attenuated vaccines have not been studied adequately in children under 2 years of age to determine the risks of adverse events; more studies are needed to address this and several other priority safety issues with all influenza vaccines in children. All vaccines intended for use in children require safety testing in the target age group, especially in young children. Safety of one influenza vaccine in children should not be extrapolated to assumed safety of all influenza vaccines in children. The low rates of adverse events from influenza vaccines should not be a deterrent to the use of influenza vaccines because of the overwhelming evidence of the burden of disease due to influenza in children. PMID:26822822

  20. Improving vaccine uptake: An overview

    PubMed Central

    Falconer, Michelle Anne

    2013-01-01

    A task group was formed with the aim to improve the quality of the service offered by ensuring that all children waiting for an appointment for vaccination would be offered one at the earliest opportunity. Children aged between 12 mo–5 y that were not completely immunized for their age were identified and included in a pilot catch-up session. Following evaluation of the pilot session, four further immunization sessions were delivered. A total of 398 children attended the four sessions, representing an improved attendance rate of 39%. Most parents brought their children between 11am–3pm and 728 vaccines were administered: 339 MMR; 255 Pre-school boosters; 53 Hib/MenC and 81 PCV. Uptake of MMR vaccine in the PCT at age 24 mo increased by 9% by Q3 2008. For children aged five years, uptake of the first dose of MMR vaccine increased from 91.9% to 94% for the first dose and from 82.3 to 82.5% for the second dose by Q3 2008. This project demonstrates that new ways of delivering immunization sessions can be successfully implemented which can enhance access through the use of alternative venues and subsequently lead to increased vaccine uptake. PMID:23732890

  1. The Vaccine Safety Datalink: a model for monitoring immunization safety.

    PubMed

    Baggs, James; Gee, Julianne; Lewis, Edwin; Fowler, Gabrielle; Benson, Patti; Lieu, Tracy; Naleway, Allison; Klein, Nicola P; Baxter, Roger; Belongia, Edward; Glanz, Jason; Hambidge, Simon J; Jacobsen, Steven J; Jackson, Lisa; Nordin, Jim; Weintraub, Eric

    2011-05-01

    The Vaccine Safety Datalink (VSD) project is a collaborative project between the Centers for Disease Control and Prevention and 8 managed care organizations (MCOs) in the United States. Established in 1990 to conduct postmarketing evaluations of vaccine safety, the project has created an infrastructure that allows for high-quality research and surveillance. The 8 participating MCOs comprise a large population of 8.8 million members annually (3% of the US population), which enables researchers to conduct studies that assess adverse events after immunization. Each MCO prepares computerized data files by using a standardized data dictionary containing demographic and medical information on its members, such as age and gender, health plan enrollment, vaccinations, hospitalizations, outpatient clinic visits, emergency department visits, urgent care visits, and mortality data, as well as additional birth information (eg, birth weight) when available. Other information sources, such as medical chart review, member surveys, and pharmacy, laboratory, and radiology data, are often used in VSD studies to validate outcomes and vaccination data. Since 2000, the VSD has undergone significant changes including an increase in the number of participating MCOs and enrolled population, changes in data-collection procedures, the creation of near real-time data files, and the development of near real-time postmarketing surveillance for newly licensed vaccines or changes in vaccine recommendations. Recognized as an important resource in vaccine safety, the VSD is working toward increasing transparency through data-sharing and external input. With its recent enhancements, the VSD provides scientific expertise, continues to develop innovative approaches for vaccine-safety research, and may serve as a model for other patient safety collaborative research projects. PMID:21502240

  2. Real-time safety surveillance of seasonal influenza vaccines in children, Australia, 2015.

    PubMed

    Pillsbury, Alexis; Cashman, Patrick; Leeb, Alan; Regan, Annette; Westphal, Darren; Snelling, Tom; Blyth, Christopher; Crawford, Nigel; Wood, Nicholas; Macartney, Kristine

    2015-01-01

    Increased febrile reactions in Australian children from one influenza vaccine brand in 2010 diminished confidence in influenza immunisation, highlighting the need for improved vaccine safety surveillance. AusVaxSafety, a national vaccine safety surveillance system collected adverse events in young children for 2015 influenza vaccine brands in real time through parent/carer reports via SMS/email. Weekly cumulative data on 3,340 children demonstrated low rates of fever (4.4%) and medical attendance (1.1%). Fever was more frequent with concomitant vaccination. PMID:26536867

  3. Safety assessment of adjuvanted vaccines: Methodological considerations

    PubMed Central

    Da Silva, Fernanda Tavares; Di Pasquale, Alberta; Yarzabal, Juan P; Garçon, Nathalie

    2015-01-01

    Adjuvants mainly interact with the innate immune response and are used to enhance the quantity and quality of the downstream adaptive immune response to vaccine antigens. Establishing the safety of a new adjuvant-antigen combination is achieved through rigorous evaluation that begins in the laboratory, and that continues throughout the vaccine life-cycle. The strategy for the evaluation of safety pre-licensure is guided by the disease profile, vaccine indication, and target population, and it is also influenced by available regulatory guidelines. In order to allow meaningful interpretation of clinical data, clinical program methodology should be optimized and standardized, making best use of all available data sources. Post-licensure safety activities are directed by field experience accumulated pre- and post-licensure clinical trial data and spontaneous adverse event reports. Continued evolution of safety evaluation processes that keep pace with advances in vaccine technology and updated communication of the benefit-risk profile is necessary to maintain public confidence in vaccines. PMID:26029975

  4. Safety assessment of adjuvanted vaccines: Methodological considerations.

    PubMed

    Da Silva, Fernanda Tavares; Di Pasquale, Alberta; Yarzabal, Juan P; Garçon, Nathalie

    2015-01-01

    Adjuvants mainly interact with the innate immune response and are used to enhance the quantity and quality of the downstream adaptive immune response to vaccine antigens. Establishing the safety of a new adjuvant-antigen combination is achieved through rigorous evaluation that begins in the laboratory, and that continues throughout the vaccine life-cycle. The strategy for the evaluation of safety pre-licensure is guided by the disease profile, vaccine indication, and target population, and it is also influenced by available regulatory guidelines. In order to allow meaningful interpretation of clinical data, clinical program methodology should be optimized and standardized, making best use of all available data sources. Post-licensure safety activities are directed by field experience accumulated pre- and post-licensure clinical trial data and spontaneous adverse event reports. Continued evolution of safety evaluation processes that keep pace with advances in vaccine technology and updated communication of the benefit-risk profile is necessary to maintain public confidence in vaccines. PMID:26029975

  5. Enhancing public confidence in vaccines through independent oversight of postlicensure vaccine safety.

    PubMed

    Salmon, Daniel A; Moulton, Lawrence H; Halsey, Neal A

    2004-06-01

    The National Immunization Program of the Centers for Disease Control and Prevention is responsible for controlling infectious diseases through vaccination, but the program also plays a key role in postlicensure vaccine safety assessment. The time has come to separate postlicensure vaccine safety assessment from vaccine risk management as recommended by the National Research Council of the National Academy of Sciences.The National Transportation Safety Board offers a useful model for developing an independent National Vaccine Safety Board that would have the authority to leverage resources and expertise of various government agencies, academia, and industry to oversee postlicensure vaccine safety investigations. Such a board would have been useful in recent vaccine safety concerns, and its independence from government programs would ensure optimal vaccine safety and enhance public confidence in vaccines. PMID:15249296

  6. 76 FR 30722 - Meeting of the National Vaccine Advisory Committee; Vaccine Safety Working Group

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-26

    ... HUMAN SERVICES Meeting of the National Vaccine Advisory Committee; Vaccine Safety Working Group AGENCY... Department of Health and Human Services (DHHS) is hereby giving notice that the Vaccine Safety Working Group (VSWG) of the National Vaccine Advisory Committee (NVAC) will hold a meeting. The meeting is open to...

  7. Safety and Immunogenicity of Improved Shigella O-Specific Polysaccharide-Protein Conjugate Vaccines in Adults in Israel

    PubMed Central

    Passwell, Justen H.; Harlev, Efrat; Ashkenazi, Shai; Chu, Chiayung; Miron, Dan; Ramon, Reut; Farzan, Naheed; Shiloach, Joseph; Bryla, Dolores A.; Majadly, Fathy; Roberson, Robin; Robbins, John B.; Schneerson, Rachel

    2001-01-01

    Data suggest that the O-specific polysaccharide (O-SP) domain of the lipopolysaccharide (LPS) of Shigella species is both an essential virulence factor and a protective antigen and that a critical level of serum immunoglobulin G (IgG) to this antigen will confer immunity to shigellosis. Because covalent attachment of polysaccharides to proteins increases their immunogenicity, especially in infants and in young children, the O-SP of Shigella species were bound to medically useful proteins, and the safety and immunogenicity of the resultant conjugates were confirmed in adults and 4- to 7-year-old children. Succinylation of the carrier protein improved the immunogenicity of Shigella conjugates in mice and increased their yield. Based on these results, a clinical trial of O-SP conjugates of Shigella sonnei and Shigella flexneri 2a bound to succinylated mutant Pseudomonas aeruginosa exotoxin A (rEPAsucc) or native or succinylated Corynebacterium diphtheriae toxin mutant (CRM9 or CRM9succ) was conducted in healthy adults. The conjugates were safe and immunogenic. S. sonnei-CRM9, S. sonnei-CRM9succ, and S. sonnei-rEPAsucc elicited significant rises of geometric mean (GM) IgG anti-LPS within 1 week of injection (P < 0.001). At 26 weeks, the GM anti-LPS levels elicited by these three conjugates were similar and higher than their prevaccination levels (P < 0.0001). GM IgG anti-LPS levels elicited by S. flexneri 2a-rEPAsucc were significantly higher than those elicited by S. flexneri 2a-rCRM9succ at all intervals after injection. At 26 weeks, the levels of IgG anti-LPS in vaccinees were higher than their prevaccination levels (P < 0.0001). The serum antibody responses were specific, as there was no significant rise of anti-LPS to the heterologous O-SP in any vaccinee. Both conjugates elicited statistically significant rises of serum antibodies to the injected carrier protein. At 6 months, these five Shigella conjugates elicited higher fold rises than similar conjugates (D. N

  8. Mucosal adjuvants to improve wildlife rabies vaccination.

    PubMed

    Fry, Tricia; Van Dalen, Kaci; Hurley, Jerome; Nash, Paul

    2012-10-01

    RABORAL V-RG(®)a is a recombinant vaccine used in oral rabies vaccination (ORV) programs for wildlife in the United States. Vaccination rates for raccoons are substantially lower than vaccination rates for gray foxes and coyotes. Research suggests that the low viscosity of the oral vaccine may preclude animals from receiving an effective dose when biting into the vaccine bait delivery system. We evaluated the possibility of using two benign compounds, chitosan and N,N,N-trimethylated chitosan (TMC), to increase the viscosity of the vaccine and potentially act as adjuvants to improve the immune response in raccoons (Procyon lotor). Forty mildly sedated raccoons were orally vaccinated via needleless syringe with either RABORAL V-RG (n = 12), chitosan+RABORAL V-RG (n = 12), TMC+ RABORAL V-RG (n = 12), or no vaccine (n = 4), on day 0 and again on day 90. We collected sera every 2-4 wk for 4 mo and evaluated rabies virus-neutralizing antibodies (rVNA). Raccoons were considered responders if rVNA titers were ≥ 0.1 IU/mL. Eleven of 12 raccoons vaccinated with TMC+RABORAL V-RG responded after one dose of vaccine, as did eight of 12 vaccinated with RABORAL V-RG, and three of 12 vaccinated with chitosan+ RABORAL V-RG. Our results suggest that the inclusion of an adjuvant, such as TMC, could increase vaccine efficacy to aid in controlling rabies virus spread in wildlife reservoirs. PMID:23060506

  9. Vaccine adjuvants--understanding molecular mechanisms to improve vaccines.

    PubMed

    Egli, Adrian; Santer, Deanna; Barakat, Khaled; Zand, Martin; Levin, Aviad; Vollmer, Madeleine; Weisser, Maja; Khanna, Nina; Kumar, Deepali; Tyrrell, Lorne; Houghton, Michael; Battegay, Manuel; O'Shea, Daire

    2014-01-01

    Infectious pathogens are responsible for high utilisation of healthcare resources globally. Attributable morbidity and mortality remains exceptionally high. Vaccines offer the potential to prime a pathogen-specific immune response and subsequently reduce disease burden. Routine vaccination has fundamentally altered the natural history of many frequently observed and serious infections. Vaccination is also recommended for persons at increased risk of severe vaccine-preventable disease. Many current nonadjuvanted vaccines are poorly effective in the elderly and immunocompromised populations, resulting in nonprotective postvaccine antibody titres, which serve as surrogate markers for protection. The vaccine-induced immune response is influenced by: (i.) vaccine factors i.e., type and composition of the antigen(s), (ii.) host factors i.e., genetic differences in immune-signalling or senescence, and (iii.) external factors such as immunosuppressive drugs or diseases. Adjuvanted vaccines offer the potential to compensate for a lack of stimulation and improve pathogen-specific protection. In this review we use influenza vaccine as a model in a discussion of the different mechanisms of action of the available adjuvants. In addition, we will appraise new approaches using "vaccine-omics" to discover novel types of adjuvants. PMID:24844935

  10. Capacity for a global vaccine safety system: the perspective of national regulatory authorities.

    PubMed

    Graham, Janice E; Borda-Rodriguez, Alexander; Huzair, Farah; Zinck, Emily

    2012-07-13

    Confidence in vaccine safety is critical to national immunization strategies and to global public health. To meet the Millenium Development Goals, and buoyed by the success of new vaccines produced in developing countries, the World Health Organization has been developing a strategy to establish a global system for effective vaccine pharmacovigilance in all countries. This paper reports the findings of a qualitative survey, conducted for the WHO Global Vaccine Safety Blueprint project, on the perspectives of national regulatory authorities responsible for vaccine safety in manufacturing and procuring countries. Capacity and capabilities of detecting, reporting and responding to adverse events following immunization (AEFI), and expectations of minimum capacity necessary for vaccine pharmacovigilance were explored. Key barriers to establishing a functional national vaccine safety system in developing countries were identified. The lack of infrastructure, information technology for stable communications and data exchange, and human resources affect vaccine safety monitoring in developing countries. A persistent "fear of reporting" in several low and middle income countries due to insufficient training and insecure employment underlies a perceived lack of political will in many governments for vaccine pharmacovigilance. Regulators recommended standardized and internationally harmonized safety reporting forms, improved surveillance mechanisms, and a global network for access and exchange of safety data independent of industry. PMID:22658930

  11. Monitoring vaccine safety using the Vaccine Safety Datalink: utilizing immunization registries for pandemic influenza.

    PubMed

    McCarthy, Natalie L; Gee, Julianne; Weintraub, Eric; Donahue, James G; Nordin, James D; Daley, Matthew F; Naleway, Allison; Henninger, Michelle; Baxter, Roger; Crane, Bradley; Aukes, Laurie; Wagner, Nicole; Fisher, Sarah; Jacobsen, Steven J; Sy, Lina; Baggs, James

    2011-07-12

    Mass vaccination campaigns during which new vaccines may be administered to many millions of people in a short period of time call for timely and accurate post-licensure surveillance to monitor vaccine safety. To address the need for timely H1N1 influenza vaccine safety information during the 2009-2010 H1N1 influenza pandemic, the Vaccine Safety Datalink (VSD) project assessed the feasibility and potential mechanisms for utilizing data from state and local immunization registries to capture vaccinations that would not otherwise be captured by the data systems of the participating VSD managed care organizations (MCOs). Three of the eight VSD sites were able to capture H1N1 immunization data electronically from the state and local registries, and one site was able to capture the immunizations through a paper-based system; however, the remaining four sites encountered various obstacles that prevented capture of such data. Additional work will be required at these sites to overcome the barriers, which included privacy and confidentiality laws, time constraints brought on by the pandemic, as well as data quality concerns. PMID:21596088

  12. The impact of the parent-physician relationship on parental vaccine safety perceptions.

    PubMed

    Kundi, Michael; Obermeier, Patrick; Helfert, Stephanie; Oubari, Hiba; Fitzinger, Stefan; Yun, Jeong A; Brix, Martin; Rath, Barbara

    2015-01-01

    In times of declining immunization rates among children in many countries and an increasing threat of potentially vaccine-preventable diseases, there is a strong need for new strategies to improve trust in vaccinations and acceptance of recommendations, especially in parents of infants and children. A survey to evaluate vaccination acceptance has been conducted in Vienna, Austria, based on a US CDC survey, applying a cross-sectional approach with districts and public as well as private kindergartens and preschools as selection base. The survey aimed to investigate the impact of parent satisfaction with, and overall trust in the physician on vaccine acceptance, as well as the impact of quality and completeness of safety information delivered during the vaccination consultation. Overall 1101 parents, predominantly (84.2%) mothers, participated in the survey. The majority (82.7%) of participants had a generally positive view concerning childhood vaccination. However, 25.1% refused at least one of the recommended vaccinations. In multivariate analysis, confidence in vaccinations was significantly influenced by education (lower confidence at higher levels of education), gender (higher confidence in females), and positively associated with trust in physician, smooth vaccination procedure, and information about vaccine risks. Similar results were obtained for compliance with recommended vaccinations with information about vaccine benefits being the most important predictor. This large survey indicates an important role of the physician in communicating balanced information about benefits and risks associated with childhood vaccinations. A trustworthy parent-physician relationship is crucial for vaccination decisions of parents. PMID:25859670

  13. Porcine reproductive and respiratory syndrome virus vaccines: Immunogenicity, efficacy and safety aspects

    PubMed Central

    Charerntantanakul, Wasin

    2012-01-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) infection is the leading cause of economic casualty in swine industry worldwide. The virus can cause reproductive failure, respiratory disease, and growth retardation in the pigs. This review deals with current status of commercial PRRS vaccines presently used to control PRRS. The review focuses on the immunogenicity, protective efficacy and safety aspects of the vaccines. Commercial PRRS modified-live virus (MLV) vaccine elicits delayed humoral and cell-mediated immune responses following vaccination. The vaccine confers late but effective protection against genetically homologous PRRSV, and partial protection against genetically heterologous virus. The MLV vaccine is of concern for its safety as the vaccine virus can revert to virulence and cause diseases. PRRS killed virus (KV) vaccine, on the other hand, is safe but confers limited protection against either homologous or heterologous virus. The KV vaccine yet helps reduce disease severity when administered to the PRRSV-infected pigs. Although efforts have been made to improve the immunogenicity, efficacy and safety of PRRS vaccines, a better vaccine is still needed in order to protect against PRRSV. PMID:24175208

  14. A Single Mutation at PB1 Residue 319 Dramatically Increases the Safety of PR8 Live Attenuated Influenza Vaccine in a Murine Model without Compromising Vaccine Efficacy

    PubMed Central

    Cox, Andrew

    2015-01-01

    The live attenuated influenza vaccine (LAIV) is preferentially recommended for use in most children yet remains unsafe for the groups most at risk. Here we have improved the safety of a mouse-adapted live attenuated influenza vaccine containing the same attenuating amino acid mutations as in human LAIV by adding an additional mutation at PB1 residue 319. This results in a vaccine with a 20-fold decrease in protective efficacy and a 10,000-fold increase in safety. PMID:26676793

  15. Toward improved influenza control through vaccination.

    PubMed

    Falleiros Arlant, Luiza Helena; Ferro Bricks, Lucia

    2015-04-01

    In August 27/2014, SLIPE organized the Master Class "Towards improved influenza control through vaccination", a panel with international influenza experts who shared their understanding of the disease and the control measures available, focusing on the most recent information about this serious diseases. In this report Dr Falleiros and Dr Bricks summarized the following topics: Global influenza epidemiology, presented by Dr Puig-Barbera; Influenza vaccine recommendations and coverage in Latin American countries, presented by Dr Bricks; Influenza vaccines efficacy and effectiveness, presented by Dr Fedson: Influenza burden ;md rational for prevention in children, presented by Dr Muiioz; Influenza burden in pregnancy, presented by Dr Ribeiro; Influenza vaccination in health care workers, presented by Dr Macias; Influenza vaccination in the elderly, presented by Dr Ribeiro; Rational to increase vaccination coverage rates Global Influenza Hospital Surveillance Network, presented by Dr Puig-Barbera; Influenza B epidemiology and vaccine strain mismatch in Latin American Region, presented by Dr Bricks; Modeling for quadrivalent influenza vaccines impact, presented by Dr Blank; Rational for quadrivalent influenza vaccines and the clinical development of QIV s, presented by Dr Desauziers and Modelling quadrivalent influenza vaccines impact, presented by Dr Blank. PMID:26065453

  16. Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS).

    PubMed

    Shimabukuro, Tom T; Nguyen, Michael; Martin, David; DeStefano, Frank

    2015-08-26

    The Centers for Disease Control and Prevention (CDC) and the U.S. Food and Drug Administration (FDA) conduct post-licensure vaccine safety monitoring using the Vaccine Adverse Event Reporting System (VAERS), a spontaneous (or passive) reporting system. This means that after a vaccine is approved, CDC and FDA continue to monitor safety while it is distributed in the marketplace for use by collecting and analyzing spontaneous reports of adverse events that occur in persons following vaccination. Various methods and statistical techniques are used to analyze VAERS data, which CDC and FDA use to guide further safety evaluations and inform decisions around vaccine recommendations and regulatory action. VAERS data must be interpreted with caution due to the inherent limitations of passive surveillance. VAERS is primarily a safety signal detection and hypothesis generating system. Generally, VAERS data cannot be used to determine if a vaccine caused an adverse event. VAERS data interpreted alone or out of context can lead to erroneous conclusions about cause and effect as well as the risk of adverse events occurring following vaccination. CDC makes VAERS data available to the public and readily accessible online. We describe fundamental vaccine safety concepts, provide an overview of VAERS for healthcare professionals who provide vaccinations and might want to report or better understand a vaccine adverse event, and explain how CDC and FDA analyze VAERS data. We also describe strengths and limitations, and address common misconceptions about VAERS. Information in this review will be helpful for healthcare professionals counseling patients, parents, and others on vaccine safety and benefit-risk balance of vaccination. PMID:26209838

  17. Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS)

    PubMed Central

    Shimabukuro, Tom T.; Nguyen, Michael; Martin, David; DeStefano, Frank

    2015-01-01

    The Centers for Disease Control and Prevention (CDC) and the U.S. Food and Drug Administration (FDA) conduct post-licensure vaccine safety monitoring using the Vaccine Adverse Event Reporting System (VAERS), a spontaneous (or passive) reporting system. This means that after a vaccine is approved, CDC and FDA continue to monitor safety while it is distributed in the marketplace for use by collecting and analyzing spontaneous reports of adverse events that occur in persons following vaccination. Various methods and statistical techniques are used to analyze VAERS data, which CDC and FDA use to guide further safety evaluations and inform decisions around vaccine recommendations and regulatory action. VAERS data must be interpreted with caution due to the inherent limitations of passive surveillance. VAERS is primarily a safety signal detection and hypothesis generating system. Generally, VAERS data cannot be used to determine if a vaccine caused an adverse event. VAERS data interpreted alone or out of context can lead to erroneous conclusions about cause and effect as well as the risk of adverse events occurring following vaccination. CDC makes VAERS data available to the public and readily accessible online. We describe fundamental vaccine safety concepts, provide an overview of VAERS for healthcare professionals who provide vaccinations and might want to report or better understand a vaccine adverse event, and explain how CDC and FDA analyze VAERS data. We also describe strengths and limitations, and address common misconceptions about VAERS. Information in this review will be helpful for healthcare professionals counseling patients, parents, and others on vaccine safety and benefit-risk balance of vaccination. PMID:26209838

  18. The Safety of Adjuvanted Vaccines Revisited: Vaccine-Induced Narcolepsy.

    PubMed

    Ahmed, S Sohail; Montomoli, Emanuele; Pasini, Franco Laghi; Steinman, Lawrence

    2016-01-01

    Despite the very high benefit-to-risk ratio of vaccines, the fear of negative side effects has discouraged many people from getting vaccinated, resulting in the reemergence of previously controlled diseases such as measles, pertussis and diphtheria. This fear has been amplified more recently by multiple epidemiologic studies that confirmed the link of an AS03-adjuvanted pandemic influenza vaccine (Pandemrix, GlaxoSmithKline Biologicals, Germany) used in Europe during the 2009 H1N1 influenza pandemic [A(H1N1) pdm09] with the development of narcolepsy, a chronic sleep disorder, in children and adolescents. However, public misperceptions of what adjuvants are and why they are used in vaccines has created in some individuals a closed "black box" attitude towards all vaccines. The focus of this review article is to revisit this "black box" using the example of narcolepsy associated with the European AS03-adjuvanted pandemic influenza vaccine. PMID:27228647

  19. Quadrivalent HPV vaccine safety review and safety monitoring plans for nine-valent HPV vaccine in the United States.

    PubMed

    Gee, Julianne; Weinbaum, Cindy; Sukumaran, Lakshmi; Markowitz, Lauri E

    2016-06-01

    Quadrivalent human papillomavirus (4vHPV) vaccine was licensed for use in the United States in 2006 and through 2015 was the predominate HPV vaccine used. With the exception of syncope, a known preventable adverse event after any injected vaccination, both pre-licensure and post-licensure 4vHPV safety data have been reassuring with no confirmed safety signals identified. Nine-valent HPV vaccine (9vHPV) was licensed in 2014. This review includes post-licensure 4vHPV safety findings published to date that have informed the US vaccination program; these data will inform US safety monitoring and evaluation for 9vHPV. PMID:27029786

  20. Pediatricians' Experience with and Response to Parental Vaccine Safety Concerns and Vaccine Refusals: A Survey of Connecticut Pediatricians

    PubMed Central

    Leib, Susan; Liberatos, Penny; Edwards, Karen

    2011-01-01

    Objectives Physicians are seeing increasing numbers of parents who question the safety of vaccines or refuse to vaccinate their children. This study examined how frequently pediatricians in one New England state encounter parental vaccine safety concerns and vaccine refusals, how often physicians dismiss families from their practices for vaccine refusal, and how parental vaccine refusal impacts pediatricians personally. Methods The study consisted of a quantitative survey of primary care pediatricians in one New England state; 133 pediatricians completed the questionnaire. Variables examined included number of parental vaccine concerns and refusals seen by each physician, physicians' response to parental vaccine concerns and refusals, the personal impact of parental vaccine safety refusals on pediatricians, and respondent estimates of socioeconomic characteristics of families seen in their practices. Results The majority of responding pediatricians reported an increase in parental vaccine safety concerns and refusals. More than 30% of responding pediatricians have dismissed families because of their refusal to immunize. Suburban physicians caring for wealthier, better educated families experience more vaccine concerns and/or refusals and are more likely to dismiss families for vaccine refusal. Vaccine refusals have a negative personal impact on one-third of physician respondents. Conclusions Pediatricians in Connecticut are reporting increased levels of parental vaccine safety concerns and refusals. Physicians who report more parental vaccine safety concerns and refusals and who care for wealthier, better educated families are more likely to dismiss families who refuse vaccines and to be negatively affected by parental vaccine refusals, which may adversely impact childhood vaccination rates. PMID:21812165

  1. Communicating vaccine safety to the media and general public.

    PubMed

    Oubari, Hiba; Tuttle, Ryan; Rath, Barbara; Bravo, Lulu

    2015-01-01

    Vaccines are among the most effective measures to control and prevent infectious diseases. Yet, the topic of vaccination is difficult to communicate, as it bears upon individual versus common good. The efficacy and safety of vaccines can only be shown by the absence of undesired events, such as vaccine-preventable diseases or adverse events following immunization. The authors of this paper view accurate, transparent and timely vaccine-safety communication to the media and general public as a core responsibility of healthcare providers. The authors wish to explore potential difficulties faced by immunization specialists when talking to the media, and suggest how to successfully convey vaccination messages to the general public. PMID:25859680

  2. Shuttle Safety Improvements

    NASA Technical Reports Server (NTRS)

    Henderson, Edward

    2001-01-01

    The Space Shuttle has been flying for over 20 years and based on the Orbiter design life of 100 missions it should be capable of flying at least 20 years more if we take care of it. The Space Shuttle Development Office established in 1997 has identified those upgrades needed to keep the Shuttle flying safely and efficiently until a new reusable launch vehicle (RLV) is available to meet the agency commitments and goals for human access to space. The upgrade requirements shown in figure 1 are to meet the program goals, support HEDS and next generation space transportation goals while protecting the country 's investment in the Space Shuttle. A major review of the shuttle hardware and processes was conducted in 1999 which identified key shuttle safety improvement priorities, as well as other system upgrades needed to reliably continue to support the shuttle miss ions well into the second decade of this century. The high priority safety upgrades selected for development and study will be addressed in this paper.

  3. Seasonal Flu Vaccine Safety and Pregnant Women

    MedlinePlus

    ... shot. Top of Page Can pregnant women with egg allergies get vaccinated? Most people who have an ... reaction following a flu shot. Special Consideration Regarding Egg Allergy The recommendations for vaccination of people with ...

  4. Long-term efficacy and safety of human papillomavirus vaccination

    PubMed Central

    De Vincenzo, Rosa; Conte, Carmine; Ricci, Caterina; Scambia, Giovanni; Capelli, Giovanni

    2014-01-01

    In this paper, we review the published evidence about the long-term efficacy of the available human papillomavirus (HPV) vaccines and their safety profile. Two prophylactic HPV vaccines – bivalent (bHPV) and quadrivalent (qHPV) – are now available, and vaccination programs are being widely implemented, primarily targeting adolescent girls. Efficacy has been widely demonstrated for both vaccines. Since the risk of HPV exposure potentially persists throughout a woman’s sexual life, vaccine duration of protection is critical to overall effectiveness. Interpreting the results of long-term efficacy studies for the two HPV vaccines can be puzzling, due to the heterogeneity of studies, different methods used in the assessment of immunogenicity, histopathological and virological end points, and statistical power issues. Moreover, an immunologic correlate of protection has not yet been established, and it is unknown whether higher antibody levels will really result in a longer duration of protection. Disease prevention remains the most important measure of long-term duration of vaccine efficacy. To date, the longest follow-up of an HPV vaccine has been 9.4 years for the bHPV vaccine. Long-term follow-up for qHPV vaccine goes up to 8 years. The vaccine continues to be immunogenic and well tolerated up to 9 years following vaccination. All randomized controlled clinical trials of the bHPV and the qHPV vaccines provide evidence of an excellent safety profile. The most common complaint reported is pain in the injection site, which is self-limiting and spontaneously resolved. The incidence of systemic adverse events (AEs), serious AEs, and discontinuations due to a serious AE reported in clinical studies are similar between the two vaccines and their control groups. In particular, no increased risk of autoimmune disease has been shown among HPV-vaccinated subjects in long-term observation studies. As these are crucial topics in HPV vaccination, it is important to establish

  5. Improving Student Safety.

    ERIC Educational Resources Information Center

    Dorn, Michael; Trump, Kenneth S.; Nichols, R. Leslie

    2001-01-01

    Presents the latest information on how schools can keep their students safe. Safety oriented actions discussed cover incident reporting and tracking, tactical site surveys, school safety and emergency operations planning, staff development efforts, and facility design. Explains the need to review and test specific prevention concepts and emergency…

  6. 21 CFR 610.11a - Inactivated influenza vaccine, general safety test.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 7 2012-04-01 2012-04-01 false Inactivated influenza vaccine, general safety test... Inactivated influenza vaccine, general safety test. For inactivated influenza vaccine, the general safety test... subcutaneous or intraperitoneal injection of 5.0 milliliters of inactivated influenza vaccine into each...

  7. 21 CFR 610.11a - Inactivated influenza vaccine, general safety test.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 7 2011-04-01 2010-04-01 true Inactivated influenza vaccine, general safety test... Inactivated influenza vaccine, general safety test. For inactivated influenza vaccine, the general safety test... subcutaneous or intraperitoneal injection of 5.0 milliliters of inactivated influenza vaccine into each...

  8. 21 CFR 610.11a - Inactivated influenza vaccine, general safety test.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Inactivated influenza vaccine, general safety test... Inactivated influenza vaccine, general safety test. For inactivated influenza vaccine, the general safety test... subcutaneous or intraperitoneal injection of 5.0 milliliters of inactivated influenza vaccine into each...

  9. 21 CFR 610.11a - Inactivated influenza vaccine, general safety test.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 7 2014-04-01 2014-04-01 false Inactivated influenza vaccine, general safety test... Inactivated influenza vaccine, general safety test. For inactivated influenza vaccine, the general safety test... subcutaneous or intraperitoneal injection of 5.0 milliliters of inactivated influenza vaccine into each...

  10. 21 CFR 610.11a - Inactivated influenza vaccine, general safety test.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 7 2013-04-01 2013-04-01 false Inactivated influenza vaccine, general safety test... Inactivated influenza vaccine, general safety test. For inactivated influenza vaccine, the general safety test... subcutaneous or intraperitoneal injection of 5.0 milliliters of inactivated influenza vaccine into each...

  11. Contributions and challenges for worldwide vaccine safety: The Global Advisory Committee on Vaccine Safety at 15 years.

    PubMed

    Asturias, Edwin J; Wharton, Melinda; Pless, Robert; MacDonald, Noni E; Chen, Robert T; Andrews, Nicholas; Salisbury, David; Dodoo, Alexander N; Hartigan-Go, Kenneth; Zuber, Patrick L F

    2016-06-17

    In 1999, the Global Advisory Committee on Vaccine Safety (GACVS) was established by the World Health Organization (WHO) to provide independent scientific advice on issues relating to the safety of vaccines and immunization. Fifteen years onward, we conducted a multi-faceted review to evaluate the impact, reach and challenges facing GACVS, including the role GACVS plays in informing global, regional and WHO member state vaccine policy. The methods included measures of organizational structure, citation impact, themes approached, and a discussion by previous and current members to evaluate past, present and future challenges. Given the increasing range of data sources and the deployment of many new vaccines, the Committee is facing the complex task of identifying the best available evidence for recommendations on vaccine safety. To help meet the increased demand for public transparency in decision making, GACVS-structured methodology for evidence-based decisions is evolving. GACVS also promotes best practices and capacity building for timely and accurate risk assessment; risk communications; outreach to help countries maintain and, if needed, rebuild public trust in vaccines; and advocacy for bridging the major gaps in vaccine safety capacity globally. PMID:27195758

  12. Current developments in avian influenza vaccines, including safety of vaccinated birds as food.

    PubMed

    Swayne, D E; Suarez, D L

    2007-01-01

    Until recently, most vaccines against avian influenza were based on oil-emulsified inactivated low- or high-pathogenicity viruses. Now, recombinant fowl pox and avian paramyxovirus type 1 vaccines with avian influenza H5 gene inserts (+ or - N1 gene insert) are available and licensed. New technologies might overcome existing limitations to make available vaccines that can be grown in tissue culture systems for more rapid production; provide optimized protection, as a result of closer genetic relations to field viruses; allow mass administration by aerosol, in drinking-water or in ovo; and allow easier strategies for identifying infected birds within vaccinated populations (DIVA). The technologies include avian influenza viruses with partial gene deletions, avian influenza-Newcastle disease virus chimeras, vectored vaccines such as adenoviruses and Marek's disease virus, and subunit vaccines. These new methods should be licensed only after their purity, safety, efficacy and potency against avian influenza viruses have been demonstrated, and, for live vectored vaccines, restriction of viral transmission to unvaccinated birds. Use of vaccines in countries affected by highly pathogenic avian influenza will not only protect poultry but will provide additional safety for consumers. Experimental studies have shown that birds vaccinated against avian influenza have no virus in meat and minimal amounts in eggs after HPAI virus challenge, and that replication and shedding from their respiratory and alimentary tracts is greatly reduced. PMID:18411943

  13. Routine surveillance of adverse events following immunization as an important tool to monitor vaccine safety.

    PubMed

    Alicino, Cristiano; Merlano, Caterina; Zappettini, Simona; Schiaffino, Sergio; Della Luna, Giovanni; Accardo, Cristina; Gasparini, Roberto; Durando, Paolo; Icardi, Giancarlo

    2015-01-01

    Post licensure surveillance of adverse events following immunization (AEFI) is a fundamental activity to improve safety and maintain public confidence in vaccines.   Since 2011, the Liguria Region has been involved in the inter-regional project of post-marketing surveillance of AEFI, coordinated by the Italian Medicine Agency and the Veneto region. The main objectives of the project are: (1) to coordinate the surveillance activities in the 8 Italian Regions included in the project; (2) to encourage the signal of AEFI by healthcare workers and patients; (3) to organize education activities addressed to health care workers, and, finally; (4) to establish vaccination counseling services in each Region. In particular, the Ligurian multidisciplinary team, composed by physicians expert in the field of vaccination and pharmacists, is involved in the causality assessment between vaccines and all adverse events signaled within the Liguria Region and in the analysis of all adverse events signaled in Italy as possibly related to influenza vaccines. During 2013, the team has organized 4 courses, addressed to healthcare personnel of vaccination outpatient clinics, focused on European and Italian legislation on pharmaco-vigilance and vaccine-vigilance and aimed at promoting signal of AEFI. Since October 2013, the Liguria Region has been participating to the inter-regional project of active surveillance of adverse events aimed at promoting the signal of AEFI by parents of vaccinated infants. After two years of implementation of the project both the number of reported AEFI and the reporting rate per 100 000 administered doses of vaccine increased. The activities need to be consolidated in the next years in order to guarantee high standard of vaccine safety, maintain the confidence in current immunization programs and reach optimal vaccination coverage rate. PMID:25483520

  14. Understanding Thimerosal, Mercury, and Vaccine Safety

    MedlinePlus

    ... dose vials, to keep the vaccine free from contamination. Thimerosal is also used during the manufacturing process ... get into the vial. The preservative, thimerosal, prevents contamination in the multi-dose vial when individual doses ...

