Science.gov

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

    ... FAQs about Vaccine Safety Research Publications HDM Reports ISO Scientific Agenda Ensuring Safety History Understanding Side Effects ... Datalink Publications Emergency Preparedness Vaccine Safety Partners About ISO File Formats Help: How do I view different ...

  3. Vaccine safety.

    PubMed

    Jacobson, Robert M

    2003-11-01

    Rates of reported adverse events are remarkably low. VAERS identifies an adverse event rate approximating 11.4 reports per 100,000 vaccine doses. Approximately 15% of these reports represent SAEs, but less than 2% involve death; in most cases, reviews have shown no causal relation between the events and the vaccine. Across the spectrum of vaccines in use (including those directed against influenza and hepatitis B virus), many claims of adverse events regarding vaccines represent typical reactions to vaccinations. These reactions can be thought of as foreign-body reactions and predominate among the inactivated vaccines. In controlled studies, the adverse event rates that occur with vaccination resemble those that occur with placebo injections. Typical reactions associated with live viral and bacterial vaccines, such as MMR and varicella vaccines, may resemble attenuated forms of the disease for which the vaccine is directed. Other claims against vaccines represent chance-coincidence or misunderstood data; further studies of claims have vindicated the overall safety of the vaccines in most cases. Two documented safety concerns with vaccines, however, have demonstrated that vaccines (like other biologics and pharmacologic) can result in harm (eg, rotavirus and OPV vaccines). The denouement with these vaccines indicates the broad postmarketing data collection and evaluation that extends efforts made with prelicensure study to balance the benefits from vaccination with the risk for harm. Overall, measures including prelicensure study and postlicensure surveillance, such as VAERS, the Vaccine Safety Datalink Project, and the Clinical Immunization Safety Assessment Centers, have resulted in an exceptional safety profile for the vaccines in use.

  4. Vaccines and Internet: characteristics of the vaccine safety net web sites and suggested improvements.

    PubMed

    Martínez-Mora, Marta; Alvarez-Pasquín, María José; Rodríguez-Salvanés, Francisco

    2008-12-09

    The Internet contains a large amount of useful information on many subjects, but also information of doubtful quality. To help identify Web sites on vaccine safety that fulfil good practice, the Global Advisory Committee on Vaccine Safety of the World Health Organization (WHO) has published criteria to which sites should adhere and a listing of Web sites that fulfil them. There are no studies describing the common attributes of these sites. To examine the attributes, design characteristics and resources of Web sites belonging to the Vaccine Safety Net (VSN) of the WHO. A cross-sectional, descriptive observational study using an evaluation questionnaire was carried out applied to the VSN web sites listed in March-April 2007. Twenty-six Web sites accredited by the VSN by April 2007 were analysed. With respect to design and quality, all sites contained information about the site manager. Postal and Email addresses were available for 84.6% of the sites. About privacy and personal data processing, 73.1% of sites specified the data protection procedure used and stated that data were not sold or passed third parties. The most-used language was English (76.9%). 96.3% of sites had links to other pro-vaccination sites and 19.2% provided the addresses of vaccination centres. 63.6% of webs were aimed at general public and health care workers but there was no clear separation of documents or different entry routes. With respect to information on vaccine safety, 84.6% of sites had information on adverse effects. In the general information section, 92.3% of sites had a new developments section. Some sites had multiple sources of financing and in 57% of sites, the financing was public. The most-important plus factors found were the transparency of financing, the lack of links to the pharmaceutical industry, the transparency of site management and responsibility and the proven scientific quality and constant updating of contents.

  5. New technology for improved vaccine safety and efficacy.

    PubMed

    Roth, J A; Henderson, L M

    2001-11-01

    Nearly all of the 2000 vaccines presently licensed by the US Department of Agriculture for veterinary use in the United States are conventional vaccines containing either killed or modified live whole bacteria or viruses. Recent advances in molecular biology, immunology, microbiology, and genetics and in understanding microbial pathogenesis have led to the development of a wide variety of new approaches for developing safer and more effective vaccines. This article briefly describes these new technologies and their potential advantages and disadvantages as compared with conventional killed and modified live vaccines.

  6. 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

  7. 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.

  8. [Improving vaccination measures].

    PubMed

    Iannazzo, S

    2014-01-01

    Despite the benefits of routine vaccination of newborns are known and widely documented, in recent years we are observing a gradual increase in the number of parents who express doubts and concerns about the safety of vaccines and the real need to submit their children to vaccinations included in the national recommendations. This attitude is reinforced by the current epidemiological profile, in Western countries, of many vaccine preventable diseases, accompanied by a low risk perception among parents. Institutions and all the actors involved in vaccination programs have a duty to investigate the reasons for the loss of confidence in vaccination among the population in order to identify and implement appropriate and effective interventions. The improvement of vaccination should, theoretically, goes on a double track, placing side by side the provision of effective vaccines, safe and necessary, and interventions designed to increase demand for vaccination among the population, improve access to vaccination services, improve the system as a whole. But to actually improve the vaccinations' offer it is necessary also to provide interventions aimed at regaining the confidence of the population in relation to vaccination and the institutions that promote them. Particular attention should be given to the aspects of communication and risk communication.

  9. Vaccine quality and safety

    PubMed Central

    Patil, Rajan R

    2014-01-01

    Background: There has been major controversy over vaccine safety in India following newspaper reports citing right to information (RTI) disclosure that there have been increasing vaccine related deaths following immunization in children in the recent years. Methods: Secondary data analysis. Results and Conclusion: Adverse effect following immunization (AEFI) events in recent years are being linked to closure of three government owned vaccine producing public sector units (PSU) closures in India. The media reports quoting government sources suggest that the total number of reported deaths due to AEFI in a pre-closure of vaccine PSUs 7 years (2001–2007) was 136, whereas it is 355 in the post vaccine PSU closure 3 years (2008 to 2010). There is an issue of comparability of numbers of AEFI deaths pre- (2001–2007) and post-vaccine PSU closure era (2008–2011) and linking increased AEFI deaths to vaccine PSU closure. PMID:24299731

  10. Improving immunogenicity, efficacy and safety of vaccines through innovation in clinical assay development and trial design: the Phacilitate Vaccine Forum, Washington D.C. 2011.

    PubMed

    Moldovan, Ioana R; Tary-Lehmann, Magdalena

    2011-06-01

    The 9th Annual Vaccine Forum organized by Phacilitate in Washington D.C. 2011 brought together 50+ senior level speakers and over 400 participants representing all the key stakeholders concerning vaccines. The main focus of the meeting was to define priorities in the global vaccines sector from funding to manufacturing and evaluation of vaccine efficacy. A special session was devoted to improving immunogenicity, efficacy and safety of vaccines through innovation in clinical assay development and trial design. The current regulatory approach to clinical assay specification, validation and standardization that enable more direct comparisons of efficacy between trials was illustrated by the success in meningococcal vaccine development. The industry approach to validation strategies was exemplified by a new serologic test used on the diagnostic of pneumococcal pneumonia. The application of the Animal Rule to bridge clinical and non-clinical studies in botulism has allowed significant progress in developing one of the first vaccines to seek approval under the FDA Animal Efficacy Rule. An example of pushing the boundaries in the correlation of immunological responses and efficacy points was represented by a recent cell-based influenza vaccine for which the same correlates of protection apply as for the traditional, egg-based flue vaccine. In the field of HIV phase 2b studies are underway, based on promising results obtained with some vaccine candidates. The conclusion of this session was that creativity in vaccine design and evaluation is beneficial and can lead to innovative new vaccine designs as well as to validated assays to assess vaccine efficacy.

  11. [Acceptance and safety of vaccines].

    PubMed

    Bartz, H; von Knebel-Döberitz, M

    2009-04-01

    As a result of decreasing willingness to be vaccinated some diseases, which seemingly had been eradicated, may reappear. One example for this is the increase of measles cases in the United Kingdom since the 1990s after a decrease of immunization rate in response to a subsequently discredited publication suggesting a link between the triple measles, mumps and rubella vaccine and autism. As the incidence of vaccine preventable diseases decreases, vaccine safety dominates personal risk-benefit analysis. To deal with such concerns this review discusses pre- and post-licensing procedures controlling vaccine safety, taking HPV vaccination as well as vaccination against rotavirus as examples.

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

    PubMed

    Kochhar, Sonali

    2015-01-01

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

  13. 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

  14. Safety of hepatitis B vaccines.

    PubMed

    Zuckerman, Arie J

    2004-05-01

    Although concerns about vaccine safety have increased, true adverse reactions associated with hepatitis B vaccines are few, apart from minor symptoms at the site of injection and occasionally systemic reactions. There is no evidence of an association with hepatitis B vaccination and Sudden Infant Death Syndrome, Multiple Sclerosis and the Chronic Fatigue Syndrome. Hepatitis B vaccines are safe and essential for the prevention of this important and common infection.

  15. 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. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. The Vaccine Safety Datalink project.

    PubMed

    DeStefano, F

    2001-01-01

    The Vaccine Safety Datalink (VSD) is a collaborative project between the National Immunization Program of the Centers for Disease Control and Prevention (CDC) and several large health maintenance organizations (HMOs) in the United States. 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. hospital discharge, outpatient visits, emergency room visits, and deaths), and covariate data (e.g. birth certificates and census) are prospectively collected at multiple HMOs (initially four) and linked under joint protocol for analyses. Approximately 6 million people (2% of the US population) are members of HMOs participating in the VSD. The VSD has proven to be a valuable resource that has provided important information on a number of vaccine safety issues. The databases and infrastructure created for the VSD have also provided opportunities to address other immunization questions including vaccination coverage and cost-effectiveness. In a recent investigation of intussusception following rotavirus vaccination, the VSD methodology was expanded to include 10 managed care organizations. A cohort study was conducted that allowed estimation of incidence rates of intussusception and attributable risks associated with rotavirus vaccine.

  17. 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

  18. 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. Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Ltd.. All rights reserved.

  19. 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. Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  20. 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.

  1. A global perspective on vaccine safety.

    PubMed

    Duclos, Philippe

    2004-05-07

    "Immunization Safety" (i.e., ensuring and monitoring the safety of all aspects of immunization, including vaccine quality, storage and handling, vaccine administration and the disposal of sharps) remains a major challenge. Any vaccine safety issue, real or perceived, may lead to rumors and undermine confidence in vaccination and, ultimately, have dramatic consequences for immunization coverage and disease incidence. In 1999, WHO's Department of Vaccines and Biologicals launched the Immunization Safety Priority Project to establish a comprehensive system to ensure the safety of all immunizations given in national immunization programmes. The project aims at strengthening each country's capacity. The principal areas of activity of the project include: research and development of safer vaccines and safer and simpler vaccine delivery technologies; assurance of vaccine safety through quality control procedures and quality specifications; implementation of tools to ensure vaccine quality up to vaccine administration; access to safe and efficient vaccine administration technologies and their disposal; and identification and management of risks related to immunization. This report focuses on the latter area and highlights challenges and critical factors in establishing a safety profile for a vaccine and the importance and limits of post market surveillance. It presents some of WHO's supporting activities among which the establishment of a Global Advisory Committee on Vaccine Safety to provide an independent scientific assessment of vaccine safety issues. WHO has a role to play not only because of its technical and normative role but also because of its privileged relation with country authorities and its global vision and mandate and being perceived as neutral and free of conflicts of interest.

  2. Vaccine safety controversies and the future of vaccination programs.

    PubMed

    François, Guido; Duclos, Philippe; Margolis, Harold; Lavanchy, Daniel; Siegrist, Claire-Anne; Meheus, André; Lambert, Paul-Henri; Emiroğlu, Nedret; Badur, Selim; Van Damme, Pierre

    2005-11-01

    In the years following the hepatitis B vaccination/multiple sclerosis controversy, a number of new issues regarding vaccine safety have been raised, in some cases leading to more debate and confusion. Against this background, an international group of experts was convened to review the current points of view concerning the use of thimerosal as a preservative and its potential risks; the suggested link between thimerosal-containing vaccines and acute lymphoblastic leukemia; the alleged association between aluminum-containing vaccines/macrophagic myofasciitis and general systemic complaints; a possible link between vaccination and autoimmune pathology; and a hypothetical link between measles-mumps-rubella vaccination and autism. At present, there are no data to conclude that childhood vaccines, and in particular hepatitis B vaccine, pose a serious health risk or justify a change in current immunization practice. However, vaccine "scares" continue to have an international impact on immunization coverage. Creating a positive environment for immunization can be achieved by repositioning the value of vaccines and vaccination, supported by evidence-based information. The role of international organizations, the media, and the industry in the implementation of communication strategies was discussed and the impact of litigation issues on vaccination was evaluated. The Viral Hepatitis Prevention Board confirms its commitment to current recommendations for universal and risk group hepatitis B vaccination and further encourages the conduct of vaccine safety studies and the dissemination of their results.

  3. Monitoring vaccine safety during an influenza pandemic.

    PubMed Central

    Iskander, John; Haber, Penina; Herrera, Guillermo

    2005-01-01

    In the event that a vaccine is available during an influenza pandemic, vaccine safety monitoring will occur as part of comprehensive public health surveillance of the vaccination campaign. Though inactivated influenza vaccines have been widely used in the United States and much is known about their safety profile, attention will need to be paid to both common self-limited adverse reactions and rarer, more serious events that may or may not be causally related to vaccination. The primary surveillance systems used to generate and test hypotheses about vaccine safety concerns are the Vaccine Adverse Event Reporting System (VAERS) and the Vaccine Safety Datalink (VSD), respectively. Examples of recent use of these systems to investigate influenza vaccine safety and enhancements planned for use during a pandemic are presented. Ethical issues that will need to be addressed as part of an overall vaccine safety response include risk communication and injury compensation. Advance planning and the use of available technologic solutions are needed to respond to the scientific and logistic challenges involved in safely implementing mass vaccination during a pandemic. PMID:17132333

  4. [Vaccination safety and media publicity strategy].

    PubMed

    Tan, Jibin; Guo, Xiaomin; Li, Keli; Zhang, Xiumin

    2016-03-01

    Due to the over negative report of adverse event following immunization (AEFI) by media, some people began to question the safety of vaccination. Date published since 2005 were collected by literature retrieval, mainly including relative AEFI date, current status of media report of AEFI, public awareness about AEFI. Public concern about the vaccination safety mainly focused on the serious diseases which might be caused, influence on immune system. Media' s over negative reactions to AEFI and lack of related knowledge in general public have led to the public' s concern about vaccination safety. Vaccination is the most economical and effective measure for the prevention of diseases and AEFI incidence rate is very low. Therefore, it is necessary for media to give more positive report about vaccination safety.

  5. A global perspective on vaccine safety and public health: the Global Advisory Committee on Vaccine Safety.

    PubMed

    Folb, Peter I; Bernatowska, Ewa; Chen, Robert; Clemens, John; Dodoo, Alex N O; Ellenberg, Susan S; Farrington, C Patrick; John, T Jacob; Lambert, Paul-Henri; Macdonald, Noni E; Miller, Elizabeth; Salisbury, David; Schmitt, Heinz-J; Siegrist, Claire-Anne; Wimalaratne, Omala

    2004-11-01

    Established in 1999, the Global Advisory Committee on Vaccine Safety advises the World Health Organization (WHO) on vaccine-related safety issues and enables WHO to respond promptly, efficiently, and with scientific rigor to issues of vaccine safety with potential global importance. The committee also assesses the implications of vaccine safety for practice worldwide and for WHO policies. We describe the principles on which the committee was established, its modus operandi, and the scope of the work undertaken, both present and future. We highlight its recent recommendations on major issues, including the purported link between the measles-mumps-rubella vaccine and autism and the safety of the mumps, influenza, yellow fever, BCG, and smallpox vaccines as well as that of thiomersal-containing vaccines.

  6. A Global Perspective on Vaccine Safety and Public Health: The Global Advisory Committee on Vaccine Safety

    PubMed Central

    Folb, Peter I.; Bernatowska, Ewa; Chen, Robert; Clemens, John; Dodoo, Alex N. O.; Ellenberg, Susan S.; Farrington, C. Patrick; John, T. Jacob; Lambert, Paul-Henri; MacDonald, Noni E.; Miller, Elizabeth; Salisbury, David; Schmitt, Heinz-J.; Siegrist, Claire-Anne; Wimalaratne, Omala

    2004-01-01

    Established in 1999, the Global Advisory Committee on Vaccine Safety advises the World Health Organization (WHO) on vaccine-related safety issues and enables WHO to respond promptly, efficiently, and with scientific rigor to issues of vaccine safety with potential global importance. The committee also assesses the implications of vaccine safety for practice worldwide and for WHO policies. We describe the principles on which the committee was established, its modus operandi, and the scope of the work undertaken, both present and future. We highlight its recent recommendations on major issues, including the purported link between the measles–mumps–rubella vaccine and autism and the safety of the mumps, influenza, yellow fever, BCG, and smallpox vaccines as well as that of thiomersal-containing vaccines. PMID:15514229

  7. Safety and efficacy of a combined parapox/BVD vaccine.

    PubMed

    Büttner, M

    1986-01-01

    The combination of a Bovine Viral Diarrhea-Mucosal Disease-attenuated vaccine strain with heat-inactivated parapoxvirus was tested with respect to safety and efficacy in mice, rabbits and fattening calves. The safety on this vaccine was guaranteed in mice and rabbits under laboratory conditions and in calves under field conditions. Laboratory investigations demonstrated a strong anti-BVD antibody response in rabbits compared to antibody formation after vaccination with the monovalent BVD-vaccine component. In mice the induction of high unspecific defence against heterologous viral challenge (VSV, Aujeszky) was possible only with the combined vaccine and the parapox (ORF) vaccine component. Two BVD-seronegative calves kept under isolated conditions showed high titers of BVD-neutralizing antibodies three weeks after a single vaccination with a three-fold vaccine dose. Leukopenia could not be detected in 13 randomly chosen BVD-seronegative calves on days 1, 2 and 4 after vaccination. In field trials each of the 69 (29%) BVD-seronegative calves developed high titers of BVD-neutralizing antibodies three weeks after a single (i.m.) inoculation. The same phenomenon occurred with animals which had low pre-vaccination BVD neutralizing antibodies, whereas the third group of calves with high prevaccination antibody titers had a moderate decrease in neutralizing antibodies within three weeks after vaccination. Mortality and morbidity rates in fattening farms decreased markedly after the experiment and during an observation period of one year. Improved immunological response of rabbits and cattle to a single vaccination with the combined parapox-BVD vaccine compared to a monospecific BVD vaccination was a result of immunomodulating effects of the parapox (ORF) vaccine component.

  8. Improving operating room safety

    PubMed Central

    2009-01-01

    Despite the introduction of the Universal Protocol, patient safety in surgery remains a daily challenge in the operating room. This present study describes one community health system's efforts to improve operating room safety through human factors training and ultimately the development of a surgical checklist. Using a combination of formal training, local studies documenting operating room safety issues and peer to peer mentoring we were able to substantially change the culture of our operating room. Our efforts have prepared us for successfully implementing a standardized checklist to improve operating room safety throughout our entire system. Based on these findings we recommend a multimodal approach to improving operating room safety. PMID:19930577

  9. Nonclinical safety assessment of vaccines and adjuvants.

    PubMed

    Wolf, Jayanthi J; Kaplanski, Catherine V; Lebron, Jose A

    2010-01-01

    To ensure the safe administration of vaccines to humans, vaccines (just like any new chemical entity) are evaluated in a series of nonclinical safety assessment studies that aim at identifying the potential toxicities associated with their administration. The nonclinical safety assessment of vaccines, however, is only part of a testing battery performed prior to human administration, which includes (1) the evaluation of the vaccine in efficacy and immunogenicity studies in animal models, (2) a quality control testing program, and (3) toxicology (nonclinical safety assessment) testing in relevant animal models. Although each of these evaluations plays a critical role in ensuring vaccine safety, the nonclinical safety assessment is the most relevant to the evaluation in human clinical trials, as it allows the identification of potential toxicities to be monitored in human trials, and in some cases, eliminates candidates that have unacceptable risks for human testing. This review summarizes the requirements for the nonclinical testing of vaccines and adjuvants needed in support of all phases of human clinical trials.

  10. DNA Vaccines: Regulatory Considerations and Safety Aspects.

    PubMed

    Myhr, Anne Ingeborg

    2017-01-01

    DNA vaccines have great potential as preventive or therapeutic vaccines against viral, bacterial, or parasitic diseases as well as cancer, and may also be used as gene therapy products. Although many human and veterinary DNA vaccines have been investigated in laboratory trials, only four of these have been approved for commercial use. In this paper an overview of the regulatory requirements for the development of DNA vaccines is given. The regulatory process in EU and USA is described. A discussion concerning the relevance of national regulations on gene technology is included. In addition the main safety concerns associated with DNA vaccines, relating to unwanted side effects in the vaccinated mammal or fish, are presented. Finally, the need for greater openness regarding the assessment information is discussed.

  11. 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. Copyright © 2016. Published by Elsevier Ltd.

  12. Safety review: squalene and thimerosal in vaccines.

    PubMed

    Montana, Marc; Verhaeghe, Pierre; Ducros, Caroline; Terme, Thierry; Vanelle, Patrice; Rathelot, Pascal

    2010-01-01

    Few studies show the reluctance of the people to get vaccinated against A (H1N1) influenza for fear of side effects of squalene (MF59, AS03, AF03) and thimerosal. The aim of this paper is to assess the safety in using these adjuvants and preservative reviewing data of clinical trials relative to which formulation includes these compounds. In the current state of knowledge, these vaccines have proved to be effective even though they more frequently give local adverse events than non-adjuvanted influenza vaccines. Systemic side effects are generally not serious. In the studies, adjuvanted vaccines do not increase neither the risk of Guillain Barre syndrome nor auto-immune diseases. There is no convincing evidence that exposure to thimerosal in vaccines had any deletorious effect on physiological outcome.

  13. [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. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  14. 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

  15. The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG).

    PubMed

    Chen, Robert T; Carbery, Baevin; Mac, Lisa; Berns, Kenneth I; Chapman, Louisa; Condit, Richard C; Excler, Jean-Louis; Gurwith, Marc; Hendry, Michael; Khan, Arifa S; Khuri-Bulos, Najwa; Klug, Bettina; Robertson, James S; Seligman, Stephen J; Sheets, Rebecca; Williamson, Anna-Lise

    2015-01-01

    Recombinant viral vectors provide an effective means for heterologous antigen expression in vivo and thus represent promising platforms for developing novel vaccines against human pathogens from Ebola to tuberculosis. An increasing number of candidate viral vector vaccines are entering human clinical trials. The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to improve our ability to anticipate potential safety issues and meaningfully assess or interpret safety data, thereby facilitating greater public acceptance when licensed.

  16. Quality Improvement Project to Reduce Delayed Vaccinations in Preterm Infants.

    PubMed

    Cuna, Alain; Winter, Lindy

    2017-08-01

    Preterm infants are especially vulnerable to infectious diseases. Although vaccinations are a safe and effective measure to protect preterm infants from vaccine-preventable diseases, delays in vaccinations are not uncommon. The goal of this quality improvement project was to improve on time vaccinations of preterm infants hospitalized in the neonatal intensive care unit. The Plan-Do-Study-Act model of quality improvement was adopted to develop, test, and implement interventions aimed at improving timely vaccination of preterm infants. The primary outcome measure of interest was the rate of on time vaccination, which was defined as the proportion of medically eligible preterm infants who received vaccinations within 2 weeks of the recommended schedule. Baseline on time vaccination rate was only 36%. Following several Plan-Do-Study-Act cycles, a steady increase in on time vaccinations of eligible infants was observed, and a new baseline on time vaccination rate of 82% was achieved. Simple interventions implemented within the context of Plan-Do-Study-Act cycles are effective in improving timely vaccinations among preterm infants. Future research that focuses on vaccinations in preterm infants is needed to further reinforce the safety and efficacy of vaccines. Effective methods on how to disseminate and apply this knowledge to practice should also be studied.Video Abstract available at http://links.lww.com/ANC/A27.

  17. Development of improved pertussis vaccine

    PubMed Central

    Rumbo, Martin; Hozbor, Daniela

    2014-01-01

    Rates of infection with Bordetella pertussis, the gram-negative bacterium that causes the respiratory disease called whooping cough or pertussis, have not abated and 16 million cases with almost 200,000 deaths are estimated by the WHO to have occurred worldwide in 2008. Despite relatively high vaccination rates, the disease has come back in recent years to afflict people in numbers not seen since the pre-vaccine days. Indeed, pertussis is now recognized as a frequent infection not only in newborn and infants but also in adults. The disease symptoms also can be induced by the non-vaccine-preventable infection with the close species B. parapertussis for which an increasing number of cases have been reported. The epidemiologic situation and current knowledge of the limitations of pertussis vaccine point out the need to design improved vaccines. Several alternative approaches and their challenges are summarized. PMID:25424954

  18. Postmarketing safety surveillance of trivalent recombinant influenza vaccine: Reports to the Vaccine Adverse Event Reporting System.