  15. Elevating standards, improving safety.

    PubMed

    Clarke, Richard

    2014-08-01

    In our latest 'technical guidance' article, Richard Clarke, sales and marketing director at one of the UK's leading lift and escalator specialists, Schindler, examines some of the key issues surrounding the specification, maintenance, and operation of lifts in hospitals to help ensure the highest standards of safety and reliability. PMID:25219081

  16. Current developments for improving efficacy of allergy vaccines.

    PubMed

    Sandrini, Alessandra; Rolland, Jennifer M; O'Hehir, Robyn E

    2015-01-01

    Allergic diseases are prevalent worldwide. Allergen immunotherapy (AIT) is a current treatment for allergy, leading to modification of the natural course of disease. Mechanisms of efficacy include Treg through release of IL-10 and TGF-β and specific IgG4 blocking antibodies. Subcutaneous and sublingual routes are popular, but uptake is limited by inconvenience and safety concerns. Inclusion criteria limit application to a small proportion of allergic patients. New forms of immunotherapy are being investigated for more efficacious, convenient and safer options with promising advances in recent years. The rationale of reducing vaccine allergenicity to increase safety while improving immunogenicity led to investigation of T-cell epitope-based peptides and recombinant allergen derivatives. Additionally, different routes of administration and adjuvants and adjunct therapies are being explored. This review discusses the current status of AIT and recent advances to improve clinical efficacy, safety and long-term immune tolerance. PMID:26013124

  17. Safety of engineered allergen-specific immunotherapy vaccines

    PubMed Central

    Focke-Tejkl, Margarete; Valenta, Rudolf

    2015-01-01

    Purpose of review The purpose of the review is to summarize and comment on recent developments regarding the safety of engineered immunotherapy vaccines. Recent findings In the last 2 years, several studies were published in which allergy vaccines were developed on the basis of chemical modification of natural allergen extracts, the engineering of allergen molecules by recombinant DNA technology and synthetic peptide chemistry, allergen genes, new application routes and conjugation with immune modulatory molecules. Several studies exemplified the general applicability of hypoallergenic vaccines on the basis of recombinant fusion proteins consisting of nonallergenic allergen-derived peptides fused to allergen-unrelated carrier molecules. These vaccines are engineered to reduce both, immunoglobulin E (IgE) as well as allergen-specific T cell epitopes in the vaccines, and thus should provoke less IgE and T-cell-mediated side-effects. They are made to induce allergen-specific IgG antibodies against the IgE-binding sites of allergens with the T-cell help of the carrier molecule. Summary Several interesting examples of allergy vaccines with potentially increased safety profiles have been published. The concept of fusion proteins consisting of allergen-derived hypoallergenic peptides fused to allergen-unrelated proteins that seems to be broadly applicable for a variety of allergens appears to be of particular interest because it promises not only to reduce side-effects but also to increase efficacy and convenience of allergy vaccines. PMID:22885888

  18. Vaccine Safety Surveillance Systems: Critical Elements and Lessons Learned in the Development of the US Vaccine Safety Datalink’s Rapid Cycle Analysis Capabilities

    PubMed Central

    Davis, Robert L.

    2013-01-01

    Since the late 1990s, there have been tremendous strides made in improving the capacity for carrying out routine active surveillance of new vaccines in the United States. These strides have led to new surveillance systems that are now in place. Some of the critical elements that are part of successful vaccine or drug safety surveillance systems include their use of (i) longitudinal data from a discrete enumerated population base, (ii) frequent, routine transfers of small amounts of data that are easy to collect and collate, (iii) avoidance of mission creep, (iv) statistical capabilities, (v) creation of an “industrialized process” approach and (vi) political safe harbor. PMID:24300403

  19. Improving the cold chain for vaccines.

    PubMed

    Lloyd, J S

    1977-01-01

    The cold chain may be defined as a system for transporting and storing vaccines at very low temperataures, particularly in tropical countries. In Ghana, efforts are being made, with the assistance of the World Health Organization (WHO) to develop and test a new cold chain technology. Emphasis is on local production in order to meet the needs of the countrywide immunization program, and, if possible, of similar programs in other West African nations. Focus in this discussion is on the losses resulting from mishandling of vaccines during storage and in transit through various stages in the cold chain as well as the problems, requirements, and proposed solutions. In most countries with immunization programs, breakdowns in refrigeration during the transport and storage of vaccines in remote rural areas or at the regional and national central stores have led to great losses of vaccine. The losses are often caused by inappropriate management and technology. The most promising recent development in the area of storage is an enzyme-based time/temperature indicator contained in a paper tab which is attached to the vaccine packet. In order to reduce to a minimum the handling of vaccines at the national central store it is proposed that the ministry of health submit details of regional requirements in their requisition to the manufacturer. Then the manufacturer can make presealed packages which are dispatched by air to the national central store and from there to the regions, while they are still sealed. Insulated boxes for this purpose have been tested in Sweden and been shown to maintain deep-freezing temperatures for 5 days. Road communications to the regional centers are good in Ghana and the 5-day cold boxes give adequate safety margins. The plan for the immunization program in Ghana is to employ a combination of teams from both fixed and mobile centers. 3 contacts, 3 months apart, will be made by the fixed teams; mobile teams will make 2 contacts, 2 months apart. Mobile

  20. Epidemiological designs for vaccine safety assessment: methods and pitfalls.

    PubMed

    Andrews, Nick

    2012-09-01

    Three commonly used designs for vaccine safety assessment post licensure are cohort, case-control and self-controlled case series. These methods are often used with routine health databases and immunisation registries. This paper considers the issues that may arise when designing an epidemiological study, such as understanding the vaccine safety question, case definition and finding, limitations of data sources, uncontrolled confounding, and pitfalls that apply to the individual designs. The example of MMR and autism, where all three designs have been used, is presented to help consider these issues. PMID:21985898

  1. Improved influenza vaccination in the skin using vaccine coated-microneedles

    PubMed Central

    Kim, Yeu-Chun; Quan, Fu-Shi; Yoo, Dae-Goon; Compans, Richard W.; Kang, Sang-Moo; Prausnitz, Mark R.

    2010-01-01

    Easy and effective vaccination methods could reduce mortality and morbidity due to vaccine-preventable influenza infections. In this study, we examined the use of microneedle patches to increase patient coverage through possible self administration and enhance vaccine immunogenicity by targeted delivery to skin. We carried out a detailed study of protective immune responses after a single influenza vaccination to the skin of mice with a novel microneedle patch designed to facilitate simple and reliable vaccine delivery. Skin vaccination with inactivated virus-coated microneedles provided superior protection against lethal challenge compared to intramuscular injection as evidenced by effective virus clearance in lungs. Detailed immunologic analysis suggests that induction of virus neutralizing antibodies as well as enhanced anamnestic humoral and cellular responses contributed to improved protection by microneedle vaccination to the skin. These findings suggest that vaccination in the skin using a microneedle patch can improve protective immunity, and simplify delivery of influenza and possibly other vaccines. PMID:19761836

  2. Safe use of vaccines and vaccine compliance with food safety requirements.

    PubMed

    Grein, K; Papadopoulos, O; Tollis, M

    2007-08-01

    Advanced technologies and regulatory regimes have contributed to the availability of veterinary vaccines that have high quality and favourable safety profiles in terms of potential risks posed to the target animals, the persons who come into contact with the vaccine, the consumers of food derived from vaccinated animals and the environment. The authorisation process requires that a range of safety studies are provided to evaluate the products. The design and production of vaccines, and their safe use, are primarily assessed by using data gathered from extensive pre-marketing studies performed on target animals and specific quality tests. The current post-marketing safeguards include good manufacturing practices, batch safety testing, inspections and pharmacovigilance. In addition to hazard identification, a full benefit/risk evaluation needs to be undertaken. The outcome of that evaluation will determine options for risk management and affect regulatory decisions on the safety of the vaccine; options might, for example, include special warnings on package inserts and labels. PMID:17892156

  3. Improving vaccine efficacy against malignant glioma.

    PubMed

    Ladomersky, Erik; Genet, Matthew; Zhai, Lijie; Gritsina, Galina; Lauing, Kristen L; Lulla, Rishi R; Fangusaro, Jason; Lenzen, Alicia; Kumthekar, Priya; Raizer, Jeffrey J; Binder, David C; James, C David; Wainwright, Derek A

    2016-08-01

    The effective treatment of adult and pediatric malignant glioma is a significant clinical challenge. In adults, glioblastoma (GBM) accounts for the majority of malignant glioma diagnoses with a median survival of 14.6 mo. In children, malignant glioma accounts for 20% of primary CNS tumors with a median survival of less than 1 y. Here, we discuss vaccine treatment for children diagnosed with malignant glioma, through targeting EphA2, IL-13Rα2 and/or histone H3 K27M, while in adults, treatments with RINTEGA, Prophage Series G-100 and dendritic cells are explored. We conclude by proposing new strategies that are built on current vaccine technologies and improved upon with novel combinatorial approaches. PMID:27622066

  4. Biological safety concepts of genetically modified live bacterial vaccines.

    PubMed

    Frey, Joachim

    2007-07-26

    Live vaccines possess the advantage of having access to induce cell-mediated and antibody-mediated immunity; thus in certain cases they are able to prevent infection, and not only disease. Furthermore, live vaccines, particularly bacterial live vaccines, are relatively cheap to produce and easy to apply. Hence they are suitable to immunize large communities or herds. The induction of both cell-mediated immunity as well as antibody-mediated immunity, which is particularly beneficial in inducing mucosal immune responses, is obtained by the vaccine-strain's ability to colonize and multiply in the host without causing disease. For this reason, live vaccines require attenuation of virulence of the bacterium to which immunity must be induced. Traditionally attenuation was achieved simply by multiple passages of the microorganism on growth medium, in animals, eggs or cell cultures or by chemical or physical mutagenesis, which resulted in random mutations that lead to attenuation. In contrast, novel molecular methods enable the development of genetically modified organisms (GMOs) targeted to specific genes that are particularly suited to induce attenuation or to reduce undesirable effects in the tissue in which the vaccine strains can multiply and survive. Since live vaccine strains (attenuated by natural selection or genetic engineering) are potentially released into the environment by the vaccinees, safety issues concerning the medical as well as environmental aspects must be considered. These involve (i) changes in cell, tissue and host tropism, (ii) virulence of the carrier through the incorporation of foreign genes, (iii) reversion to virulence by acquisition of complementation genes, (iv) exchange of genetic information with other vaccine or wild-type strains of the carrier organism and (v) spread of undesired genes such as antibiotic resistance genes. Before live vaccines are applied, the safety issues must be thoroughly evaluated case-by-case. Safety assessment

  5. Development of an improved vaccine evaluation protocol to compare the efficacy of Newcastle disease vaccines

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The failure to control and to eradicate Newcastle Disease (ND) with vaccination alone in countries where the etiological agent of the disease, virulent Newcastle Disease Virus (vNDV) is endemic underscores the need to improve the efficacy of currently available NDV vaccines and vaccination approache...

  6. Factors Associated with Intention to Receive Influenza and Tetanus, Diphtheria, and Acellular Pertussis (Tdap) Vaccines during Pregnancy: A Focus on Vaccine Hesitancy and Perceptions of Disease Severity and Vaccine Safety

    PubMed Central

    Chamberlain, Allison T.; Seib, Katherine; Ault, Kevin A.; Orenstein, Walter A.; Frew, Paula M.; Malik, Fauzia; Cortés, Marielysse; Cota, Pat; Whitney, Ellen A. S.; Flowers, Lisa C.; Berkelman, Ruth L.; Omer, Saad B.

    2015-01-01

    BACKGROUND: Improving influenza and tetanus, diphtheria and acellular pertussis (Tdap) vaccine coverage among pregnant women is needed. PURPOSE: To assess factors associated with intention to receive influenza and/or Tdap vaccinations during pregnancy with a focus on perceptions of influenza and pertussis disease severity and influenza vaccine safety. METHODS: Participants were 325 pregnant women in Georgia recruited from December 2012 – April 2013 who had not yet received a 2012/2013 influenza vaccine or a Tdap vaccine while pregnant. Women completed a survey assessing influenza vaccination history, likelihood of receiving antenatal influenza and/or Tdap vaccines, and knowledge, attitudes and beliefs about influenza, pertussis, and their associated vaccines. RESULTS: Seventy-three percent and 81% of women believed influenza and pertussis, respectively, would be serious during pregnancy while 87% and 92% believed influenza and pertussis, respectively, would be serious to their infants. Perception of pertussis severity for their infant was strongly associated with an intention to receive a Tdap vaccine before delivery (p=0.004). Despite perceptions of disease severity for themselves and their infants, only 34% and 44% intended to receive antenatal influenza and Tdap vaccines, respectively. Forty-six percent had low perceptions of safety regarding the influenza vaccine during pregnancy, and compared to women who perceived the influenza vaccine as safe, women who perceived the vaccine as unsafe were less likely to intend to receive antenatal influenza (48% vs. 20%; p < 0.001) or Tdap (53% vs. 33%; p < 0.001) vaccinations. CONCLUSIONS: Results from this baseline survey suggest that while pregnant women who remain unvaccinated against influenza within the first three months of the putative influenza season may be aware of the risks influenza and pertussis pose to themselves and their infants, many remain reluctant to receive influenza and Tdap vaccines antenatally. To

  7. Development of an improved vaccine evaluation protocol to compare the efficacy of Newcastle disease vaccines.

    PubMed

    Cardenas-Garcia, Stivalis; Diel, Diego G; Susta, Leonardo; Lucio-Decanini, Eduardo; Yu, Qingzhong; Brown, Corrie C; Miller, Patti J; Afonso, Claudio L

    2015-03-01

    While there is typically 100% survivability in birds challenged with vNDV under experimental conditions, either with vaccines formulated with a strain homologous or heterologous (different genotype) to the challenge virus, vaccine deficiencies are often noted in the field. We have developed an improved and more stringent protocol to experimentally evaluate live NDV vaccines, and showed for the first time under experimental conditions that a statistically significant reduction in mortality can be detected with genotype matched vaccines. Using both vaccine evaluation protocols (traditional and improved), birds were challenged with a vNDV of genotype XIII and the efficacy of live heterologous (genotype II) and homologous (genotype XIII) NDV vaccines was compared. Under traditional vaccination conditions there were no differences in survival upon challenge, but the homologous vaccine induced significantly higher levels of antibodies specific to the challenge virus. With the more stringent challenge system (multiple vaccine doses and early challenge with high titers of vNDV), the birds administered the homologous vaccine had superior humoral responses, reduced clinical signs, and reduced mortality levels than those vaccinated with the heterologous vaccine. These results provide basis for the implementation of more sensitive methods to evaluate vaccine efficacy. PMID:25511007

  8. Historical aspects of immunization and vaccine safety communication.

    PubMed

    Helfert, Stephanie M

    2015-01-01

    It has been a long journey starting from the beginnings of variolation [3] leading up to the greatest success in the history of immunization: the eradication of smallpox [39]. Today, vaccines are an acknowledged important medical advance [40]. Nevertheless, immunization has been the subject of public controversy on several occasions [15, 24, 31]. This article shall provide a short overview of some aspects of the early stages of immunization in Western countries, including some examples of vaccine safety controversies in the past. PMID:25859668

  9. Influenza vaccination in patients with pulmonary sarcoidosis: efficacy and safety

    PubMed Central

    Tavana, Sasan; Argani, Hassan; Gholamin, Sharareh; Razavi, Seyed‐Mostafa; Keshtkar‐Jahromi, Marzieh; Talebian, Amir S.; Moghaddam, Keivan G.; Sepehri, Zahra; Azad, Talat M.; Keshtkar‐Jahromi, Maryam

    2011-01-01

    Please cite this paper as: Tavana et al. (2011) Influenza vaccination in patients with pulmonary sarcoidosis: efficacy and safety. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750‐2659.2011.00290.x. Background  Sarcoidosis is an inflammatory, granulomatous disorder of unknown etiology. The role of cellular and humoral immune systems in this disease is unclear, whereas dysregulation of the immune system is suggested. Patients with sarcoidosis show diverse responses while exposed to various antigens. Although influenza vaccination is recommended in pulmonary sarcoidosis, its efficacy and safety has not been investigated. Objectives  To evaluate safety and immunogenicity of influenza vaccine in patients with sarcoidosis. Patients/Methods  Influenza vaccination was performed in 23 eligible patients with sarcoidosis (SP) and 26 healthy controls (HC). Antibody titers against H1N1, H3N2, and B influenza virus antigens were evaluated just before and 1 month after vaccination. Patients were followed for 6 months to assess vaccine safety. Results  Serological response and magnitude of changes in antibody titers against influenza vaccine antigens were comparable between SPs and HCs. Women showed a better serological response against B antigen (P = 0·034) than men. Twenty‐four‐hour urine calcium was associated with antibody response against H1N1 [correlation coefficient (CC) = 0·477, P = 0·003] and H3N2 (CC = 0·352, P = 0·028) antigens. Serum angiotensin‐converting enzyme correlated negatively with antibody response against B antigen (CC = −0·331, P = 0·040). Higher residual volume was associated with fewer rises in antibody titer against H3N2 antigen (CC = −0·377, P = 0·035). No major adverse events or disease flare‐up was observed during follow‐up. Conclusions  In this study, influenza vaccination did not cause any major adverse event in SPs, and their serological response was equal to HCs

  10. [Vaccination perspectives].

    PubMed

    Saliou, P; Plotkin, S

    1994-01-01

    The aim of vaccinology is to improve the available vaccines and to develop new ones in the light of progress in immunology, molecular biology and biotechnologies. But it must go beyond this, and aim to protect all populations and control diseases, even eradicate them where possible. New vaccine strategies must be developed taking into account the epidemiology of diseases and the inherent logistic problems of implementing these strategies under local conditions. There are three major thrusts to the progress of the discipline. The improvement of the vaccines available. One of the drives of vaccinology is not only to deliver vaccines of increasing safety (replacement of the current vaccine for whooping cough with an acellular vaccine for example), but also to improve vaccine efficacy and immunogenicity (in particular for flu, tuberculosis, cholera and rabies vaccines). The optimisation of vaccination programmes and strategies for vaccinations. The ideal is to protect against the greatest possible number of diseases with the smallest number of vaccinations. The development of combinations of vaccines is central to this goal. The objective for the year 2000 is a hexavalent vaccine DTPP Hib HB. The development of new vaccines. Classic techniques continue to be successfully used (inactivated hepatitis A vaccine; attenuated live vaccines for chicken pox and dengue fever; conjugated polyosidic bacterial vaccines for meningococci and Streptococcus pneumoniae). However, it will become possible to prepare vaccines against most transmissible diseases using genetic engineering techniques.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7921696

  11. Alumina-encapsulated vaccine formulation with improved thermostability and immunogenicity.

    PubMed

    Zhou, Hangyu; Wang, Guangchuan; Li, Xiao-Feng; Li, Yaling; Zhu, Shun-Ya; Qin, Cheng-Feng; Tang, Ruikang

    2016-05-11

    Developing vaccine formulations with excellent thermostability and immunogenicity remains a great challenge. By in situ encapsulating a live-attenuated strain of human enterovirus 71 (EV71) in alumina, we obtained a robust vaccine formulation named EV71@NanoAlum, which features significantly enhanced thermostability and immunogenicity. This attempt follows a material-based tactic for vaccine improvement. PMID:27098047

  12. How advances in immunology provide insight into improving vaccine efficacy

    PubMed Central

    Slifka, Mark K.; Amanna, Ian

    2014-01-01

    Vaccines represent one of the most compelling examples of how biomedical research has improved society by saving lives and dramatically reducing the burden of infectious disease. Despite the importance of vaccinology, we are still in the early stages of understanding how the best vaccines work and how we can achieve better protective efficacy through improved vaccine design. Most successful vaccines have been developed empirically, but recent advances in immunology are beginning to shed new light on the mechanisms of vaccine-mediated protection and development of long-term immunity. Although natural infection will often elicit lifelong immunity, almost all current vaccines require booster vaccination in order to achieve durable protective humoral immune responses, regardless of whether the vaccine is based on infection with replicating live-attenuated vaccine strains of the specific pathogen or whether they are derived from immunization with inactivated, non-replicating vaccines or subunit vaccines. The form of the vaccine antigen (e.g., soluble or particulate/aggregate) appears to play an important role in determining immunogenicity and the interactions between dendritic cells, B cells and T cells in the germinal center are likely to dictate the magnitude and duration of protective immunity. By learning how to optimize these interactions, we may be able to elicit more effective and long-lived immunity with fewer vaccinations. PMID:24709587

  13. The effect of falsely balanced reporting of the autism-vaccine controversy on vaccine safety perceptions and behavioral intentions.

    PubMed

    Dixon, Graham; Clarke, Christopher

    2013-04-01

    Controversy surrounding an autism-vaccine link has elicited considerable news media attention. Despite being widely discredited, research suggests that journalists report this controversy by presenting claims both for and against a link in a relatively 'balanced' fashion. To investigate how this reporting style influences judgments of vaccine risk, we randomly assigned 320 undergraduate participants to read a news article presenting either claims both for/against an autism-vaccine link, link claims only, no-link claims only or non-health-related information. Participants who read the balanced article were less certain that vaccines are safe, more likely to believe experts were less certain that vaccines are safe and less likely to have their future children vaccinated. Results suggest that balancing conflicting views of the autism-vaccine controversy may lead readers to erroneously infer the state of expert knowledge regarding vaccine safety and negatively impact vaccine intentions. PMID:23193194

  14. Genetically Engineered Poxviruses for Recombinant Gene Expression, Vaccination, and Safety

    NASA Astrophysics Data System (ADS)

    Moss, Bernard

    1996-10-01

    Vaccinia virus, no longer required for immunization against smallpox, now serves as a unique vector for expressing genes within the cytoplasm of mammalian cells. As a research tool, recombinant vaccinia viruses are used to synthesize and analyze the structure--function relationships of proteins, determine the targets of humoral and cell-mediated immunity, and investigate the types of immune response needed for protection against specific infectious diseases and cancer. The vaccine potential of recombinant vaccinia virus has been realized in the form of an effective oral wild-life rabies vaccine, although no product for humans has been licensed. A genetically altered vaccinia virus that is unable to replicate in mammalian cells and produces diminished cytopathic effects retains the capacity for high-level gene expression and immunogenicity while promising exceptional safety for laboratory workers and potential vaccine recipients.

  15. Safety and immunogenicity of a live attenuated mumps vaccine

    PubMed Central

    Liang, Yan; Ma, Jingchen; Li, Changgui; Chen, Yuguo; Liu, Longding; Liao, Yun; Zhang, Ying; Jiang, Li; Wang, Xuan-Yi; Che, Yanchun; Deng, Wei; Li, Hong; Cui, Xiaoyu; Ma, Na; Ding, Dong; Xie, Zhongping; Cui, Pingfang; Ji, Qiuyan; Wang, Jingjing; Zhao, Yuliang; Wang, Junzhi; Li, Qihan

    2014-01-01

    Background: Mumps, a communicable, acute and previously well-controlled disease, has had recent and occasional resurgences in some areas. Methods: A randomized, double-blind, controlled and multistep phase I study of an F-genotype attenuated mumps vaccine produced in human diploid cells was conducted. A total of 300 subjects were enrolled and divided into 4 age groups: 16–60 years, 5–16 years, 2–5 years and 8–24 months. The groups were immunized with one injection per subject. Three different doses of the F-genotype attenuated mumps vaccine, A (3.5 ± 0.25 logCCID50), B (4.25 ± 0.25 logCCID50) and C (5.0 ± 0.25 logCCID50), as well as a placebo control and a positive control of a licensed A-genotype vaccine (S79 strain) were used. The safety and immunogenicity of this vaccine were compared with those of the controls. Results: The safety evaluation suggested that mild adverse reactions were observed in all groups. No serious adverse event (SAE) was reported throughout the trial. The immunogenicity test showed a similar seroconversion rate of the neutralizing and ELISA antibody in the 2- to 5-year-old and 8- to 24-month-old groups compared with the seroconversion rate in the positive control. The GMT of the neutralizing anti-F-genotype virus antibodies in the vaccine groups was slightly higher than that in the positive control group. Conclusions: The F-genotype attenuated mumps vaccine evaluated in this clinical trial was demonstrated to be safe and have effective immunogenicity vs. control. PMID:24614759

  16. Immunization. Safety and Use of Polio Vaccines. Briefing Report to the Chairman, Subcommittee on Natural Resources, Agriculture Research and Environment, Committee on Science, Space, and Technology, House of Representatives.

    ERIC Educational Resources Information Center

    General Accounting Office, Washington, DC.

    This report presents information on the status of the safety and use of polio vaccines in the United States. Topics discussed include: (1) the role of the Food and Drug Administration (FDA) in processing an inactivated polio vaccine license application; (2) the steps the federal government has taken to improve the safety of the vaccine; (3) the…

  17. A design thinking approach to effective vaccine safety communication.

    PubMed

    Seeber, Lea; Michl, Bettina; Rundblad, Gabriella; Trusko, Brett; Schnjakin, Maxim; Meinel, Christoph; Weinberg, Ulrich; Gaedicke, Gerhard; Rath, Barbara

    2015-01-01

    The highly complex and controversial topic of vaccine safety communication warrants innovative, user-centered solutions that would start with gaining mutual respect while taking into account the needs, concerns and underlying motives of patients, parents and physicians. To this end, a non-profit collaborative project was conducted by The Vienna Vaccine Safety Initiative, an international think tank aiming to promote vaccine safety research and communication, and the School of Design Thinking in Potsdam, Germany, the first school for innovation in Europe. The revolutionary concept of the Design Thinking approach is to group students in small multi-disciplinary teams. As a result they can generate ground-breaking ideas by combining their expertise and different points of view. The team agreed to address the following design challenge question: "How might we enable physicians to encourage parents and children to prevent infectious diseases?" The current article describes, step-by step, the ideation and innovation process as well as first tangible outcomes of the project. PMID:25859673

  18. Safety Monitoring in Group A Meningococcal Conjugate Vaccine Trials: Description, Challenges, and Lessons

    PubMed Central

    Enwere, Godwin C.; Paranjape, Gandhali; Kulkarni, Prasad S.; Ginde, Manisha; Hartmann, Katharina; Viviani, Simonetta; Chaumont, Julie; Martellet, Lionel; Makadi, Marie-Francoise; Ivinson, Karen; Marchetti, Elisa; Herve, Jacques; Kertson, Kim; LaForce, F. Marc; Preziosi, Marie-Pierre

    2015-01-01

    Background. The determination of the safety profile of any vaccine is critical to its widespread use in any population. In addition, the application of international guidelines to fit local context could be a challenging but important step toward obtaining quality safety data. Methods. In clinical studies of PsA-TT (MenAfriVac), safety was monitored immediately after vaccination, at 4–7 days for postimmunization local and systemic reactions, within 28 days for adverse events, and throughout the duration of study for serious adverse events. Initial and ongoing training of sites' staff were undertaken during the studies, and a data and safety monitoring board reviewed all the data during and after the studies. Results. The safety of PsA-TT was evaluated according to international standards despite obvious challenges in remote areas where these studies were conducted. These challenges included the need for uniformity of methods, timely reporting in the context of frequent communication problems, occurrence of seasonal diseases such as malaria and rotavirus diarrhea, and healthcare systems that required improvement. Conclusions. The trials of PsA-TT highlighted the value of a robust vaccine development plan and design so that lessons learned in initial studies were incorporated into the subsequent ones, initial training and periodic retraining, strict monitoring of all procedures, and continuous channel of communication with all stakeholders that enabled the application of international requirements to local settings, with high quality of data. PMID:26553681

  19. Prime–Boost with Mycobacterium smegmatis Recombinant Vaccine Improves Protection in Mice Infected with Mycobacterium tuberculosis

    PubMed Central

    Junqueira-Kipnis, Ana Paula; de Oliveira, Fábio Muniz; Trentini, Monalisa Martins; Tiwari, Sangeeta; Chen, Bing; Resende, Danilo Pires; Silva, Bruna D. S.; Chen, Mei; Tesfa, Lydia; Jacobs, William R.; Kipnis, André

    2013-01-01

    The development of a new vaccine as a substitute for Bacillus Calmette–Guerin or to improve its efficacy is one of the many World Health Organization goals to control tuberculosis. Mycobacterial vectors have been used successfully in the development of vaccines against tuberculosis. To enhance the potential utility of Mycobacterium smegmatis as a vaccine, it was transformed with a recombinant plasmid containing the partial sequences of the genes Ag85c, MPT51, and HspX (CMX) from M. tuberculosis. The newly generated recombinant strain mc2-CMX was tested in a murine model of infection. The recombinant vaccine induced specific IgG1 or IgG2a responses to CMX. CD4+ and CD8+ T cells from the lungs and spleen responded ex vivo to CMX, producing IFN-γ, IL17, TNF-α, and IL2. The vaccine thus induced a significant immune response in mice. Mice vaccinated with mc2-CMX and challenged with M. tuberculosis showed better protection than mice immunized with wild-type M. smegmatis or BCG. To increase the safety and immunogenicity of the CMX antigens, we used a recombinant strain of M. smegmatis, IKE (immune killing evasion), to express CMX. The recombinant vaccine IKE-CMX induced a better protective response than mc2-CMX. The data presented here suggest that the expression of CMX antigens improves the immune response and the protection induced in mice when M. smegmatis is used as vaccine against tuberculosis. PMID:24250805

  20. An improved whole cell pertussis vaccine with reduced content of endotoxin

    PubMed Central

    Dias, Waldely Oliveira; van der Ark, Arno A.J.; Sakauchi, Maria Aparecida; Kubrusly, Flávia Saldanha; Prestes, Ana Fabíola R.O.; Borges, Monamaris Marques; Furuyama, Noemi; Horton, Denise S.P.Q.; Quintilio, Wagner; Antoniazi, Marta; Kuipers, Betsy; van der Zeijst, Bernard A.M.; Raw, Isaias

    2013-01-01

    An improved whole cell pertussis vaccine, designated as Plow, which is low in endotoxicity due to a chemical extraction of lipo-oligosaccharide (LOS) from the outer membrane, was evaluated for safety, immunogenicity and potency, comparatively to a traditional whole cell pertussis vaccine. Current whole cell pertussis vaccines are effective but contain large quantities of endotoxin and consequently display local and systemic adverse reactions after administration. Endotoxin is highly inflammatory and contributes considerably to the reactogenicity as well as the potency of these vaccines. In contrast, acellular pertussis vaccines hardly contain endotoxin and are significantly less reactogenic, but their elevated costs limit their global use, especially in developing countries. In this paper, bulk products of Plow and a traditional whole cell vaccine, formulated as plain monocomponents or combined with diphtheria and tetanus toxoids (DTPlow or DTP, respectively) were compared by in vitro and in vivo assays. Chemical extraction of LOS resulted in a significant decrease in endotoxin content (20%) and a striking decline in endotoxin related toxicity (up to 97%), depending on the used in vitro or in vivo test. The LOS extraction did not affect the integrity of the product and, more importantly, did not affect the potency and/or stability of DTPlow. Moreover, hardly any differences in antibody and T-cell responses were observed. The development of Plow is a significant improvement regarding the endotoxicity of whole cell pertussis vaccines and therefore a promising and affordable alternative to currently available whole cell or acellular pertussis vaccines for developing countries. PMID:23291935

  1. Predictive markers of safety and immunogenicity of adjuvanted vaccines.

    PubMed

    Mastelic, Beatris; Garçon, Nathalie; Del Giudice, Giuseppe; Golding, Hana; Gruber, Marion; Neels, Pieter; Fritzell, Bernard

    2013-11-01

    Vaccination represents one of the greatest public health triumphs; in part due to the effect of adjuvants that have been included in vaccine preparations to boost the immune responses through different mechanisms. Although a variety of novel adjuvants have been under development, only a limited number have been approved by regulatory authorities for human vaccines. This report reflects the conclusions of a group of scientists from academia, regulatory agencies and industry who attended a conference on the current state of the art in the adjuvant field. Held at the U.S. Pharmacopeial Convention (USP) in Rockville, Maryland, USA, from 18 to 19 April 2013 and organized by the International Association for Biologicals (IABS), the conference focused particularly on the future development of effective adjuvants and adjuvanted vaccines and on overcoming major hurdles, such as safety and immunogenicity assessment, as well as regulatory scrutiny. More information on the conference output can be found on the IABS website, http://www.iabs.org/. PMID:24071553

  2. Improving Influenza and Pneumococcal Vaccination Rates in Ambulatory Specialty Practices

    PubMed Central

    Pennant, Keyana N.; Costa, John J.; Fuhlbrigge, Anne L.; Sax, Paul E.; Szent-Gyorgyi, Lara E.; Coblyn, Jonathan; Desai, Sonali P.