    PubMed

    Woo, Emily Jane; Moro, Pedro L; Cano, Maria; Jankosky, Christopher

    2017-09-05

    On January 16, 2013, the Food and Drug Administration approved recombinant hemagglutinin influenza vaccine (RIV3) (Spodoptera frugiperda cell line; Flublok), which is the first completely egg-free flu vaccine licensed in the United States. To improve our understanding of the safety profile of this vaccine, we reviewed and summarized reports to the Vaccine Adverse Event Reporting System (VAERS) following RIV3. Through June 30, 2016, VAERS received 88 reports. Allergic reactions, including anaphylaxis, were the most common type of adverse event. Based on medical review, 10 cases met the Brighton Collaboration case definition of anaphylaxis, 21 reports described allergic reactions other than anaphylaxis, and 11 reports described signs and symptoms that suggested hypersensitivity. Other adverse events included injection site reactions, fatigue, myalgia, headache, and fever. The occurrence of anaphylaxis and other allergic reactions in some individuals may reflect an underlying predisposition to atopy that may manifest itself after an exposure to any drug or vaccine, and it does not necessarily suggest a causal relationship with the unique constituents that are specific to the vaccine product administered. Further research may elucidate the mechanism of allergic reactions following influenza vaccination: it is possible that egg proteins and influenza hemagglutinin play little or no role. Vaccination remains the single best defense against influenza and its complications. The information summarized here may enable policy makers, health officials, clinicians, and patients to make a more informed decision regarding vaccination strategies. Published by Elsevier Ltd.

  19. Enhancing Public Confidence in Vaccines Through Independent Oversight of Postlicensure Vaccine Safety

    PubMed Central

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

    2004-01-01

    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

  20. 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 the...

  1. Communicating about vaccines and vaccine safety: what are medical residents learning and what do they want to learn?

    PubMed

    Sarnquist, Clea; Sawyer, Mark; Calvin, Kris; Mason, Wilbert; Blumberg, Dean; Luther, Jeffrey; Maldonado, Yvonne

    2013-01-01

    Physicians spend significant amounts of time discussing vaccine safety concerns with patients and parents. This study aimed to better understand the educational needs of US residents regarding vaccine safety communication, primarily by quantifying the vaccine safety communication training that residents currently receive and elucidating residents' preferences around education about vaccines and vaccine safety communication. A mixed-methods needs assessment consisting of focus groups and a survey. A convenience sample of 303 medical residents in pediatrics, family medicine, and internal medicine from across the United States participated in an online, anonymous survey from March through June 2010. In addition, 9 focus groups with 47 resident participants were held. The sample included residents in pediatrics (239, 80.2%), internal or family medicine (30, 10.1%), and dual medicine-pediatrics (29, 9.7%); 20.6% of the residents reported "not learning" about vaccine safety communication in their residency programs. Preferred learning methods, which were also the most commonly used methods, included didactic lectures and role-modeling/cases. Electronic teaching method were not only less desired but also very rarely utilized. More than 95% of residents reported thinking that vaccine safety communication would be very or somewhat important in their careers. Improving education on vaccine safety communication within US residency programs, as well as offering self-learning opportunities, can better prepare physicians for their careers.

  2. Safety of vaccine adjuvants: focus on autoimmunity.

    PubMed

    van der Laan, Jan Willem; Gould, Sarah; Tanir, Jennifer Y

    2015-03-24

    Questions have been recently raised regarding the safety of vaccine adjuvants, particularly in relation to autoimmunity or autoimmune disease(s)/disorder(s) (AID). The International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) formed a scientific committee and convened a 2-day workshop, consisting of technical experts from around the world representing academia, government regulatory agencies, and industry, to investigate and openly discuss the issues around adjuvant safety in vaccines. The types of adjuvants considered included oil-in-water emulsions and toll-like receptor (TLR) agonists. The state of science around the use of animal models and biomarkers for the evaluation and prediction of AID were also discussed. Following extensive literature reviews by the HESI committee, and presentations by experts at the workshop, several key points were identified, including the value of animal models used to study autoimmunity and AID toward studying novel vaccine adjuvants; whether there is scientific evidence indicating an intrinsic risk of autoimmunity and AID with adjuvants, or a higher risk resulting from the mechanism of action; and if there is compelling clinical data linking adjuvants and AID. The tripartite group of experts concluded that there is no compelling evidence supporting the association of vaccine adjuvants with autoimmunity signals. Additionally, it is recommended that future research on the potential effects of vaccine adjuvants on AID should consider carefully the experimental design in animal models particularly if they are to be used in any risk assessment, as an improper design and model could result in misleading information. Finally, studies on the mechanistic aspects and potential biomarkers related to adjuvants and autoimmunity phenomena could be developed.

  3. Improving newcastle disease vaccination with homologous vaccines

    USDA-ARS?s Scientific Manuscript database

    All Newcastle disease viruses (NDVs) belong to a single serotype; however, current vaccine strains display important amino acid differences at the F and HN protein compared with virulent outbreak strains (vNDV). Previous studies have shown decreased viral shedding after challenge when vaccines were...

  4. 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.

  5. The role of the Vaccine Adverse Event Reporting system (VAERS) in monitoring vaccine safety.

    PubMed

    Iskander, John K; Miller, Elaine R; Chen, Robert T

    2004-09-01

    The role of the health professional in supporting the national passive surveillance system is essential, as the first hint of a potential problem usually originates with the astute clinician who reports a case to the appropriate source. The investigation that resulted in the voluntary withdrawal of rotavirus vaccine was triggered by nine reports to VAERS of intussuception, eight of which had occurred within 1 week of the first dose of this vaccine. Health professionals have access to the most complete information related to adverse events experienced by their patients. Any index of suspicion that a serious event or death may be related to vaccination is reason for the health professional to submit a VAERS report. Determination of whether an event was caused by the vaccine is not a prerequisite for filing a VAERS report. When in doubt, providers should report to VAERS. VAERS solicits reports for all events temporally related to vaccination, some of which may be coincidental and some of which may merely indicate a change in the frequency of expected events. Post-marketing surveillance relies on health professionals to report suspicious events, thus improving the quality of reported data and contributing significantly to safeguarding public health. Recommendations for healthcare professionals to report to VAERS recently have been incorporated into the Standards for Pediatric Immunization Practices, which are endorsed by multiple professional organizations. Despite the limitations of spontaneous reports, VAERS provides vital information of clinical importance. The identification of signals in adverse event surveillance may initiate further investigation of potential problems in vaccine safety or efficacy, and facilitate subsequent dissemination of safety-related information to the scientific community and the public. This process begins with voluntary submission of reports of possible vaccine-associated events to VAERS by the informed and conscientious health

  6. 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.

  7. Vaccine safety--vaccine benefits: science and the public's perception.

    PubMed

    Wilson, C B; Marcuse, E K

    2001-11-01

    The development of cowpox vaccination by Jenner led to the development of immunology as a scientific discipline. The subsequent eradication of smallpox and the remarkable effects of other vaccines are among the most important contributions of biomedical science to human health. Today, the need for new vaccines has never been greater. However, in developed countries, the public's fear of vaccine-preventable diseases has waned, and awareness of potential adverse effects has increased, which is threatening vaccine acceptance. To further the control of disease by vaccination, we must develop safe and effective new vaccines to combat infectious diseases, and address the public's concerns.

  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.

  9. 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

  10. 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

  11. Yellow fever vaccination status and safety in hemodialysis patients.

    PubMed

    Facincani, Tila; Guimarães, Maia Nogueira Crown; De Sousa Dos Santos, Sigrid

    2016-07-01

    The adverse effects of yellow fever (YF) vaccine in dialysis patients are not well known. There is concern about the risks and benefits of the vaccine in immunocompromised patients living in endemic areas, particularly given the risk of resurgence of urban YF with the spread of Aedes aegypti mosquitoes. The purpose of this study was to assess the coverage and safety of YF vaccine in chronic dialysis patients. A cross-sectional study of 130 chronic dialysis patients was performed. Data were collected on clinical characteristics and YF vaccine status. Patients not vaccinated against YF or without a booster vaccination within the last 10 years were referred to receive the vaccine, and adverse effects were monitored. Previous vaccination was verified in 44 patients within the last 10 years and in 26 patients at more than 10 years ago, with no mention of adverse effects. Thirty-six patients had never been vaccinated and 24 had an unknown vaccination status. Of the total 86 patients referred for immunization, 45 actually received the YF vaccine, with 24.4% experiencing mild local adverse effects and 4.4% experiencing fever. No serious adverse effects attributable to YF vaccine were observed (anaphylaxis, neurological or viscerotropic disease). YF vaccine coverage among hemodialysis patients is low, and the vaccine appeared to be safe in this population with a small sample size. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. The safety advantages of pentavalent vaccines.

    PubMed

    Merchant, Nida; Waldrop, Julee

    2012-04-15

    The ever-growing vaccination schedule can cause patients, parents, and nurse practitioners undue concern. Combination vaccines may provide an answer. This integrative review demonstrates that pentavalent vaccines offer adequate immunity, are well tolerated, and safe when compared to vaccines administered separately.

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

    PubMed Central

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

    2016-01-01

    ABSTRACT 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

  14. Misled and confused? Telling the public about MMR vaccine safety

    PubMed Central

    Clements, C; Ratzan, S

    2003-01-01

    The extraordinary events surrounding the measles, mumps, and rubella (MMR) vaccine in the United Kingdom have not only placed in jeopardy the use of this triple vaccine but have also spread concern to other parts of the world. Examination of the public's worry about MMR vaccine reveals they have been exposed to a range of conflicting views resulting in the feeling of having been misled about the safety of the vaccine. There are various groups and individuals who have legitimate roles in informing the public about such subjects. But is each one behaving in an ethically responsible way? And if confidence falters, vaccine coverage dips, and an outbreak of measles, mumps, or rubella ensues, who, if anyone, will stand and say "I misled them, I confused them, this is my responsibility"? We examine the ethical issues of each group with a voice in the debate about vaccine safety. PMID:12569190

  15. A Blueprint for Improving the Promotion and Delivery of Adult Vaccination in the United States.

    PubMed

    Harris, Katherine M; Uscher-Pines, Lori; Mattke, Soeren; Kellermann, Arthur L

    2012-01-01

    Vaccine-preventable disease continues to take a heavy toll on adults despite the widespread availability of effective vaccines. This article identifies where efforts to improve the delivery of adult vaccination have stalled and recommends targeted strategies that are supported by available evidence and build on existing infrastructure. The authors conducted a comprehensive review of the published literature on adult immunization, a stakeholder workshop, and follow-up interviews with meeting participants and additional experts. They also partnered with an organization represented at the workshop to conduct a telephone survey of adults to learn about the relationship between influenza vaccination and beliefs about the safety of influenza vaccine. Findings include that office-based providers remain the primary source of vaccination, though a substantial proportion of physicians who treat adults appear not to vaccinate at all and adult vaccination is infrequently discussed at health care encounters. Adult practices also lack a strong business case to offer vaccination, as it entails substantial fixed costs. In addition, achieving substantial increases in adult vaccination will require persuading large numbers of individuals disinclined to be vaccinated. Vaccination stakeholders need to engage in a collaborative fashion to promote adult vaccination and the integration of advice about vaccination into routine office-based practice. Recommendations include strengthening evidence surrounding practice gaps and the economic value of promoting vaccination in office-based settings, improving guidance to providers about vaccinating adults, and formalizing procedures for referring patients to complementary vaccinators.

  16. [STUDY OF SAFETY OF PAROTITIS VACCINE].

    PubMed

    Ignatiev, G M; Kulak, M V; Otrashevskaya, E V; Bukin, E K; Nesterov, A A E; Gorbunov, M A; Mikheev, V N

    2015-01-01

    Monitoring of post-vaccinal complications in children immunized with a parotitis vaccine. Observation of 198 945 children, immunized with 16 lots of parotitis vaccine with Leningrad-3 strain (L-3), was carried out for 3 years. Paired samples of sera and saliva were obtained from children, in whom adverse events were registered for 42 days after vaccination. Titers of specific IgM and IgG were determined in blood sera. Analysis of nucleotide sequences of genes F, SH and NH of RNA of parotitis virus was carried out from samples of blood and saliva. Intensive parameter of vaccine-associated aseptic meningitis under the conditions of the experiments was 0 for 100 000 immunized. Frequency of occurrence of post-vaccinal parotitis was 0.06% from the number of vaccinated--18 cases of vaccine-associated parotitis were registered and laboratory confirmed. A significant difference in specific activity was detected for 3 lots of the vaccine, that were associated with cases of development of parotitis, relative to that of 13 lots of vaccine, development of parotitis was not registered after administration of those. The study carried out confirmed low neurovirulence of the parotitis vaccine with the L-3 strain of parotitis virus, as well as a low degree of its reactogenicity. A relatively high immunization dose of the used vaccine could be one of the reasons of development of post-vaccinal complications in part of the immunized children.

  17. Comparative safety of vaccine adjuvants: a summary of current evidence and future needs

    PubMed Central

    Petrovsky, Nikolai

    2015-01-01

    Improved use of highly pure antigens to improve vaccine safety has led to reduced vaccine immunogenicity and efficacy. This has led to the need to use adjuvants to improve vaccine immunogenicity. The ideal adjuvant should maximize vaccine immunogenicity without compromising tolerability or safety or posing undue risk. Unfortunately, adjuvant research has lagged behind other vaccine areas such as antigen discovery, with the consequence that only a very limited number of adjuvants based on aluminum salts, monophosphoryl lipid A and oil emulsions are currently approved for human use. Recent strategic initiatives to support adjuvant development by the National Institutes of Health should translate into greater adjuvant choices in the future. Mechanistic studies have been valuable in better understanding adjuvant action but mechanisms of adjuvant toxicity are less well understood. The inflammatory or danger-signal model of adjuvant action implies that increased vaccine reactogenicity is the inevitable price for improved immunogenicity. Hence, adjuvant reactogenicity may be avoidable only if it is possible to separate inflammation from adjuvant action. The biggest remaining challenge in the adjuvant field is to decipher the potential relationship between adjuvants and rare vaccine adverse reactions such as narcolepsy, macrophagic myofasciitis or Alzheimer’s disease. While existing adjuvants based on aluminum salts have a strong safety record, there is an ongoing need for new adjuvants and for more intensive research into adjuvants and their effects. PMID:26446142

  18. New and Improved Vaccines Against Meningococcal Disease

    DTIC Science & Technology

    1990-01-01

    associated with group B meningococcal disease and their use for rapid vaccine development. Antonie Leeuwenhoek J Microbiol 1987; 53:395. 37. Gotschlich EC...Brandt B, Moran EE, Ray J. Safety and antigenicity studies of a polyvalent meningococcal protein-polysaccharide vaccine. Antonie Leeuwenhoek J Microbiol...2b and 15 antigens in complex with mixed A,CY, and W135 polysaccharides. Antonie Leeuwenhoek I Microbiol 1985; 52:239. 91. Frasch CE, Zahradnik JM

  19. 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.

  20. Understanding Thimerosal, Mercury, and Vaccine Safety

    MedlinePlus

    ... from contamination. Thimerosal is also used during the manufacturing process for some vaccines to prevent the growth ... other childhood vaccines, it is used in the manufacturing process. When each new needle is inserted into ...

  1. Improved Vaccine against PRRSV: Current Progress and Future Perspective.

    PubMed

    Nan, Yuchen; Wu, Chunyan; Gu, Guoqian; Sun, Weiyao; Zhang, Yan-Jin; Zhou, En-Min

    2017-01-01

    Porcine reproductive and respiratory syndrome virus (PRRSV), one of the most economically significant pathogens worldwide, has caused numerous outbreaks during the past 30 years. PRRSV infection causes reproductive failure in sows and respiratory disease in growing and finishing pigs, leading to huge economic losses for the swine industry. This impact has become even more significant with the recent emergence of highly pathogenic PRRSV strains from China, further exacerbating global food security. Since new PRRSV variants are constantly emerging from outbreaks, current strategies for controlling PRRSV have been largely inadequate, even though our understanding of PRRSV virology, evolution and host immune response has been rapidly expanding. Meanwhile, practical experience has revealed numerous safety and efficacy concerns for currently licensed vaccines, such as shedding of modified live virus (MLV), reversion to virulence, recombination between field strains and MLV and failure to elicit protective immunity against heterogeneous virus. Therefore, an effective vaccine against PRRSV infection is urgently needed. Here, we systematically review recent advances in PRRSV vaccine development. Antigenic variations resulting from PRRSV evolution, identification of neutralizing epitopes for heterogeneous isolates, broad neutralizing antibodies against PRRSV, chimeric virus generated by reverse genetics, and novel PRRSV strains with interferon-inducing phenotype will be discussed in detail. Moreover, techniques that could potentially transform current MLV vaccines into a superior vaccine will receive special emphasis, as will new insights for future PRRSV vaccine development. Ultimately, improved PRRSV vaccines may overcome the disadvantages of current vaccines and minimize the PRRS impact to the swine industry.

  2. Measles, mumps and rubella--safety of the combined vaccine.

    PubMed

    Bedford, Helen

    Despite the fact that scientific evidence shows no support for a link between the combined measles, mumps and rubella vaccine (MMR) and autism or bowel problems, many parents remain worried. This article discusses the reasons for the introduction of MMR and outlines the debate about its safety and the problems associated with using single vaccines.

  3. Personality and demographic correlates of New Zealanders' confidence in the safety of childhood vaccinations.

    PubMed

    Lee, Carol H J; Duck, Isabelle M; Sibley, Chris G

    2017-09-28

    Despite extensive scientific evidence on the safety of standard vaccinations, some parents express skeptical attitudes towards the safety of childhood immunisations. This paper uses data from the 2013/14 New Zealand Attitudes and Values Study (NZAVS) survey (N=16,642) to explore the distribution, and demographic and personality correlates of New Zealanders' attitudes towards the safety of childhood vaccinations. Around two thirds (68.5%) of New Zealanders strongly agreed/were confident that "it is safe to vaccinate children following the standard New Zealand immunisation schedule," 26% were skeptical and 5.5% were strongly opposed. Multiple regression analysis indicated that people lower on Conscientiousness and Agreeableness but higher on Openness to Experience expressed lower confidence about vaccine safety. Having higher subjective health satisfaction, living rurally, being Māori, single, employed and not a parent were all associated with lower confidence, while a higher income and educational attainment were associated with greater confidence. Our findings suggest that the majority of New Zealand adults trust in the safety of scheduled childhood vaccinations, but about one third do express some degree of concern. This finding highlights the importance of improving public education about the safety and necessity of vaccinations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Safety of MDCK cell culture-based influenza vaccines.

    PubMed

    Gregersen, Jens-Peter; Schmitt, Heinz-Josef; Trusheim, Heidi; Bröker, Michael

    2011-02-01

    After more than 60 years, the conventional production of influenza vaccines employing fertilized chicken eggs has reached its limits - both in terms of temporal flexibility and vaccine production volume. This problem is compounded by the fact that the pandemic-driven situation in 2009 has roughly doubled the overall vaccine demand. Modern cell culture technology has significant advantages over the conventional method of manufacturing influenza vaccines employing embryonated chicken eggs, and enables manufacturers to respond rapidly to the increasing worldwide seasonal and pandemic-driven need for influenza vaccines. Recent articles in the popular press claiming that cell culture-based influenza vaccines can cause tumors have fomented uncertainty among the general population and physicians, and also discredit officially accepted test results and product licensing. This article provides an overview of the safety profile of the cell culture technology, of the cells and of the final vaccine product.

  5. 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

  6. Safety experience with heptavalent pneumococcal CRM197-conjugate vaccine (Prevenar) since vaccine introduction.

    PubMed

    Center, Kimberly J; Strauss, Ann

    2009-05-26

    Documentation of the safety of any vaccine is of paramount importance given the nature and scale of vaccination as a public health intervention. Prevenar was first approved for use in 2000, and includes seven pneumococcal serotypes conjugated to CRM(197), a carrier protein that has been used safely in multiple conjugate vaccines for more than 20 years. The safety profile of Prevenar was established prior to licensure in 5 clinical trials involving more than 18,000 infants and children. The largest postmarketing study of the safety of Prevenar given concomitantly with other recommended vaccines was conducted in the United States, and included more than 162,000 subjects. This analysis did not suggest any new safety consideration that would alter the risk-benefit balance of the vaccine, and demonstrated the favorable safety profile of Prevenar. To date, global surveillance of spontaneously reported adverse events to the manufacturer after more than 198 million doses distributed has confirmed these findings. The WHO has recommended the priority inclusion of this vaccine in national childhood immunization programs based on both its documented efficacy and safety. We will discuss the importance of monitoring vaccine safety and the methodologies by which this may be done, using Prevenar as an illustrative example.

  7. Safety of the HPV Bivalent and Quadrivalent Vaccines During Pregnancy.

    PubMed

    Forinash, Alicia B; Yancey, Abigail M; Pitlick, Jamie M; Myles, Thomas D

    2011-02-01

    To evaluate the safety of the human papillomavirus (HPV) bivalent and quadrivalent vaccines in pregnancy. PubMed (1966-August 2010) was searched using the terms human papillomavirus, human papillomavirus vaccine, and pregnancy. References were reviewed for relevant information. All studies including humans that were published in English with data describing HPV vaccine administration in pregnancy were evaluated. Two combined analyses of 7 Phase 3 efficacy trials have retrospectively evaluated the safety of unintentional administration of either the bivalent (n = 1786) or quadrivalent (n = 2085) HPV vaccine during pregnancy. In addition, postmarketing pregnancy registry surveillance data (prospective, n = 787; retrospective, n = 76) for the quadrivalent HPV vaccine have been published. However, only 279 pregnancies from the studies and 90 pregnancies from the registry occurred within 30 days of receiving the vaccination. Overall, the vaccine does not appear to be associated with an increased risk of spontaneous abortion, fetal malformations, or adverse pregnancy outcomes beyond that found in the general population. Although the data are limited, neither HPV vaccine appears to be associated with an increased risk of adverse pregnancy outcomes. However, limitations of the data include small patient populations, minimal to no adjustments for factors known to influence pregnancy outcomes or malformations, and the majority of the available pregnancy data are from retrospective analysis of Phase 3 efficacy trials. Neither HPV vaccine should be routinely administered during pregnancy. If a pregnancy occurs midseries, the remaining vaccines should be given after pregnancy completion. Further studies are required to determine actual risk. © 2011 SAGE Publications.

  8. Safety of the yellow Fever vaccine: a retrospective study.

    PubMed

    Nordin, James D; Parker, Emily D; Vazquez-Benitez, Gabriela; Kharbanda, Elyse O; Naleway, Allison; Marcy, S Michael; Molitor, Beth; Kuckler, Leslie; Baggs, James

    2013-01-01

    Yellow fever (YF) vaccine is considered safe; however, severe illness and death following vaccination have been reported. Vaccine Safety Datalink (VSD) and US Department of Defense (DoD) data were used to identify adverse reactions following YF vaccination. Within the VSD, YF-vaccine-exposed subjects were compared to age-, site-, and gender-matched unexposed subjects. YF-vaccine-exposed DoD subjects were studied using a risk-interval design. For both cohorts, ICD-9 codes were analyzed for allergic and local reactions, mild systemic reactions, and possible visceral and neurologic adverse events (AEs). The VSD cohort received 47,159 doses from 1991 through 2006. The DoD cohort received 1.12 million doses from 1999 through 2007. Most subjects received other vaccines simultaneously. In the VSD cohort, rates of allergic, local, and mild systemic reactions were not statistically different between YF-vaccine-exposed and -unexposed subjects. In the DoD, there was an increased risk for outpatient allergic events in the period following vaccination with YF and other vaccines rate ratios [RR 3.85, 95% confidence interval (CI) 3.35-4.41] but with no increased risk for inpatient allergic reactions. In both cohorts, inpatient ICD-9 codes for visceral events were significantly less common following vaccination; inpatient codes for neurologic events were less common in the VSD YF-vaccine-exposed adult cohort, but did not differ between exposed and unexposed periods in the DoD. In the DoD, one fatal case of YF-vaccine-associated viscerotropic disease (YF-vaccine-AVD) was detected. The estimated death rate was 0.89 for 1,000,000 YF vaccine doses (95% CI 0.12-6.31/1,000,000 doses). No YF vaccine-associated deaths occurred in the VSD. In these closed cohorts we did not detect increased risk for visceral or neurologic events following YF vaccination. The death rate following YF vaccine was consistent with previous reports. These data support current recommendations for use of YF

  9. Improvement influenza HA2 DNA vaccine cellular and humoral immune responses with Mx bio adjuvant.

    PubMed

    Soleimani, Sina; Shahsavandi, Shahla; Maddadgar, Omid

    2017-03-01

    Immunization with DNA vaccines as a novel alternative to conventional vaccination strategy requires adjuvant for improving vaccine efficacy. The conserved immunogenic HA2 subunit, which harbors neutralizing epitopes is a promising vaccine candidate against influenza viruses. In this study, for the first time we explore the idea of using host interferon inducible Mx protein to increase the immunogenicity of HA2 H9N2 influenza DNA vaccine. The potency and safety of the Mx adjuvanted-HA2 vaccine was evaluated in BALB/c mice by different prime-boost strategies. To assess the effect of the vaccination on the virus clearance rate, mice were challenged with homologous influenza virus. Administration of the adjuvanted vaccine and boosting with the same regimen could effectively enhance both humoral and cellular immune responses in treated mice. These data demonstrated that Mx as host defense peptide can be potentiated for improving influenza vaccine efficacy.

  10. Vaccine safety evaluation: Practical aspects in assessing benefits and risks.

    PubMed

    Di Pasquale, Alberta; Bonanni, Paolo; Garçon, Nathalie; Stanberry, Lawrence R; El-Hodhod, Mostafa; Tavares Da Silva, Fernanda

    2016-12-20

    Vaccines are different from most medicines in that they are administered to large and mostly healthy populations including infants and children, so there is a low tolerance for potential risks or side-effects. In addition, the long-term benefits of immunisation in reducing or eliminating infectious diseases may induce complacency due to the absence of cases. However, as demonstrated in recent measles outbreaks in Europe and United States, reappearance of the disease occurs as soon as vaccine coverage falls. Unfounded vaccine scares such as those associating the combined measles-mumps-rubella vaccine with autism, and whole-cell pertussis vaccines with encephalopathy, can also have massive impacts, resulting in reduced vaccine uptake and disease resurgence. The safety assessment of vaccines is exhaustive and continuous; beginning with non-clinical evaluation of their individual components in terms of purity, stability and sterility, continuing throughout the clinical development phase and entire duration of use of the vaccine; including post-approval. The breadth and depth of safety assessments conducted at multiple levels by a range of independent organizations increases confidence in the rigour with which any potential risks or side-effects are investigated and managed. Industry, regulatory agencies, academia, the medical community and the general public all play a role in monitoring vaccine safety. Within these stakeholder groups, the healthcare professional and vaccine provider have key roles in the prevention, identification, investigation and management of adverse events following immunisation (AEFI). Guidelines and algorithms aid in determining whether AEFI may have been caused by the vaccine, or whether it is coincidental to it. Healthcare providers are encouraged to rigorously investigate AEFIs and to report them via local reporting processes. The ultimate objective for all parties is to ensure vaccines have a favourable benefit-risk profile. Copyright

  11. Current Safety Issues with Quadrivalent Meningococcal Conjugate Vaccines.

    PubMed

    Myers, Tanya R; McNeil, Michael M

    2017-09-21

    Invasive meningococcal disease, although rare, can present as sudden, life-threatening disease with high risk of mortality or severe long-term sequelae. The main prevention strategy for invasive meningococcal disease in the United States is the routine vaccination of adolescents and other persons at increased risk of meningococcal disease with quadrivalent meningococcal conjugate vaccines. Two such vaccines are currently licensed and available in the United States, Menactra® (Sanofi Pasteur) and Menveo® (Glaxo Smith Kline), and usage in the adolescent population have steadily increased since their introduction. Although early reports raised concerns about a possible association of Menactra with Guillain-Barré syndrome, a comprehensive safety review determined that if such risk existed it was no more than 0.66 cases per 1 million vaccinations. More recently, a study found an elevated risk of Bell's palsy when Menveo was administered concomitantly with other vaccines but no association was found when the vaccine was administered alone. In this commentary, we describe the current state of knowledge with respect to the safety of quadrivalent meningococcal conjugate vaccines, and we identify potential areas for safety research for these vaccines.

  12. 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

  13. Measuring populations to improve vaccination coverage

    PubMed Central

    Bharti, Nita; Djibo, Ali; Tatem, Andrew J.; Grenfell, Bryan T.; Ferrari, Matthew J.

    2016-01-01

    In low-income settings, vaccination campaigns supplement routine immunization but often fail to achieve coverage goals due to uncertainty about target population size and distribution. Accurate, updated estimates of target populations are rare but critical; short-term fluctuations can greatly impact population size and susceptibility. We use satellite imagery to quantify population fluctuations and the coverage achieved by a measles outbreak response vaccination campaign in urban Niger and compare campaign estimates to measurements from a post-campaign survey. Vaccine coverage was overestimated because the campaign underestimated resident numbers and seasonal migration further increased the target population. We combine satellite-derived measurements of fluctuations in population distribution with high-resolution measles case reports to develop a dynamic model that illustrates the potential improvement in vaccination campaign coverage if planners account for predictable population fluctuations. Satellite imagery can improve retrospective estimates of vaccination campaign impact and future campaign planning by synchronizing interventions with predictable population fluxes. PMID:27703191

  14. Measuring populations to improve vaccination coverage

    NASA Astrophysics Data System (ADS)

    Bharti, Nita; Djibo, Ali; Tatem, Andrew J.; Grenfell, Bryan T.; Ferrari, Matthew J.

    2016-10-01

    In low-income settings, vaccination campaigns supplement routine immunization but often fail to achieve coverage goals due to uncertainty about target population size and distribution. Accurate, updated estimates of target populations are rare but critical; short-term fluctuations can greatly impact population size and susceptibility. We use satellite imagery to quantify population fluctuations and the coverage achieved by a measles outbreak response vaccination campaign in urban Niger and compare campaign estimates to measurements from a post-campaign survey. Vaccine coverage was overestimated because the campaign underestimated resident numbers and seasonal migration further increased the target population. We combine satellite-derived measurements of fluctuations in population distribution with high-resolution measles case reports to develop a dynamic model that illustrates the potential improvement in vaccination campaign coverage if planners account for predictable population fluctuations. Satellite imagery can improve retrospective estimates of vaccination campaign impact and future campaign planning by synchronizing interventions with predictable population fluxes.

  15. Maternal safety of trivalent inactivated influenza vaccine in pregnant women.

    PubMed

    Nordin, James D; Kharbanda, Elyse Olshen; Benitez, Gabriela Vazquez; Nichol, Kristin; Lipkind, Heather; Naleway, Allison; Lee, Grace M; Hambidge, Simon; Shi, Wei; Olsen, Avalow

    2013-03-01

    To estimate the risks for medically attended events occurring within 42 days of receiving trivalent inactivated influenza vaccine and to evaluate specific risks of first-trimester vaccination. This retrospective observational cohort study compared rates of medically attended adverse events in trivalent inactivated influenza-vaccinated and unvaccinated pregnant women in the Vaccine Safety Datalink. Using a Poisson distribution and log link, we calculated maternal adjusted incident rate ratios for composite safety outcomes for the full cohort and the subset vaccinated during the first trimester. The cohort included 75,906 vaccinated (28.4% in the first trimester) and 147,992 unvaccinated women matched by age, site, and pregnancy start date. In the first 3 days after vaccination, trivalent inactivated influenza vaccine was not associated with increased risk of specified medically attended events, including allergic reactions, cellulitis, and seizures (full cohort adjusted incident rate ratio 1.12, 95% confidence interval [CI] 0.81-1.55; P=.48; first-trimester adjusted incident rate ratio .97, 95% CI 0.53-1.78; P=.93). In the first 42 days, no incident cases of Guillain-Barré syndrome, optic neuritis, transverse myelitis, or Bells palsy were identified. Trivalent inactivated influenza vaccine was not associated with thrombocytopenia (full cohort adjusted incident rate ratio 0.90, 95% CI 0.68--1.19; P=.45; first-trimester adjusted incident rate ratio 0.56, 95% CI 0.22-1.39; P=.21) or an acute neurologic event (full cohort adjusted incident rate ratio 0.92, 95% CI 0.54-1.6; P=.75; first-trimester adjusted incident rate ratio 1.05, 95% CI 0.46-2.38; P=.91). Receipt of trivalent inactivated influenza vaccine during pregnancy was not associated with increased risk of adverse events in the 42 days after vaccination, supporting its safety for the mother.

  16. 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 guinea...

  17. 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 guinea...

  18. 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 guinea...

  19. 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 guinea...

  20. 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 guinea...

  1. Requirements for improved vaccines against foot-and-mouth disease epidemics

    PubMed Central

    2013-01-01

    Inactivated foot-and-mouth disease (FMD) vaccines are currently used worldwide. With the emergence of various FMD virus serotypes and subtypes, vaccines must become more suitable for field-based uses under the current circumstances in terms of the fast and proper selection of vaccine strains, an extended vaccine development period for new viruses, protecting against the risk of virus leakage during vaccine manufacture, counteracting the delayed onset of immune response, counteracting shorter durations of immunity, and the accurate serological differentiation of infected and vaccinated animals and multiple vaccination. The quality of vaccines should then be improved to effectively control FMD outbreaks and minimize the problems that can arise among livestock after vaccinations. Vaccine improvement should be based on using attenuated virus strains with high levels of safety. Moreover, when vaccines are urgently required for newly spread field strains, the seed viruses for new vaccines should be developed for only a short period. Improved vaccines should offer superior immunization to all susceptible animals including cattle and swine. In addition, they should have highly protective effects without persistent infection. In this way, if vaccines are developed using new methods such as reverse genetics or vector vaccine technology, in which live viruses can be easily made by replacing specific protective antigens, even a single vaccination is likely to generate highly protective effects with an extended duration of immunity, and the safety and stability of the vaccines will be assured. We therefore reviewed the current FMD vaccines and their adjuvants, and evaluated if they provide superior immunization to all susceptible animals including cattle and swine. PMID:23596585

  2. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. A systematic review and meta-analysis on the safety of newly adjuvanted vaccines among children.

    PubMed

    Stassijns, Jorgen; Bollaerts, Kaatje; Baay, Marc; Verstraeten, Thomas

    2016-02-03

    New adjuvants such as the AS- or the MF59-adjuvants improve vaccine efficacy and facilitate dose-sparing. Their use in influenza and malaria vaccines has resulted in a large body of evidence on their clinical safety in children. We carried out a systematic search for safety data from published clinical trials on newly adjuvanted vaccines in children ≤10 years of age. Serious adverse events (SAEs), solicited AEs, unsolicited AEs and AEs of special interest were evaluated for four new adjuvants: the immuno-stimulants containing adjuvant systems AS01 and AS02, and the squalene containing oil-in-water emulsions AS03 and MF59. Relative risks (RR) were calculated, comparing children receiving newly adjuvanted vaccines to children receiving other vaccines with a variety of antigens, both adjuvanted and unadjuvanted. Twenty-nine trials were included in the meta-analysis, encompassing 25,056 children who received at least one dose of the newly adjuvanted vaccines. SAEs did not occur more frequently in adjuvanted groups (RR 0.85, 95%CI 0.75-0.96). Our meta-analyses showed higher reactogenicity following administration of newly adjuvanted vaccines, however, no consistent pattern of solicited AEs was observed across adjuvant systems. Pain was the most prevalent AE, but often mild and of short duration. No increased risks were found for unsolicited AEs, febrile convulsions, potential immune mediated diseases and new onset of chronic diseases. Our meta-analysis did not show any safety concerns in clinical trials of the newly adjuvanted vaccines in children ≤10 years of age. An unexplained increase of meningitis in one Phase III AS01-adjuvanted malaria trial and the link between narcolepsy and the AS03-adjuvanted pandemic vaccine illustrate that continued safety monitoring is warranted. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. 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.

  5. [Does patient safety justify mandatory vaccinations?].

    PubMed

    Wicker, S; Rabenau, H F; Ackermann, H; Poland, G A; Marckmann, G

    2011-06-01

    Medical and dental students belong to a group of health care workers (HCWs) who are frequently exposed to patients with occupationally transmissible infectious diseases. Vaccinations are the most effective interventions to protect HCWs and patients from vaccine-preventable infectious diseases. Despite decades of effort to encourage HCWs to be immunized, vaccination levels (e. g. influenza) remain insufficient. To assess the attitudes of German medical and dental students towards mandatory immunizations, an anonymous questionnaire was offered to medical and dental students of the University of Frankfurt/Main, Germany. Overall, 56.9 % (1823/3200) of all medical and dental students attended to the study. This study - so far the largest study done on this issue - showed that almost 88.5 % of the responding medical and dental students would accept mandatory vaccinations for HCWs. Contrary to the widespread concern that a vaccination requirement would cause resistance, our data support that mandatory vaccinations (at least for HCWs who care for immunocompromised patients) might be widely accepted. © Georg Thieme Verlag KG Stuttgart · New York.

  6. Safety and Immunogenicity of a Quadrivalent Meningococcal Conjugate Vaccine and Commonly Administered Vaccines After Coadministration.

    PubMed

    Gasparini, Roberto; Tregnaghi, Miguel; Keshavan, Pavitra; Ypma, Ellen; Han, Linda; Smolenov, Igor

    2016-01-01

    Given the broad age range across which the quadrivalent meningococcal conjugate vaccine MenACWY-CRM is used, coadministration with routine vaccines should be evaluated across age groups for possible immunologic interference and impact on vaccine reactogenicity and safety. We summarize data from a large population of infants, adolescents and international travelers from 10 phase 3 or 4 clinical studies to evaluate coadministration of MenACWY-CRM with commonly administered vaccines. Noninferiority analyses of immune responses were performed across studies and age groups for each vaccine. Reactogenicity and safety were also assessed. In infants, MenACWY-CRM coadministered with routine vaccines did not reduce immune responses to diphtheria, tetanus, poliovirus, hepatitis B, Haemophilus influenzae type b, pneumococcal conjugate, measles-mumps-rubella, varicella or pertussis antigens. Noninferiority criteria were not met for some pneumococcal conjugate serotypes at 7 months of age, but no consistent trends were observed. In adolescents, coadministration did not reduce immune responses to tetanus, diphtheria and human papilloma virus vaccine antigens. Noninferiority criteria for pertussis antigens were not uniformly met in infant and adolescent studies, although the clinical relevance is unclear. In adults, coadministration did not reduce immune responses to hepatitis A/B, typhoid fever, yellow fever, Japanese encephalitis and rabies antigens. Immune responses to MenACWY-CRM were not impacted by coadministration of commonly administered vaccines. Coadministration did not increase frequencies of postvaccination adverse events in any age group. With no clinically relevant vaccine interactions or impact on vaccine reactogenicity or safety, these results support the coadministration of MenACWY-CRM with routine vaccines in all age groups.

  7. 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

  8. Pediatricians' perceptions of vaccine effectiveness and safety are significant predictors of vaccine administration in India.

    PubMed

    Gargano, Lisa M; Thacker, Naveen; Choudhury, Panna; Weiss, Paul S; Russ, Rebecca M; Pazol, Karen; Arora, Manisha; Orenstein, Walter A; Omer, Saad B; Hughes, James M

    2013-09-01

    New vaccine introduction is important to decrease morbidity and mortality in India. The goal of this study was to identify perceptions that are associated with administration of four selected vaccines for prevention of Japanese encephalitis (JE), typhoid fever, influenza and human papillomavirus (HPV) infection. A random sample of 785 pediatricians from a national list of Indian Academy of Pediatrics members was selected for a survey to assess perceptions of vaccine effectiveness and safety, and vaccine administration practices. Logistic regression was used to assess factors associated with selective or routine use. Pediatricians reported administering typhoid (91.6%), influenza (60.1%), HPV (46.0%) and JE (41.9%) vaccines selectively or routinely. Pediatricians who perceived the vaccine to be safe were significantly more likely to report administration of JE (OR 2.6, 95% CI 1.3 to 5.3), influenza (OR 4.3, 95% CI 2.0 to 9.6) and HPV vaccine (OR 6.2, 95% CI 3.1 to 12.7). Pediatricians who perceived the vaccine to be effective were significantly more likely to report administration of JE (OR 3.3, 95% CI 1.6 to 6.5), influenza (OR 7.7, 95% CI 2.5 to 23.1) and HPV vaccine (OR 3.2, 95% CI 1.6 to 6.4) CONCLUSION: Understanding the role perceptions play provides an opportunity to design strategies to build support for vaccine use.

  9. Statistical, epidemiological, and risk-assessment approaches to evaluating safety of vaccines throughout the life cycle at the Food and Drug Administration.

    PubMed

    Ball, Robert; Horne, Dale; Izurieta, Hector; Sutherland, Andrea; Walderhaug, Mark; Hsu, Henry

    2011-05-01

    The public health community faces increasing demands for improving vaccine safety while simultaneously increasing the number of vaccines available to prevent infectious diseases. The passage of the US Food and Drug Administration (FDA) Amendment Act of 2007 formalized the concept of life-cycle management of the risks and benefits of vaccines, from early clinical development through many years of use in large numbers of people. Harnessing scientific and technologic advances is necessary to improve vaccine-safety evaluation. The Office of Biostatistics and Epidemiology in the Center for Biologics Evaluation and Research is working to improve the FDA's ability to monitor vaccine safety by improving statistical, epidemiologic, and risk-assessment methods, gaining access to new sources of data, and exploring the use of genomics data. In this article we describe the current approaches, new resources, and future directions that the FDA is taking to improve the evaluation of vaccine safety.

  10. 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

  11. 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. Copyright © 2011 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

  12. Internet-based reporting to the vaccine adverse event reporting system: a more timely and complete way for providers to support vaccine safety.

    PubMed

    Haber, Penina; Iskander, John; Walton, Kimp; Campbell, Scott R; Kohl, Katrin S

    2011-05-01

    On March 22, 2002, Internet-based reports (IBRs) were added to the Vaccine Adverse Event Reporting System (VAERS) to allow rapid, expedited reporting of adverse events (AEs) in anticipation of wider use of counter-bioterrorism vaccines such as those against smallpox and anthrax. To evaluate the impact of IBRs on the timeliness and completeness of vaccine AE reporting. To evaluate timeliness and completeness, we compared the proportions of IBRs with non-Internet-based reports (NIBRs). Report interval was analyzed for timeliness and age at vaccination, birth date, and onset date for report completeness. To evaluate the impact of the smallpox vaccination program, we compared smallpox vaccine reports separately. Because influenza vaccine is the most widely used vaccine in adults each year, we compared influenza vaccine reports separately. During the study period, VAERS received 54 364 NIBRs (85.8%) and 9008 IBRs (14.2%). Sixteen percent (1455) of IBRs followed smallpox vaccination. Overall, for all vaccines and for smallpox vaccine alone, IBRs had a greater proportion of completeness and a shorter report interval. The proportion of most frequently reported AEs did not differ between IBRs and NIBRs. A higher proportion of adults (18-64 years old) who received influenza vaccine chose to complete an IBR (62% vs 48%). The improved timeliness and completeness of IBRs allow VAERS to more rapidly detect new or rare vaccine AEs. This important advantage is critical in times of increased public concern about vaccine safety. Clinical vaccine providers should be aware of VAERS and use IBRs whenever feasible to report vaccine AEs.

  13. 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

    Cox, Andrew; Dewhurst, Stephen

    2015-12-16

    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. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  14. Molecular mimicry, inflammatory bowel disease, and the vaccine safety debate.

    PubMed

    Yusung, Susy; Braun, Jonathan

    2014-09-18

    Preventive immunization has provided one of the major advances in population health during the past century. However, a surprising cultural phenomenon is the emergence of concerns about immunization safety, in part due to prominently controversial biomedical studies. One ongoing theoretical safety concern is the possibility of human molecular mimicry by measles, mumps, rubella (MMR) antigens. The study of Polymeros et al. in this BMC Medicine presents a systematic evaluation and refutation of this safety concern. This provides significant new scientific evidence in support of the safety of pediatric vaccines, which will inform the ongoing policy and cultural understanding of this important public health measure.

  15. Potential safety issues and other factors that may affect the introduction and uptake of rotavirus vaccines.

    PubMed

    Aliabadi, N; Tate, J E; Parashar, U D

    2016-12-01

    Rotavirus vaccines have demonstrated significant impact in reducing the burden of morbidity and mortality from childhood diarrhoea in countries that have implemented routine vaccination to date. Despite this success, in many countries, rotavirus vaccine coverage remains lower than that of other routine childhood vaccines. Several issues may potentially affect vaccine uptake, namely safety concerns related to intussusception with consequent age restrictions on rotavirus vaccination, contamination with porcine circovirus, vaccine-derived reassortant strains and hospitalization in newborn nurseries at time of administration of live oral rotavirus vaccine. In addition to these safety concerns, other factors may also affect uptake, including lower vaccine efficacy in the developing world, potential emergence of strains escaping from vaccine protection resulting in lower overall impact of a vaccination programme and sustainable vaccine financing. Although further work is needed to address some of these concerns, global policy bodies have reaffirmed that the benefits of rotavirus vaccination outweigh the risks, and vaccine use is recommended globally.

  16. Influenza Vaccination During Pregnancy: Influenza Seasons 2002-2012, Vaccine Safety Datalink.

    PubMed

    Groom, Holly C; Henninger, Michelle L; Smith, Ning; Koppolu, Padma; Cheetham, T Craig; Glanz, Jason M; Hambidge, Simon J; Jackson, Lisa A; Kharbanda, Elyse O; Klein, Nicola P; McCarthy, Natalie L; Nordin, James D; Weintraub, Eric S; Naleway, Allison L

    2016-04-01

    Pregnant women are at risk for influenza-related complications and have been recommended for vaccination by the Advisory Committee on Immunization Practices (ACIP) since 1990. Annual rates of influenza coverage of pregnant women have been consistently low. The Vaccine Safety Datalink was used to assess influenza vaccine coverage over 10 consecutive years (2002-2012); assess patterns related to changes in ACIP recommendations; identify predictors of vaccination; and compare the results with those published by national U.S. surveys. Retrospective cohort study of 721,898 pregnancies conducted in 2014. Coverage rates were assessed for all pregnancies and for live births only. Multivariate regression analysis identified predictors associated with vaccination. Coverage increased from 8.8% to 50.9% in 2002-2012. Seasonal coverage rates increased slowly following the 2004 ACIP influenza vaccine recommendation (to remove the first trimester restriction), but spiked significantly during the 2009 H1N1 influenza pandemic. Significant predictors of vaccination during pregnancy included older age; vaccination in a previous season; high-risk conditions in addition to pregnancy; pregnancy during either the 2004-2005 or 2009-2010 seasons; entering the influenza season after the first trimester of pregnancy; and a pregnancy with longer overlap with the influenza season (p<0.001 for each). Influenza vaccination coverage among pregnant women increased between the 2002-2003 and 2011-2012 seasons, although it was still below the developmental Healthy People 2020 goal of 80%. The 2004 ACIP language change positively impacted first-trimester vaccination uptake. Vaccine Safety Datalink data estimates were consistent with U.S. estimates. Copyright © 2016 American Journal of Preventive Medicine. All rights reserved.

  17. Understanding the role of human variation in vaccine adverse events: the Clinical Immunization Safety Assessment Network.

    PubMed

    LaRussa, Philip S; Edwards, Kathryn M; Dekker, Cornelia L; Klein, Nicola P; Halsey, Neal A; Marchant, Colin; Baxter, Roger; Engler, Renata J M; Kissner, Jennifer; Slade, Barbara A

    2011-05-01

    The Clinical Immunization Safety Assessment (CISA) Network is a collaboration between the Centers for Disease Control and Prevention (CDC) and 6 academic medical centers to provide support for immunization safety assessment and research. The CISA Network was established by the CDC in 2001 with 4 primary goals: (1) develop research protocols for clinical evaluation, diagnosis, and management of adverse events following immunization (AEFI); (2) improve the understanding of AEFI at the individual level, including determining possible genetic and other risk factors for predisposed people and subpopulations at high risk; (3) develop evidence-based algorithms for vaccination of people at risk of serious AEFI; and (4) serve as subject-matter experts for clinical vaccine-safety inquiries. CISA Network investigators bring in-depth clinical, pathophysiologic, and epidemiologic expertise to assessing causal relationships between vaccines and adverse events and to understanding the pathogenesis of AEFI. CISA Network researchers conduct expert reviews of clinically significant adverse events and determine the validity of the recorded diagnoses on the basis of clinical and laboratory criteria. They also conduct special studies to investigate the possible pathogenesis of adverse events, assess relationships between vaccines and adverse events, and maintain a centralized repository for clinical specimens. The CISA Network provides specific clinical guidance to both health care providers who administer vaccines and those who evaluate and treat patients with possible AEFI. The CISA Network plays an important role in providing critical immunization-safety data and expertise to inform vaccine policy-makers. The CISA Network serves as a unique resource for vaccine-safety monitoring efforts conducted at the CDC.

  18. Safety of second-generation rotavirus vaccines, intussusception.

    PubMed

    Vázquez, Marietta

    2014-02-01

    This article discusses new data available on the safety of the second-generation rotavirus vaccines both in the United States and internationally. Second-generation rotavirus vaccines are both highly effective against rotavirus disease. Recent data from passive and active surveillance systems in the United States indicate that RV1 and RV5 vaccines may possibly cause a small increase in the risk of intussusception; an estimated 1-3 US infants out of 100 000 might develop intussusception within 7 days of getting their first dose of rotavirus vaccine. Parents and health providers should be aware of the small risk of intussusception, the signs and symptoms of intussusception, and the need for prompt care. Taking into consideration available data on the benefits and risks, Centers for Disease Control and Prevention (CDC) continues to recommend that all US infants receive rotavirus vaccine based on the age and precaution/contraindication criteria. The benefits of RV5 and RV1 outweigh the small excess risk of intussusception. Safety monitoring will continue, both in the United States and internationally, to further quantitate the intussusception risk following each vaccine.