    2015-01-01

    Background. Influenza and pneumococcal vaccinations are recommended for elderly and high-risk patients; however, rates of adherence are low. We sought to implement influenza and pneumococcal vaccine initiatives in 4 different ambulatory specialty practices, using 3 unique approaches. Methods. Four specialties with high-risk patient populations were selected for intervention: allergy (asthma), infectious disease (ID) (human immunodeficiency virus), pulmonary (chronic lung disease), and rheumatology (immunocompromised). Allergy and ID focused on influenza vaccination, and pulmonary and rheumatology focused on pneumococcal vaccination. We used 3 strategies for quality improvement: physician reminders, patient letters, and a nurse-driven model. Physicians were provided their performance data on a monthly basis and presented trended data on a quarterly basis at staff meetings. Results. All 4 specialties developed processes for improving vaccination rates with all showing some increase. Higher rates were achieved with pneumococcal vaccine than influenza. Pneumococcal vaccine rates showed steady improvement from year to year while influenza vaccine rates remained relatively constant. Allergy's influenza rate was 59% in 2011 and 64% in the 2014 flu season. Infectious disease influenza rates moved from 74% in the 2011 flu season to 86% for the 2014 season. Pneumococcal vaccine in pulmonary patients' rate was 52% at the start of intervention in February 2009 and 79% as of January 2015. Rheumatology rates rose from 50% in February 2009 to 87% in January 2015. Conclusions. Integrated routine workflow and performance data sharing can effectively engage specialists and staff in vaccine adherence improvement. Influenza vaccination may require other approaches to achieve the rates seen with pneumococcal vaccine. PMID:26430697

  3. Improving vaccine delivery using novel adjuvant systems.

    PubMed

    Pichichero, Michael E

    2008-01-01

    Adjuvants have been common additions to vaccines to help facilitate vaccine delivery. With advancements in vaccine technology, several adjuvants which activate immune specific responses have emerged. Available data show these adjuvants elicit important immune responses in both healthy and immunocompromised populations, as well as the elderly. Guidelines for the use and licensure of vaccine adjuvants remain under discussion. However, there is a greater understanding of the innate and adaptive immune response, and the realization of the need for immune specific adjuvants appears to be growing. This is a focused review of four adjuvants currently in clinical trial development: ASO4, ASO2A, CPG 7907, and GM-CSF. The vaccines including these adjuvants are highly relevant today, and are expected to reduce the disease burden of cervical cancer, hepatitis B and malaria. PMID:18398303

  4. Targeting dendritic cells for improved HIV-1 vaccines.

    PubMed

    Smed-Sörensen, Anna; Loré, Karin

    2013-01-01

    As dendritic cells (DCs) have the unique capacity to activate antigen-naive T cells they likely play a critical role in eliciting immune responses to vaccines. DCs are therefore being explored as attractive targets for vaccines, but understanding the interaction of DCs and clinically relevant vaccine antigens and adjuvants is a prerequisite. The HIV-1/AIDS epidemic continues to be a significant health problem, and despite intense research efforts over the past 30 years a protective vaccine has not yet been developed. A common challenge in vaccine design is to find a vaccine formulation that best shapes the immune response to protect against and/or control the given pathogen. Here, we discuss the importance of understanding the diversity, anatomical location and function of different human DC subsets in order to identify the optimal target cells for an HIV-1 vaccine. We review human DC interactions with some of the HIV-1 vaccine antigen delivery vehicles and adjuvants currently utilized in preclinical and clinical studies. Specifically, the effects of distinctly different vaccine adjuvants in terms of activation of DCs and improving DC function and vaccine efficacy are discussed. The susceptibility and responses of DCs to recombinant adenovirus vectors are reviewed, as well as the strategy of directly targeting DCs by using DC marker-specific monoclonal antibodies coupled to an antigen. PMID:22975879

  5. Safety of recombinant VSV-Ebola virus vaccine vector in pigs.

    PubMed

    de Wit, Emmie; Marzi, Andrea; Bushmaker, Trenton; Brining, Doug; Scott, Dana; Richt, Juergen A; Geisbert, Thomas W; Feldmann, Heinz

    2015-04-01

    The ongoing Ebola outbreak in West Africa has resulted in fast-track development of vaccine candidates. We tested a vesicular stomatitis virus vector expressing Ebola virus glycoprotein for safety in pigs. Inoculation did not cause disease and vaccine virus shedding was minimal, which indicated that the vaccine virus does not pose a risk of dissemination in pigs. PMID:25811738

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

    PubMed Central

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

    2000-01-01

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

  7. Storytelling in the context of vaccine refusal: a strategy to improve communication and immunisation.

    PubMed

    Cawkwell, Philip B; Oshinsky, David

    2016-03-01

    The December 2014 outbreak of measles in California impacted over 100 children and served as a reminder that this disease still plagues the USA, even 50 years following the first licensed vaccine. Refusal of vaccination is a complicated and multifaceted issue, one that clearly demands a closer look by paediatricians and public health officials alike. While medical doctors and scientists are trained to practice 'evidence-based medicine', and studies of vaccine safety and efficacy speak the language of statistics, there is reason to believe that this is not the most effective strategy for communicating with all groups of parents. Herein, we consider other methods such as narrative practices that employ stories and appeal more directly to parents. We also examine how doctors are trained to disseminate information and whether there are reasonable supplementary methods that could be used to improve vaccine communication and ultimately immunisation rates. PMID:26438615

  8. Methamphetamine Vaccines: Improvement through Hapten Design.

    PubMed

    Collins, Karen C; Schlosburg, Joel E; Bremer, Paul T; Janda, Kim D

    2016-04-28

    Methamphetamine (MA) addiction is a serious public health problem, and current methods to abate addiction and relapse are currently ineffective for mitigating this growing global epidemic. Development of a vaccine targeting MA would provide a complementary strategy to existing behavioral therapies, but this has proven challenging. Herein, we describe optimization of both hapten design and formulation, identifying a vaccine that elicited a robust anti-MA immune response in mice, decreasing methamphetamine-induced locomotor activity. PMID:27054372

  9. Improving birth dose coverage of hepatitis B vaccine.

    PubMed Central

    Hipgrave, David B.; Maynard, James E.; Biggs, Beverley-Ann

    2006-01-01

    Administration of a birth dose of hepatitis B vaccine (HepB vaccine) to neonates is recommended to prevent mother-to-infant transmission and chronic infection with the hepatitis B virus (HBV). Although manufacturers recommend HepB vaccine distribution and storage at 2-8 degrees C, recognition of the heat stability of hepatitis B surface antigen stimulated research into its use after storage at, or exposure to, ambient or high temperatures. Storage of HepB vaccine at ambient temperatures would enable birth dosing for neonates delivered at home in remote areas or at health posts lacking refrigeration. This article reviews the current evidence on the thermostability of HepB vaccine when stored outside the cold chain (OCC). The reports reviewed show that the vaccines studied were safe and effective whether stored cold or OCC. Field and laboratory data also verifies the retained potency of the vaccine after exposure to heat. The attachment of a highly stable variety of a vaccine vial monitor (measuring cumulative exposure to heat) on many HepB vaccines strongly supports policies allowing their storage OCC, when this will benefit birth dose coverage. We recommend that this strategy be introduced to improve birth dose coverage, especially in rural and remote areas. Concurrent monitoring and evaluation should be undertaken to affirm the safe implementation of this strategy, and assess its cost, feasibility and effect on reducing HBV infection rates. Meanwhile, release of manufacturer data verifying the potency of currently available HepB vaccines after exposure to heat will increase confidence in the use of vaccine vial monitors as a managerial tool during storage of HepB vaccine OCC. PMID:16501717

  10. Roadmap for the international collaborative epidemiologic monitoring of safety and effectiveness of new high priority vaccines.

    PubMed

    Izurieta, Hector S; Zuber, Patrick; Bonhoeffer, Jan; Chen, Robert T; Sankohg, Osman; Laserson, Kayla F; Sturkenboom, Miriam; Loucq, Christian; Weibel, Daniel; Dodd, Caitlin; Black, Steve

    2013-08-01

    With the advent of new vaccines targeted to highly endemic diseases in low- and middle-income countries (LMIC) and with the expansion of vaccine manufacturing globally, there is an urgent need to establish an infrastructure to evaluate the benefit-risk profiles of vaccines in LMIC. Fortunately the usual decade(s)-long time gap between introduction of new vaccines in high and low income countries is being significantly reduced or eliminated due to initiatives such as the Global Alliance for Vaccines and Immunizations (GAVI) and the Decade of Vaccines for the implementation of the Global Vaccine Action Plan. While hoping for more rapid disease control, this time shift may potentially add risk, unless appropriate capacity for reliable and timely evaluation of vaccine benefit-risk profiles in some LMIC's are developed with external assistance from regional or global level. An ideal vaccine safety and effectiveness monitoring system should be flexible and sustainable, able to quickly detect possible vaccine-associated events, distinguish them from programmatic errors, reliably and quickly evaluate the suspected event and its association with vaccination and, if associated, determine the benefit-risk of vaccines to inform appropriate action. Based upon the demonstrated feasibility of active surveillance in LMIC as shown by the Burkina Faso assessment of meningococcal A conjugate vaccine or that of rotavirus vaccine in Mexico and Brazil, and upon the proof of concept international GBS study, we suggest a sustainable, flexible, affordable and timely international collaborative vaccine safety monitoring approach for vaccines being newly introduced. While this paper discusses only the vaccine component, the same system could also be eventually used for monitoring drug effectiveness (including the use of substandard drugs) and drug safety. PMID:23707171

  11. Vaccination for tomorrow: the need to improve immunisation rates.

    PubMed

    Kassianos, George

    2010-01-01

    Since the 1998 health scare about measles mumps and rubella (MMR) immunisation, vaccination rates for measles have suffered. Although these recovered for a brief period in 2004-05, they have stalled again and latest figures suggest that only 85% of children are now immunised against this disease. The UK has become one of the five countries in the European Union with the highest measles rates. Meanwhile the wider picture indicates that other vaccination rates, including for seasonal influenza, are not meeting targets. This is a potential sign that the MMR scare and myths around immunisation are setting a worrying trend of some people losing confidence in the practice of vaccination. The UK has expanded its childhood immunisation programme to include the human papilloma virus vaccine (HPV) which protects against some types of cervical cancer. New life-saving vaccines for diseases, including meningococcal B meningitis (a strain of meningitis not yet covered by the existing vaccination programme), shingles and hepatitis C will soon become available. It is therefore important that information is available to the general public about the excellent safety record and benefits of vaccination to ensure that as many people as possible can take advantage of these new vaccines. This article explores the current uptake of, and attitudes towards, vaccination programmes and discusses some myths about immunisation. It suggests that community health care teams with access to adults, including parents of children and young people who need vaccination, are well placed to help challenge some of these myths and promote the benefits of immunisation. Practical suggestions are included on how this can be achieved. PMID:20397551

  12. Pre- and post-exposure safety and efficacy of attenuated rabies virus vaccines are enhanced by their expression of IFNγ

    SciTech Connect

    Barkhouse, Darryll A.; Faber, Milosz; Hooper, D. Craig

    2015-01-01

    Consistent with evidence of a strong correlation between interferon gamma (IFNγ) production and rabies virus (RABV) clearance from the CNS, we recently demonstrated that engineering a pathogenic RABV to express IFNγ highly attenuates the virus. Reasoning that IFNγ expression by RABV vaccines would enhance their safety and efficacy, we reverse-engineered two proven vaccine vectors, GAS and GASGAS, to express murine IFNγ. Mortality and morbidity were monitored during suckling mice infection, immunize/challenge experiments and mixed intracranial infections. We demonstrate that GASγ and GASγGAS are significantly attenuated in suckling mice compared to the GASGAS vaccine. GASγ better protects mice from lethal DRV4 RABV infection in both pre- and post-exposure experiments compared to GASGAS. Finally, GASγGAS reduces post-infection neurological sequelae, compared to control, during mixed intracranial infection with DRV4. These data show IFNγ expression by a vaccine vector can enhance its safety while increasing its efficacy as pre- and post-exposure treatment. - Highlights: • IFNγ expression improves attenuated rabies virus safety and immunogenicity. • IFNγ expression is safer and more immunogenic than doubling glycoprotein expression. • Co-infection with IFNγ-expressing RABV prevents wild-type rabies virus lethality. • Vaccine safety and efficacy is additive for IFNγ and double glycoprotein expression.

  13. INTEGRATED SAFETY MANAGEMENT SYSTEM SAFETY CULTURE IMPROVEMENT INITIATIVE

    SciTech Connect

    MCDONALD JA JR

    2009-01-16

    In 2007, the Department of Energy (DOE) identified safety culture as one of their top Integrated Safety Management System (ISMS) related priorities. A team was formed to address this issue. The team identified a consensus set of safety culture principles, along with implementation practices that could be used by DOE, NNSA, and their contractors. Documented improvement tools were identified and communicated to contractors participating in a year long pilot project. After a year, lessons learned will be collected and a path forward determined. The goal of this effort was to achieve improved safety and mission performance through ISMS continuous improvement. The focus of ISMS improvement was safety culture improvement building on operating experience from similar industries such as the domestic and international commercial nuclear and chemical industry.

  14. The use of quorum sensing to improve vaccine immune response.

    PubMed

    Sturbelle, R T; Conceição, R C S; Da Rosa, M C; Roos, T B; Dummer, L; Leite, F P L

    2013-12-17

    Enterotoxigenic Escherichia coli (ETEC) infection is an important cause of diarrhea in both newborn and post-weaning pigs, it is also responsible for economic losses on farms worldwide. Vaccines that use ETEC virulence factors have been well documented, and several vaccines containing inactivated bacteria with protective antigens, or purified (isolated) antigens are available on the market. Vaccination of pregnant sows is widely seen as an effective strategy for the control of the disease. Yet these vaccines very often do not lead to efficient protection. In this study, we produced an ETEC bacterin with the use of quorum sensing (QS), and observed a significant expression of F4 adhesin, and heat-labile toxin (LT) in the cultures when compared to the controls. Mice, and pigs vaccinated with the QS bacterin demonstrated higher antibody titers against these antigens when compared with commercial and control bacterin. Our results suggest that the system might bring promising improvements in ETEC bacterin efficacy. PMID:24188753

  15. Development of improved vaccines against whooping cough: current status.

    PubMed

    Marzouqi, Ibrahim; Richmond, Peter; Fry, Scott; Wetherall, John; Mukkur, Trilochan

    2010-07-01

    Prior to the introduction of killed whole cell pertussis vaccine [wP] in the 1940s, whooping cough was a major cause of infant death worldwide. Widespread vaccination of children with this vaccine caused a significant reduction in mortality. However in the 1990s and now more recently, there has been a resurgence of pertussis in several countries even in populations previously vaccinated with an acellular pertussis vaccine [aP]. In this review, we describe the epidemiology of whooping cough, the vast array of virulence factors produced by this pathogen potentially contributing to the resurgence of pertussis even in previously vaccinated populations of infants and children, history of whooping cough prophylaxis, possible mechanisms of immunity, lack of availability of a suitable non-toxic adjuvant capable of inducing both arms of the immune response, and the current status of development of improved vaccines with potential to induce longer-lasting protection, than is currently possible with the wP or aP vaccines, against whooping cough. PMID:20448470

  16. Safety and immunogenicity of an FP9-vectored candidate tuberculosis vaccine (FP85A), alone and with candidate vaccine MVA85A in BCG-vaccinated healthy adults

    PubMed Central

    Rowland, Rosalind; Pathan, Ansar A.; Satti, Iman; Poulton, Ian D.; Matsumiya, Magali M. L.; Whittaker, Megan; Minassian, Angela M.; O’Hara, Geraldine A.; Hamill, Matthew; Scott, Janet T.; Harris, Stephanie A.; Poyntz, Hazel C.; Bateman, Cynthia; Meyer, Joel; Williams, Nicola; Gilbert, Sarah C.; Lawrie, Alison M.; Hill, Adrian V.S.; McShane, Helen

    2013-01-01

    The safety and immunogenicity of a new candidate tuberculosis (TB) vaccine, FP85A was evaluated alone and in heterologous prime-boost regimes with another candidate TB vaccine, MVA85A. This was an open label, non-controlled, non-randomized Phase I clinical trial. Healthy previously BCG-vaccinated adult subjects were enrolled sequentially into three groups and vaccinated with FP85A alone, or both FP85A and MVA85A, with a four week interval between vaccinations. Passive and active data on adverse events were collected. Immunogenicity was evaluated by Enzyme Linked Immunospot (ELISpot), flow cytometry and Enzyme Linked Immunosorbent assay (ELISA). Most adverse events were mild and there were no vaccine-related serious adverse events. FP85A vaccination did not enhance antigen 85A-specific cellular immunity. When MVA85A vaccination was preceded by FP85A vaccination, cellular immune responses were lower compared with when MVA85A vaccination was the first immunisation. MVA85A vaccination, but not FP85A vaccination, induced anti-MVA IgG antibodies. Both MVA85A and FP85A vaccinations induced anti-FP9 IgG antibodies. In conclusion, FP85A vaccination was well tolerated but did not induce antigen-specific cellular immune responses. We hypothesize that FP85A induced anti-FP9 IgG antibodies with cross-reactivity for MVA85A, which may have mediated inhibition of the immune response to subsequent MVA85A. ClinicalTrials.gov identification number: NCT00653770 PMID:23143773

  17. Effect of Previous-Year Vaccination on the Efficacy, Immunogenicity, and Safety of High-Dose Inactivated Influenza Vaccine in Older Adults

    PubMed Central

    DiazGranados, Carlos A.; Dunning, Andrew J.; Robertson, Corwin A.; Talbot, H. Keipp; Landolfi, Victoria; Greenberg, David P.

    2016-01-01

    Background. High-dose inactivated influenza vaccine (IIV-HD) is an alternative to the standard-dose inactivated influenza vaccine (IIV-SD) in the United States for influenza prevention in older adults. IIV-HD improved efficacy relative to IIV-SD in a randomized controlled trial. Recent observational studies suggest that previous influenza vaccination may influence the immunogenicity and effectiveness of current-season vaccination. Methods. The original study was a double-blind, randomized trial comparing IIV-HD to IIV-SD in adults aged ≥65 years over 2 influenza seasons. A subset of year 1 (Y1) participants reenrolled in year 2 (Y2), receiving vaccine by random assignment in both years. We evaluated the effect of Y1 vaccination on Y2 relative vaccine efficacy (VE), immunogenicity (hemagglutination inhibition [HAI] titers), and safety among reenrolled participants. Results. Of 14 500 Y1 participants, 7643 reenrolled in Y2. Relative to participants who received IIV-SD both seasons, VE was higher for IIV-HD vaccinees in Y2 (28.3% overall; 25.1% for Y1 IIV-HD, Y2 IIV-HD; and 31.6% for Y1 IIV-SD, Y2 IIV-HD). In multivariate logistic regression models, Y1 vaccine was not a significant modifier of Y2 VE (P = .43), whereas Y2 IIV-HD remained significantly associated with lower influenza risk (P = .043). Compared to administration of IIV-SD in both years, postvaccination HAI titers were significantly higher for patterns that included IIV-HD in Y2. No safety concerns were raised with IIV-HD revaccination. Conclusions. IIV-HD is likely to provide clinical benefit over IIV-SD irrespective of previous-season vaccination with IIV-HD or IIV-SD. IIV-HD consistently improved immune responses, and no safety concerns emerged in the context of IIV-HD revaccination. PMID:26908801

  18. The need to teach vaccine safety to basic scientists and public health officials.

    PubMed

    Khamesipour, Ali

    2015-01-01

    Vaccination has been shown to be the most successful measure in preventing millions of mortalities and morbidities related to infectious diseases. Higher rates of vaccination lead to a greater number of protected individuals in the community. While vaccine safety is a primary concern, misinformation accessed through various communication channels can lead to misconceptions about vaccination that are often hard to address. When the public collects information, they usually do not check for accuracy. To overcome the problem, the most effective way is to disseminate information through teaching facts about vaccine benefits and harms to the public and the authorities in advance. To encourage the public to participate and support vaccination programs, basic scientists and public health officials must be trained and updated about vaccines and vaccination benefits and harms to be able to inform the public. PMID:25859679

  19. [VACCINES].

    PubMed

    Bellver Capella, Vincente

    2015-10-01

    Vaccines are an extraordinary instrument of immunization of the population against infectious diseases. Around them there are many ethical issues. One of the most debated is what to do with certain groups opposition to vaccination of their children. States have managed in different ways the conflict between the duty of vaccination and the refusal to use vaccines: some impose the vaccination and others simply promote it. In this article we deal with which of these two approaches is the most suitable from an ethical and legal point of view. We stand up for the second option, which is the current one in Spain, and we propose some measures which should be kept in mind to improve immunization programs. PMID:26685562

  20. Vaccine safety: medical contraindications, myths, and risk communication.

    PubMed

    Smith, Michael

    2015-06-01

    On the basis of first principles, anaphylaxis to a vaccine or vaccine component is a contraindication to future receipt of that vaccine. • On the basis of strong evidence, live viral vaccines should not be administered to severely immunocompromised children. • On the basis of some evidence with consensus, children with egg allergies may receive inactivated influenza vaccine. • On the basis of strong evidence, neither measles-mumps-rubella vaccine nor thimerosal causes autism. • On the basis of some evidence with consensus, alternative vaccination schedules have no benefit and receipt of human papillomavirus vaccines does not result in promiscuity. • On the basis of first principles and consensus, vaccine risk communication requires a tailored approach to each individual family. PMID:26034253

  1. Absence of venous thromboembolism risk following quadrivalent human papillomavirus vaccination, Vaccine Safety Datalink, 2008–2011

    PubMed Central

    Naleway, Allison L.; Crane, Brad; Smith, Ning; Daley, Matthew F.; Donahue, James; Gee, Julianne; Greene, Sharon K.; Harrington, Theresa; Jackson, Lisa A.; Klein, Nicola P.; Tseng, Hung Fu; Vellozzi, Claudia; Weintraub, Eric S.

    2016-01-01

    Background To investigate concerns about a potential association between quadrivalent human papillomavirus vaccination (HPV4) and venous thromboembolism (VTE), we conducted a self-controlled case series study in adolescents and young adults 9–26 years of age in the Vaccine Safety Datalink. Methods We identified potential VTE cases diagnosed in 2008 through 2011 who had also received at least one HPV4 dose during that period. We confirmed each presumptive diagnosis by medical record review. We calculated incidence rate ratios (IRRs) and 95% confidence intervals (CI) to estimate the risk in the 1–60 day period following HPV4 exposure and in subsets of that period. IRRs were stratified by age, gender, hormonal contraceptive use, and recent surgery or trauma. Results We identified 313 potential cases of VTE among HPV4 vaccinees, and 291 (93%) had sufficient medical records for review. Of these, we confirmed 156 (54%) cases. VTE was uncommon among males (n = 3) and 9–12 year olds (n = 4). Nearly all confirmed cases (97%) had at least one known risk factor for VTE, including hormonal contraceptive use, obesity, and hypercoagulability. Sixteen (10%) confirmed cases occurred in the 1–60 days following HPV4 exposure. The risk of VTE varied from 1.47 (95% CI: 0.47–4.64) in the 1–7 days following HPV4 exposure to 0.92 (95% CI: 0.54–1.57) in the 1–60 days following vaccination. It was not possible to calculate a stratified IRR for males due to small sample size; the other risk factors evaluated did not significantly affect the risk of VTE after HPV4 exposure. Conclusion The risk of developing VTE among 9- to 26-year-olds was not elevated following HPV4 exposure. Sample size limited our ability to rigorously evaluate potential effect modifiers, such as gender, through stratified analysis. PMID:26549361

  2. Safety, Immunogenicity and Duration of Immunity Elicited by an Inactivated Bovine Ephemeral Fever Vaccine

    PubMed Central

    Aziz-Boaron, Orly; Leibovitz, Keren; Gelman, Boris; Kedmi, Maor; Klement, Eyal

    2013-01-01

    Bovine ephemeral fever (BEF) is an economically important viral vector-borne cattle disease. Several live-attenuated, inactivated and recombinant vaccines have been tested, demonstrating varying efficacy. However, to the best of our knowledge, duration of immunity conferred by an inactivated vaccine has never been reported. In the last decade, Israel has faced an increasing number of BEF outbreaks. The need for an effective vaccine compatible with strains circulating in the Middle East region led to the development of a MONTANIDE™ ISA 206 VG (water-in-oil-in-water), inactivated vaccine based on a local strain. We tested the safety, immunogenicity and duration of immunity conferred by this vaccine. The induced neutralizing antibody (NA) response was followed for 493 days in 40 cows vaccinated by different protocols. The vaccine did not cause adverse reactions or a decrease in milk production. All cows [except 2 (6.7%) which did not respond to vaccination] showed a significant rise in NA titer of up to 1:256 following the second, third or fourth booster vaccination. Neutralizing antibody levels declined gradually to 1:16 up to 120 days post vaccination. This decline continued in cows vaccinated only twice, whereas cows vaccinated 3 or 4 times showed stable titers of approximately 1:16 for up to 267 days post vaccination. At least three vaccinations with the inactivated BEF vaccine were needed to confer long-lasting immunity. These results may have significant implications for the choice of vaccination protocol with inactivated BEF vaccines. Complementary challenge data should however be added to the above results in order to determine what is the minimal NA response conferring protection from clinical disease. PMID:24349225

  3. Safety and effectiveness of MF-59 adjuvanted influenza vaccines in children and adults.

    PubMed

    Black, Steven

    2015-06-01

    The squalene oil-in-water emulsion MF-59 adjuvant was developed initially to enhance the immunogenicity of influenza vaccines in populations such as children and adults with known suboptimal response. Developed in the 1990s, it was initially licensed in Europe for use in seasonal influenza vaccine in the elderly. Since that time, both Avian and p2009H1N1 vaccines have also been developed. Overall, more than 30,000 individuals have participated in clinical trials of MF-59 adjuvanted vaccine and more than 160 million doses of licensed vaccine have been administered. Safety and effectiveness data from clinical trials and observation studies attest to the safety of MF-59 and to its ability to enhance the effectiveness of influenza vaccines in children and the elderly. PMID:26022564

  4. Harnessing DNA-induced immune responses for improving cancer vaccines

    PubMed Central

    Herrada, Andrés A.; Rojas-Colonelli, Nicole; González-Figueroa, Paula; Roco, Jonathan; Oyarce, César; Ligtenberg, Maarten A.; Lladser, Alvaro

    2012-01-01

    DNA vaccines have emerged as an attractive strategy to promote protective cellular and humoral immunity against the encoded antigen. DNA vaccines are easy to generate, inexpensive to produce and purify at large-scale, highly stable and safe. In addition, plasmids used for DNA vaccines act as powerful “danger signals” by stimulating several DNA-sensing innate immune receptors that promote the induction of protective adaptive immunity. The induction of tumor-specific immune responses represents a major challenge for DNA vaccines because most of tumor-associated antigens are normal non-mutated self-antigens. As a consequence, induction of potentially self-reactive T cell responses against such poorly immunogenic antigens is controlled by mechanisms of central and peripheral tolerance as well as tumor-induced immunosuppression. Although several DNA vaccines against cancer have reached clinical testing, disappointing results have been observed. Therefore, the development of new adjuvants that strongly stimulate the induction of antitumor T cell immunity and counteract immune-suppressive regulation is an attractive approach to enhance the potency of DNA vaccines and overcome tumor-associated tolerance. Understanding the DNA-sensing signaling pathways of innate immunity that mediate the induction of T cell responses elicited by DNA vaccines represents a unique opportunity to develop novel adjuvants that enhance vaccine potency. The advance of DNA adjuvants needs to be complemented with the development of potent delivery systems, in order to step toward successful clinical application. Here, we briefly discuss recent evidence showing how to harness DNA-induced immune response to improve the potency of cancer vaccines and counteract tumor-associated tolerance. PMID:23111166

  5. Harnessing science to improve safety.

    PubMed

    Baillie, Jonathan

    2011-01-01

    Examining the effectiveness of various wet surface cleaning methods in combating harmful microorganisms in a hospital ward, understanding different healthcare cleaning regimes' impact on reducing slips and trips, evaluating the protection offered by surgical masks against influenza bioaerosols, and independently testing tower crane safety following a number of fatal incidents, are among the broad spectrum of recent projects undertaken by the Buxton-headquartered Health and Safety Laboratory (HSL). As HEJ editor Jonathan Baillie discovered from the organisation's healthcare and patient safety lead, Darren Whitehouse, with around 350 scientists skilled in everything from microbiology to occupational psychology, the range of scientific guidance, expertise, advice, testing, training, and investigation, that the HSL can offer to the healthcare sector is perhaps unrivalled throughout Europe. PMID:22053356

  6. Micro-fractional epidermal powder delivery for improved skin vaccination

    PubMed Central

    Chen, Xinyuan; Kositratna, Garuna; Zhou, Chang; Manstein, Dieter; Wu, Mei X.

    2014-01-01

    Skin vaccination has gained increasing attention in the last two decades due to its improved potency compared to intramuscular vaccination. Yet, the technical difficulty and frequent local reactions hamper its broad application in the clinic. In the current study, micro-fractional epidermal powder delivery (EPD) is developed to facilitate skin vaccination and minimize local adverse effects. EPD is based on ablative fractional laser or microneedle treatment of the skin to generate microchannel (MC) arrays in the epidermis followed by topical application of powder drug/vaccine-coated array patches to deliver drug/vaccine into the skin. The novel EPD delivered more than 80% sulforhodamine b (SRB) and model antigen ovalbumin (OVA) into murine, swine, and human skin within 1 hour. EPD of OVA induced anti-OVA antibody titer at a level comparable to intradermal (ID) injection and was much more efficient than tape stripping in both delivery efficiency and immune responses. Strikingly, the micro-fractional delivery significantly reduced local side effects of LPS/CpG adjuvant and BCG vaccine, leading to complete skin recovery. In contrast, ID injection induced severe local reactions that persisted for weeks. While reducing local reactogenicity, EPD of OVA/LPS/CpG and BCG vaccine generated a comparable humoral immune response to ID injection. EPD of vaccinia virus encoding OVA induced significantly higher and long-lasting interferon γ-secreting CD8+ T cells than ID injection. In conclusion, EPD represents a promising technology for needle-free, painless skin vaccination with reduced local reactogenicity and improved immunogenicity. PMID:25135790

  7. The use of a computerized database to monitor vaccine safety in Viet Nam.

    PubMed Central

    Ali, Mohammad; Canh, Gia Do; Clemens, John D.; Park, Jin-Kyung; von Seidlein, Lorenz; Minh, Tan Truong; Thiem, Dinh Vu; Tho, Huu Le; Trach, Duc Dang

    2005-01-01

    Health information systems to monitor vaccine safety are used in industrialized countries to detect adverse medical events related to vaccinations or to prove the safety of vaccines. There are no such information systems in the developing world, but they are urgently needed. A large linked database for the monitoring of vaccine-related adverse events has been established in Khanh Hoa province, Viet Nam. Data collected during the first 2 years of surveillance, a period which included a mass measles vaccination campaign, were used to evaluate the system. For this purpose the discharge diagnoses of individuals admitted to polyclinics and hospitals were coded according to the International Classification of Diseases (ICD)-10 guidelines and linked in a dynamic population database with vaccination histories. A case-series analysis was applied to the cohort of children vaccinated during the mass measles vaccination campaign. The study recorded 107,022 immunizations in a catchment area with a population of 357,458 and confirmed vaccine coverage of 87% or higher for completed routine childhood vaccinations. The measles vaccination campaign immunized at least 86% of the targeted children aged 9 months to 10 years. No medical event was detected significantly more frequently during the 14 days after measles vaccination than before it. The experience in Viet Nam confirmed the safety of a measles vaccination campaign and shows that it is feasible to establish health information systems such as a large linked database which can provide reliable data in a developing country for a modest increase in use of resources. PMID:16193545

  8. Improved antibiotic-free DNA vaccine vectors utilizing a novel RNA based plasmid selection system

    PubMed Central

    Luke, Jeremy; Carnes, Aaron E; Hodgson, Clague P; Williams, James A

    2009-01-01

    To ensure safety, regulatory agencies recommend elimination of antibiotic resistance markers from therapeutic and vaccine plasmid DNA vectors. Here, we describe the development and application of a novel antibiotic-free selection system. Vectors incorporate and express a 150 bp RNA-OUT antisense RNA. RNA-OUT represses expression of a chromosomally integrated constitutively expressed counter-selectable marker (sacB), allowing plasmid selection on sucrose. Sucrose selectable DNA vaccine vectors combine antibiotic-free selection with highly productive fermentation manufacturing (>1 gm/L plasmid DNA yields), while improving in vivo expression of encoded proteins and increasing immune responses to target antigens. These vectors are safer, more potent, alternatives for DNA therapy or vaccination. PMID:19559109

  9. “Knowledge and attitudes of Spanish adolescent girls towards human papillomavirus infection: where to intervene to improve vaccination coverage”

    PubMed Central

    2014-01-01

    Background HPV vaccine coverage is far from ideal in Valencia, Spain, and this could be partially related to the low knowledge about the disease and the vaccine, therefore we assessed these, as well as the attitude towards vaccination in adolescent girls, and tried to identify independently associated factors that could potentially be modified by an intervention in order to increase vaccine coverage. Methods A cross sectional study was conducted in a random selection of schools of the Spanish region of Valencia. We asked mothers of 1278 girls, who should have been vaccinated in the 2011 campaign, for informed consent. Those that accepted their daughters’ participation, a questionnaire regarding the Knowledge of HPV infection and vaccine was passed to the girls in the school. Results 833 mothers (65.1%) accepted participation. All their daughters’ responded the questionnaire. Of those, 89.9% had heard about HPV and they associated it to cervical cancer. Only 14% related it to other problems like genital warts. The knowledge score of the girls who had heard about HPV was 6.1/10. Knowledge was unrelated to the number of contacts with the health system (Pediatrician or nurse), and positively correlated with the discussions with classmates about the vaccine. Adolescents Spanish in origin or with an older sister vaccinated, had higher punctuation. 67% of the girls thought that the vaccine prevented cancer, and 22.6% felt that although prevented cancer the vaccine had important safety problems. 6.4% of the girls rejected the vaccine for safety problems or for not considering themselves at risk of infection. 71.5% of the girls had received at least one vaccine dose. Vaccinated girls scored higher knowledge (p = 0.05). Conclusion Knowledge about HPV infection and vaccine was fair in adolescents of Valencia, and is independent to the number of contacts with the health system, it is however correlated to the conversations about the vaccine with their peers and the

  10. Real time patient safety audits: improving safety every day

    PubMed Central

    Ursprung, R; Gray, J; Edwards, W; Horbar, J; Nickerson, J; Plsek, P; Shiono, P; Suresh, G; Goldmann, D

    2005-01-01

    Background: Timely error detection including feedback to clinical staff is a prerequisite for focused improvement in patient safety. Real time auditing, the efficacy of which has been repeatedly demonstrated in industry, has not been used previously to evaluate patient safety. Methods successful at improving quality and safety in industry may provide avenues for improvement in patient safety. Objective: Pilot study to determine the feasibility and utility of real time safety auditing during routine clinical work in an intensive care unit (ICU). Methods: A 36 item patient safety checklist was developed via a modified Delphi technique. The checklist focused on errors associated with delays in care, equipment failure, diagnostic studies, information transfer and non-compliance with hospital policy. Safety audits were performed using the checklist during and after morning work rounds thrice weekly during the 5 week study period from January to March 2003. Results: A total of 338 errors were detected; 27 (75%) of the 36 items on the checklist detected ⩾1 error. Diverse error types were found including unlabeled medication at the bedside (n = 31), ID band missing or in an inappropriate location (n = 70), inappropriate pulse oximeter alarm setting (n = 22), and delay in communication/information transfer that led to a delay in appropriate care (n = 4). Conclusions: Real time safety audits performed during routine work can detect a broad range of errors. Significant safety problems were detected promptly, leading to rapid changes in policy and practice. Staff acceptance was facilitated by fostering a blame free "culture of patient safety" involving clinical personnel in detection of remediable gaps in performance, and limiting the burden of data collection. PMID:16076794

  11. Reproductive and safety assessment of vaccination with Gavac against the cattle tick (Boophilus microplus).

    PubMed

    Boué, O; Redondo, M; Montero, C; Rodríguez, M; de la Fuente, J

    1999-06-01

    Recent developments in cattle tick control have incorporated the use of recombinant Bm86 vaccines against this ectoparasite. The vaccine developed by our group (Gavac) contains an antigen expressed in Pichia pastoris, and has been successfully employed for the control of tick infestations and transmission of tick-borne diseases. Here, we examined the safety and effect of the Gavac vaccine on reproductive parameters in cattle. Toxicity tests in mice and guinea pigs demonstrated the safety of Gavac. To study the adverse effects of vaccination on reproduction, a field trial involving 9,500 animals in Cuba was conducted. The cattle at 3 farms were vaccinated while those on a fourth farm were left unvaccinated and served as the control. Following vaccination, the control of tick infestation and the transmission of babesiosis were used to demonstrate the efficacy of the vaccine. No adverse effects were observed in any of the reproductive parameters studied when comparing the data before and after vaccination with Gavac and between the vaccinated farms and the control farm. These results demonstrate that under the conditions of our study vaccination with Gavac is safe for use on cattle. PMID:10729081

  12. Efficacy of Vaccination against HPV Infections to Prevent Cervical Cancer in France: Present Assessment and Pathways to Improve Vaccination Policies

    PubMed Central

    Ribassin-Majed, Laureen; Lounes, Rachid; Clémençon, Stephan

    2012-01-01

    Background Seventy percent of sexually active individuals will be infected with Human Papillomavirus (HPV) during their lifetime. These infections are incriminated for almost all cervical cancers. In France, 3,068 new cases of cervical cancer and 1,067 deaths from cervical cancer occurred in 2005. Two vaccines against HPV infections are currently available and vaccination policies aim to decrease the incidence of HPV infections and of cervical cancers. In France, vaccine coverage has been reported to be low. Methods We developed a dynamic model for the heterosexual transmission of Human Papillomavirus types 16 and 18, which are covered by available vaccines. A deterministic model was used with stratification on gender, age and sexual behavior. Immunity obtained from vaccination was taken into account. The model was calibrated using French data of cervical cancer incidence. Results In view of current vaccine coverage and screening, we expected a 32% and 83% reduction in the incidence of cervical cancers due to HPV 16/18, after 20 years and 50 years of vaccine introduction respectively. Vaccine coverage and screening rates were assumed to be constant. However, increasing vaccine coverage in women or vaccinating girls before 14 showed a better impact on cervical cancer incidence. On the other hand, performing vaccination in men improves the effect on cervical cancer incidence only moderately, compared to strategies in females only. Conclusion While current vaccination policies may significantly decrease cervical cancer incidence, other supplementary strategies in females could be considered in order to improve vaccination efficacy. PMID:22427828

  13. Effectiveness of interventions that apply new media to improve vaccine uptake and vaccine coverage

    PubMed Central

    Odone, Anna; Ferrari, Antonio; Spagnoli, Francesca; Visciarelli, Sara; Shefer, Abigail; Pasquarella, Cesira; Signorelli, Carlo

    2014-01-01

    %), software for physicians and health professionals (n.4, 21%), and email communication (n.1, 5%). There is some evidence that text messaging, accessing immunization campaign websites, using patient-held web-based portals and computerized reminders increase immunization coverage rates. Insufficient evidence is available on the use of social networks, email communication and smartphone applications. Conclusion Although there is great potential for improving vaccine uptake and vaccine coverage by implementing programs and interventions that apply new media, scant data are available and further rigorous research - including cost-effectiveness assessments - is needed. PMID:25483518

  14. The Vaccine Safety Datalink: immunization research in health maintenance organizations in the USA.

    PubMed Central

    Chen, R. T.; DeStefano, F.; Davis, R. L.; Jackson, L. A.; Thompson, R. S.; Mullooly, J. P.; Black, S. B.; Shinefield, H. R.; Vadheim, C. M.; Ward, J. I.; Marcy, S. M.