  19. Immunogenicity and safety among laboratory workers vaccinated with Bexsero® vaccine

    PubMed Central

    Hong, Eva; Terrade, Aude; Taha, Muhamed-Kheir

    2017-01-01

    ABSTRACT Neisseria meningitidis serogroup B is the most prevalent cause of invasive meningococcal disease in Europe and members of laboratories working on meningococci are at risk due to frequent handling. Recommendation for anti-meningococcal vaccination among these workers has been recently updated upon the licensure in Europe of Bexsero® vaccine. We tested the immunogenicity and safety of this vaccine among adults laboratory staff using the recommended schedule of 2 doses at 5 weeks interval. The vaccine was well tolerated in spite of frequent local side effects and all participants reported at least one side effect after each dose. Immunogenicity was evaluated 6 weeks and one year after the second dose. All participants showed increase in their bactericidal titers against the components of the vaccine 6 weeks after the second dose, however titers declined significantly one year later. PMID:27808594

  20. Immunogenicity and safety among laboratory workers vaccinated with Bexsero® vaccine.

    PubMed

    Hong, Eva; Terrade, Aude; Taha, Muhamed-Kheir

    2016-11-03

    Neisseria meningitidis serogroup B is the most prevalent cause of invasive meningococcal disease in Europe and members of laboratories working on meningococci are at risk due to frequent handling. Recommendation for anti-meningococcal vaccination among these workers has been recently updated upon the licensure in Europe of Bexsero® vaccine. We tested the immunogenicity and safety of this vaccine among adults laboratory staff using the recommended schedule of 2 doses at 5 weeks interval. The vaccine was well tolerated in spite of frequent local side effects and all participants reported at least one side effect after each dose. Immunogenicity was evaluated 6 weeks and one year after the second dose. All participants showed increase in their bactericidal titers against the components of the vaccine 6 weeks after the second dose, however titers declined significantly one year later.

  1. Rotavirus vaccines: safety, efficacy and public health impact.

    PubMed

    Gray, J

    2011-09-01

    Rotaviruses are the cause of acute gastroenteritis, and disease is widespread amongst infants and young children throughout the world. Also, rotavirus is associated with significant mortality in developing countries with more than 500 000 children dying each year as a result of the severe dehydration associated with rotavirus disease. Efforts have been ongoing for more than 30 years to develop a safe and effective rotavirus vaccine. Currently, two vaccines, RotaRix and RotaTeq, have been licensed for use in many countries throughout the world following comprehensive safety and efficiency trials. Monitoring their effectiveness after licensure has confirmed that their incorporation into early childhood vaccination schedules can significantly prevent severe rotavirus diarrhoea, which would have resulted in hospitalizations, emergency room visits or increased diarrhoea-related mortality. Although the efficacy of both vaccines is lower at approximately 40-59% in developing countries, their use could significantly reduce the mortality associated with rotavirus disease that is concentrated in these countries.

  2. Vaccine safety monitoring systems in developing countries: an example of the Vietnam model.

    PubMed

    Ali, Mohammad; Rath, Barbara; Thiem, Vu Dinh

    2015-01-01

    Only few health intervention programs have been as successful as vaccination programs with respect to preventing morbidity and mortality in developing countries. However, the success of a vaccination program is threatened by rumors and misunderstanding about the risks of vaccines. It is short-sighted to plan the introduction of vaccines into developing countries unless effective vaccine safety monitoring systems are in place. Such systems that track adverse events following immunization (AEFI) is currently lacking in most developing countries. Therefore, any rumor may affect the entire vaccination program. Public health authorities should implement the safety monitoring system of vaccines, and disseminate safety issues in a proactive mode. Effective safety surveillance systems should allow for the conduct of both traditional and alternative epidemiologic studies through the use of prospective data sets. The vaccine safety data link implemented in Vietnam in mid-2002 indicates that it is feasible to establish a vaccine safety monitoring system for the communication of vaccine safety in developing countries. The data link provided the investigators an opportunity to evaluate AEFI related to measles vaccine. Implementing such vaccine safety monitoring system is useful in all developing countries. The system should be able to make objective and clear communication regarding safety issues of vaccines, and the data should be reported to the public on a regular basis for maintaining their confidence in vaccination programs.

  3. The immunogenicity and safety of zoster vaccine in Taiwanese adults.

    PubMed

    Yao, Chien-An; Chen, Liang-Kung; Huang, Kuo-Chin

    2015-03-24

    The efficacy and safety of ZOSTAVAX in subjects 60 years of age and older was established in the Shingles Prevention Study (SPS) and in subjects 50 to 59 years of age in the ZOSTAVAX Efficacy and Safety Trial (ZEST). We evaluated the safety and immunogenicity of ZOSTAVAX in a total of 150 Taiwanese subjects ≥50 years of age, who received a single dose of ZOSTAVAX. gpELISA was used to determine geometric mean titers (GMT) of the varicella-zoster virus (VZV) antibody. The geometric mean fold rise (GMFR) of the VZV antibody from the pre-vaccination to the 4 week post-vaccination time point was calculated. There was an overall increase in GMT from 128.45 to 391.85 at 4 weeks post-vaccination. The estimated GMFR was 3.05 (95% CI: 2.60 to 3.57).There were no serious adverse events for 28 days following vaccination. This study demonstrated the safety and immunogenicity of ZOSTAVAX among healthy Taiwanese adults.

  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. Childhood vaccines and Kawasaki disease, Vaccine Safety Datalink, 1996-2006.

    PubMed

    Abrams, Joseph Y; Weintraub, Eric S; Baggs, James M; McCarthy, Natalie L; Schonberger, Lawrence B; Lee, Grace M; Klein, Nicola P; Belongia, Edward A; Jackson, Michael L; Naleway, Allison L; Nordin, James D; Hambidge, Simon J; Belay, Ermias D

    2015-01-03

    Kawasaki disease is a childhood vascular disorder of unknown etiology. Concerns have been raised about vaccinations being a potential risk factor for Kawasaki disease. Data from the Vaccine Safety Datalink were collected on children aged 0-6 years at seven managed care organizations across the United States. Defining exposure as one of several time periods up to 42 days after vaccination, we conducted Poisson regressions controlling for age, sex, season, and managed care organization to determine if rates of physician-diagnosed and verified Kawasaki disease were elevated following vaccination compared to rates during all unexposed periods. We also performed case-crossover analyses to control for unmeasured confounding. A total of 1,721,186 children aged 0-6 years from seven managed care organizations were followed for a combined 4,417,766 person-years. The rate of verified Kawasaki disease was significantly lower during the 1-42 days after vaccination (rate ratio=0.50, 95% CL=0.27-0.92) and 8-42 days after vaccination (rate ratio=0.45, 95% CL=0.22-0.90) compared to rates during unexposed periods. Breaking down the analysis by vaccination category did not identify a subset of vaccines which was solely responsible for this association. The case-crossover analyses revealed that children with Kawasaki disease had lower rates of vaccination in the 42 days prior to symptom onset for both physician-diagnosed Kawasaki disease (rate ratio=0.79, 95% CL=0.64-0.97) and verified Kawasaki disease (rate ratio=0.38, 95% CL=0.20-0.75). Childhood vaccinations' studied did not increase the risk of Kawasaki disease; conversely, vaccination was associated with a transient decrease in Kawasaki disease incidence. Verifying and understanding this potential protective effect could yield clues to the underlying etiology of Kawasaki disease. Copyright © 2014. Published by Elsevier Ltd.

  6. Sequential Generalized Likelihood Ratio Tests for Vaccine Safety Evaluation

    PubMed Central

    Shih, Mei-Chiung; Lai, Tze Leung; Heyse, Joseph F.; Chen, Jie

    2010-01-01

    SUMMARY The evaluation of vaccine safety involves pre-clinical animal studies, pre-licensure randomized clinical trials and post-licensure safety studies. Sequential design and analysis are of particular interest because they allow early termination of the trial or quick detection that the vaccine exceeds a prescribed bound on the adverse event rate. After a review of recent developments in this area, we propose a new class of sequential generalized likelihood ratio tests for evaluating adverse event rates in two-armed pre-licensure clinical trials and single-armed post-licensure studies. The proposed approach is illustrated using data from the Rotavirus Efficacy and Safety Trial (REST). Simulation studies of the performance of the proposed approach and other methods are also given. PMID:20799244

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

    PubMed

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

    2011-05-01

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

  8. Immunogenicity and Safety of Diphtheria-tetanus Vaccine in Adults

    PubMed Central

    Choi, Jung-Hyun; Choo, Eun Ju; Huh, Aejung; Choi, Su-Mi; Eom, Joong Sik; Lee, Jin Seo; Park, Sun Hee

    2010-01-01

    This study was conducted to evaluate the immunogenicity and safety of diphtheria-tetanus (Td) vaccine in adults over 40 yr old who had never received a diphtheria-tetanus-pertussis (DTP) vaccination. A total of 242 subject completed three-doses of Td vaccination and subsequent assays for immunogenicity. Before vaccination, 33.9% and 96.7% participants showed antibody levels of diphtheria and tetanus, respectively, which were below protective level (<0.1 U/mL). After the first dose of Td vaccine, 92.6% and 77.6% of subjects gained protective antibody concentrations (≥0.1 U/mL) for diphtheria and tetanus, with an increase to 99.6% and 100% after the third dose. Local and systemic adverse events occurred in 37.9% and 15.5% of the subjects. No serious adverse event requiring an unscheduled hospital visit occurred. In conclusion, three-doses of Td vaccination to unimmunized adults are safe and effective in inducing protective immunity against diphtheria and tetanus. PMID:21165286

  9. Immunogenicity and safety of diphtheria-tetanus vaccine in adults.

    PubMed

    Choi, Jung-Hyun; Choo, Eun Ju; Huh, Aejung; Choi, Su-Mi; Eom, Joong Sik; Lee, Jin Seo; Park, Sun Hee; Kang, Jin Han

    2010-12-01

    This study was conducted to evaluate the immunogenicity and safety of diphtheria-tetanus (Td) vaccine in adults over 40 yr old who had never received a diphtheria-tetanus-pertussis (DTP) vaccination. A total of 242 subject completed three-doses of Td vaccination and subsequent assays for immunogenicity. Before vaccination, 33.9% and 96.7% participants showed antibody levels of diphtheria and tetanus, respectively, which were below protective level (<0.1 U/mL). After the first dose of Td vaccine, 92.6% and 77.6% of subjects gained protective antibody concentrations (≥ 0.1 U/mL) for diphtheria and tetanus, with an increase to 99.6% and 100% after the third dose. Local and systemic adverse events occurred in 37.9% and 15.5% of the subjects. No serious adverse event requiring an unscheduled hospital visit occurred. In conclusion, three-doses of Td vaccination to unimmunized adults are safe and effective in inducing protective immunity against diphtheria and tetanus.

  10. Safety and immunogenicity of influenza vaccine among HIV-infected adults: Conventional vaccine vs. intradermal vaccine.

    PubMed

    Seo, Yu Bin; Lee, Jacob; Song, Joon Young; Choi, Hee Jung; Cheong, Hee Jin; Kim, Woo Joo

    2016-01-01

    Several studies have reported poor immune responses to conventional influenza vaccines in HIV-infected individuals. This study sought to elicit more potent immunogenicity in HIV-infected adults using an intradermal vaccine compared with a conventional intramuscular vaccine. This multicenter, randomized, controlled, open-label study was conducted at 3 university hospitals during the 2011/2012 pre-influenza season. Three vaccines were used in HIV-infected adults aged 18 - 60 years: an inactivated intramuscular vaccine (Agrippal), a reduced-content intradermal vaccine (IDflu9μg) and a standard-content intradermal vaccine (IDflu15μg). Serum hemagglutination-inhibiting (HI) antibodies and INF-γ ELISpot assay were measured at the time of vaccination and 1 month after vaccination. Adverse events were recorded for 7 d. A total of 28 Agrippal, 30 IDflu9μg, and 28 IDflu15μg volunteers were included in this analysis. One month after vaccination, the GMTs and differences in INF-γ ELISpot assay results were similar among the 3 groups. Seroprotection rates, seroconversion rates and mean fold increases (MFI) among the 3 groups were also similar, at approximately 80%, 50-60% and 2.5 - 10.0, respectively. All three vaccines satisfied the CHMP criteria for the A/H1N1 and A/H3N2 strains, but not those for the B strain. In univariate analysis, no demographic or clinical factors, including age, CD4+ T-cell counts, HIV viral load, ART status and vaccine type, were related to failure to achieve seroprotection. The three vaccines were all well-tolerated and all reported reactions were mild to moderate. However, there was a tendency toward a higher incidence of local and systemic reactions in the intradermal vaccine groups. The intradermal vaccine did not result in higher immunogenicity compared to the conventional intramuscular vaccine, even with increased antigen dose.

  11. Feasibility of Text Message Influenza Vaccine Safety Monitoring During Pregnancy.

    PubMed

    Stockwell, Melissa S; Cano, Maria; Jakob, Kathleen; Broder, Karen R; Gyamfi-Bannerman, Cynthia; Castaño, Paula M; Lewis, Paige; Barrett, Angela; Museru, Oidda I; Castellanos, Ormarys; LaRussa, Philip S

    2017-09-01

    The feasibility and accuracy of text messaging to monitor events after influenza vaccination throughout pregnancy and the neonatal period has not been studied, but may be important for seasonal and pandemic influenza vaccines and future maternal vaccines. This prospective observational study was conducted during 2013-2014 and analyzed in 2015-2016. Enrolled pregnant women receiving inactivated influenza vaccination at a gestational age <20 weeks were sent text messages intermittently through participant-reported pregnancy end to request fever, health events, and neonatal outcomes. Text message response rates, Day 0-2 fever (≥100.4°F), health events, and birth/neonatal outcomes were assessed. Most (80.2%, n=166) eligible women enrolled. Median gestational age was 8.9 (SD=3.9) weeks at vaccination. Response rates remained high (80.0%-95.2%). Only one Day 0-2 fever was reported. Women reported via text both pregnancy- and non-pregnancy-specific health events, not all associated with medical visits. Most pregnancy-specific events in the electronic medical record (EMR) were reported via text message. Of all enrollees, 84.9% completed the study (131 reported live birth, ten reported pregnancy loss). Two losses reported via text were not medically attended; there was one additional EMR-identified loss. Gestational age and weight at birth were similar between text message-reported and EMR-abstracted data and 95% CIs were overlapping for proportions of prematurity, low birth weight, small for gestational age, and major birth defects, as identified by text message-reported versus EMR-abstracted plus text message-reported versus EMR-abstracted data only. This study demonstrated the feasibility of text messaging for influenza vaccine safety surveillance sustained throughout pregnancy. In these women receiving inactivated influenza vaccination during pregnancy, post-vaccination fever was infrequent and a typical pattern of maternal and neonatal health outcomes was observed

  12. 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

  13. Vaccination of preterm infants by polyvalent vaccines: immunogenicity and safety- review of literature.

    PubMed

    Czajka, Hanna; Lauterbach, Ryszard; Pawlik, Dorota

    2014-01-01

    The immunization of infants against infectious diseases still raises many controversies, not only with parents, but also among physicians. This refers particularly to preterm infants. Due to the increasing popularity of polyvalent vaccines, a number of studies has recently been conducted to verify their immunogenicity and safety in preterm infants. The aim of the present paper was to review the current literature dealing with the problem in question. The following recommendations regarding the use of polyvalent vaccines in preterm infants and neonates with low birth weight can be formulated on the basis of current evidence (1). Due to sufficient immunogenicity, polyvalent vaccines can be administered to preterm infants in accordance with their calendar age (2). Booster vaccination of preterm infants after completing 12 months of age is vital for achieving complete and persistent immunity against all vaccine antigens (3). In order to reduce the risk of adverse events after the administration of a polyvalent vaccine, it is essential to carefully consider the cardiorespiratory status of preterm infants during preimmunization examination, as well as their history of any cardiorespiratory dysfunctions. In such cases administering the first dose of the vaccine in a hospital setting is strongly advised.

  14. Using reverse genetics to manipulate the NSs gene of the Rift Valley fever virus MP-12 strain to improve vaccine safety and efficacy.

    PubMed

    Kalveram, Birte; Lihoradova, Olga; Indran, Sabarish V; Ikegami, Tetsuro

    2011-11-01

    Rift Valley fever virus (RVFV), which causes hemorrhagic fever, neurological disorders or blindness in humans, and a high rate abortion and fetal malformation in ruminants, has been classified as a HHS/USDA overlap select agent and a risk group 3 pathogen. It belongs to the genus Phlebovirus in the family Bunyaviridae and is one of the most virulent members of this family. Several reverse genetics systems for the RVFV MP-12 vaccine strain as well as wild-type RVFV strains, including ZH548 and ZH501, have been developed since 2006. The MP-12 strain (which is a risk group 2 pathogen and a non-select agent) is highly attenuated by several mutations in its M- and L-segments, but still carries virulent S-segment RNA, which encodes a functional virulence factor, NSs. The rMP12-C13type (C13type) carrying 69% in-frame deletion of NSs ORF lacks all the known NSs functions, while it replicates as efficient as does MP-12 in VeroE6 cells lacking type-I IFN. NSs induces a shut-off of host transcription including interferon (IFN)-beta mRNA and promotes degradation of double-stranded RNA-dependent protein kinase (PKR) at the post-translational level. IFN-beta is transcriptionally upregulated by interferon regulatory factor 3 (IRF-3), NF-kB and activator protein-1 (AP-1), and the binding of IFN-beta to IFN-alpha/beta receptor (IFNAR) stimulates the transcription of IFN-alpha genes or other interferon stimulated genes (ISGs), which induces host antiviral activities, whereas host transcription suppression including IFN-beta gene by NSs prevents the gene upregulations of those ISGs in response to viral replication although IRF-3, NF-kB and activator protein-1 (AP-1) can be activated by RVFV7. Thus, NSs is an excellent target to further attenuate MP-12, and to enhance host innate immune responses by abolishing the IFN-beta suppression function. Here, we describe a protocol for generating a recombinant MP-12 encoding mutated NSs, and provide an example of a screening method to identify

  15. 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.

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

    PubMed

    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.

  17. 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

  18. A novel vaccinological evaluation of intranasal vaccine and adjuvant safety for preclinical tests.

    PubMed

    Sasaki, Eita; Kuramitsu, Madoka; Momose, Haruka; Kobiyama, Kouji; Aoshi, Taiki; Yamada, Hiroshi; Ishii, Ken J; Mizukami, Takuo; Hamaguchi, Isao

    2017-02-01

    Vaccines are administered to healthy humans, including infants, so the safety and efficacy must be very high. Therefore, evaluating vaccine safety in preclinical and clinical studies, according to World Health Organization guidelines, is crucial for vaccine development and clinical use. A change in the route of administration is considered to alter a vaccine's immunogenicity. Several adjuvants have also been developed and approved for use in vaccines. However, the addition of adjuvants to vaccines may cause unwanted immune responses, including facial nerve paralysis and narcolepsy. Therefore, a more accurate and comprehensive strategy must be used to develope next-generation vaccines for ensuring vaccine safety. Previously, we have developed a system with which to evaluate vaccine safety in rats using a systematic vaccinological approach and 20 marker genes. In this study, we developed a safety evaluation system for nasally administered influenza vaccines and adjuvanted influenza vaccines using these marker genes. Expression of these genes increased dose-dependent manner when mice were intranasally administered the toxicity reference vaccine. When the adjuvant CpG K3 or a CpG-K3-combined influenza vaccine was administered intranasally, marker gene expression increased in a CpG-K3-dose-dependent way. A histopathological analysis indicated that marker gene expression correlated with vaccine- or adjuvant-induced phenotypic changes in the lung and nasal mucosa. We believe that the marker genes expression analyses will be useful in preclinical testing, adjuvant development, and selecting the appropriate dose of adjuvant in nasal administration vaccines.

  19. Generation of safety enhanced Edwardsiella tarda ghost vaccine.

    PubMed

    Lee, Dong Jin; Kwon, Se Ryun; Zenke, Kosuke; Lee, Eun Hye; Nam, Yoon Kwon; Kim, Sung Koo; Kim, Ki Hong

    2008-09-24

    A dual vector expressing the ghost-inducing PhiX174 lysis E gene and the bacterial DNA degrading staphylococcal nuclease A (SNA) gene was constructed to solve the problem of remnant antibiotic resistance genes and genomic DNA with intact pathogenic islands in the final product of Edwardsiella tarda ghosts (ETG). The SNA (devoid of secretion signal sequence and the nuclease B amino terminus sequence), fused with the 26 amino acid N-terminal sequence of the lambda phage Cro gene, showed successful degradation of bacterial nucleic acids. Furthermore, the nuclease activity of SNA in E. tarda was enhanced by codon optimization of the SNA gene using site-directed mutagenesis. ETG were generated via coexpression of the SNA gene and lysis gene E under the control of each lambdaP(R) promoter. The ghost bacteria generation system we describe is advantageous as it allows the use of a single plasmid, improves safety and vaccine purity by limiting residual genetic content from the ghost bacteria, and reduces production costs through cheap means of induction that use only temperature shifts.

  20. White Paper on studying the safety of the childhood immunization schedule in the Vaccine Safety Datalink.

    PubMed

    Glanz, Jason M; Newcomer, Sophia R; Jackson, Michael L; Omer, Saad B; Bednarczyk, Robert A; Shoup, Jo Ann; DeStefano, Frank; Daley, Matthew F

    2016-02-15

    While the large majority of parents in the U.S. vaccinate their children according to the recommended immunization schedule, some parents have refused or delayed vaccinating, often citing safety concerns. In response to public concern, the U.S. Institute of Medicine (IOM) evaluated existing research regarding the safety of the recommended immunization schedule. The IOM concluded that although available evidence strongly supported the safety of the currently recommended schedule as a whole, additional observational research was warranted to compare health outcomes between fully vaccinated children and those on a delayed or alternative schedule. In addition, the IOM identified the Vaccine Safety Datalink (VSD) as an important resource for conducting this research. Guided by the IOM findings, the Centers for Disease Control and Prevention (CDC) commissioned a White Paper to assess how the VSD could be used to study the safety of the childhood immunization schedule. Guided by subject matter expert engagement, the resulting White Paper outlines a 4 stage approach for identifying exposure groups of undervaccinated children, presents a list of health outcomes of highest priority to examine in this context, and describes various study designs and statistical methods that could be used to analyze the safety of the schedule. While it appears feasible to study the safety of the recommended immunization schedule in settings such as the VSD, these studies will be inherently complex, and as with all observational studies, will need to carefully address issues of confounding and bias. In light of these considerations, decisions about conducting studies of the safety of the schedule will also need to assess epidemiological evidence of potential adverse events that could be related to the schedule, the biological plausibility of an association between an adverse event and the schedule, and public concern about the safety of the schedule.

  1. Safety of infectious bursal disease vaccines: assessment of an acceptability threshold.

    PubMed

    Guittet, M; Le Coq, H; Picault, J P; Eterradossi, N; Bennejean, G

    1992-01-01

    This study was undertaken to check the safety of commercially available infectious bursal disease (IBD) vaccines in terms of bursal damage, and their immunodepressive effects as evaluated by testing the birds after vaccination for their response to Newcastle disease vaccination. Further requirements are proposed to establish a suitable safety standard.

  2. Using Reverse Genetics to Manipulate the NSs Gene of the Rift Valley Fever Virus MP-12 Strain to Improve Vaccine Safety and Efficacy

    PubMed Central

    Kalveram, Birte; Lihoradova, Olga; Indran, Sabarish V.; Ikegami, Tetsuro

    2011-01-01

    Rift Valley fever virus (RVFV), which causes hemorrhagic fever, neurological disorders or blindness in humans, and a high rate abortion and fetal malformation in ruminants1, has been classified as a HHS/USDA overlap select agent and a risk group 3 pathogen. It belongs to the genus Phlebovirus in the family Bunyaviridae and is one of the most virulent members of this family. Several reverse genetics systems for the RVFV MP-12 vaccine strain2,3 as well as wild-type RVFV strains 4-6, including ZH548 and ZH501, have been developed since 2006. The MP-12 strain (which is a risk group 2 pathogen and a non-select agent) is highly attenuated by several mutations in its M- and L-segments, but still carries virulent S-segment RNA3, which encodes a functional virulence factor, NSs. The rMP12-C13type (C13type) carrying 69% in-frame deletion of NSs ORF lacks all the known NSs functions, while it replicates as efficient as does MP-12 in VeroE6 cells lacking type-I IFN. NSs induces a shut-off of host transcription including interferon (IFN)-beta mRNA7,8 and promotes degradation of double-stranded RNA-dependent protein kinase (PKR) at the post-translational level.9,10 IFN-beta is transcriptionally upregulated by interferon regulatory factor 3 (IRF-3), NF-kB and activator protein-1 (AP-1), and the binding of IFN-beta to IFN-alpha/beta receptor (IFNAR) stimulates the transcription of IFN-alpha genes or other interferon stimulated genes (ISGs)11, which induces host antiviral activities, whereas host transcription suppression including IFN-beta gene by NSs prevents the gene upregulations of those ISGs in response to viral replication although IRF-3, NF-kB and activator protein-1 (AP-1) can be activated by RVFV7. . Thus, NSs is an excellent target to further attenuate MP-12, and to enhance host innate immune responses by abolishing the IFN-beta suppression function. Here, we describe a protocol for generating a recombinant MP-12 encoding mutated NSs, and provide an example of a

  3. Safety and tolerability of pneumococcal vaccines in children.

    PubMed

    Esposito, Susanna; Principi, Nicola

    2016-06-01

    A number of pneumococcal vaccines have long been available and have been used to reduce the medical, social, and economic problems associated with Streptococcus pneumoniae-related diseases. The main purpose of this review was to analyze what has been, until recently, the established doctrine regarding the safety and tolerability of pneumococcal vaccines that have been used in the past and are currently being used in children. Pneumococcal vaccines available on the market are all safe and are highly recommended in clinical practice. In children, pneumococcal conjugate vaccines (PCVs) are considered the preparations of choice because of their enhanced immunogenicity and superior ability to impact nasopharyngeal carriage. All PCVs are considered safe because the incidence of severe adverse events (AEs) is marginal. Nonetheless, evidence has emerged from post-marketing surveillance regarding the occurrence of very rare but significant potential AEs following PCV administration. Therefore, post-marketing surveillance should be maintained to confirm the existence of these AEs. Over the next few years, other pneumococcal vaccines will be developed. When these new products are licensed and reach the market, new technologies and innovative epidemiological methods will permit a more rapid and more effective evaluation of AEs.

  4. 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…

  5. The importance of the patient voice in vaccination and vaccine safety-are we listening?

    PubMed

    Holt, D; Bouder, F; Elemuwa, C; Gaedicke, G; Khamesipour, A; Kisler, B; Kochhar, S; Kutalek, R; Maurer, W; Obermeier, P; Seeber, L; Trusko, B; Gould, S; Rath, B

    2016-12-01

    Much has been written about the patient-physician relationship over the years. This relationship is essential in maintaining trust in the complex arena of modern diagnostic techniques, treatment and prevention, including vaccines and vaccine safety. However, a great deal of this material was written from the viewpoint of clinicians and academics. The patient voice may be positive or negative, fragmented or complex. Information sources are weighed and treated differently, according to the value system and risk perceptions of the individual. In post-trust societies, when people have less confidence in health authorities, communication needs to be more than a paternalistic top-down process. Notions of empowerment and individual patient choice are becoming crucial in medical care. The 'voice of the patient', which includes healthy individuals receiving vaccines, needs to be heard, considered and addressed. With respect to childhood immunizations, this will be the voice of the parent or caregiver. The key to addressing any concerns could be to listen more and to develop a communication style that is trust-based and science-informed. Regulatory agencies are encouraging clinical and patient-reported outcomes research under the umbrella of personalized medicine, and this is an important step forward. This paper attempts to reflect the paradigm shift towards increasing attention to the patient voice in vaccination and vaccine safety.

  6. Improving accountability in vaccine decision-making.

    PubMed

    Timmis, James Kenneth; Black, Steven; Rappuoli, Rino

    2017-09-20

    Introduction Healthcare decisions, in particular those affecting entire populations, should be evidence-based and taken by decision-makers sharing broad alignment with affected stakeholders. However, criteria, priorities and procedures for decision-making are sometimes non-transparent, frequently vary considerably across equivalent decision-bodies, do not always consider the broader benefits of new health-measures, and therefore do not necessarily adequately represent the relevant stakeholder-spectrum. Areas covered To address these issues in the context of the evaluation of new vaccines, we have proposed a first baseline set of core evaluation criteria, primarily selected by members of the vaccine research community, and suggested their implementation in vaccine evaluation procedures. In this communication, we review the consequences and utility of stakeholder-centered core considerations to increase transparency in and accountability of decision-making procedures, in general, and of the benefits gained by their inclusion in Multi-Criteria-Decision-Analysis tools, exemplified by SMART Vaccines, specifically. Expert Commentary To increase effectiveness and comparability of health decision outcomes, decision procedures should be properly standardized across equivalent (national) decision bodies. To this end, including stakeholder-centered criteria in decision procedures would significantly increase their transparency and accountability, support international capacity building to improve health, and reduce societal costs and inequity resulting from suboptimal health decision-making.

  7. 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.

  8. Parents' Perspectives on How to Improve the Childhood Vaccination Process.

    PubMed

    Lieu, Tracy A; Zikmund-Fisher, Brian J; Chou, Cathy; Ray, G Thomas; Wittenberg, Eve

    2017-03-01

    Few national studies have asked parents how to improve the childhood vaccination process. We surveyed a nationally representative online panel of parents on how to improve this process, rationales for nonstandard approaches, and alternatives to the standard schedule. Twelve percent of the 1222 respondents reported using nonstandard approaches: 3.2% used a specific schedule, 6.0% had no specific schedule, and 2.5% declined all vaccinations. The most common rationales were that too many vaccines are given at once, and discomfort with vaccine ingredients. Regarding how to improve the process, parents using the standard schedule most often said nothing could be improved (51%), or better vaccine information (22%). Those using nonstandard approaches most often would have liked more choice (40%) or better vaccine information (26%). Parents' experiences with the vaccination process could be improved by offering information prior to visits, giving more information about side effects, and allowing more flexibility about vaccine scheduling.

  9. Understanding vaccine safety information from the Vaccine Adverse Event Reporting System.

    PubMed

    Varricchio, Frederick; Iskander, John; Destefano, Frank; Ball, Robert; Pless, Robert; Braun, M Miles; Chen, Robert T

    2004-04-01

    The Vaccine Adverse Event Reporting System (VAERS) is administered by the Food and Drug Administration and CDC and is a key component of postlicensure vaccine safety surveillance. Its primary function is to detect early warning signals and generate hypotheses about possible new vaccine adverse events or changes in frequency of known ones. VAERS is a passive surveillance system that relies on physicians and others to voluntarily submit reports of illness after vaccination. Manufacturers are required to report all adverse events of which they become aware. There are a number of well-described limitations of such reporting systems. These include, for example, variability in report quality, biased reporting, underreporting and the inability to determine whether a vaccine caused the adverse event in any individual report. Strengths of VAERS are that it is national in scope and timely. The information in VAERS reports is not necessarily complete nor is it verified systematically. Reports are classified as serious or nonserious based on regulatory criteria. Reports are coded by VAERS in a uniform way with a limited number of terms using a terminology called COSTART. Coding is useful for search purposes but is necessarily imprecise. VAERS is useful in detecting adverse events related to vaccines and most recently was used for enhanced reporting of adverse events in the national smallpox immunization campaign. VAERS data have always been publicly available. However, it is essential for users of VAERS data to be fully aware of the strengths and weaknesses of the system. VAERS data contain strong biases. Incidence rates and relative risks of specific adverse events cannot be calculated. Statistical significance tests and confidence intervals should be used with great caution and not routinely. Signals detected in VAERS should be subjected to further clinical and descriptive epidemiologic analysis. Confirmation in a controlled study is usually required. An understanding of the

  10. 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

  11. 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.

  12. Parental views on vaccine safety and future vaccinations of children who experienced an adverse event following routine or seasonal influenza vaccination in 2010.

    PubMed

    Parrella, Adriana; Gold, Michael; Marshall, Helen; Braunack-Mayer, Annette; Watson, Maureen; Baghurst, Peter

    2012-05-01

    To assess parental vaccine safety views and future vaccination decisions after an adverse event following immunization (AEFI) experienced by their child. A cross-sectional telephone survey was conducted of parents of children aged 0-7 y, identified in AEFI reports submitted to the South Australian Immunization Section, Department Health. The reports included childhood National Immunization Program (NIP), seasonal or pandemic influenza vaccines. Interviews were conducted following a national suspension of the 2010 seasonal trivalent influenza (STIV) vaccine. Parental attitudes toward vaccine safety, reasons for reporting the AEFI and impact on future vaccination intent were assessed. Of 179 parents interviewed, 88% were confident in the safety of vaccines in general. Parents reporting an AEFI to the STIV were more likely to state the event had influenced future vaccination decisions than the NIP vaccine reporters (65% vs 14%, p < 0.001), with 63% stating refusal or hesitance to re-vaccinate their children against influenza. Media reports of the 2010 STIV program suspension was the most common reason for reporting an AEFI for parents of children who received an influenza vaccination. The AEFI experience did not impact on parental decision to continue with routine childhood NIP schedules, regardless of whether children received influenza or NIP vaccines. In contrast, most parents whose child experienced an AEFI to the 2010 STIV stated decreased confidence in the safety of influenza vaccines, which is likely to have impacted on the uptake of seasonal influenza vaccination in 2011. Addressing influenza vaccine safety concerns to promote influenza vaccination in the community is required.

  13. Improving Influenza Vaccination Rate among Primary Healthcare Workers in Qatar.

    PubMed

    Elawad, Khalid H; Farag, Elmoubasher A; Abuelgasim, Dina A; Smatti, Maria K; Al-Romaihi, Hamad E; Al Thani, Mohammed; Al Mujalli, Hanan; Shehata, Zienab; Alex, Merin; Al Thani, Asmaa A; Yassine, Hadi M

    2017-10-10

    The purpose of this study was to improve influenza vaccination, and determine factors influencing vaccine declination among health care workers (HCW) in Qatar. We launched an influenza vaccination campaign to vaccinate around 4700 HCW in 22 Primary Health Care Corporation (PHCC) centers in Qatar between 1st and 15th of November, 2015. Our target was to vaccinate 60% of all HCW. Vaccine was offered free of charge at all centers, and information about the campaign and the importance of influenza vaccination was provided to employees through direct communication, emails, and social media networks. Staff were reported as vaccinated or non-vaccinated using a declination form that included their occupation, place of work and reasons for declining the vaccine. Survey responses were summarized as proportional outcomes. We exceeded our goal, and vaccinated 77% of the target population. Only 9% declined to take the vaccine, and the remaining 14% were either on leave or had already been vaccinated. Vaccine uptake was highest among aides (98.1%), followed by technicians (95.2%), and was lowest amongst pharmacists (73.2%), preceded by physicians (84%). Of those that declined the vaccine, 34% provided no reason, 18% declined it due to behavioral issues, and 21% declined it due to medical reasons. Uptake of influenza vaccine significantly increased during the 2015 immunization campaign. This is attributed to good planning, preparation, a high level of communication, and providing awareness and training to HCW with proper supervision and monitoring.

  14. Factors influencing uptake of influenza A (H1N1) vaccine amongst healthcare workers in a regional pediatric centre: lessons for improving vaccination rates.

    PubMed

    Chen, Suet Ching; Hawkins, Gillian; Aspinall, Esther; Patel, Neil

    2012-01-05

    Influenza A (H1N1) vaccination has been recommended for all frontline healthcare workers (HCWs) in the UK since October 2009, to protect individuals and their patients from infection. Understanding the factors influencing vaccine uptake by HCW may improve future vaccination programmes in current and subsequent years. To assess the uptake of influenza A (H1N1) vaccine, and factors affecting vaccine uptake, in frontline healthcare workers in a large pediatric hospital. A cross-sectional questionnaire survey conducted in a regional Pediatric Hospital in Scotland incorporating intensive care and ECMO services. One page, anonymised questionnaires were distributed to all frontline HCW in high risk departments of the hospital. 260 questionnaires were completed, capturing an estimated 52% of all staff. Vaccination rate was 49.6%, and was significantly higher amongst doctors (OR 2.4, 95% CI 1.3-4.5, P=0.005). Commonest reasons for vaccine uptake were high risk of contact with H1N1 (88%) and responsibility to protect patients (71%). Uncertainty about vaccine side-effects (47%), concern about vaccine safety (33%) and being too busy to attend the vaccine clinic (22%) were the commonest reasons for non-vaccination. Reasons for vaccination varied between staff grouping and department. 36% of non-vaccinated staff would accept the vaccine if offered. Vaccine uptake may be increased by addressing HCW knowledge and attitudes and access to vaccine. Future vaccination programmes should include targeted education and vaccine delivery, at the convenience of staff, and in their own department. Copyright © 2011. Published by Elsevier Ltd.

  15. Improving vaccine efficacy against malignant glioma

    PubMed Central

    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.

    2016-01-01

    ABSTRACT 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

  16. Safety of vaccinations in patients with cryopyrin-associated periodic syndromes: a prospective registry based study.

    PubMed

    Jaeger, Veronika K; Hoffman, Hal M; van der Poll, Tom; Tilson, Hugh; Seibert, Julia; Speziale, Antonio; Junge, Guido; Franke, Kristina; Vritzali, Eleni; Hawkins, Philip N; Kuemmerle-Deschner, Jasmin; Walker, Ulrich A

    2017-09-01

    Pneumococcal, tetanus and influenza vaccinations are recommended for patients with cryopyrin-associated periodic syndromes (CAPS) when treated with immunosuppressive medication. The aim of this publication is to report the safety of pneumococcal and other vaccinations in CAPS patients. All CAPS patients followed in the β-CONFIDENT (Clinical Outcomes and Safety Registry study of Ilaris patients) registry were analysed if they had received a vaccination. The β-CONFIDENT registry is a global, long-term, prospective, observational registry, capturing and monitoring patients treated with canakinumab. Sixty-eight CAPS patients had received a total of 159 vaccine injections, 107 injections against influenza, 19 pneumococcal vaccinations, 12 against tetanus/diphtheria antigens and 21 other vaccinations. Fourteen per cent of injections had elicited at least one vaccine reaction. All five vaccine-related serious adverse events were associated with pneumococcal vaccination. Vaccine reactions were observed in 70% of pneumococcal vaccinations, compared with 7% in influenza and 17% in tetanus/diphtheria vaccinations. The odds ratios to react to the pneumococcal vaccines compared with influenza and tetanus/diphtheria vaccines were 31.0 (95% CI: 8, 119) and 10.8 (95% CI: 2, 74). Vaccine reactions after pneumococcal vaccinations were more severe and lasted significantly longer (up to 3 weeks) compared with other vaccinations. In two patients, pneumococcal vaccination also elicited symptoms consistent with systemic inflammation due to CAPS reactivation. Pneumococcal vaccines, unlike other vaccines, frequently trigger severe local and systemic inflammation in CAPS patients. Clinicians must balance potential benefits of pneumococcal immunization against safety concerns. The 13-valent pneumococcal conjugate vaccine might be favourable over the polysaccharide vaccine in CAPS patients.

  17. 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/. Copyright © 2013. Published by Elsevier Ltd.. All rights reserved.

  18. 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.

  19. Vaccination of alpacas against Rift Valley fever virus: Safety, immunogenicity and pathogenicity of MP-12 vaccine.

    PubMed

    Rissmann, M; Ulrich, R; Schröder, C; Hammerschmidt, B; Hanke, D; Mroz, C; Groschup, M H; Eiden, M

    2017-01-23

    Rift Valley fever (RVF) is an emerging zoonosis of major public health concern in Africa and Arabia. Previous outbreaks attributed camelids a significant role in the epidemiology of Rift Valley fever virus (RVFV), making them an important target species for vaccination. Using three alpacas as model-organisms for dromedary camels, the safety, immunogenicity and pathogenicity of the MP-12 vaccine were evaluated in this study. To compare both acute and subacute effects, animals were euthanized at 3 and 31days post infection (dpi). Clinical monitoring, analysis of liver enzymes and hematological parameters demonstrated the tolerability of the vaccine, as no significant adverse effects were observed. Comprehensive analysis of serological parameters illustrated the immunogenicity of the vaccine, eliciting high neutralizing antibody titers and antibodies targeting different viral antigens. RVFV was detected in serum and liver of the alpaca euthanized 3dpi, whereas no virus was detectable at 31dpi. Viral replication was confirmed by detection of various RVFV-antigens in hepatocytes by immunohistochemistry and the presence of mild multifocal necrotizing hepatitis. In conclusion, results indicate that MP-12 is a promising vaccine candidate but still has a residual pathogenicity, which requires further investigation.

  20. Researchers' Roles in Patient Safety Improvement.

    PubMed

    Pietikäinen, Elina; Reiman, Teemu; Heikkilä, Jouko; Macchi, Luigi

    2016-03-01

    In this article, we explore how researchers can contribute to patient safety improvement. We aim to expand the instrumental role researchers have often occupied in relation to patient safety improvement. We reflect on our own improvement model and experiences as patient safety researchers in an ongoing Finnish multi-actor innovation project through self-reflective narration. Our own patient safety improvement model can be described as systemic. Based on the purpose of the innovation project, our improvement model, and the improvement models of the other actors in the project, we have carried out a wide range of activities. Our activities can be summarized in 8 overlapping patient safety improvement roles: modeler, influencer, supplier, producer, ideator, reflector, facilitator, and negotiator. When working side by side with "practice," researchers are offered and engage in several different activities. The way researchers contribute to patient safety improvement and balance between different roles depends on the purpose of the study, as well as on the underlying patient safety improvement models. Different patient safety research paradigms seem to emphasize different improvement roles, and thus, they also face different challenges. Open reflection on the underlying improvement models and roles can help researchers with different backgrounds-as well as other actors involved in patient safety improvement-in structuring their work and collaborating productively.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  2. Live-attenuated tetravalent dengue vaccines: The needs and challenges of post-licensure evaluation of vaccine safety and effectiveness.

    PubMed

    Wichmann, Ole; Vannice, Kirsten; Asturias, Edwin J; de Albuquerque Luna, Expedito José; Longini, Ira; Lopez, Anna Lena; Smith, Peter G; Tissera, Hasitha; Yoon, In-Kyu; Hombach, Joachim

    2017-10-09

    Since December 2015, the first dengue vaccine has been licensed in several Asian and Latin American countries for protection against disease from all four dengue virus serotypes. While the vaccine demonstrated an overall good safety and efficacy profile in clinical trials, some key research questions remain which make risk-benefit-assessment for some populations difficult. As for any new vaccine, several questions, such as very rare adverse events following immunization, duration of vaccine-induced protection and effectiveness when used in public health programs, will be addressed by post-licensure studies and by data from national surveillance systems after the vaccine has been introduced. However, the complexity of dengue epidemiology, pathogenesis and population immunity, as well as some characteristics of the currently licensed vaccine, and potentially also future, live-attenuated dengue vaccines, poses a challenge for evaluation through existing monitoring systems, especially in low and middle-income countries. Most notable are the different efficacies of the currently licensed vaccine by dengue serostatus at time of first vaccination and by dengue virus serotype, as well as the increased risk of dengue hospitalization among young vaccinated children observed three years after the start of vaccination in one of the trials. Currently, it is unknown if the last phenomenon is restricted to younger ages or could affect also seronegative individuals aged 9years and older, who are included in the group for whom the vaccine has been licensed. In this paper, we summarize scientific and methodological considerations for public health surveillance and targeted post-licensure studies to address some key research questions related to live-attenuated dengue vaccines. Countries intending to introduce a dengue vaccine should assess their capacities to monitor and evaluate the vaccine's effectiveness and safety and, where appropriate and possible, enhance their surveillance

  3. 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. Published by Elsevier Ltd.

  4. 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

  5. Total safety management: An approach to improving safety culture

    SciTech Connect

    Blush, S.M. )

    1993-01-01

    A little over 4 yr ago, Admiral James D. Watkins became Secretary of Energy. President Bush, who had appointed him, informed Watkins that his principal task would be to clean up the nuclear weapons complex and put the US Department of Energy (DOE) back in the business of producing tritium for the nation's nuclear deterrent. Watkins recognized that in order to achieve these objectives, he would have to substantially improve the DOE's safety culture. Safety culture is a relatively new term. The International Atomic Energy Agency (IAEA) used it in a 1986 report on the root causes of the Chernobyl nuclear accident. In 1990, the IAEA's International Nuclear Safety Advisory Group issued a document focusing directly on safety culture. It provides guidelines to the international nuclear community for measuring the effectiveness of safety culture in nuclear organizations. Safety culture has two principal aspects: an organizational framework conducive to safety and the necessary organizational and individual attitudes that promote safety. These obviously go hand in hand. An organization must create the right framework to foster the right attitudes, but individuals must have the right attitudes to create the organizational framework that will support a good safety culture. The difficulty in developing such a synergistic relationship suggests that achieving and sustaining a strong safety culture is not easy, particularly in an organization whose safety culture is in serious disrepair.

  6. Safety of licensed vaccines in HIV-infected persons: a systematic review protocol.

    PubMed

    Kagina, Benjamin M; Wiysonge, Charles S; Lesosky, Maia; Madhi, Shabir A; Hussey, Gregory D

    2014-09-11

    Safety of vaccines remains a cornerstone of building public trust on the use of these cost-effective and life-saving public health interventions. In some settings, particularly Sub-Saharan Africa, there is a high prevalence of HIV infection and a high burden of vaccine-preventable diseases. There is evidence suggesting that the immunity induced by some commonly used vaccines is not durable in HIV-infected persons, and therefore, repeated vaccination may be considered to ensure optimal vaccine-induced immunity in this population. However, some vaccines, particularly the live vaccines, may be unsafe in HIV-infected persons. There is lack of evidence on the safety profile of commonly used vaccines among HIV-infected persons. We are therefore conducting a systematic review to assess the safety profile of routine vaccines administered to HIV-infected persons. We will select studies conducted in any setting where licensed and effective vaccines were administered to HIV-infected persons. We will search for eligible studies in PubMed, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, Africa-Wide, PDQ-Evidence and CINAHL as well as reference lists of relevant publications. We will screen search outputs, select studies and extract data in duplicate, resolving discrepancies by discussion and consensus. Globally, immunisation is a major public health strategy to mitigate morbidity and mortality caused by various infectious disease-causing agents. In general, there are efforts to increase vaccination coverage worldwide, and for these efforts to be successful, safety of the vaccines is paramount, even among people living with HIV, who in some situations may require repeated vaccination. Results from this systematic review will be discussed in the context of the safety of routine vaccines among HIV-infected persons. From the safety perspective, we will also discuss whether repeat vaccination strategies may be feasible among HIV-infected persons

  7. Safety of licensed vaccines in HIV-infected persons: a systematic review protocol

    PubMed Central

    2014-01-01

    Background Safety of vaccines remains a cornerstone of building public trust on the use of these cost-effective and life-saving public health interventions. In some settings, particularly Sub-Saharan Africa, there is a high prevalence of HIV infection and a high burden of vaccine-preventable diseases. There is evidence suggesting that the immunity induced by some commonly used vaccines is not durable in HIV-infected persons, and therefore, repeated vaccination may be considered to ensure optimal vaccine-induced immunity in this population. However, some vaccines, particularly the live vaccines, may be unsafe in HIV-infected persons. There is lack of evidence on the safety profile of commonly used vaccines among HIV-infected persons. We are therefore conducting a systematic review to assess the safety profile of routine vaccines administered to HIV-infected persons. Methods/Design We will select studies conducted in any setting where licensed and effective vaccines were administered to HIV-infected persons. We will search for eligible studies in PubMed, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, Africa-Wide, PDQ-Evidence and CINAHL as well as reference lists of relevant publications. We will screen search outputs, select studies and extract data in duplicate, resolving discrepancies by discussion and consensus. Discussion Globally, immunisation is a major public health strategy to mitigate morbidity and mortality caused by various infectious disease-causing agents. In general, there are efforts to increase vaccination coverage worldwide, and for these efforts to be successful, safety of the vaccines is paramount, even among people living with HIV, who in some situations may require repeated vaccination. Results from this systematic review will be discussed in the context of the safety of routine vaccines among HIV-infected persons. From the safety perspective, we will also discuss whether repeat vaccination strategies may be

  8. 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

  9. Risk perception, risk management and safety assessment: what can governments do to increase public confidence in their vaccine system?

    PubMed

    MacDonald, Noni E; Smith, Jennifer; Appleton, Mary

    2012-09-01

    For decades vaccine program managers and governments have devoted many resources to addressing public vaccine concerns, vaccine risk perception, risk management and safety assessment. Despite ever growing evidence that vaccines are safe and effective, public concerns continue. Education and evidence based scientific messages have not ended concerns. How can governments and programs more effectively address the public's vaccine concerns and increase confidence in the vaccine safety system? Vaccination hesitation has been attributed to concerns about vaccine safety, perceptions of high vaccine risks and low disease risk and consequences. Even when the public believes vaccines are important for protection many still have concerns about vaccine safety. This overview explores how heuristics affect public perception of vaccines and vaccine safety, how the public finds and uses vaccine information, and then proposes strategies for changes in the approach to vaccine safety communications. Facts and evidence confirming the safety of vaccines are not enough. Vaccine beliefs and behaviours must be shaped. This will require a shift in the what, when, how and why of vaccine risk and benefit communication content and practice. A change to a behavioural change strategy such as the WHO COMBI program that has been applied to disease eradication efforts is suggested. Copyright © 2011. Published by Elsevier Ltd.. All rights reserved.