    2000-01-01

    The Vaccine Safety Datalink is a collaborative project involving the National Immunization Program of the Centers for Disease Control and Prevention and several large health maintenance organizations in the USA. The project began in 1990 with the primary purpose of rigorously evaluating concerns about the safety of vaccines. Computerized data on vaccination, medical outcome (e.g. outpatient visits, emergency room visits, hospitalizations, and deaths) and covariates (e.g. birth certificates, census data) are prospectively collected and linked under joint protocol at multiple health maintenance organizations for analysis. Approximately 6 million persons (2% of the population of the USA) are now members of health maintenance organizations participating in the Vaccine Safety Datalink, which has proved to be a valuable resource providing important information on a number of vaccine safety issues. The databases and infrastructure created for the Vaccine Safety Datalink have also provided opportunities to address vaccination coverage, cost-effectiveness and other matters connected with immunization as well as matters outside this field. PMID:10743283

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

    PubMed Central

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

    2015-01-01

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

  16. Immunogenicity and Safety of an Inactivated Quadrivalent Influenza Vaccine Candidate: A Phase III Randomized Controlled Trial in Children

    PubMed Central

    Langley, Joanne M.; Carmona Martinez, Alfonso; Chatterjee, Archana; Halperin, Scott A.; McNeil, Shelly; Reisinger, Keith S.; Aggarwal, Naresh; Huang, Li-Min; Peng, Ching-Tien; Garcia-Sicilia, José; Salamanca de la Cueva, Ignacio; Cabañas, Fernando; Treviño-Garza, Consuelo; Rodríguez-Weber, Miguel Angel; de la O, Manuel; Chandrasekaran, Vijayalakshmi; Dewé, Walthère; Liu, Aixue; Innis, Bruce L.; Jain, Varsha K.

    2013-01-01

    Background. Mismatch between circulating influenza B viruses (Yamagata and Victoria lineages) and vaccine strains occurs frequently. Methods. In a randomized controlled trial, immunogenicity and safety of an inactivated quadrivalent influenza vaccine candidate (QIV) versus trivalent inactivated influenza vaccine (TIV)-Victoria(Vic) and TIV-Yamagata(Yam) in children 3–17 years of age was evaluated. In an open-label study arm, QIV only was assessed in children 6–35 months of age. Results. A total of 3094 children (932 QIV, 929 TIV-Vic, 932 TIV-Yam, and 301 QIV only) were vaccinated. QIV was noninferior to the TIVs for shared strains (A/H3N2 and A/H1N1) based on hemagglutination-inhibition (HI) antibodies 28 days after last vaccination, and superior for the unique B strains Victoria and Yamagata (geometric mean titer ratios 2.61, 3.78; seroconversion rate differences 33.96%, 44.63%). Among children in the randomized trial, adverse event rates were similar except for injection site pain (dose 1: 65.4% QIV, 54.6% TIV-Vic, 55.7% TIV-Yam). Conclusion. QIV elicited superior HI responses to the added B strains compared to TIV controls, potentially improving its effectiveness against influenza B. HI responses were similar between QIV and TIV controls for the shared strains. QIV had an acceptable safety profile relative to TIVs. Clinical Trials Registration. NCT01198756. PMID:23847058

  17. Meta-Analysis on Randomized Controlled Trials of Vaccines with QS-21 or ISCOMATRIX Adjuvant: Safety and Tolerability

    PubMed Central

    Bigaeva, Emilia; van Doorn, Eva; Liu, Heng; Hak, Eelko

    2016-01-01

    Background and Objectives QS-21 shows in vitro hemolytic effect and causes side effects in vivo. New saponin adjuvant formulations with better toxicity profiles are needed. This study aims to evaluate the safety and tolerability of QS-21 and the improved saponin adjuvants (ISCOM, ISCOMATRIX and Matrix-M™) from vaccine trials. Methods A systematic literature search was conducted from MEDLINE, EMBASE, Cochrane library and Clinicaltrials.gov. We selected for the meta-analysis randomized controlled trials (RCTs) of vaccines adjuvanted with QS-21, ISCOM, ISCOMATRIX or Matrix-M™, which included a placebo control group and reported safety outcomes. Pooled risk ratios (RRs) and their 95% confidence intervals (CIs) were calculated using a random-effects model. Jadad scale was used to assess the study quality. Results Nine RCTs were eligible for the meta-analysis: six trials on QS-21-adjuvanted vaccines and three trials on ISCOMATRIX-adjuvanted, with 907 patients in total. There were no studies on ISCOM or Matrix-M™ adjuvanted vaccines matching the inclusion criteria. Meta-analysis identified an increased risk for diarrhea in patients receiving QS21-adjuvanted vaccines (RR 2.55, 95% CI 1.04–6.24). No increase in the incidence of the reported systemic AEs was observed for ISCOMATRIX-adjuvanted vaccines. QS-21- and ISCOMATRIX-adjuvanted vaccines caused a significantly higher incidence of injection site pain (RR 4.11, 95% CI 1.10–15.35 and RR 2.55, 95% CI 1.41–4.59, respectively). ISCOMATRIX-adjuvanted vaccines also increased the incidence of injection site swelling (RR 3.43, 95% CI 1.08–10.97). Conclusions Our findings suggest that vaccines adjuvanted with either QS-21 or ISCOMATRIX posed no specific safety concern. Furthermore, our results indicate that the use of ISCOMATRIX enables a better systemic tolerability profile when compared to the use of QS-21. However, no better local tolerance was observed for ISCOMATRIX-adjuvanted vaccines in immunized non

  18. Current developments in avian influenza vaccines including food safety aspects in vaccinated birds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Historically, vaccines against avian influenza (AI) have had more limited use in poultry than vaccines for other poultry diseases such as Newcastle disease (ND) and infectious bronchitis. These AI vaccines have been primarily based on low or high pathogenicity (HP) AI viruses that were grown in emb...

  19. Enhancing knowledge--improving safety.

    PubMed

    Baillie, Jonathan

    2012-01-01

    With the opening of a new 1.4 m sterling pounds training facility at its Charlton House head office site in Cheltenham, steam system specialist, Spirax Sarco, believes it is now in a better position than at any time in its history to offer specialist steam system training that will enable those operating and maintaining such equipment in environments such as hospital plant rooms to optimise its performance and efficiency, cut their energy bills and carbon footprint, and ensure the safety of their staff. As HEJ editor Jonathan Baillie reports, around 10-15% of those trained to date in the new facility, and at the previous training centre, are from the healthcare engineering and estates management sector. PMID:22332315

  20. Efficacy, Safety, and Interactions of a Live Infectious Bursal Disease Virus Vaccine for Chickens Based on Strain IBD V877.

    PubMed

    Geerligs, Harm J; Ons, Ellen; Boelm, Gert Jan; Vancraeynest, Dieter

    2015-03-01

    Infectious bursal disease (IBD) is a highly contagious disease in young chickens which can result in high morbidity and mortality and also in great economic losses. The main target for the virus is the lymphoid tissue with a special predilection for the bursa of Fabricius. Several vaccines are available to control the disease. Intermediate plus vaccines are used in chickens with high maternal antibody titers which face high infection pressure. An example of an intermediate plus vaccine is a live vaccine based on IBD strain V877. The results of an efficacy study in commercial broilers with different levels of maternally derived antibodies (MDA) showed that the V877-based IBD vaccine can break through maternal antibody titers of higher than 1100 as determined by an IBD ELISA. The safety of the vaccine was demonstrated in a study in which specific-pathogen-free (SPF) chickens were vaccinated with a tenfold dose of the vaccine strain and a tenfold dose of the vaccine strain after five back passages in SPF chickens. The vaccine virus caused lesions, as could be expected for an intermediate plus vaccine, but the scores were not much higher than the maximal scores allowed for mild IBD vaccines in the European Pharmacopoeia, and reversion to virulence was absent. In studies in SPF chickens, there were no negative impacts by the IBD V877 vaccine on the efficacy of a live QX-like IB vaccine and a live Newcastle disease La Sota vaccine in vaccination challenge studies, although the IBD vaccine had a negative effect on the antibody response generated by the QX-like IB vaccine. It is concluded that the IBD V877 vaccine has the capacity to break through high levels of MDA, has a satisfactory safety profile, and interactions with other live vaccines are limited. In order to limit bursal lesions after vaccination it is recommended to confirm the presence of MDA before vaccinating with the V877 vaccine. PMID:26292544

  1. Methods to Evaluate the Preclinical Safety and Immunogenicity of Genetically Modified Live-Attenuated Leishmania Parasite Vaccines.

    PubMed

    Gannavaram, Sreenivas; Bhattacharya, Parna; Dey, Ranadhir; Ismail, Nevien; Avishek, Kumar; Salotra, Poonam; Selvapandiyan, Angamuthu; Satoskar, Abhay; Nakhasi, Hira L

    2016-01-01

    Live-attenuated parasite vaccines are being explored as potential vaccine candidates since other approaches of vaccination have not produced an effective vaccine so far. In order for live-attenuated parasite vaccines to be tested in preclinical studies and possibly in clinical studies, the safety and immunogenicity of these organisms must be rigorously evaluated. Here we describe methods to test persistence in the immunized host and immunogenicity, and to identify biomarkers of vaccine safety and efficacy with particular reference to genetically attenuated Leishmania parasites. PMID:27076157

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

    PubMed Central

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

    2015-01-01

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

  3. Effect of vaccine administration modality on immunogenicity and efficacy.

    PubMed

    Zhang, Lu; Wang, Wei; Wang, Shixia

    2015-01-01

    The many factors impacting the efficacy of a vaccine can be broadly divided into three categories: features of the vaccine itself, including immunogen design, vaccine type, formulation, adjuvant and dosing; individual variations among vaccine recipients and vaccine administration-related parameters. While much literature exists related to vaccines, and recently systems biology has started to dissect the impact of individual subject variation on vaccine efficacy, few studies have focused on the role of vaccine administration-related parameters on vaccine efficacy. Parenteral and mucosal vaccinations are traditional approaches for licensed vaccines; novel vaccine delivery approaches, including needless injection and adjuvant formulations, are being developed to further improve vaccine safety and efficacy. This review provides a brief summary of vaccine administration-related factors, including vaccination approach, delivery route and method of administration, to gain a better understanding of their potential impact on the safety and immunogenicity of candidate vaccines. PMID:26313239

  4. SAFETY OF A CRM197-CONJUGATED HAEMOPHILUS INFLUENZAE TYPE B VACCINE IN KOREAN CHILDREN.

    PubMed

    Song, Hyoyoung; Bock, Hans; Guadagno, Alana; Costantini, Marco; Baehner, Frank; Kim, Yeon Ho; Ahn, Seung In; Son, Ki Hyuk; Yim, Dong-Seok

    2015-07-01

    Haemophilus influenzae type b (Hib) is a major cause of meningitis and pneumonia with high morbidity and mortality rates in young children. The introduction of effective and well-tolerated conjugate Hib vaccines, has nearly eradicated this disease in many countries. We investigated the safety of the Hib PRP-CRM197 vaccine in a multi-center post-marketing surveillance (PMS) study. Korean children (N = 764) aged 1-33 months were enrolled when receiving a routine primary immunization or a booster vaccine with Hib PRP-CRM197 and solicited and unsolicited adverse events (AEs) were recorded using a diary card for 7 and 28 days after each vaccination, respectively. In this study, AEs were reported by 66% of subjects but were generally mild, with 42% of subjects reporting solicited AEs and 46% reporting unsolicited AEs. Among the unsolicited AEs, 98% were determined to be unrelated to the study vaccine. The studied Hib PRP-CRM197 vaccine was well tolerated by the study group and found to have a similar safety profile to that reported in other clinical studies. This vaccine is suitable for routine immunization against Hib disease among Korean children. AEs due to this vaccine will continue to be monitored. PMID:26867395

  5. Targeting Skin Dendritic Cells to Improve Intradermal Vaccination

    PubMed Central

    Romani, N.; Flacher, V.; Tripp, C. H.; Sparber, F.; Ebner, S.; Stoitzner, P.

    2014-01-01

    Vaccinations in medicine are typically administered into the muscle beneath the skin or into the subcutaneous fat. As a consequence, the vaccine is immunologically processed by antigen-presenting cells of the skin or the muscle. Recent evidence suggests that the clinically seldom used intradermal route is effective and possibly even superior to the conventional subcutaneous or intramuscular route. Several types of professional antigen-presenting cells inhabit the healthy skin. Epidermal Langerhans cells (CD207/langerin+), dermal langerinneg, and dermal langerin+ dendritic cells (DC) have been described, the latter subset so far only in mouse skin. In human skin langerinneg dermal DC can be further classified based on their reciprocal expression of CD1a and CD14. The relative contributions of these subsets to the generation of immunity or tolerance are still unclear. Yet, specializations of these different populations have become apparent. Langerhans cells in human skin appear to be specialized for induction of cytotoxic T lymphocytes; human CD14+ dermal DC can promote antibody production by B cells. It is currently attempted to rationally devise and improve vaccines by harnessing such specific properties of skin DC. This could be achieved by specifically targeting functionally diverse skin DC subsets. We discuss here advances in our knowledge on the immunological properties of skin DC and strategies to significantly improve the outcome of vaccinations by applying this knowledge. PMID:21253784

  6. Improving patient safety in haemodialysis

    PubMed Central

    Bray, Benjamin D.; Metcalfe, Wendy

    2015-01-01

    Thomas Inman (1820–76) wrote ‘Practice two things in your dealings with disease: either help or do not harm the patient’, echoing writings from the Hippocratic school. The challenge of practicing safely with the avoidance of complications or harm is perhaps only heightened in the context of modern medical settings such as the haemodialysis unit where complex interventions and treatment are routine. The current issue of CKJ reports two studies aimed at improving the care of haemodialysis patients targeting early use of arteriovenous grafts as access for haemodialysis and the implementation of a dialysis checklist to ensure the prescribed dialysis treatment is delivered. The further challenge of ensuring that such evidence-based tools are used appropriately and consistently falls to all members of the clinical team. PMID:26034585

  7. Rethinking the antivaccine movement concept: A case study of public criticism of the swine flu vaccine's safety in France.

    PubMed

    Ward, Jeremy K

    2016-06-01

    In this article I discuss the definition of "the Antivaccine Movement" using the case of the French controversy over the safety of the 2009 pandemic flu vaccine. I show that the group of main actors who criticized the vaccine's safety is heterogeneous. This heterogeneity can be found in the type of arguments mobilized to question the vaccine's safety and in these actors' likelihood of being involved in any vaccine-related controversies. I show that only a minority of these actors rejected vaccination in general and mobilized against all vaccination campaigns. Most of these actors only occasionally mobilized against a given vaccine or vaccination campaign and they did so to promote a political or cultural agenda that went beyond the vaccine itself. Using these results, I argue that in order to better understand how vaccine-related controversies emerge and why some activists devote time and resources to spread vaccine-critical arguments, social scientists should use three distinct concepts to refer to vaccine criticism: The Antivaccine Movement, the Marginally Antivaccine Movements and the Occasionally Vaccine Critical Movements. To do so would enable social scientists and public health experts to better understand the different ways in which vaccination can become politicized and the evolution of this politicization. PMID:27173740

  8. Evaluation of the safety and immunogenicity of a candidate tuberculosis vaccine, MVA85A, delivered by aerosol to the lungs of macaques.

    PubMed

    White, A D; Sibley, L; Dennis, M J; Gooch, K; Betts, G; Edwards, N; Reyes-Sandoval, A; Carroll, M W; Williams, A; Marsh, P D; McShane, H; Sharpe, S A

    2013-05-01

    Tuberculosis (TB) is a reemerging disease. The only available vaccine, Mycobacterium bovis BCG, is delivered intradermally and confers highly variable efficacy against pulmonary disease. There is an urgent need for improved vaccination strategies. Murine studies suggest that immunizations delivered directly to the respiratory mucosa might be a more effective route of vaccination. This study compared the immunogenicity of a leading candidate tuberculosis (TB) vaccine, modified vaccinia virus Ankara expressing antigen 85A (MVA85A), in rhesus macaques, delivered either as an aerosol or as an intradermal boost immunization 12 weeks after an intradermal BCG prime vaccine. Aerosol vaccination was well tolerated. MVA85A delivered by aerosol or by intradermal injection induced antigen-specific immune responses in the periphery and the lung, with a trend toward the highest response when the compartment and route of delivery were matched. The ability of poxvirus-vectored vaccines delivered by the systemic route to induce responses in the mucosal immune compartment in macaques is in contrast to the independent compartmentalization of mucosal and systemic immune systems described in mice. Unlike intradermal vaccination, aerosol vaccination did not induce a detectable serum anti-vector antibody response. The delivery of vaccines to the lungs might provide an immunization strategy that limits the induction of systemic anti-vector immunity, which would be extremely useful in the development of improved vaccine strategies. This is the first study to show a recombinant MVA-vectored vaccine to be highly immunogenic when delivered by the aerosol route to nonhuman primates. These results provide important safety and proof-of-concept data for further evaluation of this route of immunization for use in human clinical trials. PMID:23446219

  9. 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

  10. Evaluation of the immunogenicity and safety of Brucella melitensis B115 vaccination in pregnant sheep.

    PubMed

    Pérez-Sancho, Marta; Adone, Rosanna; García-Seco, Teresa; Tarantino, Michaela; Diez-Guerrier, Alberto; Drumo, Rosanna; Francia, Massimiliano; Domínguez, Lucas; Pasquali, Paolo; Álvarez, Julio

    2014-04-01

    In spite of its limitations, Rev.1 is currently recognized as the most suitable vaccine against Brucella melitensis (the causative agent of ovine and caprine brucellosis). However, its use is limited to young animals when test-and-slaughter programs are in place because of the occurrence of false positive-reactions due to Rev.1 vaccination. The B. melitensis B115 rough strain has demonstrated its efficacy against B. melitensis virulent strains in the mouse model, but there is a lack of information regarding its potential use in small ruminants for brucellosis control. Here, the safety and immune response elicited by B115 strain inoculation were evaluated in pregnant ewes vaccinated at their midpregnancy. Vaccinated (n=8) and non-vaccinated (n=3) sheep were periodically sampled and analyzed for the 108 days following inoculations using tests designed for the detection of the response elicited by the B115 strain and routine serological tests for brucellosis [Rose Bengal Test (RBT), Complement Fixation Test (CFT) and blocking ELISA (ELISAb)]. Five out of the 8 vaccinated animals aborted, indicating a significant abortifacient effect of B115 inoculation at midpregnancy. In addition, a smooth strain was recovered from one vaccinated animal, suggesting the occurrence of an in vivo reversion phenomenon. Only one animal was positive in both RBT and CFT simultaneously (91 days after vaccination) confirming the lack of induction of cross-reacting antibody responses interfering with routine brucellosis diagnostic tests in most B115-vaccinated animals. PMID:24508034

  11. Immunogenicity and safety of currently available Japanese encephalitis vaccines: A systematic review

    PubMed Central

    Li, Xing; Ma, Shu-Juan; Liu, Xie; Jiang, Li-Na; Zhou, Jun-Hua; Xiong, Yi-Quan; Ding, Hong; Chen, Qing

    2015-01-01

    A number of Japanese encephalitis (JE) vaccines have been used for preventing Japanese encephalitis around the world. We here reviewed the immunogenicity and safety of the currently available Japanese encephalitis vaccines. We searched Pubmed, Embase, Web of Science, the Cochrane Library and other online databases up to March 25, 2014 for studies focusing on currently used JE vaccines in any language. The primary outcomes were the seroconversion rate against JEV and adverse events. Meta-analysis was performed for the primary outcome when available. A total of 51 articles were included. Studies were grouped on the basic types of vaccines. This systematic review led to 2 aspects of the conclusions. On one hand, all the currently available JE vaccines are safe and effective. On the other hand, the overall of JE vaccine evaluation is disorganized, the large variation in study designs, vaccine types, schedules, doses, population and few hand-to-hand trails, make direct comparisons difficult. In order to make a more evidence-based decision on optimizing the JE vaccine, it is warranted to standardize the JE vaccine evaluation research. PMID:25668666

  12. Study designs for the nonclinical safety testing of new vaccine products.

    PubMed

    Forster, Roy

    2012-07-01

    During the development of a new vaccine, the purpose of nonclinical studies is to provide safety information to support the clinical development and licensure of the product. In this article the study designs currently accepted for the nonclinical safety testing of new vaccines are described for single dose, local tolerance, repeat dose toxicity and safety pharmacology studies; these studies together form the basis of a typical nonclinical safety evaluation dossier. The detailed design of the preclinical package must take account of the intended clinical use, patient population, route of administration, formulation, dose level and immunisation schedule. The test item that is used for these studies must be adequately representative of the intended clinical formulation. The animal model used for these studies must be selected on criteria of relevance. Single dose toxicity studies provide information on acute actions or the potential effect of accidental overdose, but this information is often available from the repeat dose toxicity study, obviating the need for the acute study. Local tolerance studies provide information on tissue reactions at the site of administration. Evaluation of the findings must distinguish between normal tissue responses to injected material and findings indicative of undesirable pathological changes. The repeated dose toxicity studies are the principal studies that support the safety profile of the vaccines. The design of these studies must take full account of the features of the vaccine in the choice of treatment regime, dose levels, pharmacodynamic monitoring and timing of investigations and sacrifice. Safety pharmacology studies are performed to evaluate the potential for undesirable secondary pharmacological actions of vaccines if there is data to suggest that such studies are needed; this evaluation is made on a case by case basis. In the absence of specific guidance the design of studies for therapeutic vaccines follows the same

  13. DNA vaccines

    NASA Astrophysics Data System (ADS)

    Gregersen, Jens-Peter

    2001-12-01

    Immunization by genes encoding immunogens, rather than with the immunogen itself, has opened up new possibilities for vaccine research and development and offers chances for new applications and indications for future vaccines. The underlying mechanisms of antigen processing, immune presentation and regulation of immune responses raise high expectations for new and more effective prophylactic or therapeutic vaccines, particularly for vaccines against chronic or persistent infectious diseases and tumors. Our current knowledge and experience of DNA vaccination is summarized and critically reviewed with particular attention to basic immunological mechanisms, the construction of plasmids, screening for protective immunogens to be encoded by these plasmids, modes of application, pharmacokinetics, safety and immunotoxicological aspects. DNA vaccines have the potential to accelerate the research phase of new vaccines and to improve the chances of success, since finding new immunogens with the desired properties is at least technically less demanding than for conventional vaccines. However, on the way to innovative vaccine products, several hurdles have to be overcome. The efficacy of DNA vaccines in humans appears to be much less than indicated by early studies in mice. Open questions remain concerning the persistence and distribution of inoculated plasmid DNA in vivo, its potential to express antigens inappropriately, or the potentially deleterious ability to insert genes into the host cell's genome. Furthermore, the possibility of inducing immunotolerance or autoimmune diseases also needs to be investigated more thoroughly, in order to arrive at a well-founded consensus, which justifies the widespread application of DNA vaccines in a healthy population.

  14. Improving Capture of Vaccine History: Case Study from an Evaluation of 10-Valent Pneumococcal Conjugate Vaccine Introduction in Kenya.

    PubMed

    Harris, Aaron M; Aol, George; Ouma, Dominic; Bigogo, Godfrey; Montgomery, Joel M; Whitney, Cynthia G; Breiman, Robert F; Kim, Lindsay

    2016-06-01

    With the accelerated introduction of new vaccines in low-income settings, understanding immunization program performance is critical. We sought to improve immunization history acquisition from Ministry of Health vaccination cards during a vaccine impact study of 10-valent pneumococcal conjugate vaccine on pneumococcal carriage among young children in Kenya in 2012 and 2013. We captured immunization history in a low proportion of study participants in 2012 using vaccination cards. To overcome this challenge, we implemented a household-based reminder system in 2013 using community health workers (CHWs), and increased the retrieval of vaccine cards from 62% in 2012 to 89% in 2013 (P < 0.001). The home-based reminder system using CHWs is an example of an approach that improved immunization history data quality in a resource-poor setting. PMID:27139446

  15. Current developments in avian influenza vaccines including food safety aspects in vaccinated birds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Oil emulsified inactivated low or high pathogenicity (HP) avian influenza AI viruses were the only type of vaccines available for many years. More recently, recombinant fowl poxvirus and avian paramyxovirus type 1 vaccines with AI H5 gene inserts (+ or - N1 gene insert) have been licensed for use. ...

  16. Multicenter Safety and Immunogenicity Trial of an Attenuated Measles Vaccine for NHP.

    PubMed

    Yee, Joann L; McChesney, Michael B; Christe, Kari L

    2015-10-01

    Measles is a highly contagious viral disease in NHP. The infection can range from asymptomatic to rapidly fatal, resulting in significant morbidity and mortality in captive populations. In addition to appropriate quarantine practices, restricted access, the immunization of all personnel in contact with NHP, and the wearing of protective clothing including face masks, measles immunization further reduces the infection risk. Commercially available measles vaccines are effective for use in NHP, but interruptions in their availability have prevented the implementation of ongoing, consistent vaccination programs. This need for a readily available vaccine led us to perform a broad, multicenter safety and immunogenicity study of another candidate vaccine, MVac (Serum Institute of India), a monovalent measles vaccine derived from live Edmonston-Zagreb strain virus that had been attenuated after 22 passages on human diploid cells. PMID:26473350

  17. Multicenter Safety and Immunogenicity Trial of an Attenuated Measles Vaccine for NHP

    PubMed Central

    Yee, JoAnn L; McChesney, Michael B; Christe, Kari L

    2015-01-01

    Measles is a highly contagious viral disease in NHP. The infection can range from asymptomatic to rapidly fatal, resulting in significant morbidity and mortality in captive populations. In addition to appropriate quarantine practices, restricted access, the immunization of all personnel in contact with NHP, and the wearing of protective clothing including face masks, measles immunization further reduces the infection risk. Commercially available measles vaccines are effective for use in NHP, but interruptions in their availability have prevented the implementation of ongoing, consistent vaccination programs. This need for a readily available vaccine led us to perform a broad, multicenter safety and immunogenicity study of another candidate vaccine, MVac (Serum Institute of India), a monovalent measles vaccine derived from live Edmonston–Zagreb strain virus that had been attenuated after 22 passages on human diploid cells. PMID:26473350

  18. Safety of West Nile Virus vaccines in sandhill crane chicks

    USGS Publications Warehouse

    Olsen, G.H.; Miller, K.J.; Docherty, D.E.; Bochsler, V.S.

    2008-01-01

    West Nile virus arrived in North America in 1999 and has spread across the continent in the ensuing years. The virus has proven deadly to a variety of native avian species including sandhill cranes (Grus canadensis). In order to provide safe and efficacious protection for captive and released populations of whooping cranes (G. americana), we have conducted a series of four research projects. The last of these was a study of the effects of two different West Nile virus vaccines on young Florida sandhill crane (G. c. pratensis) chicks and subsequent challenge with the virus. We found that vaccinating crane chicks as early as day 7 post-hatch caused no adverse reactions or noticeable morbidity. We tested both a commercial equine vaccine West Nile - Innovator (Fort Dodge Laboratories, Fort Dodge, Iowa) and a new recombinant DNA vaccine (Centers for Disease Control). We had a 33% mortality in control chicks (n =6) from West Nile virus infection, versus 0% mortality in two groups of vaccinated chicks (n = 12), indicating the two vaccines tested were not only safe but effective in preventing West Nile virus.

  19. Teaching vaccine safety communication to medical students and health professionals.

    PubMed

    Rath, Barbara; Muhlhans, Susann; Gaedicke, Gerhard

    2015-01-01

    Not only the general public, but also those studying to become health professionals, are struggling to keep up with a growing body of evidence and increasingly complex information about the many different types of vaccines available to date. At the same time, a number of increasingly complex subjects of study are competing for their attention during undergraduate and graduate education. In many medical school curricula in German-speaking countries, the subject of vaccines has been entirely omitted, or is regarded a minor subtopic. During the studies, most medical school curricula in German-speaking countries do not offer obligatory courses and/ or hands-on training vaccinology in vaccination. In Germany, private pediatricians administer the majority of immunizations. Even during postgraduate training programs in pediatrics, which are largely hospital-based, vaccinations are rarely a topic, and vaccinology remains a "hobby" and a "field without lobby" lacking specific certification requirements. Studies of acceptance of vaccines among health professionals and medical students have shown that many may still have their own doubts and uncertainties about vaccines revealing a number of unanswered questions during their studies and postgraduate training. PMID:25859671

  20. Safety and immunogenicity of an inactivated thimerosal‐free influenza vaccine in infants and children

    PubMed Central

    Nolan, Terry; Richmond, Peter C.; McVernon, Jodie; Skeljo, Maryanne V.; Hartel, Gunter F.; Bennet, Jillian; Basser, Russell L.

    2009-01-01

    Objective  Few prospective studies of inactivated split virion influenza vaccine have been conducted in infants and children. Our objective was to evaluate the safety, reactogenicity and immunogenicity of a thimerosal‐free inactivated influenza vaccine (Fluvax®; CSL Limited, Parkville, Australia) in children aged 6 months to <9 years. Methods  A prospective, open‐label, phase III clinical trial was conducted in 298 healthy children previously unvaccinated with influenza, commencing in the Southern Hemisphere 2005 autumn. Participants were divided into two groups (Group A: ≥6 months to <3 years; Group B: ≥3 years to <9 years), and received two doses of the 2005 vaccine, and one dose of the 2006 vaccine one year later (Group A: 0·25 ml per dose; Group B: 0·5 ml per dose). Vaccine safety and reactogenicity was evaluated for 30 days after each dose. Immunogenicity was assessed using hemagglutination inhibition and single radial hemolysis assays. Results  There were no withdrawals due to adverse events (AEs). The majority of solicited local and systemic AEs were of mild severity. A maximum intensity of severe was reported for injection site pain and fever by only 3·0% and 3·4% of participants, respectively. The vaccine was immunogenic for all antigens, with ≥95% of both younger and older children achieving seroprotection after dose 2. Conclusions  This thimerosal‐free inactivated influenza vaccine had a favorable safety profile and was immunogenic in children aged ≥6 months and <9 years. Primary and booster vaccination produced consistently immunogenic responses including in children under 3 years of age receiving 0·25 ml doses of vaccine. PMID:19903213

  1. Transportation Safety Excellence in Operations Through Improved Transportation Safety Document

    SciTech Connect

    Dr. Michael A. Lehto; MAL

    2007-05-01

    A recent accomplishment of the Idaho National Laboratory (INL) Materials and Fuels Complex (MFC) Nuclear Safety analysis group was to obtain DOE-ID approval for the inter-facility transfer of greater-than-Hazard-Category-3 quantity radioactive/fissionable waste in Department of Transportation (DOT) Type A drums at MFC. This accomplishment supported excellence in operations through safety analysis by better integrating nuclear safety requirements with waste requirements in the Transportation Safety Document (TSD); reducing container and transport costs; and making facility operations more efficient. The MFC TSD governs and controls the inter-facility transfer of greater-than-Hazard-Category-3 radioactive and/or fissionable materials in non-DOT approved containers. Previously, the TSD did not include the capability to transfer payloads of greater-than-Hazard-Category-3 radioactive and/or fissionable materials using DOT Type A drums. Previous practice was to package the waste materials to less-than-Hazard-Category-3 quantities when loading DOT Type A drums for transfer out of facilities to reduce facility waste accumulations. This practice allowed operations to proceed, but resulted in drums being loaded to less than the Waste Isolation Pilot Plant (WIPP) waste acceptance criteria (WAC) waste limits, which was not cost effective or operations friendly. An improved and revised safety analysis was used to gain DOE-ID approval for adding this container configuration to the MFC TSD safety basis. In the process of obtaining approval of the revised safety basis, safety analysis practices were used effectively to directly support excellence in operations. Several factors contributed to the success of MFC’s effort to obtain approval for the use of DOT Type A drums, including two practices that could help in future safety basis changes at other facilities. 1) The process of incorporating the DOT Type A drums into the TSD at MFC helped to better integrate nuclear safety

  2. Communicating vaccine safety in the context of immunization programs in low resource settings.

    PubMed

    Arwanire, Edison M; Mbabazi, William; Mugyenyi, Possy

    2015-01-01

    Vaccines are effective in preventing infectious diseases and their complications, hence reducing morbidity and infectious disease mortaity. Successful immunization programs, however, depend on high vaccine acceptance and coverage rates. In recent years there has been an increased level of public concern towards real or perceived adverse events associated with immunizations, leading to many people in high- as well as low-resource settings to refuse vaccines. Health care workers therefore must be able to provide parents and guardians of children with the most current and accurate information about the benefits and risks of vaccination. Communicating vaccine safety using appropriate channels plays a crucial role in maintaining public trust and confidence in vaccination programs. Several factors render this endeavor especially challenging in low-resource settings where literacy rates are low and access to information is often limited. Many languages are spoken in most countries in low-resource settings, making the provision of appropriate information difficult. Poor infrastructure often results in inadequate logistics. Recently, some concerned consumer groups have been able to propagate misinformation and rumors. To successfully communicate vaccine safety in a resource limited setting it is crucial to use a mix of communication channels that are both culturally acceptable and effective. Social mobilization through cultural, administrative and political leaders, the media or text messages (SMS) as well as the adoption of the Village Health Team (VHT) strategy whereby trained community members (Community Health Workers (CHWs)) are providing primary healthcare, can all be effective in increasing the demand for immunization. PMID:25859678

  3. Improving global access to new vaccines: intellectual property, technology transfer, and regulatory pathways.

    PubMed

    Crager, Sara Eve

    2014-11-01

    The 2012 World Health Assembly Global Vaccine Action Plan called for global access to new vaccines within 5 years of licensure. Current approaches have proven insufficient to achieve sustainable vaccine pricing within such a timeline. Paralleling the successful strategy of generic competition to bring down drug prices, a clear consensus is emerging that market entry of multiple suppliers is a critical factor in expeditiously bringing down prices of new vaccines. In this context, key target objectives for improving access to new vaccines include overcoming intellectual property obstacles, streamlining regulatory pathways for biosimilar vaccines, and reducing market entry timelines for developing-country vaccine manufacturers by transfer of technology and know-how. I propose an intellectual property, technology, and know-how bank as a new approach to facilitate widespread access to new vaccines in low- and middle-income countries by efficient transfer of patented vaccine technologies to multiple developing-country vaccine manufacturers. PMID:25211753

  4. [Improving global access to new vaccines: intellectual property, technology transfer, and regulatory pathways].

    PubMed

    Crager, Sara Eve

    2015-01-01

    The 2012 World Health Assembly Global Vaccine Action Plan called for global access to new vaccines within 5 years of licensure. Current approaches have proven insufficient to achieve sustainable vaccine pricing within such a timeline. Paralleling the successful strategy of generic competition to bring down drug prices, a clear consensus is emerging that market entry of multiple suppliers is a critical factor in expeditiously bringing down prices of new vaccines. In this context, key target objectives for improving access to new vaccines include overcoming intellectual property obstacles, streamlining regulatory pathways for biosimilar vaccines, and reducing market entry timelines for developing-country vaccine manufacturers by transfer of technology and know-how. I propose an intellectual property, technology, and know-how bank as a new approach to facilitate widespread access to new vaccines in low- and middle-income countries by efficient transfer of patented vaccine technologies to multiple developing-country vaccine manufacturers. PMID:25791189

  5. Controlled viral glycoprotein expression as a safety feature in a bivalent rabies-ebola vaccine.

    PubMed

    Papaneri, Amy B; Bernbaum, John G; Blaney, Joseph E; Jahrling, Peter B; Schnell, Matthias J; Johnson, Reed F

    2015-02-01

    Using a recombinant rabies (RABV) vaccine platform, we have developed several safe and effective vaccines. Most recently, we have developed a RABV-based ebolavirus (EBOV) vaccine that is efficacious in nonhuman primates. One safety feature of this vaccine is the utilization of a live but replication-deficient RABV construct. In this construct, the RABV glycoprotein (G) has been deleted from the genome, requiring G trans complementation in order for new infectious viruses to be released from the initial infected cell. Here we analyze this safety feature of the bivalent RABV-based EBOV vaccine comprised of the G-deleted RABV backbone expressing EBOV glycoprotein (GP). We found that, while the level of RABV genome in infected cells is equivalent regardless of G supplementation, the production of infectious virus is indeed restricted by the lack of G, and most importantly, that the presence of EBOV GP does not substitute for G. These findings further support the safety profile of this replication-deficient RABV-EBOV bivalent vaccine. PMID:25481284

  6. Safety, immunogenicity and protective efficacy in mice of a new cell-cultured Lister smallpox vaccine candidate.

    PubMed

    Ferrier-Rembert, Audrey; Drillien, Robert; Meignier, Bernard; Garin, Daniel; Crance, Jean-Marc

    2007-11-28

    It is now difficult to manufacture the first-generation smallpox vaccine, as the process could not comply with current safety and manufacturing regulations. In this study, a candidate non-clonal second-generation smallpox vaccine developed by Sanofi-Pasteur from the Lister strain has been assessed using a cowpox virus challenge in mice. We have observed similar safety, immunogenicity and protection (from disease and death) after a short or long interval following vaccination, as well as similar virus clearance post-challenge, with the second-generation smallpox vaccine candidate as compared to the traditional vaccine used as a benchmark. PMID:17964011

  7. Safety of Tdap vaccine in pregnant women: an observational study

    PubMed Central

    Petousis-Harris, Helen; Walls, Tony; Watson, Donna; Paynter, Janine; Graham, Patricia; Turner, Nikki

    2016-01-01

    Objectives Actively recruit and intensively follow pregnant women receiving a dose of acellular pertussis vaccine for 4 weeks after vaccination. Design and settings A prospective observational study conducted in 2 New Zealand regions. Participants Women in their 28th–38th week of pregnancy, recruited from primary care and antenatal clinics at the time of Tdap administration. Telephone interviews were conducted at 48 h and 4 weeks postvaccination. Main outcomes measures Outcomes were injection site reactions, systemic symptoms and serious adverse events (SAEs). Where available, data have been classified and reported according to Brighton Collaboration definitions. Results 793 women participated with 27.9% receiving trivalent inactivated influenza vaccine concomitantly. 79% of participants reported mild or moderate pain and 2.6% severe pain. Any swelling was reported by 7.6%, induration by 12.0% (collected from 1 site only, n=326), and erythema by 5.8% of participants. Fever was reported by 17 (2.1%) participants, 14 of these occurred within 24 h. Headache, dizziness, nausea, myalgia or arthralgia was reported by <4% of participants, respectively, and fatigue by 8.4%. During the study period, there were 115 adverse events in 113 participants, most of which were minor. At the end of the reporting period, 31 events were classified as serious (eg, obstetric bleeding, hypertension, infection, tachycardia, preterm labour, exacerbation of pre-existing condition and pre-eclampsia). All had variable onset time from vaccination. There were two perinatal deaths. Clinician assessment of all SAEs found none likely to be vaccine related. Conclusions Vaccination with Tdap in pregnant women was well tolerated with no SAE likely to be caused by the vaccine. Trial registration number ACTRN12613001045707. PMID:27091823

  8. Safety evaluation of adenovirus type 4 and type 7 vaccine live, oral in military recruits.

    PubMed

    Choudhry, Azhar; Mathena, Julie; Albano, Jessica D; Yacovone, Margaret; Collins, Limone

    2016-08-31

    Before the widespread adoption of vaccination, adenovirus type 4 and type 7 were long associated with respiratory illnesses among military recruits. When supplies were depleted and vaccination was suspended in 1999 for approximately a decade, respiratory illnesses due to adenovirus infections resurged. In March 2011, a new live, oral adenovirus vaccine was licensed by the US Food and Drug Administration and was first universally administered to military recruits in October 2011, leading to rapid, dramatic elimination of the disease within a few months. As part of licensure, a postmarketing study (Sentinel Surveillance Plan) was performed to detect potential safety signals within 42days after immunization of military recruits. This study retrospectively evaluated possible adverse events related to vaccination using data from the Armed Forces Health Surveillance Branch Defense Medical Surveillance System (DMSS) database. Among 100,000 recruits who received the adenovirus vaccine, no statistically significant greater risk of prespecified medical events was observed within 42days after vaccination when compared with a historical cohort of 100,000 unvaccinated recruits. In an initial statistical analysis of International Classification of Disease, 9th Revision, Clinical Modification codes, a statistically significant higher risk for 19 other (not prespecified) medical events occurring in 5 or more recruits was observed among vaccinated compared with unvaccinated groups. After case record data abstraction for attribution and validation, two events (psoriasis [21 vs 7 cases] and serum reactions [12 vs 4 cases]) occurred more frequently in the vaccinated cohort. A causal relation of these rare events with adenovirus vaccination could not be established given confounding factors in the DMSS, such as coadministration of other vaccines and incomplete or inaccurate medical information, for some recruits. Prospective surveillance assessing these uncommon, but potentially

  9. Safety of the intradermal Copenhagen 1331 BCG vaccine in neonates in Durban, South Africa.

    PubMed Central

    Jeena, P. M.; Chhagan, M. K.; Topley, J.; Coovadia, H. M.

    2001-01-01

    OBJECTIVE: To evaluate the safety of the intradermal Copenhagen BCG vaccine in neonates at different levels of delivery and neonatal units of the Durban Functional Region and surrounding regions. METHODS: A prospective study was carried out over a two-year period between July 1997 and June 1999. All neonates who had been vaccinated with the intradermal vaccine were evaluated at immunization clinics six weeks after immunization, or earlier if adverse effects occurred. FINDINGS: In total, 9763 neonates were examined: in 95.4% the vaccination scar had healed and 1.5% had no visible scar. Adverse events occurred in 3.1%. The proportion of neonates with no visible vaccination scars decreased over the study period, as did the number with adverse events. The lowest rate of adverse events and the highest rates of healed vaccination scars were seen in the tertiary hospital and regional and district hospitals that were in close proximity to the academic centre involved in this study. CONCLUSIONS: In the study sites, the transition from the percutaneous to intradermal route of administration of BCG vaccine was successful and took place without incurring unacceptably high rates of adverse events. To minimize adverse events, however, it is essential to continue training health personnel involved in implementing intradermal BCG vaccination programmes. PMID:11357213

  10. How Can We Improve School Safety Research?

    ERIC Educational Resources Information Center

    Astor, Ron Avi; Guerra, Nancy; Van Acker, Richard

    2010-01-01

    The authors of this article consider how education researchers can improve school violence and school safety research by (a) examining gaps in theoretical, conceptual, and basic research on the phenomena of school violence; (b) reviewing key issues in the design and evaluation of evidence-based practices to prevent school violence; and (c)…

  11. Synthetic DNA Vaccines: Improved Vaccine Potency by Electroporation and Co-Delivered Genetic Adjuvants

    PubMed Central

    Flingai, Seleeke; Czerwonko, Matias; Goodman, Jonathan; Kudchodkar, Sagar B.; Muthumani, Kar; Weiner, David B.

    2013-01-01

    In recent years, DNA vaccines have undergone a number of technological advancements that have incited renewed interest and heightened promise in the field. Two such improvements are the use of genetically engineered cytokine adjuvants and plasmid delivery via in vivo electroporation (EP), the latter of which has been shown to increase antigen delivery by nearly 1000-fold compared to naked DNA plasmid delivery alone. Both strategies, either separately or in combination, have been shown to augment cellular and humoral immune responses in not only mice, but also in large animal models. These promising results, coupled with recent clinical trials that have shown enhanced immune responses in humans, highlight the bright prospects for DNA vaccines to address many human diseases. PMID:24204366

  12. Evaluation of the safety, immunogenicity and efficacy of three capripoxvirus vaccine strains against lumpy skin disease virus.

    PubMed

    Gari, Getachew; Abie, Getnet; Gizaw, Daniel; Wubete, Alehegn; Kidane, Membere; Asgedom, Hagos; Bayissa, Berecha; Ayelet, Gelagay; Oura, Christopher A L; Roger, Francois; Tuppurainen, Eeva S M

    2015-06-22

    The safety, immunogenicity and efficacy of three commercially available vaccines against lumpy skin disease (LSD) in cattle have been evaluated using a combination of vaccine challenge experiments and the monitoring of immune responses in vaccinated animals in the field. The three vaccines evaluated in the study included two locally produced (Ethiopian) vaccines (lumpy skin disease virus (LSDV) Neethling and Kenyan sheep and goat pox (KSGP) O-180 strain vaccines) and a Gorgan goat pox (GTP) vaccine manufactured by Jordan Bio-Industries Centre (JOVAC). The latter vaccine was evaluated for the first time in cattle against LSDV. The Ethiopian Neethling and KSGPO-180 vaccines failed to provide protection in cattle against LSDV, whereas the Gorgan GTP vaccine protected all the vaccinated calves from clinical signs of LSD. There was no significant difference in protective efficacy detected between two dosage levels (P=0.2, P=0.25, and P=0.1 for KSGP, Neethling and Gorgan vaccines, respectively). Additionally, the Gorgan GTP vaccinated cattle showed stronger levels of cellular immune responses measured using Delayed-Type Hypersensitivity (DTH) reactions at the vaccination site indicating higher levels of immunogenicity produced by the GTPV vaccine in cattle, as opposed to the other two vaccines. This study indicated, for the first time, that the Gorgan GTP vaccine can effectively protect cattle against LSDV and that the Neethling and KSGP O-180 vaccine were not protective. The results emphasise the need for molecular characterization of the Neethling and KSGP O-180 vaccine seed viruses used for vaccine production in Ethiopia. In addition, the potency and efficacy testing process of the Ethiopian LSD Neethling and KSGP O-180 vaccines should be re-evaluated. PMID:26056063

  13. [Analysis of the evidence on the efficacy and safety of CYD-TDV dengue vaccine and its potential licensing and implementation through Mexico's Universal Vaccination Program].

    PubMed

    Hernández-Ávila, Mauricio; Lazcano-Ponce, Eduardo; Hernández-Ávila, Juan Eugenio; Alpuche-Aranda, Celia M; Rodríguez-López, Mario Henry; García-García, Lourdes; Madrid-Marina, Vicente; López Gatell-Ramírez, Hugo; Lanz-Mendoza, Humberto; Martínez-Barnetche, Jesús; Díaz-Ortega, José Luis; Ángeles-Llerenas, Angélica; Barrientos-Gutiérrez, Tonatiuh; Bautista-Arredondo, Sergio; Santos-Preciado, José Ignacio

    2016-02-01

    Dengue is a major global public health problem affecting Latin America and Mexico Prevention and control measures, focusing on epidemiological surveillance and vector control, have been partially effective and costly, thus, the development of a vaccine against dengue has created great expectations among health authorities and scientific communities worldwide. The CYD-TDV dengue vaccine produced by Sanofi-Pasteur is the only dengue vaccine evaluated in phase 3 controlled clinical trials. Notwithstanding the significant contribution to the development of a vaccine against dengue, the three phase 3 clinical studies of CYD-TDV and the meta-analysis of the long-term follow up of those studies, have provided evidence that this vaccine exhibited partial vaccine efficacy to protect against virologically confirmed dengue and lead to four considerations: a) adequate vaccine efficacy against dengue virus (DENV) infections 3 and 4, less vaccine efficacy against DENV 1 and no protection against infection by DENV 2; b) decreased vaccine efficacy in dengue seronegative individuals at the beginning of the vaccination; c) 83% and 90% protection against hospitalizations and severe forms of dengue, respectively, at 25 months follow-up; and d) increased hospitalization for dengue in the vaccinated group, in children under nine years of age at the time of vaccination, detected since the third year of follow-up. The benefit of the CYD-TDV vaccine can be summarized in the protection against infection by DENV 3 and 4, as well as protection for hospitalizations and severe cases in people over nine years, who have had previous dengue infection, working mainly as a booster. In this review we identified elements on efficacy and safety of this vaccine that must be taken into account in the licensing process and potential inclusion in the national vaccination program of Mexico. The available scientific evidence on the CYD-TDV vaccine shows merits, but also leads to relevant questions that

  14. Safety and Immunogenicity of Cuban Antipneumococcal Conjugate Vaccine PCV7-TT in Healthy Adults.

    PubMed

    González, Nadezhda; Paredes, Beatriz; Pérez, Sonia; Mirabal, Mayelín; Rivero, Ivonne; González, Carlos A; Díaz, Alina; García, Dagmar; Rodríguez, Laura; Pérez, Amarilis; Soroa, Yamilka; Santana, Darielis; Alvarez, Alina; Valdés, Yury; Vérez, Vicente

    2015-10-01

    INTRODUCTION Pneumococcal infections are a major cause of morbidity and mortality and are associated with considerable economic burden on health systems. To prevent pneumococcal infections, 7-valent conjugate vaccines have been available for over a decade; more recently, 10- and 13-valent conjugate vaccines have been formulated, which are more immunogenic than vaccines with capsular polysaccharides only. In Cuba, a new vaccine candidate has been developed, PCV7-TT, a conjugate of tetanus toxoid with antigens of seven of the serotypes of Streptococcus pneumoniae with highest circulation in Cuba and in the world: 1, 5, 6B, 14, 18C, 19F and 23F. OBJECTIVE Assess the safety of the vaccine candidate PCV7-TT in healthy adults and conduct a preliminary assessment of its immunogenicity. METHODS A phase I, double-blind clinical trial was performed at the National Toxicology Center in Havana, Cuba. Healthy male volunteers aged 18-35 years were randomly assigned to two groups: 20 received the vaccine candidate PCV7-TT and 20 the polyvalent antipneumococcal vaccine PNEUMO-23 used as control, each in a single intramuscular dose. To assess safety, the occurrence of adverse events was monitored for 30 days following inoculation. To explore immunogenicity, concentrations of serotype-specific antibodies was quantified before and 30 days after inoculation, as well titers of opsonophagocytic antibodies. (National Clinical Trial Registry RPCEC00000133) RESULTS Local adverse events were pain, redness, induration, increased sensitivity to touch, and warmth in the injection area. Pain was registered in 70% of individuals who received PCV7-TT and in 75% of those vaccinated with PNEUMO-23. Reported systemic adverse events were general malaise, headache and drowsiness. All adverse events appeared in the first 72 hours post inoculation and lasted no longer than 3 days. One event was reported that was classified as severe in intensity and serious in consequences, but it was unrelated to

  15. Safety, tolerability and side effects of human papillomavirus vaccines: a systematic quantitative review.

    PubMed

    Gonçalves, Ana Katherine; Cobucci, Ricardo Ney; Rodrigues, Hugo Marcus; de Melo, Amanda Gosson; Giraldo, Paulo César

    2014-01-01

    Recently, many studies have evaluated HPV vaccine safety and adverse effects. Two vaccines have been recently evaluated in randomized controlled trials: the bivalent vaccine for HPV 16 and 18 (Cervarix, GlaxoSmithKline Biologicals, Rixensart, Belgium) and the quadrivalent vaccine for HPV 6, 11, 16, and 18 (Gardasil, Merck and Co., Inc., Whitehouse Station, NJ). We have performed a systematic review of all randomized controlled trials in which HPV vaccines were compared with placebo regarding safety, tolerability and adverse effects. Studies were searched up to March 2013 in the databases: Pubmed, Embase, Scielo and Cancerlit. Odds Ratios (OR) of most incident adverse effects were obtained. Twelve reports, involving 29,540 subjects, were included. In the HPV 16/18 group, the most frequently reported events related to the vaccine were pain (OR 3.29; 95% CI: 3.00-3.60), swelling (OR 3.14; 95% CI: 2.79-3.53) and redness (OR 2.41; 95% CI: 2.17-2.68). For the HPV 6/11/16/18 group the events were pain (OR 2.88; 95% CI: 2.42-3.43) and swelling (OR 2.65; 95% CI: 2.0-3.44). Concerning the HPV 16/18 vaccine, pain was the most common outcome detected. These effects can be due to a possible VLP-related inflammation process. Fatigue was the most relevant general effect observed followed by fever, gastrointestinal symptoms, and headache. In the HPV 6/11/16/18 group, only general symptoms, pain and swelling were observed. Pain and swelling were the most frequent. Comparing HPV 16/18 to HPV 6/11/16/18 vaccines, the former presented more adverse effects, perhaps because there are many more trials evaluating the bivalent vaccine. Other studies are needed to clarify this issue. PMID:24780368

  16. Improving patient safety: lessons from other disciplines.

    PubMed

    Golemboski, Karen

    2011-01-01

    Other industries and certain healthcare specialties have employed a variety of methods to improve safety and quality of services. Techniques such as industry-wide standardized collection and reporting of error data, standardization of practice through checklists, application of electronic health records, and simulator-based interdisciplinary training have improved outcomes in aviation, anesthesiology, and surgery. Although traditionally the clinical laboratory has concentrated on analytical performance, pre- and post-analytical aspects of laboratory services may also be improved through the application of these methods. PMID:21657145

  17. Roads to the development of improved pertussis vaccines paved by immunology

    PubMed Central

    Brummelman, Jolanda; Wilk, Mieszko M.; Han, Wanda G.H.; van Els, Cécile A.C.M.; Mills, Kingston H.G.

    2015-01-01

    Current acellular pertussis vaccines have various shortcomings, which may contribute to their suboptimal efficacy and waning immunity in vaccinated populations. This calls for the development of new pertussis vaccines capable of inducing long-lived protective immunity. Immunization with whole cell pertussis vaccines and natural infection with Bordetella pertussis induce distinct and more protective immune responses when compared with immunization with acellular pertussis vaccines. Therefore, the immune responses induced with whole cell vaccine or after infection can be used as a benchmark for the development of third-generation vaccines against pertussis. Here, we review the literature on the immunology of B. pertussis infection and vaccination and discuss the lessons learned that will help in the design of improved pertussis vaccines. PMID:26347400

  18. Vaccinations

    MedlinePlus

    ... vaccinated? For many years, a set of annual vaccinations was considered normal and necessary for dogs and ... to protect for a full year. Consequently, one vaccination schedule will not work well for all pets. ...

  19. Examination of the Safety of Pediatric Vaccine Schedules in a Non-Human Primate Model: Assessments of Neurodevelopment, Learning, and Social Behavior

    PubMed Central

    Curtis, Britni; Liberato, Noelle; Rulien, Megan; Morrisroe, Kelly; Kenney, Caroline; Yutuc, Vernon; Ferrier, Clayton; Marti, C. Nathan; Mandell, Dorothy; Burbacher, Thomas M.; Sackett, Gene P.

    2015-01-01

    Background In the 1990s, the mercury-based preservative thimerosal was used in most pediatric vaccines. Although there are currently only two thimerosal-containing vaccines (TCVs) recommended for pediatric use, parental perceptions that vaccines pose safety concerns are affecting vaccination rates, particularly in light of the much expanded and more complex schedule in place today. Objectives The objective of this study was to examine the safety of pediatric vaccine schedules in a non-human primate model. Methods We administered vaccines to six groups of infant male rhesus macaques (n = 12–16/group) using a standardized thimerosal dose where appropriate. Study groups included the recommended 1990s Pediatric vaccine schedule, an accelerated 1990s Primate schedule with or without the measles–mumps–rubella (MMR) vaccine, the MMR vaccine only, and the expanded 2008 schedule. We administered saline injections to age-matched control animals (n = 16). Infant development was assessed from birth to 12 months of age by examining the acquisition of neonatal reflexes, the development of object concept permanence (OCP), computerized tests of discrimination learning, and infant social behavior. Data were analyzed using analysis of variance, multilevel modeling, and survival analyses, where appropriate. Results We observed no group differences in the acquisition of OCP. During discrimination learning, animals receiving TCVs had improved performance on reversal testing, although some of these same animals showed poorer performance in subsequent learning-set testing. Analysis of social and nonsocial behaviors identified few instances of negative behaviors across the entire infancy period. Although some group differences in specific behaviors were reported at 2 months of age, by 12 months all infants, irrespective of vaccination status, had developed the typical repertoire of macaque behaviors. Conclusions This comprehensive 5-year case–control study, which closely examined

  20. Safety and immunogenicity of a live attenuated Japanese encephalitis chimeric virus vaccine (IMOJEV®) in children.

    PubMed

    Chokephaibulkit, K; Houillon, G; Feroldi, E; Bouckenooghe, A

    2016-01-01

    JE-CV (IMOJEV®, Sanofi Pasteur, France) is a live attenuated virus vaccine constructed by inserting coding sequences of the prM and E structural proteins of the Japanese encephalitis SA14-14-2 virus into the genome of yellow fever 17D virus. Primary immunization with JE-CV requires a single dose of the vaccine. This article reviews clinical trials of JE-CV in children aged up to 6 years conducted in countries across South-East Asia. Strong and persistent antibody responses were observed after single primary and booster doses, with 97% of children seroprotected up to five years after booster vaccination. Models of long-term antibody persistence predict a median duration of protection of approximately 30 years after a booster dose. The safety and reactogenicity profiles of JE-CV primary and booster doses are comparable to other widely used childhood vaccines. PMID:26588242

  1. Safety of Attenuated Smallpox Vaccine LC16m8 in Immunodeficient Mice

    PubMed Central

    Shinmura, Yasuhiko; Kanehara, Tomomi; Maruno, Shinichi; Kuranaga, Masahiko; Matsui, Hajime; Hashizume, So

    2014-01-01

    Freeze-dried live attenuated smallpox vaccine LC16m8 prepared in cell culture has been the sole smallpox vaccine licensed in Japan since 1975 and was recently recommended as a WHO stockpile vaccine. We evaluated the safety of recently remanufactured lots of LC16m8 using a series of immunodeficient mouse models. These models included suckling mice, severe combined immunodeficiency disease (SCID) mice, and wild-type mice treated with cyclosporine. LC16m8 showed extremely low virulence in each of the three mouse models compared with that of its parental strains, Lister and LC16mO. These results provide further evidence that LC16m8 is one of the safest replication-competent smallpox vaccines in the world and may be considered for use in immunodeficient patients. PMID:24990910

  2. Oral vaccination with inhibin DNA delivered using attenuated Salmonella choleraesuis for improving reproductive traits in mice.

    PubMed

    Han, Li; Zhen, Yan-Hong; Liang, Ai-Xin; Zhang, Jian; Riaz, Hasan; Xiong, Jia-Jun; Guo, Ai-Zhen; Yang, Li-Guo

    2014-09-01

    The objective of this study was to examine the efficacy and safety of a novel inhibin vaccine containing inhibin α (1-32) fragments in mice. A recombinant plasmid pVAX-asd-IS was constructed by inserting recombinant inhibin α (1-32) and the hepatitis B surface antigen S into the plasmid in which the asd gene, rather than the kanamycin gene, was a selection marker. Ninety Kuming mice were divided into six groups consisting of 15 mice each. First group was (C1) injected with 200 µl of PBS, second (C2) received 1 × 10(10) CFU of crp(-) /asd(-) C500/pVAX-asd and served as vector control, third did not receive any treatment (C3), while fourth, fifth, and sixth group received 1 × 10(10) , 1 × 10(9) , 1 × 10(8) CFU of the recombinant inhibin vaccine crp(-) /asd(-) C500/pVAX-asd-IS (group T1, T2, T3), respectively. Western blotting demonstrated that recombinant expressed inhibin protein possessed immune function and that this plasmid could replicate for up to 40 generations stably. Vaccination with this strain at a dose of 1 × 10(10) CFU/200 µl per mouse induced high anti-inhibin antibody levels, significantly increased large-follicle production in T1 group (p < 0.05) and average litter size (p > 0.05) compared with control groups. Integration studies showed no evidence of inhibin fusion gene integrated into mice's genome 2-month after immunization. These results suggest that the vaccine described in the present study may provide a safe method to improve reproductive traits in animals. A trend towards increased litter size and significant increase in large follicle population depict that this vaccine may have direct application in large animal industry. PMID:24123188

  3. How vaccine safety can become political--the example of polio in Nigeria.

    PubMed

    Clements, Christopher J; Greenough, Paul; Shull, Diana

    2006-01-01

    Vaccine safety is increasingly a major aspect of immunization programmes. Parents are becoming more aware of safety issues relating to vaccines their babies might receive. As a consequence, public health initiatives have had to take note of pressures brought to bear by individual parents and groups. Now we document a new phase in vaccine safety where it has been used to achieve political objectives. In 1988, the World Health Assembly declared its intention to eradicate poliomyelitis from the globe by the year 2000. This goal had to be postponed to 2005 for a number of reasons. Although the progress has been spectacular in achieving eradication in almost all nations and areas, the goal has been tantalizingly elusive. But arguably the most difficult country from which to eradicate the virus has been Nigeria. Over the past two years, tension has arisen in the north against immunizing against polio using the oral polio vaccine (OPV). Although this vaccine has been used in every other country in the world including other Muslim states, some religious leaders in the north found reason in August 2003 to advise their followers not to have their children vaccinated with OPV. Subsequent to this boycott, which the Kano governor had endorsed for a year and then ended in July 2004, cases of polio occurred in African nations previously free of the virus, and the DNA finger-print of the virus indicated it had come from Nigeria. In other words, Nigeria became a net exporter of polio virus to its African neighbours and beyond. Now the disease has spread to a dozen formerly polio-free countries, including Sudan and Indonesia. We show that, while the outward manifestations of the northern Nigerian intransigence were that of distrust of vaccine, the underlying problem was actually part of a longstanding dispute about political and religious power vis a vis Abuja. It is unlikely that polio transmission will be interrupted by 2005 if this dispute is allowed to run its course. PMID

  4. A postmarket safety comparison of 2 vaccination strategies for measles, mumps, rubella and varicella in Italy.

    PubMed

    Cocchio, Silvia; Zanoni, Giovanna; Opri, Roberta; Russo, Francesca; Baldo, Vincenzo

    2016-03-01

    It is strategically important to monitor the safety profile of vaccination schedules in order to achieve and maintain high levels of coverage. We analyzed the cohort of individuals actively invited for measles, mumps, rubella and varicella (MMRV) vaccination in the Veneto region (north-east Italy) from 8/1/2013 to 7/31/2014, assessing the onset of adverse events (AE) relating to 2 different vaccination strategies for MMRV (MMR+V vs MMRV). During the vaccination session at 14 months old, parents were given a form for recording local and systemic reactions to vaccinations for 4 weeks afterwards. Overall, 12,288 forms were returned, and 84.6% of them were included in this analysis (5,130 relating to MMR+V and 5,265 to MMRV); 37.3% of the sample reported no AEs, with no difference between the 2 groups. Local reactions were more common in the MMR+V group (9.6% vs 2.9%; RR 3.33; 95% CI 2.79-3.98), while there was no difference in general reactions between the 2 groups (50% MMR+V vs 52% MMRV). The events most often reported were "fever <39.5°C," which was more frequently associated with the MMRV strategy (p<0.001), and "skin blotches and marks," which occurred more often in the MMR+V group (p<0.001). Reports of "fever ≥39.5°C" were equally distributed between the 2 groups. Sixteen cases of febrile seizures were reported (0.14% in the MMR+V group and 0.17% in the MMRV group). Similar safety profiles were identified for the 2 vaccination strategies. Although the method used to record reactions to vaccination demanded considerable resources, it enabled important information to be collected on parents' perception of the AEs occurring in response to their child's vaccination. PMID:26528829

  5. Immunogenicity and safety of the human papillomavirus vaccine in patients with autoimmune diseases: A systematic review.

    PubMed

    Pellegrino, Paolo; Radice, Sonia; Clementi, Emilio

    2015-07-01

    Whereas safety and efficacy of HPV vaccines in healthy women have been shown in several randomised controlled clinical trials and in post marketing analyses, only few data exist in patients affected by autoimmune diseases. These issues are significant as autoimmune conditions are recognised as a risk factor for the persistence of HPV infection. Herein we review and systematise the existing literature to assess immunogenicity and safety of HPV vaccination in patients with autoimmune diseases, including systemic lupus erythematosus and juvenile idiopathic arthritis. The results of our literature revision suggest that the HPV vaccines are efficacious and safe in most of the patients affected by autoimmune diseases. Yet, some points of concern remain to be tackled, including the effects of concomitant therapies, the risk of disease exacerbation and the cost-effectiveness of such immunisation programmes in these populations. PMID:26036945

  6. [Anti-pneumococcal vaccine coverage for hospitalized risk patients: Assessment and suggestions for improvements].

    PubMed

    Richard, C; Le Garlantezec, P; Lamand, V; Rasamijao, V; Rapp, C

    2016-05-01

    Streptococcus pneumoniae can cause invasive infections. Incidence and severity are linked to patients' risk factors. Due to the resistance to leading antibiotics, the anti-pneumococcal vaccination has become a major public health issue. The purpose of this survey was to evaluate the anti-pneumococcal vaccine coverage in a population of adults with risk factors. This was a prospective study that included patients with at least one recommendation for pneumococcal vaccination as indicated by the Weekly Epidemiological Bulletin (BEH), to which three further US recommendations were added (diabetes, obesity and age>65years). One hundred and thirty-four patients with an average age of 70 years were included. The physician could only confirm 68 % of the patients' vaccination status. Vaccination coverage as recommended by the BEH board was 30 % (n=54). All HIV patients were vaccinated (n=2) and the vaccination coverage was 75 % (n=8) for patients treated for autoimmune diseases and only 10 % (n=20) for patients treated with chemotherapy. Patients with no vaccination didn't know the existence of the vaccine or didn't know that vaccination was recommended to them. This study has highlighted a deficit in pneumococcal vaccination coverage and a high level of ignorance of the existence of recommended vaccination. In addition to awareness campaign for patients and caregiver training, the expansion of the vaccine e-book utilization could improve the vaccination status. PMID:26619926

  7. Immuogenicity and safety of a natural rough mutant of Brucella suis as a vaccine for swine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of the current study was to evaluate the safety, immunogenicity and clearance of the natural rough mutant of Brucella suis strain 353-1 (353-1) as a vaccine in domestic swine. In three studies encompassing 155 animals, pigs were inoculated with 353-1 by conjunctival (5 x 10**7 CFU), p...

  8. Template protocol for clinical trials investigating vaccines--focus on safety elements.

    PubMed

    Bonhoeffer, Jan; Imoukhuede, Egeruan B; Aldrovandi, Grace; Bachtiar, Novilia S; Chan, Eng-Soon; Chang, Soju; Chen, Robert T; Fernandopulle, Rohini; Goldenthal, Karen L; Heffelfinger, James D; Hossain, Shah; Jevaji, Indira; Khamesipour, Ali; Kochhar, Sonali; Makhene, Mamodikoe; Malkin, Elissa; Nalin, David; Prevots, Rebecca; Ramasamy, Ranjan; Sellers, Sarah; Vekemans, Johan; Walker, Kenneth B; Wilson, Pam; Wong, Virginia; Zaman, Khalequz; Heininger, Ulrich

    2013-11-12

    This document is intended as a guide to the protocol development for trials of prophylactic vaccines. The template may serve phases I-IV clinical trials protocol development to include safety relevant information as required by the regulatory authorities and as deemed useful by the investigators. This document may also be helpful for future site strengthening efforts. PMID:23499603

  9. Hepatitis B vaccine safety monitoring in the chimpanzee: interpretation of results.

    PubMed

    Berthelot, P; Courouce, A M; Eyquem, A; Feldmann, G; Jacob, J; Ravisse, P; Vacher, B; Moor-Jankowski, J; Muchmore, E; Prince, A

    1984-01-01

    In September, 1983, a group of French and American experts met at the French National Health Laboratory to discuss their experience in monitoring for the safety of a hepatitis B vaccine in 42 chimpanzees. The observations made, conclusions reached, and recommendations for future studies are presented. PMID:6239039

  10. Safety of immunisation and adverse events following vaccination against hepatitis B.

    PubMed

    Duclos, Philippe

    2003-05-01

    Hepatitis B vaccines (HBVs) are composed of highly purified preparations of hepatitis B virus surface antigen (HBsAg). An adjuvant, either aluminium phosphate or aluminium hydroxide, is added to the vaccines, which are sometimes preserved with thiomersal. In placebo-controlled studies, common side effects other than local reactions were reported no more frequently among vaccine recipients than among individuals receiving a placebo. A number of controversial adverse events have, however, been purported to be associated with HBVs, including rheumatoid arthritis (RA), diabetes, demyelinating diseases (e.g., multiple sclerosis [MS]), chronic fatigue syndrome, and more recently, lymphoblastic leukaemia. In addition, the safety of the thiomersal and aluminium contained in the vaccine has also been under close scrutiny. These issues have been reviewed by a number of country-specific or international independent review committees such as that of the US Institute of Medicine (IOM) and the World Health Organization's (WHO) Global Advisory Committee on Vaccine Safety (GACVS). Upon review of the scientific evidence, none of the serious allegations have so far been confirmed. On the contrary, scientific evidence has accumulated to disprove many of the allegations. In particular, the IOM committee has concluded that the evidence favoured rejection of a causal relationship between HBV administered to adults and incident MS or MS relapse. Whilst it is important to continue monitoring some of the safety issues, there is no evidence to suggest that the WHO should consider altering its recommendation that all countries should have universal infant and/or adolescent immunisation programmes. The risks of hepatitis B vaccination are only theoretical in comparison with clear benefits in terms of cirrhosis and cancer prevention, and the HBV remains one with an excellent safety profile. PMID:12904102

  11. Speech Recognition Interfaces Improve Flight Safety

    NASA Technical Reports Server (NTRS)

    2013-01-01

    "Alpha, Golf, November, Echo, Zulu." "Sierra, Alpha, Golf, Echo, Sierra." "Lima, Hotel, Yankee." It looks like some strange word game, but the combinations of words above actually communicate the first three points of a flight plan from Albany, New York to Florence, South Carolina. Spoken by air traffic controllers and pilots, the aviation industry s standard International Civil Aviation Organization phonetic alphabet uses words to represent letters. The first letter of each word in the series is combined to spell waypoints, or reference points, used in flight navigation. The first waypoint above is AGNEZ (alpha for A, golf for G, etc.). The second is SAGES, and the third is LHY. For pilots of general aviation aircraft, the traditional method of entering the letters of each waypoint into a GPS device is a time-consuming process. For each of the 16 waypoints required for the complete flight plan from Albany to Florence, the pilot uses a knob to scroll through each letter of the alphabet. It takes approximately 5 minutes of the pilot s focused attention to complete this particular plan. Entering such a long flight plan into a GPS can pose a safety hazard because it can take the pilot s attention from other critical tasks like scanning gauges or avoiding other aircraft. For more than five decades, NASA has supported research and development in aviation safety, including through its Vehicle Systems Safety Technology (VSST) program, which works to advance safer and more capable flight decks (cockpits) in aircraft. Randy Bailey, a lead aerospace engineer in the VSST program at Langley Research Center, says the technology in cockpits is directly related to flight safety. For example, "GPS navigation systems are wonderful as far as improving a pilot s ability to navigate, but if you can find ways to reduce the draw of the pilot s attention into the cockpit while using the GPS, it could potentially improve safety," he says.