  10. Improving Bicycle Safety for Children.

    ERIC Educational Resources Information Center

    Ward, Amy

    1987-01-01

    Bicycle-related injuries and deaths are a significant child health problem that family physicians and pediatricians can help prevent. Children should be required to wear protective helmets and to learn good safety practices. (Author)

  11. Safety, immunogenicity, and tolerability of three influenza vaccines in older adults

    PubMed Central

    Scheifele, David W.; McNeil, Shelly A.; Ward, Brian J.; Dionne, Marc; Cooper, Curtis; Coleman, Brenda; Loeb, Mark; Rubinstein, Ethan; McElhaney, Janet; Hatchette, Todd; Li, Yan; Montomoli, Emanuele; Schneeberg, Amy; Bettinger, Julie A.; Halperin, Scott A.; Research Network, PHAC/CIHR Influenza

    2013-01-01

    To determine if newer influenza vaccines can safely improve seroprotection rates of older adults, we compared three licensed trivalent inactivated vaccines (TIVs) in a randomized, controlled trial with evaluator blinding. Participants were non-frail adults ≥ 65 y old, annually TIV-immunized. Study vaccines included intradermal (IDV), MF59-adjuvanted (ADV) and subunit (TIV) formulations of equal potency and strain composition. Blood was obtained before vaccination (V1) and 21 (V2) and 180 d (V3) afterward and tested by hemagglutination inhibition (HAI) assay. Safety diaries were completed daily by participants and specific tolerability questions were posed regarding injections and symptoms. In total, 911 participants were immunized and 887 (97.4%) completed V3. Groups had similar demographics. General symptom rates post-vaccination were similar among groups. Rates of injection site redness after IDV/ADV/TIV were 75%/13%/13% and rates of pain were 29%/38%/20%, respectively, but each vaccine was well tolerated, with symptoms causing little bother. Baseline antibody titers did not differ significantly among groups but B/Brisbane titers were too high for meaningful response assessments. At V2, seroprotection rates (HAI titer ≥ 40) were highest after ADV, the rate advantage over IDV and TIV being significant at 11.8% and 11.4% for H3N2 and 10.2% and 12.5% for H1N1, respectively. At day 180, seroprotection rates had declined ~25% and no longer differed significantly among groups. While IDV and TIV were also well tolerated, ADV induced modestly higher antibody titers in seniors to influenza A strains at 3 weeks but not 6 months post-vaccination. Immune responses to IDV and TIV were similar in this population. PMID:23839537

  12. Improving Human Papillomavirus Vaccinations in Military Women.

    PubMed

    Wedel, Sarah; Navarrete, Rebecca; Burkard, Joseph F; Clark, Mary Jo

    2016-10-01

    The purpose of this evidence-based project was to provide patient education to increase human papillomavirus (HPV) vaccination rates in military women. Despite the availability of a vaccine, HPV continues to be the most common sexually transmitted infection in the United States. The goal of this program was to increase patient knowledge and HPV vaccination rates by providing education and a verbal recommendation for vaccination during regularly scheduled well-woman exams. The project resulted in a 65% increase in vaccination rates, raising the preprogram vaccination rate of 55% to a postintervention vaccine percentage of 91%. The results demonstrate the importance of patient education and provider recommendation in vaccine acceptance. Reprint & Copyright © 2016 Association of Military Surgeons of the U.S.

  13. Vaccine safety surveillance using large linked databases: opportunities, hazards and proposed guidelines.

    PubMed

    Verstraeten, Thomas; DeStefano, Frank; Chen, Robert T; Miller, Elizabeth

    2003-02-01

    Combined administrative databases are referred to as 'large linked databases' because of their relatively large size and the need for linkage of different data sets that were created separately from each other. Such linked databases have become popular in vaccine safety surveillance. Whereas their use offers some unique opportunities, their increasingly widespread use can also lead to wrongful linkage of vaccines to adverse events. We review the opportunities and hazards of using large linked databases for vaccine safety surveillance and propose some guidelines to increase the reliability of the outcomes. We also offer our opinion on the future use of large linked databases for vaccine safety surveillance purposes.

  14. Operational lessons learned in conducting a multi-country collaboration for vaccine safety signal verification and hypothesis testing: The global vaccine safety multi country collaboration initiative.

    PubMed

    Guillard-Maure, Christine; Elango, Varalakshmi; Black, Steven; Perez-Vilar, Silvia; Castro, Jose Luis; Bravo-Alcántara, Pamela; Molina-León, Helvert Felipe; Weibel, Daniel; Sturkenboom, Miriam; Zuber, Patrick L F

    2017-08-02

    Timely and effective evaluation of vaccine safety signals for newly developed vaccines introduced in low and middle- income countries (LMICs) is essential. The study tested the development of a global network of hospital-based sentinel sites for vaccine safety signal verification and hypothesis testing. Twenty-six sentinel sites in sixteen countries across all WHO regions participated, and 65% of the sites were from LMIC. We describe the process for the establishment and operationalization of such a network and the lessons learned in conducting a multi-country collaborative initiative. 24 out of the 26 sites successfully contributed data for the global analysis using standardised tools and procedures. Our study successfully confirmed the well-known risk estimates for the outcomes of interest. The main challenges faced by investigators were lack of adequate information in the medical records for case ascertainment and classification, and access to immunization data. The results suggest that sentinel hospitals intending to participate in vaccine safety studies strengthen their systems for discharge diagnosis coding, medical records and linkage to vaccination data. Our study confirms that a multi-country hospital-based network initiative for vaccine safety monitoring is feasible and demonstrates the validity and utility of large collaborative international studies to monitor the safety of new vaccines introduced in LMICs. Copyright © 2017. Published by Elsevier Ltd.

  15. Safety and Efficacy Profile of Commercial Veterinary Vaccines against Rift Valley Fever: A Review Study.

    PubMed

    Alhaj, Moataz

    Rift Valley Fever (RVF) is an infectious illness with serious clinical manifestations and health consequences in humans as well as a wide range of domestic ruminants. This review provides significant information about the prevention options of RVF along with the safety-efficacy profile of commercial vaccines and some of RVF vaccination strategies. Information presented in this paper was obtained through a systematic investigation of published data about RVF vaccines. Like other viral diseases, the prevention of RVF relies heavily on immunization of susceptible herds with safe and cost-effective vaccine that is able to confer long-term protective immunity. Several strains of RVF vaccines have been developed and are available in commercial production including Formalin-Inactivated vaccine, live attenuated Smithburn vaccine, and the most recent Clone13. Although Formalin-Inactivated vaccine and live attenuated Smithburn vaccine are immunogenic and widely used in prevention programs, they proved to be accompanied by significant concerns. Despite Clone13 vaccine being suggested as safe in pregnant ewes and as highly immunogenic along with its potential for differentiating infected from vaccinated animals (DIVA), a recent study raised concerns about the safety of the vaccine during the first trimester of gestation. Accordingly, RVF vaccines that are currently available in the market to a significant extent do not fulfill the requirements of safety, potency, and DIVA. These adverse effects stressed the need for developing new vaccines with an excellent safety profile to bridge the gap in safety and immunity. Bringing RVF vaccine candidates to local markets besides the absence of validated serological test for DIVA remain the major challenges of RVF control.

  16. Safety and Efficacy Profile of Commercial Veterinary Vaccines against Rift Valley Fever: A Review Study

    PubMed Central

    2016-01-01

    Rift Valley Fever (RVF) is an infectious illness with serious clinical manifestations and health consequences in humans as well as a wide range of domestic ruminants. This review provides significant information about the prevention options of RVF along with the safety-efficacy profile of commercial vaccines and some of RVF vaccination strategies. Information presented in this paper was obtained through a systematic investigation of published data about RVF vaccines. Like other viral diseases, the prevention of RVF relies heavily on immunization of susceptible herds with safe and cost-effective vaccine that is able to confer long-term protective immunity. Several strains of RVF vaccines have been developed and are available in commercial production including Formalin-Inactivated vaccine, live attenuated Smithburn vaccine, and the most recent Clone13. Although Formalin-Inactivated vaccine and live attenuated Smithburn vaccine are immunogenic and widely used in prevention programs, they proved to be accompanied by significant concerns. Despite Clone13 vaccine being suggested as safe in pregnant ewes and as highly immunogenic along with its potential for differentiating infected from vaccinated animals (DIVA), a recent study raised concerns about the safety of the vaccine during the first trimester of gestation. Accordingly, RVF vaccines that are currently available in the market to a significant extent do not fulfill the requirements of safety, potency, and DIVA. These adverse effects stressed the need for developing new vaccines with an excellent safety profile to bridge the gap in safety and immunity. Bringing RVF vaccine candidates to local markets besides the absence of validated serological test for DIVA remain the major challenges of RVF control. PMID:27689098

  17. 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

  18. 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.

  19. 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

    2013-08-02

    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. Published by Elsevier Ltd.

  20. 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.

  1. Improved hepatitis B vaccination rates in ESRD patients in California.

    PubMed

    Brown, J; Peters, V

    2000-10-01

    According to the Centers for Disease Control (CDC) Survey of Dialysis Associated Diseases, California, which includes Network 17 and 18, had one of the lowest hepatitis B vaccination rates in the country for 1994, 1995, and 1996. With 3 outbreaks of hepatitis B (HBV) in California in 1994, hepatitis B vaccination was chosen as a quality improvement project in both Network 17 and 18. With input from both Medical Review Boards and HCFA Region X, a project was formulated which focused on the improvement of the number of facilities which had hepatitis B vaccination rates which are greater than 50%. The overall purpose of both projects was to: (1) achieve access to preventative services for end-stage renal disease (ESRD) Medicare beneficiaries; (2) increase the number of ESRD patients in California who are vaccinated for HBV; (3) eliminate dialysis in California as an independent risk factor for contracting HBV; (4) decrease the number of ESRD facilities with HBV vaccination rates of 0%; and (5) increase the number of ESRD facilities with HBV vaccination rates greater than 50%. In 1998, both Network 17 and 18 denominators were adjusted to reflect the population which is eligible for vaccination. Because of historically low vaccination rate in California, the 1998 data collection sought to ascertain precise numbers for the ESRD patient population. Data were used from the 1996 and 1997 CDC Survey of Dialysis Associated Diseases from baseline measurements of HBV vaccination rates for all facilities in both Network 17 and 18. The CDC did not conduct a survey in 1998, however, Network 17 and 18 conducted a survey of dialysis associated diseases for all of California ESRD facilities. A data collection tool was designed to gather information on processes and outcomes in each facility. This allowed a continuous quality improvement (CQI)-based approach to analyze the problem, where tools like cause/effect and Pareto diagrams provided information on factors and issues affecting

  2. Questions regarding the safety and duration of immunity following live yellow fever vaccination.

    PubMed

    Amanna, Ian J; Slifka, Mark K

    2016-12-01

    The World Health Organization (WHO) and other health agencies have concluded that yellow fever booster vaccination is unnecessary since a single dose of vaccine confers lifelong immunity. Areas covered: We reviewed the clinical studies cited by health authorities in their investigation of both the safety profile and duration of immunity for the YFV-17D vaccine and examined the position that booster vaccination is no longer needed. We found that antiviral immunity may be lost in 1-in-3 to 1-in-5 individuals within 5 to 10 years after a single vaccination and that children may be at greater risk for primary vaccine failure. The safety profile of YFV-17D was compared to other licensed vaccines including oral polio vaccine (OPV) and the rotavirus vaccine, RotaShield, which have subsequently been withdrawn from the US and world market, respectively. Expert commentary: Based on these results and recent epidemiological data on vaccine failures (particularly evident at >10 years after vaccination), we believe that current recommendations to no longer administer YFV-17D booster vaccination be carefully re-evaluated, and that further development of safer vaccine approaches should be considered.

  3. Efficacy and safety of pentavalent rotavirus vaccine in Japan

    PubMed Central

    Iwata, Satoshi; Nakata, Shuji; Ukae, Susumu; Koizumi, Yoshitugu; Morita, Yasuyuki; Kuroki, Haruo; Tanaka, Yoshiyuki; Shizuya, Toshiyuki; Schödel, Florian; Brown, Michelle L; Lawrence, Jody

    2013-01-01

    Rotavirus is the most common cause of severe gastroenteritis in children under 5 y of age. Estimates of disease burden in Japan suggest that between 26,500 and 78,000 children in this age group need hospitalization each year, resulting in a direct medical cost of 10 to 24 billion Yen. Since being introduced in routine infant immunization schedules in the United States in 2006, the oral live pentavalent rotavirus vaccine RV5 (RotaTeq™) has contributed to dramatic reductions in the incidence of rotavirus gastroenteritis (RVGE) and in health care resource utilization. This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of a 3-dose regimen of RV5 in healthy infants, age 6 to 12 weeks, at 32 sites across Japan. The results indicate that RV5 was significantly efficacious in preventing any severity [74.5% (95% confidence interval [CI]: 39.9%, 90.6%; p < 0.001)], moderate-to-severe [80.2% (95% CI: 47.4%, 94.1%)], and severe [100% (95% CI: 55.4%, 100%)] RVGE caused by viruses with serotypes contained in the vaccine. The observed cases of RVGE included rotavirus types G1 (n = 19), G3 (n = 9), G9 (n = 5) and one unspecified G serotype with P1A[8]. No G2 or G4 RVGE cases were observed, and this study was not powered to evaluate efficacy against individual serotypes. RV5 was generally safe and well tolerated in Japanese infants. These results are comparable to those observed in clinical studies conducted in other developed countries. Introduction of the vaccine in Japan may reduce disease burden and associated health care costs. PMID:23732903

  4. Rift Valley fever vaccines: an overview of the safety and efficacy of the live-attenuated MP-12 vaccine candidate.

    PubMed

    Ikegami, Tetsuro

    2017-06-01

    Rift Valley fever (RVF) is a mosquito-borne zoonotic viral disease endemic to Africa and the Arabian Peninsula. High rates of abortion among infected ruminants and hemorrhagic fever in infected humans are major public health concerns. Commercially available veterinary RVF vaccines are important for preventing the spread of the Rift Valley fever virus (RVFV) in endemic countries; however, RVFV outbreaks continue to occur frequently in endemic countries in the 21st century. In the U.S., the live-attenuated MP-12 vaccine has been developed for both animal and human vaccination. This vaccine strain is well attenuated, and a single dose induces neutralizing antibodies in both ruminants and humans. Areas covered: This review describes scientific evidences of MP-12 vaccine efficacy and safety, as well as MP-12 variants recently developed by reverse genetics, in comparison with other RVF vaccines. Expert commentary: The containment of active RVF outbreaks and long-term protection from RVF exposure to infected mosquitoes are important goals for RVF vaccination. MP-12 vaccine will allow immediate vaccination of susceptible animals in case of an unexpected RVF outbreak in the U.S., whereas MP-12 vaccine may be also useful for the RVF control in endemic regions.

  5. Improving patient safety: just do it!

    PubMed

    Etchells, E; Bernstein, M

    2001-01-01

    Clinicians must celebrate and study medical errors. The dark culture of blame must be replaced by a scholarly culture of safety. This commentary presents six cases that show what we can learn from errors. The first step to identifying and understanding patient safety problems is to develop a common language for discussing patient safety. Latent unsafe conditions are ongoing circumstances of daily practice that reduce the safety of patients. An error is the failure ofa planned action to be completed as intended (error of execution), or the use of a wrong plan to achieve an aim (error of planning). Errors can be intercepted by appropriate action that minimizes the threat to patient safety. An adverse event is any unintended result of medical treatment that results in prolonged hospital stay, morbidity or mortality. If an adverse event is caused by an error, or series of errors, then it is a preventable adverse event. The teaching hospital is the first place where students (physicians, nurses, pharmacists and all other disciplines) are exposed to the culture of healthcare. It is essential to expose students to a culture of safety early in their training. Clinicians can make safety an academically important activity. Clinicians will find it difficult to undertake major safety initiatives given the existing constraints on time and energy. Although clinicians can identify the safety problems,there must also be a commitment to understand safety problems and make improvements. It is strongly recommended that hospitals train, implement and support Patient Safety Consultation Teams.

  6. Development of a Mouse-Adapted Live Attenuated Influenza Virus That Permits In Vivo Analysis of Enhancements to the Safety of Live Attenuated Influenza Virus Vaccine

    PubMed Central

    Cox, Andrew; Baker, Steven F.; Nogales, Aitor

    2014-01-01

    The live attenuated influenza virus vaccine (LAIV) is preferentially recommended for use in persons 2 through 49 years of age but has not been approved for children under 2 or asthmatics due to safety concerns. Therefore, increasing safety is desirable. Here we describe a murine LAIV with reduced pathogenicity that retains lethality at high doses and further demonstrate that we can enhance safety in vivo through mutations within NS1. This model may permit preliminary safety analysis of improved LAIVs. PMID:25552727

  7. The Food and Drug Administration's Post-Licensure Rapid Immunization Safety Monitoring program: strengthening the federal vaccine safety enterprise.

    PubMed

    Nguyen, Michael; Ball, Robert; Midthun, Karen; Lieu, Tracy A

    2012-01-01

    In 2009, the Department of Health and Human Services created the new Post-Licensure Rapid Immunization Safety Monitoring (PRISM) program, which used data from national health insurance plans and immunization registries to monitor the safety of the H1N1 influenza vaccine. PRISM has now been integrated into the FDA's Mini-Sentinel pilot program. It strengthens the federal vaccine safety enterprise in two important ways. First, PRISM monitors the largest US general population cohort designated for active surveillance of vaccine safety. Second, PRISM links data from health plans with data from state and city immunization registries, which were a crucial source of exposure data in the H1N1 vaccine evaluation. The Mini-Sentinel data that support PRISM are updated quarterly, and PRISM can conduct medical record review for validation of computerized data. The FDA has structured PRISM as a program that includes specific vaccine evaluations, development of an operational framework to guide the design of vaccine safety evaluations, and development of new statistical methods. A human papillomavirus vaccine, Gardasil, and two rotavirus vaccines, RotaTeq and Rotarix, have been chosen for surveillance in the current cycle because their evaluations would benefit most from PRISM's large cohort size. The PRISM program creates important opportunities by offering a robust, responsive new surveillance program with features complementary to existing systems. Methodological and logistical lessons can be shared among PRISM and other surveillance systems, offering potential synergies. FDA and PRISM will work to maximize the program's unique strengths and contributions to a unified federal vaccine safety enterprise.

  8. Surveillance of vaccine safety: comparison of parental reports with routine surveillance and a clinical trial.

    PubMed

    Netterlid, Eva; Månsson, Marie Edwinson; Håkansson, Anders

    2009-03-23

    One way to maintain confidence in vaccination programmes is to improve monitoring of immunisation safety. We studied active parental reporting of adverse events after a booster dose of diphtheria-tetanus toxoid (DT). 7193 children received the vaccine. Questionnaires were submitted by 84.2% of the parents, who reported reactions for 9.2% of the children. Four percent of events were classified as moderate/severe by interviews. Relative risk of redness and swelling reported was 0.24 (95% CI, 0.13-0.42) compared to a clinical trial, while it was 71.0 (44-114) compared to passive surveillance. Active surveillance by parental reports is a useful complement to passive surveillance of childhood immunisations to generate hypotheses for evaluation in controlled studies.

  9. Sign up to Safety: developing a safety improvement plan.

    PubMed

    Dight, Carol; Peters, Hayley

    2015-04-01

    The Sign up to Safety (SutS) programme was launched in June 2014 by health secretary Jeremy Hunt. It focuses on listening to patients, carers and staff, learning from what they say when things go wrong, and then taking action to improve patient safety. The programme aims to make the NHS the safest healthcare system in the world by creating a culture devoted to continuous learning and improvement (NHS England 2014). Musgrove Park Hospital, part of Taunton and Somerset NHS Foundation Trust, was one of 12 NHS organisations that signed up to the SutS programme, making public its commitment to the national pledges to be 'open and transparent' and to develop a safety improvement plan. This paper describes the development of the strategy.

  10. Safety of human therapeutic morphine vaccine employing Lohmann specific pathogen free eggs.

    PubMed

    Farhangi, A; Akbarzadeh, A; Mehrabi, M R; Chiani, M; Saffari, Z; Ghassemi, S; Kheiri, M; Bashar, R

    2010-11-01

    One of the sensitive and standard tests to control the safety of a vaccine is the inoculation of such vaccine to the air pocket of Lohmann specific pathogen free eggs. The aim of this study is to control the safety of morphine vaccine. This study reveals the safety of morphine vaccine by employing Lohmann specific pathogen free embryo eggs. The changeable parameters in this test were: weight of eggs, safety of eggs embryo, vaccine concentration, normal saline and temperature of the incubator. To study, the safety of morphine vaccine, we used 30 eggs (after controlling the safety of eggs and their embryos) which were divided into two groups of control (15 eggs) and test (15 eggs). After weighing the eggs, the eggs under experiment were inoculated with morphine vaccine and the control group was inoculated with physiological solution. Both groups were incubated and weight of the eggs and chickens were determined accordingly. The eggs of each group were controlled by their weights showing healthy, normal growth and evolution. The comparison between the weights of control and experimental groups did not show any significant changes. Exactly growth and evolution of each group were found equally to be balancing for three weeks after injection. Finally all eggs were observed to be safe, alive and in evolutionary form. By comparing the growth and evolution amongst each egg in the group under experiment, after injection, the eggs did not show any adverse reaction after inoculation with therapeutic human morphine vaccine.

  11. Safety and Immunogenicity of Sequential Rotavirus Vaccine Schedules

    PubMed Central

    Libster, Romina; McNeal, Monica; Walter, Emmanuel B.; Shane, Andi L.; Winokur, Patricia; Cress, Gretchen; Berry, Andrea A.; Kotloff, Karen L.; Sarpong, Kwabena; Turley, Christine B.; Harrison, Christopher J.; Pahud, Barbara A.; Marbin, Jyothi; Dunn, John; El-Khorazaty, Jill; Barrett, Jill

    2016-01-01

    BACKGROUND AND OBJECTIVES: Although both licensed rotavirus vaccines are safe and effective, it is often not possible to complete the schedule by using the same vaccine formulation. The goal of this study was to investigate the noninferiority of the immune responses to the 2 licensed rotavirus vaccines when administered as a mixed schedule compared with administering a single vaccine formulation alone. METHODS: Randomized, multicenter, open-label study. Healthy infants (6–14 weeks of age) were randomized to receive rotavirus vaccines in 1 of 5 different schedules (2 using a single vaccine for all doses, and 3 using mixed schedules). The group receiving only the monovalent rotavirus vaccine received 2 doses of vaccine and the other 4 groups received 3 doses of vaccine. Serum for immunogenicity testing was obtained 1 month after the last vaccine dose and the proportion of seropositive children (rotavirus immunoglobulin A ≥20 U/mL) were compared in all the vaccine groups. RESULTS: Between March 2011 and September 2013, 1393 children were enrolled and randomized. Immune responses to all the sequential mixed vaccine schedules were shown to be noninferior when compared with the 2 single vaccine reference groups. The proportion of children seropositive to at least 1 vaccine antigen at 1 month after vaccination ranged from 77% to 96%, and was not significantly different among all the study groups. All schedules were well tolerated. CONCLUSIONS: Mixed schedules are safe and induced comparable immune responses when compared with the licensed rotavirus vaccines given alone. PMID:26823540

  12. Intranasal Inactivated Influenza Vaccines: a Reasonable Approach to Improve the Efficacy of Influenza Vaccine?

    PubMed

    Tamura, Shin-Ichi; Ainai, Akira; Suzuki, Tadaki; Kurata, Takeshi; Hasegawa, Hideki

    2016-01-01

    on this parameter. Data suggest that adjuvant-combined nasal-inactivated vaccines have advantages over the current injectable vaccine because the former induce both S-IgA and serum IgG Abs. In addition, nasal-inactivated vaccines seem to be superior to the LAIV vaccines, because non-infectious preparations could be used in high-risk groups. Thus, the development of intranasal inactivated vaccines is recommended, because such vaccines are expected to improve the efficacy of influenza vaccines.

  13. Safety and efficacy studies on trivalent inactivated vaccines against infectious coryza.

    PubMed

    Gong, Yumei; Zhang, Peijun; Wang, Hongjun; Zhu, Wenge; Sun, Huiling; He, Yunxia; Shao, Qinghong; Blackall, P J

    2014-03-15

    The safety and efficacy of an inactivated oil-emulsion infectious coryza vaccine containing three Avibacterium paragallinarum isolates (one each of Page serovars A, B, and C) was evaluated. The safety of six batches of the vaccine was confirmed by testing with chickens vaccinated with a single large dose or vaccinated repeatedly with a normal dose. Efficacy tests were carried out on three batches of vaccine using both specific pathogen free (SPF) chickens and conventional chickens. In SPF chickens given a single vaccination at 42 days of age, the protection rate against all three serovars of Av. paragallinarum was at least 80% at 30 days post vaccination. The conventional chickens, which were immunized at 42 and 110 days of age, were challenged at 9 months post the second vaccination and the protection rate was at least 80% for all three serovars. The effect of storage on the vaccine was evaluated in SPF chickens using three batches of vaccine stored at 4-8°C for 1 year. The protection rate against challenge from all three serovars (single vaccination at 42 days of age and challenge at 30 days post-vaccination) was at least 80%.

  14. Safety studies of the oral rabies vaccine SAD B19 in striped skunk (Mephitis mephitis).

    PubMed

    Vos, A; Pommerening, E; Neubert, L; Kachel, S; Neubert, A

    2002-04-01

    Safety of the modified live rabies virus vaccine, SAD B19, was studied in striped skunks (Mephitis mephitis). Seven skunks received 10(7.9) foci formatting units by direct oral administration. In four cages, a vaccinated animal was placed with a control animal, the other three vaccinated skunks were housed individually. Saliva and nasal swabs were collected 1, 2, 4, 24, 48, and 72 hr post-vaccination. From all vaccinated and control animals (n = 11) blood samples were collected 0, 28, 56, 84, and 296 days post-vaccination. Three of seven vaccinated skunks seroconverted. None of the control animals had detectable levels of rabies virus neutralizing antibodies. Also no vaccine virus was isolated from the nasal and saliva swabs collected from any animal. Thus, SAD B19 was innocuous for skunks in our study after direct oral administration at field concentration.

  15. Global Efforts in the Development of Vaccines for Tuberculosis: Requirements for Improved Vaccines Against Mycobacterium tuberculosis.

    PubMed

    Méndez-Samperio, P

    2016-10-01

    Currently, more than 9.0 million people develop acute pulmonary tuberculosis (TB) each year and about 1.5 million people worldwide die from this infection. Thus, developing vaccines to prevent active TB disease remains a priority. This article discusses recent progress in the development of new vaccines against TB and focusses on the main requirements for development of improved vaccines against Mycobacterium tuberculosis (M. tb). Over the last two decades, significant progress has been made in TB vaccine development, and some TB vaccine candidates have currently completed a phase III clinical trial. The potential public health benefits of these vaccines are possible, but it will need much more effort, including new global governance investment on this research. This investment would certainly be less than the annual global financial toll of TB treatment.

  16. 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.

  17. Twenty years of improvements in LWR safety

    SciTech Connect

    Franks, S. III; Mulkey, J.P.; Deitrich, L.W.; Moonka, A.

    1996-05-01

    Substantial improvements have been made in the safety of light-water reactors in the US during the past two decades, making currently operating reactors safer than ever before. Safety improvements have resulted both from regulatory and operational changes and from new knowledge and technology. The US Nuclear Regulatory Commission, the US Department of Energy, and the American nuclear power industry have worked together and with the international community to enhance the safety of existing plants and to incorporate lessons learned from prior operation into designs for a new generation of advanced, inherently safer reactors.

  18. 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

  19. Quality and safety of human hepatitis B vaccine.

    PubMed

    Hilleman, M R; McAleer, W J; Buynak, E B; McLean, A A

    1983-01-01

    Preparation of hepatitis B vaccine in our laboratories consists of a series of steps that include initial concentration of surface antigen by ammonium sulfate precipitation, followed by isopycnic banding and rate zonal centrifugation in a K-II centrifuge. The partially purified antigen concentrate is digested with pepsin at pH2 and the antigen is unfolded in 8M urea solution followed by renaturation. After gel filtration, the antigen is treated with formalin in 1:4000 dilution, adsorbed onto alum, and preserved with thimerosal. The final product contains essentially pure hepatitis B surface antigen. The process relies both on physical elimination of infectious virus particles and treatment with highly viral-destructive reagents in the pepsin, urea and formalin steps. The process is known to be highly destructive of all known viruses tested and to include procedures that are known to be highly destructive of representatives of all known groups of animal viral agents. The three-step process in inactivation provides a fail-safe system for establishing safety of the product. Tests in more than 20'000 persons, who are under surveillance, have shown no untoward effect and have confirmed the safety of the product.

  20. The preparation and safety of hepatitis B vaccine.

    PubMed

    Hilleman, M R; McAleer, W J; Buynak, E B; McLean, A A

    1983-07-01

    Preparation of hepatitis B vaccine in our laboratories consists of a series of steps that include initial concentration of surface antigen by ammonium sulphate precipitation, followed by isopycnic banding and rate zonal centrifugation in a K-II centrifuge. The partially purified antigen concentrate is digested with pepsin at pH 2 and the antigen is unfolded in 8 M urea solution followed by renaturation. After gel filtration, the antigen is treated with formalin in I :4000 dilution, adsorbed on to alum, and preserved with thimerosal. The final product contains essentially pure hepatitis B surface antigen. The process relies both on physical elimination of infectious virus particles and treatment with highly viral-destructive reagents in the pepsin (pH 2), urea and formalin steps. The process is known to be highly destructive of all known viruses tested and to include procedures that are known to be highly destructive of representatives of all known groups of animal viral agents. The three-step process in inactivation provides a fail-safe system for establishing safety of the product. Tests in more than 20000 persons, who are under surveillance, have shown no untoward effect and have confirmed the safety of the product.

  1. Improving immunogenicity and effectiveness of influenza vaccine in older adults.

    PubMed

    Cao, Weiping; Kim, Jin Hyang; Chirkova, Tatiana; Reber, Adrian J; Biber, Renata; Shay, David K; Sambhara, Suryaprakash

    2011-11-01

    Aging is associated with a decline in immune function (immunosenescence) that leads to progressive deterioration in both innate and adaptive immune functions. These changes contribute to the subsequent increased risk for infectious diseases and their sequelae. Vaccination is the most effective and inexpensive public health strategy for prevention of infection, despite the decreased efficacy of vaccines in older adults due to immunosenescence. The rapid rise in the older adult population globally represents a great challenge for vaccination programs. This article first addresses the status of innate and adaptive immune functions in aging and then focuses on influenza vaccine. The development history of influenza vaccines, current status, and potential strategies to improve the immunogenicity and vaccine effectiveness in older adults are discussed.

  2. Barriers and strategies to improve influenza vaccination in Pakistan.

    PubMed

    Farrukh, Muhammad Junaid; Ming, Long Chiau; Zaidi, Syed Tabish Razi; Khan, Tahir Mehmood

    2017-02-06

    Influenza vaccination is strongly recommended by World Health Organisation on a yearly basis. The rate of immunization in Pakistan is suboptimal. High cost, traditional norms, customs and low levels of education in Pakistan are preventing people from getting vaccinated. It is timely to include influenza vaccination in the expanded programme on immunization (EPI), which is a disease prevention programme aiming to eradicate preventable diseases through subsidized or free immunization. The Ministry of National Health Services, Regulation and Coordination, Government of Pakistan should launch a national influenza vaccine policy in view of this current situation and oversee its implementation. Healthcare professionals should promote influenza vaccination and focus on high risk groups such as the elderly, pregnant women and children. Convincing and educating family members regarding immunization of pregnant women and follow-up with parents regarding a second influenza shot for their children will further improve vaccination rates in Pakistan.

  3. Perception of safety, importance, and effectiveness of vaccinations among urban school employees in Utah.

    PubMed

    Luthy, Karlen E; Thompson, Kim E; Beckstrand, Renea L; Macintosh, Janelle L B; Eden, Lacey M

    2015-06-01

    School employees are in direct contact with children in confined areas, a setting in which communicable infection can quickly spread. Therefore, it is important for school employees to be fully vaccinated. The purpose of this study is to ascertain the current vaccination status and perceptions of school employees in an urban school district. The study employed a nonexperimental mixed-method design. School employee participants (N = 1400) completed a questionnaire to evaluate vaccination status, availability of vaccination records, and vaccination awareness. Participants were randomly selected from 85 schools within one urban school district. Two common perceptions about vaccines emerged from the questionnaire: (a) vaccines are only for children and (b) vaccinations received during childhood are still effective. School employees are unaware of their own vaccination status and the recommended vaccination schedule for adults. Additionally, accessibility to immunization records for adults is frequently inadequate. Healthcare providers (HCPs), including nurse practitioners (NPs), are the first line of defense to ensure adults are adequately vaccinated. When vaccinations are tracked and recommended by HCPs, vaccination uptake is improved. NPs who discuss recommended vaccinations with adult patients are instrumental in improving vaccination rates among school employees. ©2015 American Association of Nurse Practitioners.

  4. Re-designing the Mozambique vaccine supply chain to improve access to vaccines.

    PubMed

    Lee, Bruce Y; Haidari, Leila A; Prosser, Wendy; Connor, Diana L; Bechtel, Ruth; Dipuve, Amelia; Kassim, Hidayat; Khanlawia, Balbina; Brown, Shawn T

    2016-09-22

    Populations and routine childhood vaccine regimens have changed substantially since supply chains were designed in the 1980s, and introducing new vaccines during the "Decade of Vaccine" may exacerbate existing bottlenecks, further inhibiting the flow of all vaccines. Working with the Mozambique Ministry of Health, our team implemented a new process that integrated HERMES computational simulation modeling and on-the-ground implementers to evaluate and improve the Mozambique vaccine supply chain using a system-re-design that integrated new supply chain structures, information technology, equipment, personnel, and policies. The alternative system design raised vaccine availability (from 66% to 93% in Gaza; from 76% to 84% in Cabo Delgado) and reduced the logistics cost per dose administered (from $0.53 to $0.32 in Gaza; from $0.38 to $0.24 in Cabo Delgado) as compared to the multi-tiered system under the current EPI. The alternative system also produced higher availability at lower costs after new vaccine introductions. Since reviewing scenarios modeling deliveries every two months in the north of Gaza, the provincial directorate has decided to pilot this approach diverging from decades of policies dictating monthly deliveries. Re-design improved not only supply chain efficacy but also efficiency, important since resources to deliver vaccines are limited. The Mozambique experience and process can serve as a model for other countries during the Decade of Vaccines. For the Decade of Vaccines, getting vaccines at affordable prices to the market is not enough. Vaccines must reach the population to be successful. Copyright © 2016. Published by Elsevier Ltd.

  5. Safety, immunogenicity and preliminary efficacy of multiple-site vaccination with an Epidermal Growth Factor (EGF) based cancer vaccine in advanced non small cell lung cancer (NSCLC) patients

    PubMed Central

    2011-01-01

    The prognosis of patients with advanced non small cell lung (NSCLC) cancer remains dismal. Epidermal Growth Factor Receptor is over-expressed in many epithelial derived tumors and its role in the development and progression of NSCLC is widely documented. CimaVax-EGF is a therapeutic cancer vaccine composed by human recombinant Epidermal Growth Factor (EGF) conjugated to a carrier protein, P64K from Neisseria Meningitides. The vaccine is intended to induce antibodies against self EGF that would block EGF-EGFR interaction. CimaVax-EGF has been evaluated so far in more than 1000 advanced NSCLC patients, as second line therapy. Two separate studies were compared to assess the impact of high dose vaccination at multiple anatomic sites in terms of immunogenicity, safety and preliminary efficacy in stage IIIb/IV NSCLC patients. In both clinical trials, patients started vaccination 1 month after finishing first line chemotherapy. Vaccination at 4 sites with 2.4 mg of EGF (high dose) was very safe. The most frequent adverse events were grade 1 or 2 injection site reactions, fever, headache and vomiting. Patients had a trend toward higher antibody response. The percent of very good responders significantly augmented and there was a faster decrease of circulating EGF. All vaccinated patients and those classified as good responders immunized with high dose at 4 sites, had a large tendency to improved survival. PMID:22024351

  6. Safety of vaccines used for routine immunization of U.S. children: a systematic review.

    PubMed

    Maglione, Margaret A; Das, Lopamudra; Raaen, Laura; Smith, Alexandria; Chari, Ramya; Newberry, Sydne; Shanman, Roberta; Perry, Tanja; Goetz, Matthew Bidwell; Gidengil, Courtney

    2014-08-01

    Concerns about vaccine safety have led some parents to decline recommended vaccination of their children, leading to the resurgence of diseases. Reassurance of vaccine safety remains critical for population health. This study systematically reviewed the literature on the safety of routine vaccines recommended for children in the United States. Data sources included PubMed, Advisory Committee on Immunization Practices statements, package inserts, existing reviews, manufacturer information packets, and the 2011 Institute of Medicine consensus report on vaccine safety. We augmented the Institute of Medicine report with more recent studies and increased the scope to include more vaccines. Only studies that used active surveillance and had a control mechanism were included. Formulations not used in the United States were excluded. Adverse events and patient and vaccine characteristics were abstracted. Adverse event collection and reporting was evaluated by using the McHarm scale. We were unable to pool results. Strength of evidence was rated as high, moderate, low, or insufficient. Of 20 478 titles identified, 67 were included. Strength of evidence was high for measles/mumps/rubella (MMR) vaccine and febrile seizures; the varicella vaccine was associated with complications in immunodeficient individuals. There is strong evidence that MMR vaccine is not associated with autism. There is moderate evidence that rotavirus vaccines are associated with intussusception. Limitations of the study include that the majority of studies did not investigate or identify risk factors for AEs; and the severity of AEs was inconsistently reported. We found evidence that some vaccines are associated with serious AEs; however, these events are extremely rare and must be weighed against the protective benefits that vaccines provide. Copyright © 2014 by the American Academy of Pediatrics.

  7. 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

  8. Rotavirus vaccines

    PubMed Central

    Yen, Catherine; Tate, Jacqueline E; Hyde, Terri B; Cortese, Margaret M; Lopman, Benjamin A; Jiang, Baoming; Glass, Roger I; Parashar, Umesh D

    2016-01-01

    Rotavirus is the leading cause of severe diarrhea among children <5 years worldwide. Currently licensed rotavirus vaccines have been efficacious and effective, with many countries reporting substantial declines in diarrheal and rotavirus-specific morbidity and mortality. However, the full public health impact of these vaccines has not been realized. Most countries, including those with the highest disease burden, have not yet introduced rotavirus vaccines into their national immunization programs. Research activities that may help inform vaccine introduction decisions include (1) establishing effectiveness, impact, and safety for rotavirus vaccines in low-income settings; (2) identifying potential strategies to improve performance of oral rotavirus vaccines in developing countries, such as zinc supplementation; and (3) pursuing alternate approaches to oral vaccines, such as parenteral immunization. Policy- and program-level barriers, such as financial implications of new vaccine introductions, should be addressed to ensure that countries are able to make informed decisions regarding rotavirus vaccine introduction. PMID:24755452

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

    PubMed

    Black, Steven

    2015-06-08

    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.

  10. Immunogenicity and safety of 3-dose primary vaccination with combined DTPa-HBV-IPV/Hib in Indian infants

    PubMed Central

    Lalwani, Sanjay K.; Agarkhedkar, Sharad; Sundaram, Balasubramanian; Mahantashetti, Niranjana S.; Malshe, Nandini; Agarkhedkar, Shalaka; Van Der Meeren, Olivier; Mehta, Shailesh; Karkada, Naveen; Han, Htay Htay; Mesaros, Narcisa

    2017-01-01

    ABSTRACT Multivalent combination vaccines have reduced the number of injections and therefore improved vaccine acceptance, timeliness of administration and global coverage. The hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus/Haemophilus influenzae type b (DTPa-HBV-IPV/Hib; Infanrix hexa™) vaccine, administered according to various schedules, is widely used for the primary vaccination of infants worldwide. In the current publication, we are presenting the immunogenicity and safety of 3 doses of DTPa-HBV-IPV/Hib vaccine when administered to Indian infants. 224 healthy infants (mean age 6.8 weeks) were vaccinated at 6–10–14 weeks (W) of age (n = 112) or 2–4–6 months (M) of age (n = 112). One month after the third vaccine dose, the seroprotection/seropositivity status against diphtheria, pertussis, tetanus, polio, hepatitis B and Hib antigens ranged from 98.6% to 100% in both groups. The vaccine response rate to the pertussis antigens ranged from 97% to 100%. Pain (6–10–14W group: 25.2%; 2–4–6M group: 13.4%) and fever (15.3% and; 15.2%, respectively) were the most frequently reported solicited local and general symptoms. Unsolicited adverse events were reported for 35.7% (6–10–14W group) and 22.3% (2–4–6M group) of subjects. No vaccine related serious adverse events were reported. In conclusion, the hexavalent DTPa-HBV-IPV/Hib vaccine was immunogenic and well tolerated, irrespective of the dosing schedule. PMID:27629913

  11. Immunogenicity and safety of 3-dose primary vaccination with combined DTPa-HBV-IPV/Hib in Indian infants.

    PubMed

    Lalwani, Sanjay K; Agarkhedkar, Sharad; Sundaram, Balasubramanian; Mahantashetti, Niranjana S; Malshe, Nandini; Agarkhedkar, Shalaka; Van Der Meeren, Olivier; Mehta, Shailesh; Karkada, Naveen; Han, Htay Htay; Mesaros, Narcisa

    2017-01-02

    Multivalent combination vaccines have reduced the number of injections and therefore improved vaccine acceptance, timeliness of administration and global coverage. The hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus/Haemophilus influenzae type b (DTPa-HBV-IPV/Hib; Infanrix hexa™) vaccine, administered according to various schedules, is widely used for the primary vaccination of infants worldwide. In the current publication, we are presenting the immunogenicity and safety of 3 doses of DTPa-HBV-IPV/Hib vaccine when administered to Indian infants. 224 healthy infants (mean age 6.8 weeks) were vaccinated at 6-10-14 weeks (W) of age (n = 112) or 2-4-6 months (M) of age (n = 112). One month after the third vaccine dose, the seroprotection/seropositivity status against diphtheria, pertussis, tetanus, polio, hepatitis B and Hib antigens ranged from 98.6% to 100% in both groups. The vaccine response rate to the pertussis antigens ranged from 97% to 100%. Pain (6-10-14W group: 25.2%; 2-4-6M group: 13.4%) and fever (15.3% and; 15.2%, respectively) were the most frequently reported solicited local and general symptoms. Unsolicited adverse events were reported for 35.7% (6-10-14W group) and 22.3% (2-4-6M group) of subjects. No vaccine related serious adverse events were reported. In conclusion, the hexavalent DTPa-HBV-IPV/Hib vaccine was immunogenic and well tolerated, irrespective of the dosing schedule.

  12. 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.

  13. Safety of pandemic H1N1 vaccines in children and adolescents.

    PubMed

    Wijnans, Leonoor; de Bie, Sandra; Dieleman, Jeanne; Bonhoeffer, Jan; Sturkenboom, Miriam

    2011-10-06

    During the 2009 influenza A (H1N1) pandemic several pandemic H1N1 vaccines were licensed using fast track procedures, with relatively limited data on the safety in children and adolescents. Different extensive safety monitoring efforts were put in place to ensure timely detection of adverse events following immunization. These combined efforts have generated large amounts of data on the safety of the different pandemic H1N1 vaccines, also in children and adolescents. In this overview we shortly summarize the safety experience with seasonal influenza vaccines as a background and focus on the clinical and post marketing safety data of the pandemic H1N1 vaccines in children. We identified 25 different clinical studies including 10,505 children and adolescents, both healthy and with underlying medical conditions, between the ages of 6 months and 23 years. In addition, large monitoring efforts have resulted in large amounts of data, with almost 13,000 individual case reports in children and adolescents to the WHO. However, the diversity in methods and data presentation in clinical study publications and publications of spontaneous reports hampered the analysis of safety of the different vaccines. As a result, relatively little has been learned on the comparative safety of these pandemic H1N1 vaccines - particularly in children. It should be a collective effort to give added value to the enormous work going into the individual studies by adhering to available guidelines for the collection, analysis, and presentation of vaccine safety data in clinical studies and to guidance for the clinical investigation of medicinal products in the pediatric population. Importantly the pandemic has brought us the beginning of an infrastructure for collaborative vaccine safety studies in the EU, USA and globally. Copyright © 2011 Elsevier Ltd. All rights reserved.

  14. 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

  15. Re-designing the Mozambique vaccine supply chain to improve access to vaccines

    PubMed Central

    Lee, Bruce Y.; Haidari, Leila A.; Prosser, Wendy; Connor, Diana L.; Bechtel, Ruth; Dipuve, Amelia; Kassim, Hidayat; Khanlawia, Balbina; Brown, Shawn T.

    2017-01-01

    Introduction Populations and routine childhood vaccine regimens have changed substantially since supply chains were designed in the 1980s, and introducing new vaccines during the “Decade of Vaccine” may exacerbate existing bottlenecks, further inhibiting the flow of all vaccines. Methods Working with the Mozambique Ministry of Health, our team implemented a new process that integrated HERMES computational simulation modeling and on-the-ground implementers to evaluate and improve the Mozambique vaccine supply chain using a system-re-design that integrated new supply chain structures, information technology, equipment, personnel, and policies. Results The alternative system design raised vaccine availability (from 66% to 93% in Gaza; from 76% to 84% in Cabo Delgado) and reduced the logistics cost per dose administered (from $0.53 to $0.32 in Gaza; from $0.38 to $0.24 in Cabo Delgado) as compared to the multi-tiered system under the current EPI. The alternative system also produced higher availability at lower costs after new vaccine introductions. Since reviewing scenarios modeling deliveries every two months in the north of Gaza, the provincial directorate has decided to pilot this approach diverging from decades of policies dictating monthly deliveries. Discussion Re-design improved not only supply chain efficacy but also efficiency, important since resources to deliver vaccines are limited. The Mozambique experience and process can serve as a model for other countries during the Decade of Vaccines. For the Decade of Vaccines, getting vaccines at affordable prices to the market is not enough. Vaccines must reach the population to be successful. PMID:27576077

  16. A vaccine study design selection framework for the postlicensure rapid immunization safety monitoring program.

    PubMed

    Baker, Meghan A; Lieu, Tracy A; Li, Lingling; Hua, Wei; Qiang, Yandong; Kawai, Alison Tse; Fireman, Bruce H; Martin, David B; Nguyen, Michael D

    2015-04-15

    The Postlicensure Rapid Immunization Safety Monitoring Program, the vaccination safety monitoring component of the US Food and Drug Administration's Mini-Sentinel project, is currently the largest cohort in the US general population for vaccine safety surveillance. We developed a study design selection framework to provide a roadmap and description of methods that may be utilized to evaluate potential associations between vaccines and health outcomes of interest in the Postlicensure Rapid Immunization Safety Monitoring Program and other systems using administrative data. The strengths and weaknesses of designs for vaccine safety monitoring, including the cohort design, the case-centered design, the risk interval design, the case-control design, the self-controlled risk interval design, the self-controlled case series method, and the case-crossover design, are described and summarized in tabular form. A structured decision table is provided to aid in planning of future vaccine safety monitoring activities, and the data components comprising the structured decision table are delineated. The study design selection framework provides a starting point for planning vaccine safety evaluations using claims-based data sources.

  17. 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

  18. 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

  19. [Clinical trial of safety and immunogenicity of new influenza vaccine Grifor in children].

    PubMed

    Erofeeva, M K; Mel'nikov, S Ia; Semchenko, A V; Korovkin, S A; Nikonorov, I Iu; Maksakova, V L; Voĭtsekhovskaia, E M; Erman, E S; Gonchar, V V; Pozdeev, V K; Drinevskiĭ, V P

    2010-01-01

    Assessment of reactogenicity, safety and immunogenicity after single intramuscular immunization of children with Grifor vaccine. Reactogenicity, safety, and immunogenicity of Grifor vaccine compared with Vaxigrip vaccine was evaluated during phase III clinical trial in the Institute of Influenza. Thirty-six children aged 12 - 17 years, divided on 2 groups, participated in single blind comparative prospective randomized trial. Seroconversion factor, seroconversion and seroprotection levels were evaluated by hemagglutination inhibition assay. Results of study of systemic and local reactogenicity in children during first 7 days after immunization with Grifor and Vaxigrip vaccine showed good tolerability, areactogenicity and safety of both vaccines. Complete blood count, serum biochemistry and urinalysis results as well as serum IgE level did not change after vaccination. After immunization with Grifor vaccine, seroconversion rate to influenza virus subtypes A/H1N1, A/H3N2, and B was 70%, 50%, and 70% respectively, seroprotection rate--90%, 80%, and 85% respectively, and seroconversion factor--6.5, 2.7, and 4.0 respectively. This trial, which was performed in tightly controlled conditions, had demonstrated that Grifor vaccine is safe and highly immunogenic against influenza viruses A and B and satisfies criteria of both Federal Service for Surveillance for Protection of Consumers Rights and Human Welfare and CHMP of EMA. Obtained results allow to recommend the Grifor vaccine for use in pediatric practice according to national immunization schedule.

  20. Safety and immunogenicity of a quadrivalent influenza vaccine in adults 65 y of age and older.

    PubMed

    Greenberg, David P; Robertson, Corwin A; Talbot, H Keipp; Decker, Michael D

    2017-09-02

    Frequent mismatches between the predominant circulating B strain lineage and the B strain lineage in trivalent influenza vaccines have resulted in missed opportunities to prevent influenza illness. Quadrivalent influenza vaccines containing B strains from each of the 2 lineages have been developed for improved prevention of influenza B infections. Here, we describe the results of a phase III, randomized, double-blind, active-controlled, multicenter trial examining the safety and immunogenicity of a split-virion inactivated quadrivalent influenza vaccine (IIV4) in 675 adults ≥ 65 y of age (NCT01218646). Participants were randomly assigned 1:1:1 to receive a single intramuscular injection with the investigational IIV4, or one of 2 split-virion trivalent inactivated influenza vaccines (IIV3s): a licensed IIV3 containing a B Victoria-lineage strain or an investigational IIV3 containing a B Yamagata-lineage strain. Post-vaccination (day 21) hemagglutinin inhibition titers to all strains induced by IIV4 were statistically non-inferior to those induced by the 2 IIV3s. In addition, for each B strain, rates of seroconversion in the IIV4 group were superior to those induced by the comparator IIV3 not containing that B strain. For all vaccines, the most common solicited reaction was injection-site pain, and most reactions were mild to moderate in intensity and transient. Overall safety profiles were similar between IIV4 and the IIV3s, and no vaccine-related serious adverse events were reported. These results confirm that in adults ≥ 65 y of age, IIV4 was well tolerated and immunogenic against the additional B lineage strain without compromising the immunogenicity of the other 3 vaccine strains.

  1. Underestimating the safety benefits of a new vaccine: the impact of acellular pertussis vaccine versus whole-cell pertussis vaccine on health services utilization.

    PubMed

    Hawken, Steven; Manuel, Douglas G; Deeks, Shelley L; Kwong, Jeffrey C; Crowcroft, Natasha S; Wilson, Kumanan

    2012-12-01

    The population-level safety benefits of the acellular pertussis vaccine may have been underestimated because only specific adverse events were considered, not overall impact on health services utilization. Using the Vaccine and Immunization Surveillance in Ontario (VISION) system, the authors analyzed data on 567,378 children born between April 1994 and March 1996 (before introduction of acellular pertussis vaccine) and between April 1998 and March 2000 (after introduction of acellular pertussis vaccine) in Ontario, Canada. Using the self-controlled case series study design, they examined emergency room visits and hospital admissions occurring after routine pediatric vaccinations. The authors determined the relative incidence of events taking place before introduction of the acellular vaccine versus after introduction by calculating relative incidence ratios (RIRs). The observed RIRs demonstrated a highly statistically significant reduction in relative incidence after introduction of the acellular vaccine. RIRs for vaccine administered at ages 2, 4, 6, and 18 months were 1.82 (95% confidence interval (CI): 1.64, 2.01), 1.91 (95% CI: 1.71, 2.13), 1.54 (95% CI: 1.38, 1.72), and 1.51 (95% CI: 1.34, 1.69), respectively, comparing event rates before the introduction of acellular vaccine with those after introduction. The authors estimated that approximately 90 emergency room visits and 9 admissions per month were avoided by switching to the acellular vaccine, which is a 38-fold higher impact than when they considered only admissions for febrile and afebrile convulsions. Future analyses comparing vaccines for safety should examine specific endpoints and general health services utilization.