  12. Improving safety for children with cardiac disease.

    PubMed

    Thiagarajan, Ravi R; Bird, Geoffrey L; Harrington, Karen; Charpie, John R; Ohye, Richard C; Steven, James M; Epstein, Michael; Laussen, Peter C

    2007-09-01

    The complexity of the modern systems providing health care presents a unique challenge in delivering care of the required quality in a safe environment. Issues of safety have been thrust into the limelight because of adverse events highly publicized in the general media. In the United States of America, improving the safety and quality in health care has been set forth as a priority for improvements in the 21st century in the report from the Institute of Medicine. Many measures have now been initiated for improving the safety of patients at hospital, regional, and national level, and through initiatives sponsored by governments and private organizations. In this review, we summarize known concepts and current issues on the safety of patients, and their applicability to children with congenital cardiac disease. Prior to examining the issues of medical error and safety, it is important to define the terminology. An error is defined as the failure of a planned action to be completed as intended, also known as an execution error, or the use of a wrong plan to achieve an aim, this representing a planning error. An active error is an error that occurs at the level of the frontline operator, and the effects of which are felt immediately. A latent error is an error in the design, organization, training and maintenance, that leads to operator errors, and the effects of which are typically dormant in the system for lengthy periods of time. Latent errors may cause harm given the right circumstances and environment. An adverse event is defined as an injury resulting from medical intervention. A preventable adverse event is an adverse event that occurs due to medical error. Negligent adverse events are a subset of preventable adverse events where the care provided did not meet the standard of care expected of that practitioner. The study of improving the delivery of safe care for our patients is a rapidly growing field. Important components for development of programmes to

  13. Post-marketing safety monitoring of a new group B meningococcal vaccine in New Zealand, 2004-2006.

    PubMed

    McNicholas, Anne; Galloway, Yvonne; Stehr-Green, Paul; Reid, Stewart; Radke, Sarah; Sexton, Kerry; Kieft, Charlotte; Macdonald, Claire; Neutze, Jocelyn; Drake, Ross; Isaac, Dorothy; O'Donnell, Mary; Tatley, Michael; Oster, Philipp; O'Hallahan, Jane

    2007-01-01

    New Zealand introduced a new outer membrane vesicle vaccine in 2004 to combat an epidemic of group B meningococcal disease. An Independent Safety Monitoring Board oversaw intensive safety monitoring, which included hospital surveillance, health professional reporting (passive and active) and mortality monitoring. With over three million doses administered to individuals aged under 20 years, the monitoring results provide consistent evidence supporting the vaccine's safety. PMID:17660718

  14. BRICS: opportunities to improve road safety.

    PubMed

    Hyder, Adnan A; Vecino-Ortiz, Andres I

    2014-06-01

    Brazil, the Russian Federation, India, China and South Africa--the countries known as BRICS--are currently undergoing a deep epidemiological transition that is mainly driven by rapid economic growth and technological change. The changes being observed in the distribution of the burden of diseases and injuries--such as recent increases in the incidence of road traffic injuries--are matters of concern. BRICS may need stronger institutional capacity to address such changes in a timely way. In this paper, we present data on road traffic injuries in BRICS and illustrate the enormous challenge that these countries currently face in reducing the incidence of such injuries. There is an urgent need to improve road safety indicators in every country constituting BRICS. It is imperative for BRICS to invest in system-wide road safety interventions and reduce the mortality and morbidity from road traffic injuries. PMID:24940016

  15. Lithium ion battery with improved safety

    DOEpatents

    Chen, Chun-hua; Hyung, Yoo Eup; Vissers, Donald R.; Amine, Khalil

    2006-04-11

    A lithium battery with improved safety that utilizes one or more additives in the battery electrolyte solution wherein a lithium salt is dissolved in an organic solvent, which may contain propylene, carbonate. For example, a blend of 2 wt % triphenyl phosphate (TPP), 1 wt % diphenyl monobutyl phosphate (DMP) and 2 wt % vinyl ethylene carbonate additives has been found to significantly enhance the safety and performance of Li-ion batteries using a LiPF6 salt in EC/DEC electrolyte solvent. The invention relates to both the use of individual additives and to blends of additives such as that shown in the above example at concentrations of 1 to 4-wt % in the lithium battery electrolyte. This invention relates to additives that suppress gas evolution in the cell, passivate graphite electrode and protect it from exfoliating in the presence of propylene carbonate solvents in the electrolyte, and retard flames in the lithium batteries.

  16. BRICS: opportunities to improve road safety

    PubMed Central

    Vecino-Ortiz, Andres I

    2014-01-01

    Abstract Brazil, the Russian Federation, India, China and South Africa – the countries known as BRICS – are currently undergoing a deep epidemiological transition that is mainly driven by rapid economic growth and technological change. The changes being observed in the distribution of the burden of diseases and injuries – such as recent increases in the incidence of road traffic injuries – are matters of concern. BRICS may need stronger institutional capacity to address such changes in a timely way. In this paper, we present data on road traffic injuries in BRICS and illustrate the enormous challenge that these countries currently face in reducing the incidence of such injuries. There is an urgent need to improve road safety indicators in every country constituting BRICS. It is imperative for BRICS to invest in system-wide road safety interventions and reduce the mortality and morbidity from road traffic injuries. PMID:24940016

  17. Safety of pertussis vaccination in pregnant women in UK: observational study

    PubMed Central

    King, Bridget; Bryan, Phil

    2014-01-01

    Objective To examine the safety of pertussis vaccination in pregnancy. Design Observational cohort study. Setting The UK Clinical Practice Research Datalink. Participants 20 074 pregnant women with a median age of 30 who received the pertussis vaccine and a matched historical unvaccinated control group. Main outcome measure Adverse events identified from clinical diagnoses during pregnancy, with additional data from the matched child record identified through mother-child linkage. The primary event of interest was stillbirth (intrauterine death after 24 weeks’ gestation). Results There was no evidence of an increased risk of stillbirth in the 14 days immediately after vaccination (incidence rate ratio 0.69, 95% confidence interval 0.23 to 1.62) or later in pregnancy (0.85, 0.44 to 1.61) compared with historical national rates. Compared with a matched historical cohort of unvaccinated pregnant women, there was no evidence that vaccination accelerated the time to delivery (hazard ratio 1.00, 0.97 to 1.02). Furthermore, there was no evidence of an increased risk of stillbirth, maternal or neonatal death, pre-eclampsia or eclampsia, haemorrhage, fetal distress, uterine rupture, placenta or vasa praevia, caesarean delivery, low birth weight, or neonatal renal failure, all serious events that can occur naturally in pregnancy. Conclusion In women given pertussis vaccination in the third trimester, there is no evidence of an increased risk of any of an extensive predefined list of adverse events related to pregnancy. In particular, there was no evidence of an increased risk of stillbirth. Given the recent increases in the rate of pertussis infection and morbidity and mortality in neonates, these early data provide initial evidence for evaluating the safety of the vaccine in pregnancy for health professionals and the public and can help to inform vaccination policy making. PMID:25015137

  18. Extended Preclinical Safety, Efficacy and Stability Testing of a Live-attenuated Chikungunya Vaccine Candidate

    PubMed Central

    Plante, Kenneth S; Rossi, Shannan L.; Bergren, Nicholas A.; Seymour, Robert L.; Weaver, Scott C.

    2015-01-01

    We recently described a new, live-attenuated vaccine candidate for chikungunya (CHIK) fever, CHIKV/IRES. This vaccine was shown to be well attenuated, immunogenic and efficacious in protecting against CHIK virus (CHIKV) challenge of mice and nonhuman primates. To further evaluate its preclinical safety, we compared CHIKV/IRES distribution and viral loads in interferon-α/β receptor-incompetent A129 mice to another CHIK vaccine candidate, 181/clone25, which proved highly immunogenic but mildly reactive in human Phase I/II clinical trials. Compared to wild-type CHIK virus, (wt-CHIKV), both vaccines generated lower viral loads in a wide variety of tissues and organs, including the brain and leg muscle, but CHIKV/IRES exhibited marked restrictions in dissemination and viral loads compared to 181/clone25, and was never found outside the blood, spleen and muscle. Unlike wt-CHIKV, which caused disrupted splenic architecture and hepatic lesions, histopathological lesions were not observed in animals infected with either vaccine strain. To examine the stability of attenuation, both vaccines were passaged 5 times intracranially in infant A129 mice, then assessed for changes in virulence by comparing parental and passaged viruses for footpad swelling, weight stability and survival after subcutaneous infection. Whereas strain 181/clone25 p5 underwent a significant increase in virulence as measured by weight loss (from <10% to >30%) and mortality (from 0 to 100%), CHIKV/IRES underwent no detectible change in any measure of virulence (no significant weight loss and no mortality). These data indicate greater nonclinical safety of the CHIKV/IRES vaccine candidate compared to 181/clone25, further supporting its eligibility for human testing. PMID:26340754

  19. Assessing safety and immunogenicity of post-exposure prophylaxis following interchangeability of rabies vaccines in humans

    PubMed Central

    Ravish, Hardanahalli S; Sudarshan, Mysore K; Madhusudana, Shampur N; Annadani, Rachana R; Narayana, Doddabele H Ashwath; Belludi, Ashwin Y; Anandaiah, Gangaboraiah; Vijayashankar, Veena

    2014-01-01

    Rabies post exposure prophylaxis with cell culture vaccines by either intramuscular route or intradermal route spans over a period of one month. World Health Organization recommends completing post exposure prophylaxis against rabies with the same cell culture or embryonated egg rabies vaccine and with same route of administration and any deviation from this shall be an exception. In the present study, the safety and immunogenicity of rabies post-exposure prophylaxis was studied prospectively in 90 animal bite cases that had interchangeability of rabies vaccines either by route of administration or brand/type and such changes had occurred due to logistical/financial problems. Among them, 47 had change in route of administration from intramuscular to intradermal or vice versa and 43 had change in the brand/type of cell culture rabies vaccine. All of them had category III rabies exposure and received equine rabies immunoglobulin along with the rabies vaccine. None of the study subjects had any adverse reactions. The rabies virus neutralizing antibody titers was assessed by rapid fluorescent focus inhibition test and all the vaccinees had titers ≥0.5 IU per mL on day 14 which is considered as adequate for protection against rabies. Thus, the present study showed that, rabies post-exposure prophylaxis was safe and immunogenic despite changes in the route of administration and brand/type of rabies vaccine. PMID:24584134

  20. The efficacy and safety of the quadrivalent human papillomavirus 6/11/16/18 vaccine gardasil.

    PubMed

    Haupt, Richard M; Sings, Heather L

    2011-11-01

    Human papillomavirus (HPV) infection causes cervical cancer, a significant portion of anal, genital, and oropharyngeal cancers, genital warts, and recurrent respiratory papillomatosis. In June 2006, a quadrivalent HPV-6/11/16/18 vaccine (Gardasil/Silgard) was licensed in the United States, and subsequently in the European Union (September 2006). It has since been approved in 121 countries, with >74 million doses distributed globally as of March 2011. As the incidence of HPV infection peaks 5-10 years after the onset of sexual activity, preadolescents and adolescents represent an appropriate target group to implement HPV vaccination programs so as to achieve the maximal public health benefit. In this article, we provide an overview of the prophylactic efficacy of the vaccine in young women who were found to be negative to at least one of the four vaccine HPV types, thus approximating sexually naive adolescents. Because adolescents are also at high risk for other infections which are preventable by currently available vaccines, the development of concurrent immunization strategies may lead to better compliance, thereby contributing to the overall goal of protection against preventable diseases. We also summarize concomitant administration studies with meningococcal, diphtheria, tetanus, and pertussis vaccines, which were conducted in adolescents aged 9-15 years. Prophylactic efficacy in other populations (males aged 16-26 years) is also summarized along with long-term safety and efficacy studies. PMID:22018560

  1. Assessing safety and immunogenicity of post-exposure prophylaxis following interchangeability of rabies vaccines in humans.

    PubMed

    Ravish, Hardanahalli S; Sudarshan, Mysore K; Madhusudana, Shampur N; Annadani, Rachana R; Narayana, Doddabele H Ashwath; Belludi, Ashwin Y; Anandaiah, Gangaboraiah; Vijayashankar, Veena

    2014-01-01

    Rabies post exposure prophylaxis with cell culture vaccines by either intramuscular route or intradermal route spans over a period of one month. World Health Organization recommends completing post exposure prophylaxis against rabies with the same cell culture or embryonated egg rabies vaccine and with same route of administration and any deviation from this shall be an exception. In the present study, the safety and immunogenicity of rabies post-exposure prophylaxis was studied prospectively in 90 animal bite cases that had interchangeability of rabies vaccines either by route of administration or brand/type and such changes had occurred due to logistical/financial problems. Among them, 47 had change in route of administration from intramuscular to intradermal or vice versa and 43 had change in the brand/type of cell culture rabies vaccine. All of them had category III rabies exposure and received equine rabies immunoglobulin along with the rabies vaccine. None of the study subjects had any adverse reactions. The rabies virus neutralizing antibody titers was assessed by rapid fluorescent focus inhibition test and all the vaccinees had titers ≥0.5 IU per mL on day 14 which is considered as adequate for protection against rabies. Thus, the present study showed that, rabies post-exposure prophylaxis was safe and immunogenic despite changes in the route of administration and brand/type of rabies vaccine. PMID:24584134

  2. Safety and Efficacy Data on Vaccines and Immunization to Human Papillomavirus

    PubMed Central

    Kash, Natalie; Lee, Michael A.; Kollipara, Ramya; Downing, Christopher; Guidry, Jacqueline; Tyring, Stephen K.

    2015-01-01

    Since the discovery of the causal association between human papillomavirus (HPV) and cervical cancer, efforts to develop an effective prophylactic vaccine to prevent high-risk HPV infections have been at the forefront of modern medical research. HPV causes 530,000 cervical cancer cases worldwide, which is the second most common cause of cancer deaths in women; a worldwide collaboration among epidemiologists, molecular biologists, vaccinologists, virologists, and clinicians helped lead to the development of two highly effective prophylactive HPV vaccines. The first, Gardasil, is a quadrivalent vaccine made up of recombinant HPV L1 capsid proteins from the two high-risk HPV types (16/18) responsible for 70% of cervical cancer cases as well as two low-risk HPV types (6/11) which are the causative agent for genital warts. The second, Cervarix, is a bivalent vaccine that was FDA approved three years after Gardasil and is also composed of L1 capsid proteins from HPV types 16/18. This review article focuses on the safety and efficacy data of both FDA-approved vaccines, as well as highlighting a few advances in future HPV vaccines that show promise in becoming additional treatment options for this worldwide disease. PMID:26239350

  3. Safety of classical swine fever virus vaccine strain LOM in pregnant sows and their offspring.

    PubMed

    Lim, Seong-In; Song, Jae-Young; Kim, Jaejo; Hyun, Bang-Hun; Kim, Ha-Young; Cho, In-Soo; Kim, Byounghan; Woo, Gye-Hyeong; Lee, Jung-Bok; An, Dong-Jun

    2016-04-12

    The present study aimed to evaluate the safety of the classical swine fever virus (CSFV) vaccine strain LOM in pregnant sows. Pregnant sows with free CSFV antibody were inoculated with a commercial LOM vaccine during early pregnancy (day 38; n=3) or mid-pregnancy (days 49-59; n=11). In pregnant sows vaccinated during the early stages of gestation, abortion (day 109) was observed in one case, with two stillbirths and seven mummified fetuses. The viability of live-born piglets was 34.9% in sows vaccinated during mid-pregnancy compared with 81.8% in the control group. Post-mortem examination of the organs of the sows and piglets did not reveal any pathological lesions caused by CSFV; however, CSFV RNA was detected in the organs of several vaccinated sows and their litters. The LOM strain was transmitted from sows with free CSFV antibody to their fetus, but did not appear to induce immune tolerance in the offspring from vaccinated pregnant sows. Side effects were not observed in pregnant sows with antibody to the LOM strain: transmission from sow to their litters and stillbirth or mummified fetuses. The LOM strain may induce sterile immunity and provide rapid, long-lasting, and complete protection against CSFV; however, it should be contraindicated in pregnant sows due to potential adverse effects in pregnant sows with free CSFV antibody. PMID:26947495

  4. Safety, tolerability, and immunologic noninferiority of a 13-valent pneumococcal conjugate vaccine compared to a 7-valent pneumococcal conjugate vaccine given with routine pediatric vaccinations in Germany.

    PubMed

    Kieninger, Dorothee M; Kueper, Kathrin; Steul, Katrin; Juergens, Christine; Ahlers, Norbert; Baker, Sherryl; Jansen, Kathrin U; Devlin, Carmel; Gruber, William C; Emini, Emilio A; Scott, Daniel A

    2010-06-01

    13-valent pneumococcal conjugate vaccine (PCV13) was compared to PCV7 in infants administered 4 doses. For the 7 common serotypes, PCV13- and PCV7-elicited responses showed comparable percent responders achieving 0.35mug/mL IgG threshold (exception 6B, 77.5% versus 87.1%, respectively) and OPA titers of 1:8; IgGs were lower than PCV7 but functional responses were generally comparable. For the 6 additional serotypes, PCV13-elicited IgG and functional OPA responses were notably greater than PCV7. The toddler dose boosted immune responses. Vaccines were comparable with regard to safety. PCV13 should be as effective as PCV7 in preventing pneumococcal disease caused by the common serotypes and may provide protection against the additional serotypes. PMID:20417262

  5. Vaccine Adverse Events

    MedlinePlus

    ... Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Vaccines, Blood & Biologics Home Vaccines, Blood & Biologics Safety & Availability ( ... Center for Biologics Evaluation & Research Vaccine Adverse Events Vaccine Adverse Events Share Tweet Linkedin Pin it More ...

  6. A first-in-human phase 1 trial to evaluate the safety and immunogenicity of the candidate tuberculosis vaccine MVA85A-IMX313, administered to BCG-vaccinated adults

    PubMed Central

    Minhinnick, Alice; Satti, Iman; Harris, Stephanie; Wilkie, Morven; Sheehan, Sharon; Stockdale, Lisa; Thomas, Zita-Rose Manjaly; Lopez-Ramon, Raquel; Poulton, Ian; Lawrie, Alison; Vermaak, Samantha; Le Vert, Alexandre; Del Campo, Judith; Hill, Fergal; Moss, Paul; McShane, Helen

    2016-01-01

    Introduction There is an urgent need for a new and effective tuberculosis vaccine because BCG does not sufficiently prevent pulmonary disease. IMX313 is a novel carrier protein designed to improve cellular and humoral immunity. MVA85A-IMX313 is a novel vaccine candidate designed to boost immunity primed by bacillus Calmette-Guérin (BCG) that has been immunogenic in pre-clinical studies. This is the first evaluation of IMX313 delivered as MVA85A-IMX313 in humans. Methods In this phase 1, open-label first-in-human trial, 30 healthy previously BCG-vaccinated adults were enrolled into three treatment groups and vaccinated with low dose MVA85A-IMX313 (group A), standard dose MVA85A-IMX313 (group B), or MVA85A (group C). Volunteers were followed up for 6 months for safety and immunogenicity assessment. Results The majority of adverse events were mild and there were no vaccine-related serious AEs. Both MVA85A-IMX313 and MVA85A induced a significant increase in IFN-γ ELISpot responses. There were no significant differences between the Ag85A ELISpot and intracellular cytokine responses between the two study groups B (MVA85A-IMX313) and C (MVA85A) at any time point post-vaccination. Conclusion MVA85A-IMX313 was well tolerated and immunogenic. There was no significant difference in the number of vaccine-related, local or systemic adverse reactions between MVA85A and MVA85A-IMX313 groups. The mycobacteria-specific cellular immune responses induced by MVA85A-IMX313 were not significantly different to those detected in the MVA85A group. In light of this encouraging safety data, further work to improve the potency of molecular adjuvants like IMX313 is merited. This trial was registered on clinicatrials.gov ref. NCT01879163. PMID:26854906

  7. Long-term safety assessment of live attenuated tetravalent dengue vaccines: deliberations from a WHO technical consultation.

    PubMed

    Bentsi-Enchill, Adwoa D; Schmitz, Julia; Edelman, Robert; Durbin, Anna; Roehrig, John T; Smith, Peter G; Hombach, Joachim; Farrar, Jeremy

    2013-05-28

    Dengue is a rapidly growing public health threat with approximately 2.5 billion people estimated to be at risk. Several vaccine candidates are at various stages of pre-clinical and clinical development. Thus far, live dengue vaccine candidates have been administered to several thousands of volunteers and were well-tolerated, with minimal short-term safety effects reported in Phase I and Phase II clinical trials. Based on the natural history of dengue, a theoretical possibility of an increased risk of severe dengue as a consequence of vaccination has been hypothesized but not yet observed. In October 2011, the World Health Organization (WHO) convened a consultation of experts in dengue, vaccine regulation and vaccine safety to review the current scientific evidence regarding safety concerns associated with live attenuated dengue vaccines and, in particular, to consider methodological approaches for their long-term evaluation. In this paper we summarize the scientific background and methodological considerations relevant to the safety assessment of these vaccines. Careful planning and a coordinated approach to safety assessment are recommended to ensure adequate long-term evaluation of dengue vaccines that will support their introduction and continued use. PMID:23570986

  8. Safety and efficacy of a turkey herpesvirus vector laryngotracheitis vaccine for chickens.

    PubMed

    Esaki, Motoyuki; Noland, Lauren; Eddins, Tim; Godoy, Alecia; Saeki, Sakiko; Saitoh, Shuji; Yasuda, Atsushi; Dorsey, Kristi Moore

    2013-06-01

    Turkey herpesvirus vector laryngotracheitis vaccine (HVT/LT) expressing the glycoprotein B gene of laryngotracheitis virus (LTV) has been developed. In vitro growth kinetics of HVT/LT were similar to those of parental turkey herpesvirus (HVT), FC-126 strain. Genetic and phenotypic stabilities of HVT/LT after in vitro (in cell culture) or in vivo (in chickens) passage were confirmed by various assays, including Southern blot analysis, western blot analysis, and an indirect immunofluorescence assay. Safety of HVT/LT was assessed by an overdose study as well as by a backpassage study in specific-pathogen-free (SPF) chickens. The overdose study indicated that HVT/LT did not cause any adverse effects in chickens. The backpassage study confirmed that HVT/LT does not revert to virulence after five passages in chickens. The vaccine did not transmit laterally from vaccinated chickens to commingled nonvaccinated chickens. Efficacy of HVT/LT was evaluated in SPF layer chickens after vaccination by the subcutaneous route at 1 day of age. The majority of the vaccinated chickens (92%-100%) were protected against challenge with virulent LTV at 7 wk of age. Efficacy of HVT/LT was further evaluated in broiler chickens from a commercial source after in ovo vaccination to embryos at 18 days of incubation. After challenge with virulent LTV at 21 and 35 days of age, 67% and 87% of HVT/LT-vaccinated chickens did not develop LT clinical signs, respectively, while 100% (21 days of age) and 73% (35 days of age) of the challenge control chickens showed clinical signs of LT. These results suggest that HVT/LT is a safe and efficacious vaccine for control of laryngotracheitis (LT). PMID:24689173

  9. Dose site reactions and related findings after vaccine administration in safety studies.

    PubMed

    Baldrick, Paul

    2016-08-01

    Potential new human vaccines undergo toxicology testing to evaluate local reactogenicity and systemic toxicity. A review of 30 recently published and in-house repeat dose toxicity studies with a variety of vaccines was performed. Species tested were generally rat or rabbit, usually by intramuscular (although occasionally subcutaneous) injection. Results showed no unexpected findings indicating vaccine toxicity, but classic signs of enhanced acute and/or chronic inflammation at the dose site compared with that seen in injected control animals, often accompanied by changes in draining lymph nodes and the spleen (lymphoid hyperplasia and/or increased weight). Other associated signs of a response to vaccine dosing were altered clinical pathology parameters (commonly raised blood neutrophil count and altered globulin level). No obvious difference in dose site or systemic reaction was seen across vaccine, species or the dose route used. A non-dose recovery period of 2 to 4 weeks was sufficient to show evidence of reversibility of dose site effects. Injection site, lymphoid tissue and clinical pathological changes can be interpreted as related to an expected reaction after vaccine dosing, with generation of an immune response largely as a result of the presence of adjuvant, although direct vaccine antigen involvement was also occasionally demonstrated by the presence of a slightly increased inflammatory response seen over adjuvant treatment only. Overall, the need for toxicity testing of vaccines is in line with current regulatory guideline requirements and has proven to be a valuable part of the safety evaluation process prior to human use. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26968331

  10. Immunogenicity and safety of tetravalent dengue vaccine in 2-11 year-olds previously vaccinated against yellow fever: randomized, controlled, phase II study in Piura, Peru.

    PubMed

    Lanata, Claudio F; Andrade, Teresa; Gil, Ana I; Terrones, Cynthia; Valladolid, Omar; Zambrano, Betzana; Saville, Melanie; Crevat, Denis

    2012-09-01

    In a randomized, placebo-controlled, monocenter, observer blinded study conducted in an area where dengue is endemic, we assessed the safety and immunogenicity of a recombinant, live, attenuated, tetravalent dengue vaccine candidate (CYD-TDV) in 2-11 year-olds with varying levels of pre-existing yellow-fever immunity due to vaccination 1-7 years previously. 199 children received 3 injections of CYD-TDV (months 0, 6 and 12) and 99 received placebo (months 0 and 6) or pneumococcal polysaccharide vaccine (month 12). One month after the third dengue vaccination, serotype specific neutralizing antibody GMTs were in the range of 178-190 (1/dil) (versus 16.7-38.1 in the control group), a 10-20 fold-increase from baseline, and 94% of vaccines were seropositive to all four serotypes (versus 39% in the control group). There were no vaccine-related SAEs. The observed reactogenicity profile was consistent with phase I studies, with severity grade 1-2 injection site pain, headache, malaise and fever most frequently reported and no increase after subsequent vaccinations. Virologically confirmed dengue cases were seen after completion of the 3 doses: 1 in the CYD-TDV group (N=199), and 3 in the control group (N=99). A 3-dose regimen of CYD-TDV had a good safety profile in 2-11 year olds with a history of YF vaccination and elicited robust antibody responses that were balanced against the four serotypes. PMID:22863660

  11. Comparison of safety and immunogenicity of a Vi polysaccharide typhoid vaccine with a whole-cell killed vaccine in Malaysian Air Force recruits.

    PubMed Central

    Panchanathan, V.; Kumar, S.; Yeap, W.; Devi, S.; Ismail, R.; Sarijan, S.; Sam, S. M.; Jusoh, Z.; Nordin, S.; Leboulleux, D.; Pang, T.

    2001-01-01

    OBJECTIVE: To carry out a comparative study of the safety and immunogenicity of Vi polysaccharide vaccine against whole-cell killed (WCK) typhoid vaccine. METHODS: The study was carried out on young adult recruits (aged 18-25 years) of the Malaysian Air Force. A total of 125 subjects received the Vi polysaccharide vaccine and 114 received the WCK vaccine. FINDINGS: The Vi vaccine was significantly less reactogenic than the WCK vaccine with regard to systemic and local reactions. Following administration of the Vi vaccine, seroconversion rates (defined as the percentage of subjects with a 4-fold rise of baseline antibody level) of 75.5% and 67% were observed at 2 weeks and 6 weeks, respectively, after immunization, compared with 25% and 31.3% among recipients of the WCK vaccine. Of the 110 Vi vaccinees with serological data, 21 (19%) had high, seroprotective, pre-immunization levels of anti-Vi antibodies (> or = 1 microgram/ml). The majority of subjects in this group came from a region in Malaysia which is known to have high typhoid endemicity. Interestingly, these antibody levels were boosted considerably following administration of vaccine at a level that was 5-fold higher than in subjects with low pre-immunization levels. In contrast, the seroconversion rates in those receiving the Vi vaccine were higher in subjects with low pre-immunization levels of anti-Vi antibodies (76-84%), compared to those with protective levels of > or = 1 microgram/ml prior to immunization (48-57%). CONCLUSIONS: The study reaffirms the safety and efficacy of the Vi polysaccharide vaccine and identifies a hitherto unrecognized advantage in its use, i.e. it is a potent immunogen that boosted considerably the protective antibody levels among a significant number of immunologically sensitized individuals living in typhoid-endemic regions. PMID:11584728

  12. Immunogenicity and safety of an inactivated quadrivalent influenza vaccine in healthy adults: a phase II, open-label, uncontrolled trial in Japan.

    PubMed

    Tsurudome, Yukari; Kimachi, Kazuhiko; Okada, Yusuke; Matsuura, Kenta; Ooyama, Yusuke; Ibaragi, Kayo; Kino, Yoichiro; Ueda, Kohji

    2015-10-01

    Two antigenically distinct B strain lineages of influenza virus have co-circulated since the mid-1980s; however, inactivated trivalent influenza vaccines contain only one B lineage. The mismatch between the circulating and vaccine lineages has been a worldwide issue. In this study, an inactivated quadrivalent influenza vaccine (QIV) candidate containing two B lineages was manufactured and its immunogenicity and safety evaluated in an open-label, uncontrolled trial. In this phase II trial, 50 subjects aged 20-64 years received two doses of QIV s.c. 1 to 4 weeks apart. Sera were collected pre- and post-vaccination and safety assessed from the first vaccination to 21 ± 7 days after the second vaccination. After the first vaccination, hemagglutination inhibition titers against each strain increased markedly; the seroconversion rate, geometric mean titer ratio and seroprotection rate being 94.0%, 24.93, and 100.0%, respectively, for the A/H1N1pdm09 strain; 94.0%, 12.47, and 98.0%, respectively, for the A/H3N2 strain; 54.0%, 4.99, and 66.0%, respectively, for B/Yamagata strain, and 72.0%, 6.23 and 80.0%, respectively, for the B/Victoria strain, thus fulfilling the criteria of the European Medical Agency's Committee for Medicinal Products for Human Use. Also, the QIV induced sufficient single radial hemolysis and neutralizing antibodies against all four vaccine strains. No noteworthy adverse events were noted. The results of this trial demonstrate that QIV is well tolerated and immunogenic for each strain, suggesting that QIV potentially improves protection against influenza B by resolving the issue of B lineage mismatch. PMID:26272602

  13. An update on safety studies on the attenuated "RIEMSER Schweinepestoralvakzine" for vaccination of wild boar against classical swine fever.

    PubMed

    Kaden, Volker; Lange, Elke; Küster, Heike; Müller, Thomas; Lange, Bodo

    2010-07-14

    The RIEMSER Schweinepestoralvakzine is an attenuated vaccine for oral vaccination of wild boar against classical swine fever (CSF). The safety of this licensed bait vaccine which is based on the CSF virus (CSFV) strain "C" was investigated in eight animal species, e.g. weaner pigs (n=111), wild boar (n=11), ruminants (cattle, goats and sheep, n=11), foxes (n=5), rabbits (n=12), and mice (n=10). Animals were vaccinated either with a single vaccine dose containing at least 10(4.5) TCID(50), or with overdoses, i.e. the 10-fold dose, or they were subjected to repeated application schemes. During the entire observation period none of the animals which were given the vaccine virus showed clinical signs, with the exception of rabbits. These reacted to the vaccination with fever. Orally vaccinated pigs did not transmit vaccine virus to susceptible contact animals (sentinels). In none of the species examined neither vaccine virus nor viral RNA could be detected in blood after vaccination. In one wild boar viral RNA could be established in the tonsil 21 days post-vaccination (dpv); all other organ samples tested virologically negative. Up to 77.5% of the pigs and wild boar developed virus neutralising antibodies (VNA) already 14 dpv. The mean VNA titres observed in the vaccination groups seemed to depend rather on individual factors than on the administered virus dose (virus titre per dose) or the vaccination scheme. These results are comparable with findings obtained during oral vaccination campaigns in wild boar and after parenteral vaccination with this C-strain virus. From the results presented here it can be concluded that RIEMSER Schweinepestoralvakzine is safe for target and non-target species. PMID:20022716

  14. Stories from the Sharp End: Case Studies in Safety Improvement

    PubMed Central

    McCarthy, Douglas; Blumenthal, David

    2006-01-01

    Motivated by pressure and a wish to improve, health care organizations are implementing programs to improve patient safety. This article describes six natural experiments in health care safety that show where the safety field is heading and opportunities for and barriers to improvement. All these programs identified organizational culture change as critical to making patients safer, differing chiefly in their methods of creating a patient safety culture. Their goal is a safety culture that promotes continuing innovation and improvement, transcending whatever particular safety methodology is used. Policymakers could help stimulate a culture of safety by linking regulatory goals to safety culture expectations, sponsoring voluntary learning collaborations, rewarding safety improvements, better using publicly reported data, encouraging consumer involvement, and supporting research and education. PMID:16529572

  15. [Public Health initiative for improved vaccination for asylum seekers].

    PubMed

    Brockmann, Stefan O; Wjst, Stephanie; Zelmer, Ursula; Carollo, Stefanie; Schmid, Mirjam; Roller, Gottfried; Eichner, Martin

    2016-05-01

    The number of asylum seekers in Germany has increased dramatically in 2015. Their medical care includes the officially recommended vaccinations; yet, no detailed information on this is yet available in Germany. In light of the rising number of asylum seekers, we have developed a concept to facilitate their vaccination. This concept includes the coordination of different partners, the supply of vaccines and other materials through the local health office, and the cooperation with the local physicians' association. To evaluate and accelerate progress, we compared the number of vaccinations conducted by physicians independently of the vaccination concept with those conducted within the new concept. For the period of investigation, 2,256 new asylum seekers were temporarily accommodated in the facilities. The vaccination concept was applied in only some of the facilities. Twenty-eight percent of all asylum seekers (642) were vaccinated at least once; 89 % of the vaccinees (571) were vaccinated within the newly developed concept. In the facilities that were not included in this concept, only 6 % of the refugees were vaccinated, whereas in the facilities that were included up to 58 % were vaccinated. Even though the new concept has started successfully, further innovations are required to reach sufficient vaccination coverage among asylum seekers. In view of the large number of new asylum seekers expected, the adjustment and expansion of the new concept requires professional planning and coordination. Furthermore, additional resources are required. PMID:27072499

  16. Vaccines

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    Vaccinations are injections of antigens into the body. Once the antigens enter the blood, they circulate along ... suppressor T cells stop the attack. After a vaccination, the body will have a memory of an ...

  17. Post-Genomics and Vaccine Improvement for Leishmania

    PubMed Central

    Seyed, Negar; Taheri, Tahereh; Rafati, Sima

    2016-01-01

    Leishmaniasis is a parasitic disease that primarily affects Asia, Africa, South America, and the Mediterranean basin. Despite extensive efforts to develop an effective prophylactic vaccine, no promising vaccine is available yet. However, recent advancements in computational vaccinology on the one hand and genome sequencing approaches on the other have generated new hopes in vaccine development. Computational genome mining for new vaccine candidates is known as reverse vaccinology and is believed to further extend the current list of Leishmania vaccine candidates. Reverse vaccinology can also reduce the intrinsic risks associated with live attenuated vaccines. Individual epitopes arranged in tandem as polytopes are also a possible outcome of reverse genome mining. Here, we will briefly compare reverse vaccinology with conventional vaccinology in respect to Leishmania vaccine, and we will discuss how it influences the aforementioned topics. We will also introduce new in vivo models that will bridge the gap between human and laboratory animal models in future studies. PMID:27092123

  18. Immunogenicity and Safety of an Inactivated Trivalent Split Influenza Virus Vaccine in Young Children with Recurrent Wheezing

    PubMed Central

    Bae, E. Young; Choi, Ui Yoon; Kwon, Hyo Jin; Jeong, Dae Chul; Rhim, Jung Woo; Ma, Sang Hyuk; Lee, Kyung Il

    2013-01-01

    Influenza virus vaccination is recommended for children, but so far, active vaccination has not been achieved because most parents lack knowledge of vaccine safety and many doctors are reluctant to administer vaccine due to concerns that steroids might alter immunogenicity. The aim of this study was to compare the immunogenicity and safety of inactivated trivalent split influenza virus vaccine between children with recurrent wheezing and healthy children of the same age group. Sixty-eight healthy children and 62 children with recurrent wheezing took part in this study. Seroconversion rates, seroprotection rates, geometric mean titers (GMTs), and geometric mean titer ratios (GMTRs) were measured by a hemagglutination inhibition assay for the assessment of immunogenicity. Solicited and unsolicited local and systemic adverse events were measured for the assessment of safety. Regarding immunogenicity, the seroconversion and seroprotection rates showed no difference overall between healthy children and children with recurrent wheezing. Also, no difference was observed between steroid-treated and nontreated groups with recurrent wheezing. Generally, the GMTs after vaccination were higher in the one-dose vaccination groups for healthy children and children with recurrent wheezing, but the GMTRs revealed different results according to strain in the two groups. Regarding safety, solicited local and systemic adverse events showed no differences between healthy children and children with recurrent wheezing. This study demonstrates that inactivated split influenza virus vaccine is able to induce protective immune responses in healthy children, as observed in previous studies, as well as in children with recurrent wheezing who require frequent steroid treatment. PMID:23536692

  19. Adenovirus type 35-vectored tuberculosis vaccine has an acceptable safety and tolerability profile in healthy, BCG-vaccinated, QuantiFERON(®)-TB Gold (+) Kenyan adults without evidence of tuberculosis.

    PubMed

    Walsh, Douglas S; Owira, Victorine; Polhemus, Mark; Otieno, Lucas; Andagalu, Ben; Ogutu, Bernhards; Waitumbi, John; Hawkridge, Anthony; Shepherd, Barbara; Pau, Maria Grazia; Sadoff, Jerald; Douoguih, Macaya; McClain, J Bruce

    2016-05-01

    In a Phase 1 trial, we evaluated the safety of AERAS-402, an adenovirus 35-vectored TB vaccine candidate expressing 3 Mycobacterium tuberculosis (Mtb) immunodominant antigens, in subjects with and without latent Mtb infection. HIV-negative, BCG-vaccinated Kenyan adults without evidence of tuberculosis, 10 QuantiFERON(®)-TB Gold In-Tube test (QFT-G)(-) and 10 QFT-G(+), were randomized 4:1 to receive AERAS-402 or placebo as two doses, on Days 0 and 56, with follow up to Day 182. There were no deaths, serious adverse events or withdrawals. For 1 AERAS-402 QFT-G(-) and 1 AERAS-402 QFT-G(+) subject, there were 3 self-limiting severe AEs of injection site pain: 1 after the first vaccination and 1 after each vaccination, respectively. Two additional severe AEs considered vaccine-related were reported after the first vaccination in AERAS-402 QFT-G(+) subjects: elevated blood creatine phosphokinase and neutropenia, the latter slowly improving but remaining abnormal until study end. AERAS-402 was not detected in urine or throat cultures for any subject. In intracellular cytokine staining studies, curtailed by technical issues, we saw modest CD4+ and CD8+ T cell responses to Mtb Ag85A/b peptide pools among both QFT-G(-) and (+) subjects, with trends in the CD4+ T cells suggestive of boosting after the second vaccine dose, slightly more so in QFT-G(+) subjects. CD4+ and CD8+ responses to Mtb antigen TB10.4 were minimal. Increases in Adenovirus 35 neutralizing antibodies from screening to end of study, seen in 50% of AERAS-402 recipients, were mostly minimal. This small study confirms acceptable safety and tolerability profiles for AERAS-402, in line with other Phase 1 studies of AERAS-402, now to include QFT-G(+) subjects. PMID:27026148

  20. Phase III Clinical Trials Comparing the Immunogenicity and Safety of the Vero Cell-Derived Japanese Encephalitis Vaccine Encevac with Those of Mouse Brain-Derived Vaccine by Using the Beijing-1 Strain

    PubMed Central

    Miyazaki, Chiaki; Okada, Kenji; Ozaki, Takao; Hirose, Mizuo; Iribe, Kaneshige; Ishikawa, Yuji; Togashi, Takehiro; Ueda, Kohji

    2014-01-01

    The immunogenicity and safety of an inactivated cell culture Japanese encephalitis vaccine (CC-JEV) were compared with those of an inactivated mouse brain-derived Japanese encephalitis vaccine (MB-JEV) in phase III clinical multicenter trials conducted in children. The vaccines contain the same Japanese encephalitis virus strain, the Beijing-1 strain. Two independent clinical trials (trials 1 and 2) were conducted. Trial 1 was conducted in 468 healthy children. Each subject was injected with 17 μg per dose of either CC-JEV or MB-JEV, and the immunogenicity and safety of the vaccines were investigated. Trial 1 showed that CC-JEV was more immunogenic and reactive than MB-JEV at the same dose. Therefore, to adjust the immunogenicity of CC-JEV to that of MB-JEV, a vaccine that has had a good track record regarding its efficacy for a long time, trial 2 was conducted in 484 healthy children. To improve the stability, CC-JEV was converted from a liquid type to a freeze-dried type of vaccine. Each subject was injected subcutaneously with either 4 μg per dose of CC-JEV, 8 μg per dose of CC-JEV, or 17 μg per dose of MB-JEV twice, at an interval of 2 to 4 weeks, followed by an additional booster immunization 1 to 15 months after the primary immunization. Based on the results of trial 2, 4 μg per dose of the freeze-dried CC-JEV (under the label Encevac) was selected as a substitute for the MB-JEV. Encevac was approved and launched in 2011 and has since been in use as a 2nd-generation Japanese encephalitis vaccine in Japan. (These studies have been registered at the JapicCTI under registration no. JapicCTI-132063 and JapicCTI-080586 for trials 1 and 2, respectively.) PMID:24334689

  1. Ensuring the safety of vaccine cell substrates by massively parallel sequencing of the transcriptome.

    PubMed

    Onions, D; Côté, C; Love, B; Toms, B; Koduri, S; Armstrong, A; Chang, A; Kolman, J

    2011-09-22

    Massively parallel, deep, sequencing of the transcriptome coupled with algorithmic analysis to identify adventitious agents (MP-Seq™) is an important adjunct in ensuring the safety of cells used in vaccine production. Such cells may harbour novel viruses whose sequences are unknown or latent viruses that are only expressed following stress to the cells. MP-Seq is an unbiased and comprehensive method to identify such viruses and other adventitious agents without prior knowledge of the nature of those agents. Here we demonstrate its utility as part of an integrated approach to identify and characterise potential contaminants within commonly used virus and vaccine production cell lines. Through this analysis, in combination with more traditional approaches, we have excluded the presence of porcine circoviruses in the ATCC Vero cell bank (CCL-81), however, we found that a full length betaretrovirus related to SRV can be expressed in these cells, a factor that may be of importance in the production of certain vaccines. Similarly, insect cells are proving to be valuable for the production of virus like particles and sub-unit vaccines, but they can harbour a range of latent viruses. We show that following MP-Seq of the Trichoplusia ni (High Five cell line) transcriptome we were able to detect a contaminating, latent nodavirus and identify an expressed errantivirus genome. Collectively, these studies have reinforced the role of MP-Seq as an integral tool for the identification of contaminating agents in vaccine cell substrates. PMID:21651935

  2. Assessing Interventions To Improve Influenza Vaccine Uptake Among Health Care Workers.

    PubMed

    Rashid, Harunor; Yin, Jiehui Kevin; Ward, Kirsten; King, Catherine; Seale, Holly; Booy, Robert

    2016-02-01

    Despite official recommendations for health care workers to receive the influenza vaccine, uptake remains low. This systematic review of randomized controlled trials was conducted to understand the evidence about interventions to improve influenza vaccine uptake among health care workers. We identified twelve randomized controlled trials that, collectively, assessed six major categories of interventions involving 193,924 health care workers in high-income countries. The categories were educational materials and training sessions, improved access to the vaccine, rewards following vaccination, organized efforts to raise vaccine awareness, reminders to get vaccinated, and the use of lead advocates for vaccination. Only one of the four studies that evaluated the effect of a single intervention in isolation demonstrated a significantly higher vaccine uptake rate in the intervention group, compared to controls. However, five of the eight studies that evaluated a combination of strategies showed significantly higher vaccine uptake. Despite the low quality of the studies identified, the data suggest that combined interventions can moderately increase vaccine uptake among health care workers. Further methodologically appropriate trials of combined interventions tailored to individual health care settings and incorporating less-studied strategies would enhance the evidence about interventions to improve immunization uptake among health care workers. PMID:26858382

  3. Rabies DNA vaccine in the horse: strategies to improve serological responses.

    PubMed

    Fischer, Laurent; Minke, Jules; Dufay, Nathalie; Baudu, Philippe; Audonnet, Jean Christophe

    2003-11-01

    In order for DNA vaccines to become a practical alternative to conventional vaccines their ability to induce antibody responses in large mammals needs to be improved. We used DNA vaccination against rabies in the horse as a model to test the potential of two different strategies to enhance antibody responses in a large mammalian species. The administration of the DNA vaccine in the presence of aluminum phosphate improved both the onset and the intensity of serological responses but was not potent enough to achieve seroconversion in all vaccinated ponies. However, when the DNA vaccine was formulated with the cationic lipid DMRIE-DOPE instead of aluminum phosphate, a very strong impact on both onset and intensity of serological responses was observed. This latter strategy ensured excellent seroconversion in all vaccinated ponies after a primary course of two injections, demonstrating a clear improvement of the homogeneity of the induced responses. These data indicate that rabies DNA vaccination is feasible in horses and further suggests that properly formulated DNA vaccines can generate immune responses in large veterinary species at a level comparable to the responses achieved with conventional vaccines. PMID:14575772

  4. Health innovation for patient safety improvement.

    PubMed

    Sellappans, Renukha; Chua, Siew Siang; Tajuddin, Nur Amani Ahmad; Mei Lai, Pauline Siew

    2013-01-01

    Medication error has been identified as a major factor affecting patient safety. Many innovative efforts such as Computerised Physician Order Entry (CPOE), a Pharmacy Information System, automated dispensing machines and Point of Administration Systems have been carried out with the aim of improving medication safety. However, areas remain that require urgent attention. One main area will be the lack of continuity of care due to the breakdown of communication between multiple healthcare providers. Solutions may include consideration of "health smart cards" that carry vital patient medical information in the form of a "credit card" or use of the Malaysian identification card. However, costs and technical aspects associated with the implementation of this health smart card will be a significant barrier. Security and confidentiality, on the other hand, are expected to be of primary concern to patients. Challenges associated with the implementation of a health smart card might include physician buy-in for use in his or her everyday practice. Training and technical support should also be available to ensure the smooth implementation of this system. Despite these challenges, implementation of a health smart card moves us closer to seamless care in our country, thereby increasing the productivity and quality of healthcare. PMID:23423150

  5. Cardiac Safety of Modified Vaccinia Ankara for Vaccination against Smallpox in a Young, Healthy Study Population

    PubMed Central

    Zitzmann-Roth, Eva-Maria; von Sonnenburg, Frank; de la Motte, Stephan; Arndtz-Wiedemann, Nathaly; von Krempelhuber, Alfred; Uebler, Nadine; Vollmar, Jens; Virgin, Garth; Chaplin, Paul

    2015-01-01

    Background Conventional smallpox vaccines based on replicating vaccinia virus (VV) strains (e.g. Lister Elstree, NYCBOH) are associated with a high incidence of myo-/pericarditis, a severe inflammatory cardiac complication. A new smallpox vaccine candidate based on a non-replicating Modified Vaccinia Ankara (MVA) poxvirus has been assessed for cardiac safety in a large placebo-controlled clinical trial. Methods Cardiac safety of one and two doses of MVA compared to placebo was assessed in 745 healthy subjects. Vaccinia-naïve subjects received either one dose of MVA and one dose of placebo, two doses of MVA, or two doses of placebo by subcutaneous injection four weeks apart; vaccinia-experienced subjects received a single dose of MVA. Solicited and unsolicited adverse events (AE) and cardiac safety parameters (recorded as Adverse Events of Special Interest, AESI) were monitored after each injection. Results A total of 5 possibly related AESI (3 cases of palpitations, 2 of tachycardia) were reported during the study. No case of myo- or pericarditis occurred. One possibly related serious AE (SAE) was reported during the 6-month follow-up period (sarcoidosis). The most frequently observed AEs were injection site reactions. Conclusions Vaccination with MVA was safe and well tolerated and did not increase the risk for development of myo-/pericarditis. Trial Registration ClinicalTrials.gov NCT00316524 PMID:25879867

  6. Safety and effectiveness of the new inactivated hepatitis A virus vaccine.

    PubMed Central

    Furesz, J; Scheifele, D W; Palkonyay, L

    1995-01-01

    PURPOSE: To examine the evidence concerning the safety and effectiveness of the inactivated hepatitis A virus vaccine recently licensed for use in Canada. DATA SOURCES: The main source of information were papers presented at the International Symposium on Active Immunization against Hepatitis A, held in Vienna, Austria, Jan. 27-29, 1992. The bibliographies of these papers were searched for additional references. Recent articles describing the new vaccine and the epidemiologic aspects of infection with hepatitis A virus (HAV) were also reviewed. STUDY SELECTION: Peer-reviewed reports of trials approved by a government regulatory agency on the safety, immunogenic properties and efficacy of the vaccine. DATA EXTRACTION: The authors assembled key reports on adverse reactions, protection from disease and serologic assessment of immune response in vaccine recipients; data from these reports were tabulated and analysed. RESULTS OF DATA SYNTHESIS: The new vaccine contains the HM175 strain of HAV, which is adapted to grow in tissue culture. The virus is purified, inactivated with the use of formaldehyde and adsorbed onto aluminum hydroxide. The recommended dose for adults is 720 enzyme-linked immunosorbent assay (ELISA) units in a 1.0-mL dose and for children 360 ELISA units in a 0.5-mL dose, injected intramuscularly. The usual schedule is three serial doses, the second given 1 month and the third 6 to 12 months after the initial dose. Reported side effects are infrequent and minor. In healthy persons who have received two doses, the seroconversion rate is almost 100%. Protective efficacy after two doses is estimated to be 94%. However, the persistence of protective antibodies has been studied only over the short term (3 years). CONCLUSIONS: The new HAV vaccine is safe, effective and best suited to pre-exposure prophylaxis in people with an increased risk of infection for an extended period, such as travellers to areas where the disease is endemic. Further studies are

  7. Improvement of trivalent leptospira vaccine by removal of anaphylactic agents.

    PubMed

    Moazenijula, Gholamreza; Jabbari, A R; Geravand, M Moradi; Banihashemi, R; Hajizadeh, A

    2011-12-01

    The anaphylactic reactions in cattle following leptospira vaccination mostly booster dose in different parts of Iran have been reported. The serum proteins as allergic substances are components of liquid phase of the vaccine. Therefore, the vaccine was modified by washing the whole cultures by centrifugations. The modified vaccine was safe in laboratory animals and cattle as well as under field conditions. Microagglutination test revealed a similar pattern of antibody response to the three Leptospira interrogans serovars (Canicola, Grippotyphosa, and Sejro hardjo) in all vaccinated cattle groups while was higher than the response of control animals. The results of the present investigation revealed that we can minimize postvaccination shock in vaccinated cattle populations with removing the shock proteins. PMID:21698521

  8. The Role of Attitudes about Vaccine Safety, Efficacy, and Value in Explaining Parents' Reported Vaccination Behavior

    ERIC Educational Resources Information Center

    LaVail, Katherine Hart; Kennedy, Allison Michelle

    2013-01-01

    Objectives: To explain vaccine confidence as it related to parents' decisions to vaccinate their children with recommended vaccines, and to develop a confidence measure to efficiently and effectively predict parents' self-reported vaccine behaviors. Method: A sample of parents with at least one child younger than 6 years ("n" =…

  9. Evaluation of safety of A/H1N1 pandemic vaccination during pregnancy: cohort study

    PubMed Central

    Trotta, Francesco; Da Cas, Roberto; Spila Alegiani, Stefania; Gramegna, Maria; Venegoni, Mauro; Zocchetti, Carlo

    2014-01-01

    Objective To assess the risk of maternal, fetal, and neonatal outcomes associated with the administration of an MF59 adjuvanted A/H1N1 vaccine during pregnancy. Design Historical cohort study. Setting Singleton pregnancies of the resident population of the Lombardy region of Italy. Participants All deliveries between 1 October 2009 and 30 September 2010. Data on exposure to A/H1N1 pandemic vaccine, pregnancy, and birth outcomes were retrieved from regional databases. Vaccinated and non-vaccinated women were compared in a propensity score matched analysis to estimate risks of adverse outcomes. Main outcome measures Main maternal outcomes included type of delivery, admission to intensive care unit, eclampsia, and gestational diabetes; fetal and neonatal outcomes included perinatal deaths, small for gestational age births, and congenital malformations. Results Among the 86 171 eligible pregnancies, 6246 women were vaccinated (3615 (57.9%) in the third trimester and 2557 (40.9%) in the second trimester). No difference was observed in terms of spontaneous deliveries (adjusted odds ratio 1.02, 95% confidence interval 0.96 to 1.08) or admissions to intensive care units (0.95, 0.47 to 1.88), whereas a limited increase in the prevalence of gestational diabetes (1.26, 1.04 to 1.53) and eclampsia (1.19, 1.04 to 1.39) was seen in vaccinated women. Rates of fetal and neonatal outcomes were similar in vaccinated and non-vaccinated women. A slight increase in congenital malformations, although not statistically significant, was present in the exposed cohort (1.14, 0.99 to 1.31). Conclusions Our findings add relevant information about the safety of the MF59 adjuvanted A/H1N1 vaccine in pregnancy. Residual confounding may partly explain the increased risk of some maternal outcomes. Meta-analysis of published studies should be conducted to further clarify the risk of infrequent outcomes, such as specific congenital malformations. PMID:24874845

  10. TLR3 and TLR9 Agonists Improve Postexposure Vaccination Efficacy of Live Smallpox Vaccines

    PubMed Central

    Israely, Tomer; Erez, Noam; Politi, Boaz; Waner, Trevor; Lustig, Shlomo; Paran, Nir

    2014-01-01

    Eradication of smallpox and discontinuation of the vaccination campaign resulted in an increase in the percentage of unvaccinated individuals, highlighting the need for postexposure efficient countermeasures in case of accidental or deliberate viral release. Intranasal infection of mice with ectromelia virus (ECTV), a model for human smallpox, is curable by vaccination with a high vaccine dose given up to 3 days postexposure. To further extend this protective window and to reduce morbidity, mice were vaccinated postexposure with Vaccinia-Lister, the conventional smallpox vaccine or Modified Vaccinia Ankara, a highly attenuated vaccine in conjunction with TLR3 or TLR9 agonists. We show that co-administration of the TLR3 agonist poly(I:C) even 5 days postexposure conferred protection, avoiding the need to increase the vaccination dose. Efficacious treatments prevented death, ameliorated disease symptoms, reduced viral load and maintained tissue integrity of target organs. Protection was associated with significant elevation of serum IFNα and anti-vaccinia IgM antibodies, modulation of IFNγ response, and balanced activation of NK and T cells. TLR9 agonists (CpG ODNs) were less protective than the TLR3 agonist poly(I:C). We show that activation of type 1 IFN by poly(I:C) and protection is achievable even without co-vaccination, requiring sufficient amount of the viral antigens of the infective agent or the vaccine. This study demonstrated the therapeutic potential of postexposure immune modulation by TLR activation, allowing to alleviate the disease symptoms and to further extend the protective window of postexposure vaccination. PMID:25350003

  11. Improved immunogenicity of biodegradable polymer particles entrapped rotavirus vaccine.

    PubMed

    Nayak, Bismita; Ray, Alok R; Panda, Amulya K; Ray, Pratima

    2011-01-01

    Rotavirus (RV) entrapped in polylactide (PLA) and polylactide-coglycolide (PLGA) polymer particles were formulated and evaluated in mice for improved immunogenicity using oral, intranasal (IN), and intramuscular (IM) routes of administration. Microparticles of size ranges between 1 and 8 µm were prepared using double emulsion solvent evaporation technique. Stabilizers like mouse serum albumin, sucrose, and sodium bicarbonate that were used during particle formulation helped in minimizing the denaturation of the entrapped antigen. Immunization with 20 µg of antigen entrapped in polymeric particles through various routes of administration elicited measurable amount of antibody titer in mice. The immunoglobulin A (IgA) and immunoglobulin G (IgG) titer (≥4-fold rise between pre and post immunized sera) was analyzed by the use of enzyme-linked immunosorbent assay. PLGA encapsulated RV microparticles elicited better antibody response through IN route (90%) where as PLA encapsulated RV microparticles showed improved response when administrated through oral route (83.3%). Overall, the performance of IN route based immunization was significantly higher than oral and IM route ( p<0.001) with both the polymers. The results are of indication that, PLGA encapsulated RV microparticles have greater potential for vaccine formulation to combat rotavirus infection. PMID:20207774

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

    PubMed

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

    2012-04-01

    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

  13. New tuberculosis vaccines.

    PubMed

    Martín Montañés, Carlos; Gicquel, Brigitte

    2011-03-01

    The current tuberculosis (TB) vaccine, bacille Calmette-Guerin (BCG), is a live vaccine used worldwide, as it protects against severe forms of the disease, saving thousands of lives every year, but its efficacy against pulmonary forms of TB, responsible for transmission of the diseases, is variable. For more than 80 years now no new TB vaccines have been successfully developed. Over the last decade the effort of the scientific community has resulted in the design and construction of promising vaccine candidates. The goal is to develop a new generation of vaccines effective against respiratory forms of the disease. We will focus this review on new prophylactic vaccine candidates that aim to prevent TB diseases. Two are the main strategies used to improve the immunity conferred by the current BCG vaccine, by boosting it with new subunit vaccines, and a second strategy is focused on the construction of new more effective live vaccines, capable to replace the current BCG and to be used as prime vaccines. After rigorous preclinical studies in different animal models new TB vaccine candidates enter in clinical trials in humans. First, a small Phase I for safety followed by immunological evaluation in Phase II trials and finally evaluated in large population Phase III efficacy trials in endemic countries. At present BCG prime and boost with different subunit vaccine candidates are the more advanced assessed in Phase II. Two prime vaccines (based on recombinant BCG) have been successfully evaluated for safety in Phase I trials. A short number of live attenuated vaccines are in advance preclinical studies and the candidates ready to enter Phase I safety trials are produced under current good manufacturing practices. PMID:21420568

  14. Utilizing health information technology to improve vaccine communication and coverage

    PubMed Central

    Stockwell, Melissa S; Fiks, Alexander G

    2013-01-01

    Vaccination coverage is still below the Healthy People 2010 and 2020 goals. Technology use in the US is widespread by patients and providers including text message, email, internet, social media and electronic health records. Health information technology (IT) interventions can facilitate the rapid or real-time identification of children in need of vaccination and provide the foundation for vaccine-oriented parental communication or clinical alerts in a flexible and tailored manner. There has been a small but burgeoning field of work integrating IT into vaccination interventions including reminder/recall using non-traditional methods, clinical decision support for providers in the electronic health record, use of technology to affect work-flow and the use of social media. The aim of this review is to introduce and present current data regarding the effectiveness of a range of technology tools to promote vaccination, describe gaps in the literature and offer insights into future directions for research and intervention. PMID:23807361

  15. Utilizing health information technology to improve vaccine communication and coverage.

    PubMed

    Stockwell, Melissa S; Fiks, Alexander G

    2013-08-01

    Vaccination coverage is still below the Healthy People 2010 and 2020 goals. Technology use in the US is widespread by patients and providers including text message, email, internet, social media and electronic health records. Health information technology (IT) interventions can facilitate the rapid or real-time identification of children in need of vaccination and provide the foundation for vaccine-oriented parental communication or clinical alerts in a flexible and tailored manner. There has been a small but burgeoning field of work integrating IT into vaccination interventions including reminder/recall using non-traditional methods, clinical decision support for providers in the electronic health record, use of technology to affect work-flow and the use of social media. The aim of this review is to introduce and present current data regarding the effectiveness of a range of technology tools to promote vaccination, describe gaps in the literature and offer insights into future directions for research and intervention. PMID:23807361

  16. [Review of the 2016 Swiss immunization schedule and technology update for improving vaccine management].

    PubMed

    Diana, Alessandro

    2016-05-11

    The 2016 immunization schedule published by the Swiss Federal Office of Public Health includes three new clauses: reimbursement of the additional Human Papillomavirus (HPV) vaccination in young males (11-26 years) as recommended by local canton programs, the end of franchise exemption for the measles, mumps and rubella (MMR) vaccination, and the creation of a new system of indemnities and moral compensation in the event of personal injury resulting from vaccinations. This article presents the main features of the 2016 immunization schedule with details of the technology available to physicians to improve vaccine management. PMID:27352591

  17. Trials of vaccines for pancreatic ductal adenocarcinoma: Is there any hope of an improved prognosis?

    PubMed

    Mizuguchi, Toru; Torigoe, Toshihiko; Satomi, Fukino; Shima, Hiroaki; Kutomi, Goro; Ota, Shigenori; Ishii, Masayuki; Hayashi, Hiroshi; Asakura, Sumiyo; Hirohashi, Yoshihiko; Meguro, Makoto; Kimura, Yasutoshi; Nishidate, Toshihiko; Okita, Kenji; Ishino, Masaho; Miyamoto, Atsushi; Hatakenaka, Masamitsu; Sato, Noriyuki; Hirata, Koichi

    2016-02-01

    Pancreatic tumors are chemoresistant and malignant, and there are very few therapeutic options for pancreatic cancer, as the disease is normally diagnosed at an advanced stage. Although attempts have been made to develop vaccine therapies for pancreatic cancer for a couple of decades, none of the resultant protocols or regimens have succeeded in improving the clinical outcomes of patients. We herein review vaccines tested within the past few years, including peptide, biological and multiple vaccines, and describe the three sets of criteria used to evaluate the therapeutic activity of vaccines in solid tumors. PMID:25649538

  18. A quality improvement initiative to increase pneumococcal vaccination coverage among children after kidney transplant.

    PubMed

    Malone, Kathryn; Clark, Stephanie; Palmer, Jo Ann; Lopez, Sonya; Pradhan, Madhura; Furth, Susan; Kim, Jason; Fisher, Brian; Laskin, Benjamin

    2016-09-01

    Pneumococcal vaccination rates among children receiving a kidney transplant remain suboptimal. Current practice guidelines in the United States recommend giving the PPSV23 after priming with the PCV13. We conducted a QI initiative to increase pneumococcal vaccine rates in our kidney transplant recipients by developing an age-based vaccine algorithm, obtaining vaccine records, and generating reminders for patients and clinicians. A monthly report from the EHR tracked outcomes. The process metric was missed vaccine opportunities, and the overall objective was to improve coverage with both the PCV13 and PPSV23. Over the first six months, we increased the percentage of visits where the vaccine was given from a baseline of 4% to 33%. However, by the end of the 12-month period, the percentage of eligible visits where the vaccine was given decreased to 8.7%. Nevertheless, over the 12-month observation period, we were able to increase the percentage of transplant patients receiving the PCV13 and PPSV23 from 6% to 52%. Utilizing an age-based algorithm and the electronic medical record, vaccine champions can track both missed visit opportunities and the number of vaccinated patients to improve pneumococcal immunization coverage for these high-risk patients. PMID:27334506

  19. Improving vaccination coverage in urban areas through a health communication campaign: the 1990 Philippine experience.

    PubMed Central

    Zimicki, S.; Hornik, R. C.; Verzosa, C. C.; Hernandez, J. R.; de Guzman, E.; Dayrit, M.; Fausto, A.; Lee, M. B.; Abad, M.

    1994-01-01

    From March to September 1990 the Philippine Department of Health, with the assistance of the HEALTHCOM Project, carried out a national mass-media communication campaign to support routine vaccination services. The essential elements of the campaign strategy were as follows: focusing on measles as a way to get mothers to bring their children to the health centre; emphasizing logistic knowledge in the mass-media messages, in particular popularizing a single day of the week as "vaccination day" and giving clear information about the age for measles vaccination; and focusing on urban areas, which had lower vaccination rates than rural areas. Evaluation of the effects of the campaign indicates an increase in vaccination coverage and a substantial increase in the timeliness of vaccination that can be attributed to improvement in carers' knowledge about vaccination. Furthermore, most of the observed increase in knowledge was related to exposure to the mass-media campaign. There was no evidence of any programmatic change that could account for the increase in vaccination or evidence that increased health education efforts at health centres could account for the change in knowledge. These results indicate that when countries meet certain conditions--a high level of access to the media, sufficient expertise and funds available to develop and produce high-quality radio and television advertisements, and a routine system that is able to serve the increased demand--a mass communication campaign can significantly improve vaccination coverage. PMID:8062399

  20. Improving patient safety in radiology: concepts for a comprehensive patient safety program.

    PubMed

    Donnelly, Lane F; Dickerson, Julie M; Goodfriend, Martha A; Muething, Stephen E

    2010-04-01

    A comprehensive safety program can have a positive influence on safety performance and safety culture within a department of radiology. The program should include both vertical interventions aimed at specific areas of potential safety errors as well as horizontal interventions aimed at improving safety culture and decreasing the baseline rate of human error. In our opinion, the key cultural transformations that must occur to improve safety culture include recognition that safety is an issue, emphasis that everyone is accountable for patient safety, and creating a culture where people are expected and encouraged to speak up in the face of uncertainty. The article describes the horizontal interventions to improve patient safety used in our department. PMID:20304316

  1. Postmarketing safety surveillance for typhoid fever vaccines from the Vaccine Adverse Event Reporting System, July 1990 through June 2002.

    PubMed

    Begier, Elizabeth M; Burwen, Dale R; Haber, Penina; Ball, Robert

    2004-03-15

    Vaccines against Salmonella enterica serotype Typhi are used for prophylaxis of international travelers and have potential use as counterbioterrorism agents. The Vaccine Adverse Event Reporting System (VAERS) cannot usually establish causal relationships between vaccines and reported adverse events without further research but has successfully detected unrecognized side effects of vaccine. We reviewed reports to VAERS for US-licensed typhoid fever vaccines for the period of July 1990 through June 2002. We received 321 reports for parenteral Vi capsular polysaccharide vaccine and 345 reports for live, oral, attenuated Ty21a vaccine, with 7.5% and 5.5%, respectively, describing death, hospitalization, permanent disability, or life-threatening illness. Unexpected frequently reported symptoms included dizziness and pruritus for Vi vaccine and fatigue and myalgia for Ty21a vaccine. Gastroenteritis-like illness after receipt of Ty21a vaccine and abdominal pain after receipt of Vi vaccine, which are previously recognized events, occasionally required hospitalization. Nonfatal anaphylaxis was reported after both vaccines. VAERS reports do not indicate any unexpected serious side effects that compromise these vaccines' use for travelers' prophylaxis. PMID:14999618

  2. Safety of influenza vaccination during pregnancy: a review of subsequent maternal obstetric events and findings from two recent cohort studies.

    PubMed

    Naleway, Allison L; Irving, Stephanie A; Henninger, Michelle L; Li, De-Kun; Shifflett, Pat; Ball, Sarah; Williams, Jennifer L; Cragan, Janet; Gee, Julianne; Thompson, Mark G

    2014-05-30

    Pregnant women and their infants are vulnerable to severe disease and secondary complications from influenza infection. For this reason, annual influenza vaccination is recommended for all pregnant women in the United States. Women frequently cite concerns about vaccine safety as a barrier to vaccination. This review describes the safety of inactivated influenza vaccination during pregnancy with a focus on maternal obstetric events, including hypertensive disorders, gestational diabetes, and chorioamnionitis. Included in the review are new findings from two studies which examined the safety of seasonal inactivated influenza vaccination during pregnancy. The first study enrolled 641 pregnant women during the 2010-2011 season and prospectively followed them until delivery or pregnancy termination. The second study enrolled 1616 pregnant women during the 2010-2011 influenza season, and followed the women and their infants for six months after delivery. No associations between inactivated influenza vaccination and gestational diabetes, gestational hypertension, preeclampsia/eclampsia, or chorioamnionitis were observed in either cohort. When considered as a whole, these studies should further reassure women and clinicians that influenza vaccination during pregnancy is safe for mothers. PMID:24742490

  3. Immunogenicity and safety of xenogeneic vascular endothelial growth factor receptor-2 DNA vaccination in mice and dogs.

    PubMed

    Denies, Sofie; Cicchelero, Laetitia; Polis, Ingeborgh; Sanders, Niek N

    2016-03-01

    Vascular endothelial growth factor receptor-2 (VEGFR-2) is an attractive target in oncology due to its crucial role in angiogenesis. In this study a DNA vaccine coding for human VEGFR-2 was evaluated in healthy mice and dogs, administered by intradermal injection and electroporation. In mice, three doses and vaccination schedules were evaluated. Cellular immune responses were measured by intracellular IFN-gamma staining and a cytotoxicity assay and antibodies by ELISA. Safety was assessed by measuring regulatory T cells and myeloid derived suppressor cells and a wound healing assay. The vaccine was subsequently evaluated in dogs, which were vaccinated three times with 100µg. Cellular immune responses were measured by intracellular IFN-gamma staining and antibodies by a flow cytometric assay. In mice, maximal cellular responses were observed after two vaccinations with 5µg. Humoral responses continued to increase with higher dose and number of vaccinations. No abnormalities in the measured safety parameters were observed. The vaccine was also capable of eliciting a cellular and humoral immune response in dogs. No adverse effects were observed, but tolerability of the electroporation was poor. This study will facilitate the evaluation of the vaccine in tumor bearing animals, ranging from rodent models to dogs with spontaneous tumors. PMID:26871296

  4. Assessment of safety and interferon gamma responses of Mycobacterium bovis BCG vaccine in goat kids and milking goats.

    PubMed

    Pérez de Val, Bernat; Vidal, Enric; López-Soria, Sergio; Marco, Alberto; Cervera, Zoraida; Martín, Maite; Mercader, Irene; Singh, Mahavir; Raeber, Alex; Domingo, Mariano

    2016-02-10

    Vaccination of domestic animals has emerged as an alternative long-term strategy for the control of tuberculosis (TB). A trial under field conditions was conducted in a TB-free goat herd to assess the safety of the Mycobacterium bovis BCG vaccine. Eleven kids and 10 milking goats were vaccinated with BCG. Bacterial shedding and interferon gamma (IFN-γ) responses were monitored throughout the study. Comprehensive pathological examination and mycobacterial culture of target tissues were performed. BCG vaccine strain was only isolated from the draining lymph node of the injection site of a kid euthanized at week 8 post-vaccination. The remaining animals were euthanized at week 24. Six out of 20 showed small granulomas at the injection site. BCG shedding was not detected in either faeces or in milk throughout the study. All vaccinated kids showed BCG-induced IFN-γ responses at week 8 post-vaccination. BCG vaccination of goats showed no lack of biological safety for the animals, environment and public health, and local adverse reactions were negligible. PMID:26795364

  5. Immunogenicity and safety of xenogeneic vascular endothelial growth factor receptor-2 DNA vaccination in mice and dogs

    PubMed Central

    Denies, Sofie; Cicchelero, Laetitia; Polis, Ingeborgh; Sanders, Niek N.

    2016-01-01

    Vascular endothelial growth factor receptor-2 (VEGFR-2) is an attractive target in oncology due to its crucial role in angiogenesis. In this study a DNA vaccine coding for human VEGFR-2 was evaluated in healthy mice and dogs, administered by intradermal injection and electroporation. In mice, three doses and vaccination schedules were evaluated. Cellular immune responses were measured by intracellular IFN-gamma staining and a cytotoxicity assay and antibodies by ELISA. Safety was assessed by measuring regulatory T cells and myeloid derived suppressor cells and a wound healing assay. The vaccine was subsequently evaluated in dogs, which were vaccinated three times with 100μg. Cellular immune responses were measured by intracellular IFN-gamma staining and antibodies by a flow cytometric assay. In mice, maximal cellular responses were observed after two vaccinations with 5μg. Humoral responses continued to increase with higher dose and number of vaccinations. No abnormalities in the measured safety parameters were observed. The vaccine was also capable of eliciting a cellular and humoral immune response in dogs. No adverse effects were observed, but tolerability of the electroporation was poor. This study will facilitate the evaluation of the vaccine in tumor bearing animals, ranging from rodent models to dogs with spontaneous tumors. PMID:26871296

  6. Improvement of DNA vaccination by adjuvants and sophisticated delivery devices: vaccine-platforms for the battle against infectious diseases

    PubMed Central

    2015-01-01

    Advantages of DNA vaccination against infectious diseases over more classical immunization methods include the possibilities for rapid manufacture, fast adaptation to newly emerging pathogens and high stability at ambient temperatures. In addition, upon DNA immunization the antigen is produced by the cells of the vaccinated individual, which leads to activation of both cellular and humoral immune responses due to antigen presentation via MHC I and MHC II molecules. However, so far DNA vaccines have shown most efficient immunogenicity mainly in small rodent models, whereas in larger animals including humans there is still the need to improve effectiveness. This is mostly due to inefficient delivery of the DNA plasmid into cells and nuclei. Here, we discuss technologies used to overcome this problem, including physical means such as in vivo electroporation and co-administration of adjuvants. Several of these methods have already entered clinical testing in humans. PMID:25648133

  7. Safety and tolerability of 13-valent pneumococcal conjugate vaccine in healthy Chinese adults, children and infants

    PubMed Central

    Zhu, Fengcai; Hu, Yuemei; Liang, Qi; Young, Mariano; Zhou, Xin; Chen, Zhangjing; Liang, John Z.; Gruber, William C.; Scott, Daniel A.

    2015-01-01

    Objective: Pneumococcal disease is a global problem, including in China. The objective of this study was to provide safety data for single-dose 13-valent pneumococcal conjugate vaccine (PCV13) in Chinese subjects, needed to begin a phase III safety and immunogenicity study in Chinese infants. Methods: Healthy Chinese adults (18−55 years), children (3−5 years), and infants (42–98 days) received a single dose of PCV13 in this open-label safety study. Local reactions and systemic events were collected for 7 days via an electronic diary; adverse events were recorded for 1 month after vaccination. Results: All 72 (24 per group) screened subjects (58.3% males; mean ± standard deviation [SD] age: 43.3 ± 9.1 years [adults], 4.5 ± 0.7 years [children], and 79.6 ± 15.2 days [infants]) were enrolled, received vaccine, and completed the study. The most frequently reported local reactions per group were pain at the injection site (n = 23 adults [95.8%]), tenderness (n = 18 children [75%]), and swelling (n = 6 infants [25%]), none of which were severe. The mean duration of each local reaction was ⩽2.0 days in infants and ⩽2.4 days in children but in adults was 3.3 days for pain at the injection site and 9 days each for redness and swelling. Systemic events in adults were muscle pain (n = 5), fatigue (n = 3), and headache and joint pain (n = 1 each). One child and seven infants had disturbed sleep (increased or decreased). One adult and one child had mild fever (37.7–38.5°C, as per China Food and Drug Administration guidelines). No subject used antipyretic medication. One adverse event (bronchopneumonia in an infant) was reported, which was serious, severe, and unrelated to vaccination. There were no deaths. Conclusions: A single dose of PCV13 was safe and well tolerated in healthy Chinese adults, children, and infants. This study provided the safety data to enable a phase III safety and immunogenicity registration trial in Chinese infants to proceed. PMID

  8. Developing vaccines against pandemic influenza.

    PubMed Central

    Wood, J M

    2001-01-01

    Pandemic influenza presents special problems for vaccine development. There must be a balance between rapid availability of vaccine and the safeguards to ensure safety, quality and efficacy of vaccine. Vaccine was developed for the pandemics of 1957, 1968, 1977 and for the pandemic alert of 1976. This experience is compared with that gained in developing vaccines for a possible H5N1 pandemic in 1997-1998. Our ability to mass produce influenza vaccines against a pandemic threat was well illustrated by the production of over 150 million doses of 'swine flu' vaccine in the USA within a 3 month period in 1976. However, there is cause for concern that the lead time to begin vaccine production is likely to be about 7-8 months. Attempts to reduce this time should receive urgent attention. Immunogenicity of vaccines in pandemic situations is compared over the period 1968-1998. A consistent feature of the vaccine trials is the demonstration that one conventional 15 microg haemagglutinin dose of vaccine is not sufficiently immunogenic in naive individuals. Much larger doses or two lower doses are needed to induce satisfactory immunity. There is some evidence that whole-virus vaccines are more immunogenic than split or subunit vaccines, but this needs substantiating by further studies. H5 vaccines appeared to be particularly poor immunogens and there is evidence that an adjuvant may be needed. Prospects for improving the development of pandemic vaccines are discussed. PMID:11779397

  9. Improving patient safety by examining pathology errors.

    PubMed

    Raab, Stephen S

    2004-12-01

    A considerable void exists in the information available regarding anatomic pathology diagnostic errors and their impact on clinical outcomes. To fill this void and improve patient safety, four institutional pathology departments (University of Pittsburgh, Western Pennsylvania Hospital, University of Iowa Hospitals and Clinics, and Henry Ford Hospital System) have proposed the development of a voluntary, Web-based, multi-institutional database for the collection and analysis of diagnostic errors. These institutions intend to use these data proactively to implement internal changes in pathology practice and to measure the effect of such changes on errors and clinical outcomes. They believe that the successful implementation of this project will result in the study of other types of diagnostic pathology error and the expansion to national participation. The project will involve the collection of multi-institutional anatomic pathology diagnostic errors in a large database that will facilitate a more detailed analysis of these errors, including their effect on patient outcomes. Participating institutions will perform root cause analysis for diagnostic errors and plan and execute appropriate process changes aimed at error reduction. The success of these interventions will be tracked through analysis of postintervention error data collected in the database. Based on their preliminary studies, these institutions proposed the following specific aims: Specific aim #1: To use a Web-based database to collect diagnostic errors detected by cytologic histologic correlation and by second-pathologist review of conference cases. Specific aim #2: To analyze the collected error data quantitatively and generate quality performance reports that are useful for institutional quality improvement programs. Specific aim #3: To plan and implement interventions to reduce errors and improve clinical outcomes, based on information derived from root cause analysis of diagnostic errors. Specific

  10. Improving Safety through Human Factors Engineering.

    PubMed

    Siewert, Bettina; Hochman, Mary G

    2015-10-01

    Human factors engineering (HFE) focuses on the design and analysis of interactive systems that involve people, technical equipment, and work environment. HFE is informed by knowledge of human characteristics. It complements existing patient safety efforts by specifically taking into consideration that, as humans, frontline staff will inevitably make mistakes. Therefore, the systems with which they interact should be designed for the anticipation and mitigation of human errors. The goal of HFE is to optimize the interaction of humans with their work environment and technical equipment to maximize safety and efficiency. Special safeguards include usability testing, standardization of processes, and use of checklists and forcing functions. However, the effectiveness of the safety program and resiliency of the organization depend on timely reporting of all safety events independent of patient harm, including perceived potential risks, bad outcomes that occur even when proper protocols have been followed, and episodes of "improvisation" when formal guidelines are found not to exist. Therefore, an institution must adopt a robust culture of safety, where the focus is shifted from blaming individuals for errors to preventing future errors, and where barriers to speaking up-including barriers introduced by steep authority gradients-are minimized. This requires creation of formal guidelines to address safety concerns, establishment of unified teams with open communication and shared responsibility for patient safety, and education of managers and senior physicians to perceive the reporting of safety concerns as a benefit rather than a threat. PMID:26466179

  11. Community pharmacist–administered influenza immunization improves patient access to vaccination

    PubMed Central

    Folkins, Chris; Li, Wilson; Zervas, John

    2014-01-01

    Objectives: To describe the demographic characteristics and risk factors of patients receiving influenza vaccination in community pharmacies and to understand patient experiences and perceptions surrounding being vaccinated by a pharmacist. Methods: Survey data were collected by research pharmacists at 4 different community pharmacy locations in Toronto throughout a period of 8 weeks during October and November 2013. Participation in the survey was voluntary, and all patients vaccinated by pharmacists were invited to complete a survey following immunization. Results: During the course of the study, 2498 vaccine doses were administered among all study sites, and 1502 surveys were completed. Our data showed a high degree of patient satisfaction, with 92% of patients indicating they were very satisfied with the pharmacist’s injection technique and the services they received. Furthermore, 86% of patients were very comfortable with being vaccinated by a pharmacist, and 99% of patients reported they would recommend that friends and family be vaccinated by a pharmacist. Convenience and accessibility were major determinants of patient satisfaction, as shown by 46% of all written comments specifically addressing these factors. Of the patients surveyed, 25% were not regular annual vaccine recipients, and 47% were classified as being at high risk for influenza complications according to Public Health Agency of Canada criteria. Notably, 28% of total patients and 21% of high-risk patients reported that they would not have been immunized this year if pharmacy-based vaccination were not available. Conclusions: Our findings suggest that pharmacists provide a highly convenient and accessible option for seasonal flu vaccination that is viewed favourably by patients. Administration of the flu vaccine by pharmacists has the potential to positively affect public health by improving vaccination rates among high-risk patients, first-time or occasional vaccine recipients, and patients

  12. ChimeriVax-West Nile Virus Live-Attenuated Vaccine: Preclinical Evaluation of Safety, Immunogenicity, and Efficacy

    PubMed Central

    Arroyo, Juan; Miller, Chuck; Catalan, John; Myers, Gwendolyn A.; Ratterree, Marion S.; Trent, Dennis W.; Monath, Thomas P.

    2004-01-01

    The availability of ChimeriVax vaccine technology for delivery of flavivirus protective antigens at the time West Nile (WN) virus was first detected in North America in 1999 contributed to the rapid development of the vaccine candidate against WN virus described here. ChimeriVax-Japanese encephalitis (JE), the first live- attenuated vaccine developed with this technology has successfully undergone phase I and II clinical trials. The ChimeriVax technology utilizes yellow fever virus (YF) 17D vaccine strain capsid and nonstructural genes to deliver the envelope gene of other flaviviruses as live-attenuated chimeric viruses. Amino acid sequence homology between the envelope protein (E) of JE and WN viruses facilitated targeting attenuating mutation sites to develop the WN vaccine. Here we discuss preclinical studies with the ChimeriVax-WN virus in mice and macaques. ChimeriVax-WN virus vaccine is less neurovirulent than the commercial YF 17D vaccine in mice and nonhuman primates. Attenuation of the virus is determined by the chimeric nature of the construct containing attenuating mutations in the YF 17D virus backbone and three point mutations introduced to alter residues 107, 316, and 440 in the WN virus E protein gene. The safety, immunogenicity, and efficacy of the ChimeriVax-WN02 vaccine in the macaque model indicate the vaccine candidate is expected to be safe and immunogenic for humans. PMID:15507637

  13. Approaches to improve development methods for therapeutic cancer vaccines.

    PubMed

    Ogi, Chizuru; Aruga, Atsushi

    2015-04-01

    Therapeutic cancer vaccines are an immunotherapy that amplify or induce an active immune response against tumors. Notably, limitations in the methodology for existing anti-cancer drugs may subsist while applying them to cancer vaccine therapy. A retrospective analysis was performed using information obtained from ClinicalTrials.gov, PubMed, and published articles. Our research evaluated the optimal methodologies for therapeutic cancer vaccines based on (1) patient populations, (2) immune monitoring, (3) tumor response evaluation, and (4) supplementary therapies. Failure to optimize these methodologies at an early phase may impact development at later stages; thus, we have proposed some points to be considered during the early phase. Moreover, we compared our proposal with the guidance for industry issued by the US Food and Drug Administration in October 2011 entitled "Clinical Considerations for Therapeutic Cancer Vaccines". Consequently, while our research was aligned with the guidance, we hope it provides further insights in order to predict the risks and benefits and facilitate decisions for a new technology. We identified the following points for consideration: (1) include in the selection criteria the immunological stage with a prognostic value, which is as important as the tumor stage; (2) select immunological assays such as phenotype analysis of lymphocytes, based on their features and standardize assay methods; (3) utilize optimal response criteria for immunotherapy in therapeutic cancer vaccine trials; and (4) consider supplementary therapies, including immune checkpoint inhibitors, for future therapeutic cancer vaccines. PMID:25746315

  14. National Childhood Vaccine Improvement Act of 1986. Report To Accompany S.827. Senate, 99th Congress, 2nd Session.

    ERIC Educational Resources Information Center

    Congress of the U.S., Washington, DC. Senate Committee on Labor and Human Resources.

    This report on the proposed National Childhood Vaccine Improvement Act of 1986 describes the background and need for legislation to safeguard the supply of vaccines for childhood diseases, to improve knowledge about adverse reactions, and to assist in the development of safer vaccines. This bill is a substitute amendment for a bill previously…

  15. A UMLS-based spell checker for natural language processing in vaccine safety

    PubMed Central

    Tolentino, Herman D; Matters, Michael D; Walop, Wikke; Law, Barbara; Tong, Wesley; Liu, Fang; Fontelo, Paul; Kohl, Katrin; Payne, Daniel C

    2007-01-01

    Background The Institute of Medicine has identified patient safety as a key goal for health care in the United States. Detecting vaccine adverse events is an important public health activity that contributes to patient safety. Reports about adverse events following immunization (AEFI) from surveillance systems contain free-text components that can be analyzed using natural language processing. To extract Unified Medical Language System (UMLS) concepts from free text and classify AEFI reports based on concepts they contain, we first needed to clean the text by expanding abbreviations and shortcuts and correcting spelling errors. Our objective in this paper was to create a UMLS-based spelling error correction tool as a first step in the natural language processing (NLP) pipeline for AEFI reports. Methods We developed spell checking algorithms using open source tools. We used de-identified AEFI surveillance reports to create free-text data sets for analysis. After expansion of abbreviated clinical terms and shortcuts, we performed spelling correction in four steps: (1) error detection, (2) word list generation, (3) word list disambiguation and (4) error correction. We then measured the performance of the resulting spell checker by comparing it to manual correction. Results We used 12,056 words to train the spell checker and tested its performance on 8,131 words. During testing, sensitivity, specificity, and positive predictive value (PPV) for the spell checker were 74% (95% CI: 74–75), 100% (95% CI: 100–100), and 47% (95% CI: 46%–48%), respectively. Conclusion We created a prototype spell checker that can be used to process AEFI reports. We used the UMLS Specialist Lexicon as the primary source of dictionary terms and the WordNet lexicon as a secondary source. We used the UMLS as a domain-specific source of dictionary terms to compare potentially misspelled words in the corpus. The prototype sensitivity was comparable to currently available tools, but the

  16. Process safety improvement--quality and target zero.

    PubMed

    Van Scyoc, Karl

    2008-11-15

    Process safety practitioners have adopted quality management principles in design of process safety management systems with positive effect, yet achieving safety objectives sometimes remain a distant target. Companies regularly apply tools and methods which have roots in quality and productivity improvement. The "plan, do, check, act" improvement loop, statistical analysis of incidents (non-conformities), and performance trending popularized by Dr. Deming are now commonly used in the context of process safety. Significant advancements in HSE performance are reported after applying methods viewed as fundamental for quality management. In pursuit of continual process safety improvement, the paper examines various quality improvement methods, and explores how methods intended for product quality can be additionally applied to continual improvement of process safety. Methods such as Kaizen, Poke yoke, and TRIZ, while long established for quality improvement, are quite unfamiliar in the process safety arena. These methods are discussed for application in improving both process safety leadership and field work team performance. Practical ways to advance process safety, based on the methods, are given. PMID:18374483

  17. Improving the safety of LWR power plants. Final report

    SciTech Connect

    Not Available

    1980-04-01

    This report documents the results of the Study to identify current, potential research issues and efforts for improving the safety of Light Water Reactor (LWR) power plants. This final report describes the work accomplished, the results obtained, the problem areas, and the recommended solutions. Specifically, for each of the issues identified in this report for improving the safety of LWR power plants, a description is provided in detail of the safety significance, the current status (including information sources, status of technical knowledge, problem solution and current activities), and the suggestions for further research and development. Further, the issues are ranked for action into high, medium, and low priority with respect to primarily (a) improved safety (e.g. potential reduction in public risk and occupational exposure), and secondly (b) reduction in safety-related costs (improving or maintaining level of safety with simpler systems or in a more cost-effective manner).

  18. How Stereochemistry Considerations can Improve Pesticide Safety

    EPA Science Inventory

    About 30% of pesticides are chiral molecules and therefore exist as two or more stereoisomers, which can differ significantly in their toxicity, biodegradation, and persistence. Such differences can impact their relative safety to humans and environmental species. Enantiomers, mi...

  19. Promoting Vaccine Confidence.

    PubMed

    Smith, Michael J

    2015-12-01

    Vaccine hesitancy incorporates a wide range of parental attitudes and behaviors surrounding vaccines. Ironically, the very success of the immunization program has fueled vaccine concerns; because vaccine-preventable diseases are no longer prevalent, attention has shifted to the safety and necessity of vaccines themselves. This article reviews some of the underlying themes of vaccine hesitancy as well as specific vaccine safety concerns. Strategies for discussing vaccines with concerned parents are also discussed. PMID:26337737

  20. A randomized study of the immunogenicity and safety of Japanese Encephalitis Chimeric Virus Vaccine (JE-CV) in comparison with SA14-14-2 Vaccine in children in the Republic of Korea

    PubMed Central

    Kim, Dong Soo; Houillon, Guy; Jang, Gwang Cheon; Cha, Sung-Ho; Choi, Soo-Han; Lee, Jin; Kim, Hwang Min; Kim, Ji Hong; Kang, Jin Han; Kim, Jong-Hyun; Kim, Ki Hwan; Kim, Hee Soo; Bang, Joon; Naimi, Zulaikha; Bosch-Castells, Valérie; Boaz, Mark; Bouckenooghe, Alain

    2014-01-01

    A new live attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) has been developed based on innovative technology to give protection against JE with an improved immunogenicity and safety profile. In this phase 3, observer-blind study, 274 children aged 12−24 months were randomized 1:1 to receive one dose of JE-CV (Group JE-CV) or the SA14–14–2 vaccine currently used to vaccinate against JE in the Republic of Korea (Group SA14–14–2). JE neutralizing antibody titers were assessed using PRNT50 before and 28 days after vaccination. The primary endpoint of non-inferiority of seroconversion rates on D28 was demonstrated in the Per Protocol analysis set as the difference between Group JE-CV and Group SA14–14–2 was 0.9 percentage points (95% confidence interval [CI]: −2.35; 4.68), which was above the required −10%. Seroconversion and seroprotection rates 28 days after administration of a single vaccine dose were 100% in Group JE-CV and 99.1% in Group SA14–14–2; all children except one (Group SA14–14–2) were seroprotected. Geometric mean titers (GMTs) increased in both groups from D0 to D28; GM of titer ratios were slightly higher in Group JE-CV (182 [95% CI: 131; 251]) than Group SA14–14–2 (116 [95% CI: 85.5, 157]). A single dose of JE-CV was well tolerated and no safety concerns were identified. In conclusion, a single dose of JE-CV or SA14–14–2 vaccine elicited a comparable immune response with a good safety profile. Results obtained in healthy Korean children aged 12−24 months vaccinated with JE-CV are consistent with those obtained in previous studies conducted with JE-CV in toddlers. PMID:25483480

  1. Safety and immunogenicity of two freeze-dried Vero cell rabies vaccines for human use in post-exposure prophylaxis.

    PubMed

    Wang, Ling-yun; Sun, Mei-ping; Zhang, Xue-chun; Suo, Luo-dan; Xu, Ruo-hui; Zou, Yan-jie; Zuo, Li-bo; Qi, Hua

    2011-03-24

    To provide basis for human rabies vaccination in China, the safety and immunogenicity of two freeze-dried Vero cell rabies vaccines for human use were assessed. A total of 250 volunteers were enrolled and divided into two groups: volunteers in Group A (n=200) were vaccinated five doses of Speeda Vero cell rabies vaccine manufactured by Liaoning Chengda Biotechnology Co. Ltd. on day 0, 3, 7, 14, 28 after exposure. Volunteers in Group B (n=50) were treated with Verorab Vero cell rabies vaccine manufactured by Sanofi Pasteur on the same schedule. The local and systematic adverse reactions were observed. Serum neutralizing antibody levels of 80 individuals in Group A and 50 individuals in Group B were tested with RFFIT on day 7, 14, 45, 180, 360 after the first dose. The seroconversion rates in Groups A and B were 40.3% and 37.0% on day 7 after the first dose, 95.5% and 97.7% on day 14, 100% and 100% on day 45, 100% and 100% on day 180, 89.1% and 89.5% on day 360 respectively, indicating no significant differences between the two groups. And no significant differences were found between the neutralizing antibody geometric mean titers (GMTs) of the two groups on day 7, 14, 45, 180 and 360 after the first dose, with the GMTs of day 14, 45, 180 and 360 all higher than 0.5IU/ml. Antibody levels of the two groups peaked around 2 weeks after the full vaccination program, followed by a 55% decrease up to day 180 and another 76% decrease up to day 360. Both groups experienced occasions of transient fever, rash, edema, and scleroma after vaccination. Neither group had any severe adverse reactions. It was concluded that both vaccines showed satisfactory safety and immunogenicity. Booster vaccination is recommended following another exposure after six months since the full vaccination program. PMID:21296694

  2. 78 FR 48029 - Improving Chemical Facility Safety and Security

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-07

    .... [FR Doc. 2013-19220 Filed 8-6-13; 8:45 am] Billing code 3295-F3 ... Documents#0;#0; ] Executive Order 13650 of August 1, 2013 Improving Chemical Facility Safety and Security By... departments and agencies (agencies) with regulatory authority to further improve chemical facility safety...

  3. Vaccines

    MedlinePlus Videos and Cool Tools

    ... help the body defend itself against foreign invaders. As the antigens invade the body's tissues, they attract ... the suppressor T cells stop the attack. After a vaccination, the body will have a memory of ...

  4. Evaluation of adjuvant effects of fucoidan for improving vaccine efficacy.

    PubMed

    Kim, Su-Yeon; Joo, Hong-Gu

    2015-01-01

    Fucoidan is a sulfated polysaccharide derived from brown seaweed, including Fucus vesiculosus. This compound is known to have immunostimulatory effects on various types of immune cells including macrophages and dendritic cells. A recent study described the application of fucoidan as a vaccine adjuvant. Vaccination is regarded as the most efficient prophylactic method for preventing harmful or epidemic diseases. To increase vaccine efficacy, effective adjuvants are needed. In the present study, we determined whether fucoidan can function as an adjuvant using vaccine antigens. Flow cytometric analysis revealed that fucoidan increases the expression of the activation markers major histocompatibility complex class II, cluster of differentiation (CD)25, and CD69 in spleen cells. In combination with Bordetella bronchiseptica antigen, fucoidan increased the viability and tumor necrosis factor-α production of spleen cells. Furthermore, fucoidan increased the in vivo production of antigen-specific antibodies in mice inoculated with Mycoplasma hyopneumoniae antigen. Overall, this study has provided valuable information about the use of fucoidan as a vaccine adjuvant. PMID:25549218

  5. Evaluation of adjuvant effects of fucoidan for improving vaccine efficacy

    PubMed Central

    Kim, Su-Yeon

    2015-01-01

    Fucoidan is a sulfated polysaccharide derived from brown seaweed, including Fucus vesiculosus. This compound is known to have immunostimulatory effects on various types of immune cells including macrophages and dendritic cells. A recent study described the application of fucoidan as a vaccine adjuvant. Vaccination is regarded as the most efficient prophylactic method for preventing harmful or epidemic diseases. To increase vaccine efficacy, effective adjuvants are needed. In the present study, we determined whether fucoidan can function as an adjuvant using vaccine antigens. Flow cytometric analysis revealed that fucoidan increases the expression of the activation markers major histocompatibility complex class II, cluster of differentiation (CD)25, and CD69 in spleen cells. In combination with Bordetella bronchiseptica antigen, fucoidan increased the viability and tumor necrosis factor-α production of spleen cells. Furthermore, fucoidan increased the in vivo production of antigen-specific antibodies in mice inoculated with Mycoplasma hyopneumoniae antigen. Overall, this study has provided valuable information about the use of fucoidan as a vaccine adjuvant. PMID:25549218

  6. Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 vaccine and HPV-6/11/16/18 vaccine

    PubMed Central

    Baron, Mira; Levin, Myron J; Chatterjee, Archana; Fox, Bradley; Scholar, Sofia; Rosen, Jeffrey; Chakhtoura, Nahida; Meric, Dorothée; Dessy, Francis J; Datta, Sanjoy K; Descamps, Dominique; Dubin, Gary

    2011-01-01

    In this observer-blind study (NCT00423046), women (N = 1,106), stratified by age (18–26, 27–35, 36–45 y), were randomized (1:1) to receive the HPV-16/18 vaccine (Cervarix®, GlaxoSmithKline Biologicals, Months 0, 1, 6) or the HPV-6/11/16/18 vaccine (Gardasil® Merck and Co., Inc., Months 0, 2, 6). Month 7 results were previously reported; we now report Month 24 results. In the according-to-protocol cohort for immunogenicity (seronegative and DNA-negative at baseline for HPV type analyzed), seropositivity rates of neutralizing antibodies (nAbs) [pseudovirion-based neutralization assay] were, across all age strata, 100% (HPV-16/18 vaccine) and 97.5–100% (HPV-6/11/16/18 vaccine) for HPV-16, and 99.0–100% (HPV-16/18 vaccine) and 72.3–84.4% (HPV-6/11/16/18 vaccine) for HPV-18. Corresponding geometric mean titers (GMTs) were 2.4–5.8-fold higher for HPV-16 and 7.7–9.4-fold higher for HPV-18 with the HPV-16/18 vaccine vs. the HPV-6/11/16/18 vaccine; HPV-16 and HPV-18 GMTs were significantly higher with the HPV-16/18 vaccine than the HPV-6/11/16/18 vaccine (p < 0.0001) in the total vaccinated cohort (received ≥1 vaccine dose, irrespective of baseline sero/DNA-status). Similar results were obtained using enzyme-linked immunosorbent assay (ELISA ). Positivity rates and GMTs of antigen-specific IgG antibodies in cervicovaginal secretions (ELISA) were not significantly different between vaccines. At Month 24, CD4+ T-cell responses for HPV-16 and HPV-18 were higher with the HPV-16/18 vaccine; memory B-cell response was higher for HPV-18 with the HPV-16/18 vaccine and similar between vaccines for HPV-16. Both vaccines were generally well tolerated. Although an immunological correlate of protection has not been defined, differences in the magnitude of immune response between vaccines may represent determinants of duration of protection. PMID:22048173

  7. Sustained efficacy, immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine

    PubMed Central

    Naud, Paulo S; Roteli-Martins, Cecilia M; De Carvalho, Newton S; Teixeira, Julio C; de Borba, Paola C; Sanchez, Nervo; Zahaf, Toufik; Catteau, Gregory; Geeraerts, Brecht; Descamps, Dominique

    2014-01-01

    HPV-023 (NCT00518336; ClinicalTrial.gov) is a long-term follow-up of an initial double-blind, randomized (1:1), placebo-controlled study (HPV-001, NCT00689741) evaluating the efficacy against human papillomavirus (HPV)-16/18 infection and associated cyto-histopathological abnormalities, persistence of immunogenicity, and safety of the HPV-16/18 AS04-adjuvanted vaccine. Among the women, aged 15–25 years, enrolled in HPV-001 and who participated in the follow-up study HPV-007 (NCT00120848), a subset of 437 women from five Brazilian centers participated in this 36-month long-term follow-up (HPV-023) for a total of 113 months (9.4 years). During HPV-023, anti-HPV-16/18 antibodies were measured annually by enzyme-linked immunosorbent assay (ELISA) and pseudovirion-based neutralisation assay (PBNA). Cervical samples were tested for HPV DNA every 6 months, and cyto-pathological examinations were performed annually. During HPV-023, no new HPV-16/18-associated infections and cyto-histopathological abnormalities occurred in the vaccine group. Vaccine efficacy (VE) against HPV-16/18 incident infection was 100% (95%CI: 66.1, 100). Over the 113 months (9.4 years), VE was 95.6% (86.2, 99.1; 3/50 cases in vaccine and placebo groups, respectively) against incident infection, 100% (84·1, 100; 0/21) against 6-month persistent infection (PI); 100% (61·4, 100; 0/10) against 12-month PI; 97·1% (82.5, 99.9; 1/30) against ≥ ASC-US; 95·0% (68.0, 99.9; 1/18) against ≥ LSIL; 100% (45.2, 100; 0/8) against CIN1+; and 100% (–128.1, 100; 0/3) against CIN2+ associated with HPV-16/18. All vaccinees remained seropositive to HPV-16/18, with antibody titers remaining several folds above natural infection levels, as measured by ELISA and PBNA. There were no safety concerns. To date, these data represent the longest follow-up reported for a licensed HPV vaccine. PMID:25424918

  8. Emerging Vaccine Informatics

    PubMed Central

    He, Yongqun; Rappuoli, Rino; De Groot, Anne S.; Chen, Robert T.

    2010-01-01

    Vaccine informatics is an emerging research area that focuses on development and applications of bioinformatics methods that can be used to facilitate every aspect of the preclinical, clinical, and postlicensure vaccine enterprises. Many immunoinformatics algorithms and resources have been developed to predict T- and B-cell immune epitopes for epitope vaccine development and protective immunity analysis. Vaccine protein candidates are predictable in silico from genome sequences using reverse vaccinology. Systematic transcriptomics and proteomics gene expression analyses facilitate rational vaccine design and identification of gene responses that are correlates of protection in vivo. Mathematical simulations have been used to model host-pathogen interactions and improve vaccine production and vaccination protocols. Computational methods have also been used for development of immunization registries or immunization information systems, assessment of vaccine safety and efficacy, and immunization modeling. Computational literature mining and databases effectively process, mine, and store large amounts of vaccine literature and data. Vaccine Ontology (VO) has been initiated to integrate various vaccine data and support automated reasoning. PMID:21772787

  9. Immunogenicity and safety of a trivalent inactivated 2010-2011 influenza vaccine in Taiwan infants aged 6-12 months.

    PubMed

    Hwang, Kao-Pin; Hsu, Yu-Lung; Hsieh, Tsung-Hsueh; Lin, Hsiao-Chuan; Yen, Ting-Yu; Wei, Hsiu-Mei; Lin, Hung-Chih; Chen, An-Chyi; Chow, Julie Chi; Huang, Li-Min

    2014-05-01

    This prospective study aimed to investigate the immune responses and safety of an influenza vaccine in vaccine-naïve infants aged 6-12 months, and was conducted from November 2010 to May 2011. Fifty-nine infants aged 6-12 months received two doses of trivalent inactivated influenza vaccine 4 weeks apart. Hemagglutination inhibition titers were measured 4 weeks after the two doses of study vaccine. Based on the assumption that a hemagglutination inhibition titer of 1:40 or greater against the antigen would be protective in adults, two doses of the study vaccine generated a protective immune response of 63.2% against influenza A(H1N1), 82.5% against influenza A(H3N2) and 38.6% against influenza B viruses in infants aged 6-12 months. The geometric mean fold rises against influenza type A and B viruses also met the European Medicines Agency criteria for flu vaccines. The solicited events within 7 days after vaccination were mild in intensity. No deaths or adverse events such as optic neuritis, cranial neuropathy, and brachial neuropathy or Guillain-Barre syndrome were reported. Two doses of inactivated influenza vaccine were well tolerated and induced a protective immune response against influenza in infants aged 6-12 months. PMID:24625341

  10. A Single Human Papillomavirus Vaccine Dose Improves B Cell Memory in Previously Infected Subjects.

    PubMed

    Scherer, Erin M; Smith, Robin A; Gallego, Daniel F; Carter, Joseph J; Wipf, Gregory C; Hoyos, Manuela; Stern, Michael; Thurston, Tate; Trinklein, Nathan D; Wald, Anna; Galloway, Denise A

    2016-08-01

    Although licensed human papillomavirus (HPV) vaccines are most efficacious in persons never infected with HPV, they also reduce infection and disease in previously infected subjects, indicating natural immunity is not entirely protective against HPV re-infection. The aim of this exploratory study was to examine the B cell memory elicited by HPV infection and evaluate whether vaccination merely boosts antibody (Ab) levels in previously infected subjects or also improves the quality of B cell memory. Toward this end, the memory B cells (Bmem) of five unvaccinated, HPV-seropositive subjects were isolated and characterized, and subject recall responses to a single HPV vaccine dose were analyzed. Vaccination boosted Ab levels 24- to 930-fold (median 77-fold) and Bmem numbers 3- to 27-fold (median 6-fold). In addition, Abs cloned from naturally elicited Bmem were generally non-neutralizing, whereas all those isolated following vaccination were neutralizing. Moreover, Ab and plasmablast responses indicative of memory recall responses were only observed in two subjects. These results suggest HPV vaccination augments both the magnitude and quality of natural immunity and demonstrate that sexually active persons could also benefit from HPV vaccination. This study may have important public policy implications, especially for the older 'catch-up' group within the vaccine's target population. PMID:27423190