  2. 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" = 376) was…

  3. 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" = 376) was…

  4. 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

  5. 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

  6. 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

  7. The role of non-human primates in the neurological safety of live viral vaccines (review).

    PubMed

    Levenbook, Inessa

    2011-01-01

    This review covers comprehensive data accumulated during the long history of using monkeys in the determination of neurovirulence activity and safety of live poliomyelitis, flaviviral, smallpox and mumps vaccines, as well as newly developed transgenic mouse and molecular-biological tests. The review also analyzes processes caused by some of these viruses in infant rodents (mice, rats) and evaluates the role of these processes in vaccine safety control. Recommendations resulting from this analysis are presented.

  8. Effectiveness and safety of inactivated influenza vaccination in pediatric liver transplant recipients over three influenza seasons.

    PubMed

    Gotoh, Kensei; Ito, Yoshinori; Suzuki, Eitaro; Kaneko, Kenitiro; Kiuchi, Tetsuya; Ando, Hisami; Kimura, Hiroshi

    2011-02-01

    Annual influenza vaccination is recommended for pediatric liver transplant recipients, who are at high risk of influenza-related complications. However, effectiveness and safety of vaccination may differ among influenza seasons in this population and have not been fully evaluated. Subjects comprised 38 pediatric liver transplant recipients with or without influenza vaccination through the 2006-2007, 2007-2008 and 2008-2009 influenza seasons. Recipients received inactivated trivalent (AH1/AH3/B) influenza vaccine, and comparisons were made to non-vaccinated recipients with regard to effectiveness and safety. No significant differences were seen between recipient groups for acute allograft rejection, acute febrile illness, or influenza virus infection. No serious systemic adverse events were observed in vaccinated recipients. Seroprotection rate (defined as the proportion of recipients with HI antibody titer ≥ 1:40), seroconversion rate (proportion of recipients with a ≥ 4-fold increase in HI titers), and geometric mean titers were mostly elevated after vaccination for the three influenza antigens in each season. These three indicators of immunogenicity showed similar results in both vaccinated recipients and vaccinated healthy children in the 2007-2008 season. These findings suggest that pediatric liver transplant patients may respond safely to inactivated seasonal influenza vaccines in a similar manner to healthy children, and effectiveness varies among influenza seasons.

  9. A Review of the Safety and Efficacy of Vaccines as Prophylaxis for Clostridium difficile Infections.

    PubMed

    Henderson, Mackenzie; Bragg, Amanda; Fahim, Germin; Shah, Monica; Hermes-DeSantis, Evelyn R

    2017-09-02

    This review aims to evaluate the literature on the safety and efficacy of novel toxoid vaccines for the prophylaxis of Clostridium difficile infections (CDI) in healthy adults. Literature searches for clinical trials were performed through MEDLINE, ClinicalTrials.gov, and Web of Science using the keywords bacterial vaccines, Clostridium difficile, and vaccine. English-language clinical trials evaluating the efficacy and/or safety of Clostridium difficile toxoid vaccines that were completed and had results posted on ClinicalTrials.gov or in a published journal article were included. Six clinical trials were included. The vaccines were associated with mild self-reported adverse reactions, most commonly injection site reactions and flu-like symptoms, and minimal serious adverse events. Five clinical trials found marked increases in antibody production in vaccinated participants following each dose of the vaccine. Clinical trials evaluating C. difficile toxoid vaccines have shown them to be well tolerated and relatively safe. Surrogate markers of efficacy (seroconversion and geometric mean antibody levels) have shown significant immune responses to a vaccination series in healthy adults, indicating that they have the potential to be used as prophylaxis for CDI. However, more research is needed to determine the clinical benefits of the vaccines.

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

    PubMed

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

    2013-07-01

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

  11. HPV vaccination: Population approaches for improving rates

    PubMed Central

    Oliver, Kristin; Frawley, Alean; Garland, Elizabeth

    2016-01-01

    ABSTRACT Objective: To review the literature on interventions to increase HPV vaccinations and assess whether The Community Preventive Services Task Force recommendations are supported by current evidence. Methods: We used a PubMed search to identify studies that assessed interventions that looked at provider assessment and feedback, provider reminders, client reminder and recall, and clinic based education programs. Results: Of the 13 studies identified, 8 included client reminder and recall interventions, 4 included provider assessment and feedback and/or provider reminders and 2 included clinic based education. 11 of the 13 studies demonstrated a positive effect on HPV vaccine initiation or completion. Provider assessment and feedback studies were more likely to report a positive effect on HPV vaccine initiation than on series completion, while client reminder recall interventions more frequently produced an effect on series completion than on initiation. Conclusions: There is evidence to support the application of the Community Preventive Services Task Force recommendations specifically to HPV vaccination both for client reminder and recall programs and for provider assessment and feedback interventions. Multiple targeted approaches will be needed to substantially impact HPV vaccine rates. PMID:26890685

  12. [Strategies to improve influenza vaccination coverage in Primary Health Care].

    PubMed

    Antón, F; Richart, M J; Serrano, S; Martínez, A M; Pruteanu, D F

    2016-04-01

    Vaccination coverage reached in adults is insufficient, and there is a real need for new strategies. To compare strategies for improving influenza vaccination coverage in persons older than 64 years. New strategies were introduced in our health care centre during 2013-2014 influenza vaccination campaign, which included vaccinating patients in homes for the aged as well as in the health care centre. A comparison was made on vaccination coverage over the last 4 years in 3 practices of our health care centre: P1, the general physician vaccinated patients older than 64 that came to the practice; P2, the general physician systematically insisted in vaccination in elderly patients, strongly advising to book appointments, and P3, the general physician did not insist. These practices looked after P1: 278; P2: 320; P3: 294 patients older than 64 years. Overall/P1/P2/P3 coverages in 2010: 51.2/51.4/55/46.9% (P=NS), in 2011: 52.4/52.9/53.8/50.3% (P=NS), in 2012: 51.9/52.5/55.3/47.6% (P=NS), and in 2013: 63.5/79.1/59.7/52.7 (P=.000, P1 versus P2 and P3; P=NS between P2 and P3). Comparing the coverages in 2012-2013 within each practice P1 (P=.000); P2 (P=.045); P3 (P=.018). In P2 and P3 all vaccinations were given by the nurses as previously scheduled. In P3, 55% of the vaccinations were given by the nurses, 24.1% by the GP, 9.7% rejected vaccination, and the remainder did not come to the practice during the vaccination period (October 2013-February 2014). The strategy of vaccinating in the homes for the aged improved the vaccination coverage by 5% in each practice. The strategy of "I've got you here, I jab you here" in P1 improved the vaccination coverage by 22%. Copyright © 2014 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

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

    PubMed

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

    2015-07-01

    Despite the enormous population benefits of routine vaccination, vaccine adverse events (AEs) 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 AEs, 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 AEs/reactions, and outline a plan for the further development of this emerging research field.

  14. 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

  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.

  16. Immunogenicity, safety and efficacy of tetravalent rhesus-human, reassortant rotavirus vaccine in Belém, Brazil.

    PubMed Central

    Linhares, A. C.; Gabbay, Y. B.; Mascarenhas, J. D.; de Freitas, R. B.; Oliveira, C. S.; Bellesi, N.; Monteiro, T. A.; Lins-Lainson, Z.; Ramos, F. L.; Valente, S. A.

    1996-01-01

    A tetravalent rhesus-human reassortant rotavirus (RRV-TV) vaccine (4 x 10(4) plaque-forming units/dose) was evaluated for safety, immunogenicity and efficacy in a prospective, randomized, double-blind, placebo-controlled trial involving 540 Brazilian infants. Doses of vaccine or placebo were given at ages 1, 3 and 5 months. No significant differences were noted in the occurrence of diarrhoea or vomiting in vaccine and placebo recipients following each dose. Low-grade fever occurred on days 3-5 in 2-3% of vaccinees after the first dose, but not after the second or third doses of vaccine. An IgA antibody response to rhesus rotavirus (RRV) occurred in 58% of vaccinees and 33% of placebo recipients. Neutralizing antibody responses to individual serotypes did not exceed 20% when measured by fluorescent focus reduction, but exceeded 40% when assayed by plaque reduction neutralization. There were 91 cases of rotavirus diarrhoea among the 3-dose (vaccine or placebo) recipients during two years of follow-up, 36 of them among children given the vaccine. Overall vaccine efficacy was 8% (P = 0.005) against any diarrhoea and 35% (P = 0.03) against any rotavirus diarrhoea. Protection during the first year of follow-up, when G serotype 1 rotavirus predominated, was 57% (P = 0.008), but fell to 12% in the second year. Similar results were obtained when analysis was restricted to episodes in which rotavirus was the only identified pathogen. There was a tendency for enhanced protection by vaccine against illness associated with an average of 6 or more stools per day. These results are sufficiently encouraging to warrant further studies of this vaccine in developing countries using a higher dosage in an attempt to improve its immunogenicity and efficacy. PMID:9002329

  17. Influenza and respiratory syncytial virus (RSV) vaccines for infants: safety, immunogenicity, and efficacy.

    PubMed

    Beeler, Judy A; Eichelberger, Maryna C

    2013-02-01

    Respiratory viral infections in infants and young children frequently cause illness that can easily progress to hospitalization and death. There are currently no licensed vaccines to prevent respiratory viral disease in children younger than 6 months, reflecting safety concerns and the difficulty in inducing effective immune responses in infants. This review discusses vaccines that have been developed, or are currently being developed, against influenza and respiratory syncytial virus, with a focus on studies performed to demonstrate their safety and efficacy, and the impact of immunologic immaturity and maternal antibodies on the infant response to vaccines.

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

    PubMed

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

    2016-01-01

    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. 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. 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). 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-healthy subjects. This meta-analysis is limited by the relatively

  19. Safety of measles-containing vaccines in post-marketing surveillance in Anhui, China.

    PubMed

    Meng, Fan-Ya; Sun, Yong; Shen, Yong-Gang; Pan, Hai-Feng; Tang, Ji-Hai; Wang, Bin-Bing; Wu, Chang-Hao; Ye, Dong-Qing

    2017-01-01

    The safety of measles vaccination is of great interest and importance to public health practice and the general society. We have analyzed the adverse events following immunization (AEFIs) of currently used measles-containing vaccines (including live attenuated measles vaccine, live attenuated measles and rubella combined vaccine, live attenuated measles and mumps combined vaccine, live attenuated Measles, Mumps and Rubella Combined Vaccine) in Anhui Province, China. From 2009 to 2014, 9.9 million doses of measles-containing vaccines were administrated and 1893 AEFIs were found (191.4 per million doses), of which, 33 serious AEFIs (3.3 per million vaccine doses) were reported. 59.4% (1124 cases) were male cases, and 85.1% (1611 cases) occurred in persons aged < 1 year. 93.3% (1766 cases) occurred at the first dose of vaccination and 95.9% (1815 cases) were found within 3 days after vaccination. This study presents up-to-date data and suggests that the measles-containing vaccines used in Anhui Province of China are safe.

  20. Safety, Tolerability, and Immunogenicity of a Recombinant, Genetically Engineered, Live-Attenuated Vaccine against Canine Blastomycosis▿

    PubMed Central

    Wüthrich, Marcel; Krajaejun, Theerapong; Shearn-Bochsler, Valerie; Bass, Chris; Filutowicz, Hanna I.; Legendre, Alfred M.; Klein, Bruce S.

    2011-01-01

    Blastomycosis is a severe, commonly fatal infection caused by the dimorphic fungus Blastomyces dermatitidis in dogs that live in the United States, Canada, and parts of Africa. The cost of treating an infection can be expensive, and no vaccine against this infection is commercially available. A genetically engineered live-attenuated strain of B. dermatitidis lacking the major virulence factor BAD-1 successfully vaccinates against lethal experimental infection in mice. Here we studied the safety, toxicity, and immunogenicity of this strain as a vaccine in dogs, using 25 beagles at a teaching laboratory and 78 foxhounds in a field trial. In the beagles, escalating doses of live vaccine ranging from 2 × 104 to 2 × 107 yeast cells given subcutaneously were safe and did not disseminate to the lung or induce systemic illness, but a dose of <2 × 106 yeast cells induced less fever and local inflammation. A vaccine dose of 105 yeast cells was also well tolerated in vaccinated foxhounds who had never had blastomycosis; however, vaccinated dogs with prior infection had more local reactions at the vaccine site. The draining lymph node cells and peripheral blood lymphocytes from vaccinated dogs demonstrated gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), and granulocyte-macrophage colony-stimulating factor (GM-CSF) specifically in response to stimulation with Blastomyces antigens. Thus, the live-attenuated vaccine against blastomycosis studied here proved safe, well tolerated, and immunogenic in dogs and merits further studies of vaccine efficacy. PMID:21367980

  1. Safety of measles-containing vaccines in post-marketing surveillance in Anhui, China

    PubMed Central

    Meng, Fan-Ya; Sun, Yong; Shen, Yong-Gang; Pan, Hai-Feng; Tang, Ji-Hai; Wang, Bin-Bing; Wu, Chang-Hao; Ye, Dong-Qing

    2017-01-01

    The safety of measles vaccination is of great interest and importance to public health practice and the general society. We have analyzed the adverse events following immunization (AEFIs) of currently used measles-containing vaccines (including live attenuated measles vaccine, live attenuated measles and rubella combined vaccine, live attenuated measles and mumps combined vaccine, live attenuated Measles, Mumps and Rubella Combined Vaccine) in Anhui Province, China. From 2009 to 2014, 9.9 million doses of measles-containing vaccines were administrated and 1893 AEFIs were found (191.4 per million doses), of which, 33 serious AEFIs (3.3 per million vaccine doses) were reported. 59.4% (1124 cases) were male cases, and 85.1% (1611 cases) occurred in persons aged < 1 year. 93.3% (1766 cases) occurred at the first dose of vaccination and 95.9% (1815 cases) were found within 3 days after vaccination. This study presents up-to-date data and suggests that the measles-containing vaccines used in Anhui Province of China are safe. PMID:28192490

  2. Safety and immunogenicity of live attenuated and inactivated influenza vaccines in children with cancer.

    PubMed

    Carr, Silvana; Allison, Kim J; Van De Velde, Lee-Ann; Zhang, Kelly; English, Elizabeth Y; Iverson, Amy; Daw, Najat C; Howard, Scott C; Navid, Fariba; Rodriguez-Galindo, Carlos; Yang, Jie; Adderson, Elisabeth E; McCullers, Jonathan A; Flynn, Patricia M

    2011-11-15

    The safety and immunogenicity of live, attenuated influenza vaccine (LAIV) has not been compared to that of the standard trivalent inactivated vaccine (TIV) in children with cancer. Randomized study of LAIV versus TIV in children with cancer, age 2-21 years, vaccinated according to recommendations based on age and prior vaccination. Data on reactogenicity and other adverse events and blood and nasal swab samples were obtained following vaccination. Fifty-five eligible subjects (mean age, 10.4 years) received vaccine (28 LAIV/27 TIV). Both vaccines were well tolerated. Rhinorrhea reported within 10 days of vaccination was similar in both groups (36% LAIV vs 33% TIV, P > .999). Ten LAIV recipients shed virus; the latest viral shedding was detected 7 days after vaccination. Immunogenicity data were available for 52 subjects, or 26 in each group. TIV induced significantly higher postvaccination geometric mean titers against influenza A viruses (P < .001), greater seroprotection against influenza A/H1N1 (P = .01), and greater seroconversion against A/H3N2 (P = .004), compared with LAIV. No differences after vaccination were observed against influenza B viruses. As expected, serum antibody response against influenza A strains were greater with TIV than with LAIV in children with cancer. Both vaccines were well tolerated, and prolonged viral shedding after LAIV was not detected. NCT00906750.

  3. Safety testing of veterinary vaccines using magnetic resonance imaging in pigs.

    PubMed

    Bernau, Maren; Kremer, Prisca V; Pappenberger, Elke; Kreuzer, Lena S; Cussler, Klaus; Hoffmann, Andreas; Scholz, Armin M

    2015-01-01

    Safety testing of veterinary vaccines requires the use of a large number of animals to investigate possible local and systemic reactions. This includes amongst others the pathological examination of the injection site in frequent intervals. For this a selected killing of animals in frequent intervals is inevitable. To reduce the number of animals needed for this kind of safety testing, magnetic resonance imaging (MRI) was used to detect and quantify possible inflammatory reactions after vaccination in vivo. Sixty four pigs were subdivided into 4 experimental groups (n=16); two groups consisting of 12 weeks old pigs and 2 of 6 month old pigs at vaccination day. The pigs were vaccinated with four licensed products (each group receiving one vaccine) and examined up to 6 times using MRI during a period of 5 weeks. The MRI images were evaluated semi-automatically comparing the volumes of altered signal intensities at the vaccination side (VS) with the volumes of the signal intensities at the control side (CS). A paired t-Test was used to identify significant differences (p<0.05) between VS and CS. The results show that MRI allows a 3D-quantification of the extent of local reactions in vivo, scanning the same animals at several points of time after vaccination. MRI is a suitable alternative method for non-invasive safety testing of injectable medicines and can therefore be used as an alternative method to reduce animal numbers for safety testing purposes.

  4. Preclinical immunogenicity and safety of a Group A streptococcal M protein-based vaccine candidate.

    PubMed

    Batzloff, Michael R; Fane, Anne; Gorton, Davina; Pandey, Manisha; Rivera-Hernandez, Tania; Calcutt, Ainslie; Yeung, Grace; Hartas, Jon; Johnson, Linda; Rush, Catherine M; McCarthy, James; Ketheesan, Natkunam; Good, Michael F

    2016-12-01

    Streptococcus pyogenes (group A streptococcus, GAS) causes a wide range of clinical manifestations ranging from mild self-limiting pyoderma to invasive diseases such as sepsis. Also of concern are the post-infectious immune-mediated diseases including rheumatic heart disease. The development of a vaccine against GAS would have a large health impact on populations at risk of these diseases. However, there is a lack of suitable models for the safety evaluation of vaccines with respect to post-infectious complications. We have utilized the Lewis Rat model for cardiac valvulitis to evaluate the safety of the J8-DT vaccine formulation in parallel with a rabbit toxicology study. These studies demonstrated that the vaccine did not induce abnormal pathology. We also show that in mice the vaccine is highly immunogenic but that 3 doses are required to induce protection from a GAS skin challenge even though 2 doses are sufficient to induce a high antibody titer.

  5. Recent advances and safety issues of transgenic plant-derived vaccines.

    PubMed

    Guan, Zheng-jun; Guo, Bin; Huo, Yan-lin; Guan, Zheng-ping; Dai, Jia-kun; Wei, Ya-hui

    2013-04-01

    Transgenic plant-derived vaccines comprise a new type of bioreactor that combines plant genetic engineering technology with an organism's immunological response. This combination can be considered as a bioreactor that is produced by introducing foreign genes into plants that elicit special immunogenicity when introduced into animals or human beings. In comparison with traditional vaccines, plant vaccines have some significant advantages, such as low cost, greater safety, and greater effectiveness. In a number of recent studies, antigen-specific proteins have been successfully expressed in various plant tissues and have even been tested in animals and human beings. Therefore, edible vaccines of transgenic plants have a bright future. This review begins with a discussion of the immune mechanism and expression systems for transgenic plant vaccines. Then, current advances in different transgenic plant vaccines will be analyzed, including vaccines against pathogenic viruses, bacteria, and eukaryotic parasites. In view of the low expression levels for antigens in plants, high-level expression strategies of foreign protein in transgenic plants are recommended. Finally, the existing safety problems in transgenic plant vaccines were put forward will be discussed along with a number of appropriate solutions that will hopefully lead to future clinical application of edible plant vaccines.

  6. Safety of immunization during pregnancy: a review of the evidence of selected inactivated and live attenuated vaccines.

    PubMed

    Keller-Stanislawski, Brigitte; Englund, Janet A; Kang, Gagandeep; Mangtani, Punam; Neuzil, Kathleen; Nohynek, Hanna; Pless, Robert; Lambach, Philipp; Zuber, Patrick

    2014-12-12

    Vaccine-preventable infectious diseases are responsible for significant maternal, neonatal, and young infant morbidity and mortality. While there is emerging scientific evidence, as well as theoretical considerations, indicating that certain vaccines are safe for pregnant women and fetuses, policy formulation is challenging because of perceived potential risks to the fetus. This report presents an overview of available evidence on pregnant women vaccination safety monitoring in pregnant women, from both published literature and ongoing surveillance programs. Safety data were reviewed for vaccines against diseases which increase morbidity in pregnant women, their fetus or infant as well as vaccines which are used in mass vaccination campaigns against diseases. They include inactivated seasonal and pandemic influenza, mono- and combined meningococcal polysaccharide and conjugated vaccines, tetanus toxoid and acellular pertussis combination vaccines, as well as monovalent or combined rubella, oral poliomyelitis virus and yellow fever vaccines. No evidence of adverse pregnancy outcomes has been identified from immunization of pregnant women with these vaccines.

  7. Safety of diphtheria, tetanus, acellular pertussis and inactivated poliovirus (DTaP-IPV) vaccine.

    PubMed

    Daley, Matthew F; Yih, W Katherine; Glanz, Jason M; Hambidge, Simon J; Narwaney, Komal J; Yin, Ruihua; Li, Lingling; Nelson, Jennifer C; Nordin, James D; Klein, Nicola P; Jacobsen, Steven J; Weintraub, Eric

    2014-05-23

    In 2008, a diphtheria, tetanus, acellular pertussis, and inactivated poliovirus combined vaccine (DTaP-IPV) was licensed for use in children 4 through 6 years of age. While pre-licensure studies did not demonstrate significant safety concerns, the number vaccinated in these studies was not sufficient to examine the risk of uncommon but serious adverse events. To assess the risk of serious adverse events following DTaP-IPV vaccination. The study was conducted from January 2009 through September 2012 in the Vaccine Safety Datalink (VSD) project. In the VSD, electronic vaccination and encounter data are updated and aggregated weekly as part of ongoing surveillance activities. Based on previous reports and biologic plausibility, eight potential adverse events were monitored: meningitis/encephalitis; seizures; stroke; Guillain-Barré syndrome; Stevens-Johnson syndrome; anaphylaxis; serious allergic reactions other than anaphylaxis; and serious local reactions. Adverse event rates in DTaP-IPV recipients were compared to historical incidence rates in the VSD population prior to 2009. Sequential probability ratio testing was used to analyze the data on a weekly basis. During the study period, 201,116 children received DTaP-IPV vaccine. Ninety-seven percent of DTaP-IPV recipients also received other vaccines on the same day, typically measles-mumps-rubella and varicella vaccines. There was no statistically significant increased risk of any of the eight pre-specified adverse events among DTaP-IPV recipients when compared to historical incidence rates. In this safety surveillance study of more than 200,000 DTaP-IPV vaccine recipients, there was no evidence of increased risk for any of the pre-specified adverse events monitored. Continued surveillance of DTaP-IPV vaccine safety may be warranted to monitor for rare adverse events, such as Guillain-Barré syndrome. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. 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)…

  9. 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)…

  10. Comparison of immunogenicity and safety of an influenza vaccine administered concomitantly with a 13-valent pneumococcal conjugate vaccine or 23-valent polysaccharide pneumococcal vaccine in the elderly

    PubMed Central

    2017-01-01

    Purpose Previous studies have demonstrated the immunogenicity and safety of the co-administration of the trivalent inactivated influenza vaccine (IIV3) with the polysaccharide pneumococcal vaccine (PPV) or pneumococcal conjugate vaccine (PCV). However, there is no direct comparison study that evaluates the immunogenicity and safety of IIV3 given concomitantly with PCV13 or PPV23 in the elderly. Materials and Methods During the 2012-2013 influenza vaccination period, 224 healthy elderly volunteers aged 65 years and older randomly received IIV3 given concomitantly with either PCV13 (PCV13+IIV3) or PPV23 (PPV23+IIV3) in a 1:1 ratio. Serum hemagglutination-inhibiting antibodies for IIV3 were measured at the time of vaccination and 1 month after vaccination. Adverse events were recorded prospectively in a clinical diary during a 7-day period. Results A total of 220 participants blood samples for analysis of immunogenicity and kept a clinical diary for safety analysis (PCV13+IIV3, n=110; PPV23+IIV3, n=110). One month after vaccination, both groups satisfied the Committee for Medical Products for Human Use criteria for A/H1N1, A/H3N2 and B strains, showing comparable seroprotection rates, seroconversion rates and geometric mean titer fold. The assessments of immunogenicity were similar in both groups. The most common local and systemic reactions were pain at the injection site and generalized myalgia. They were generally mild or moderate in intensity. The adverse events were not statistically different between the two groups. Conclusion PCV13+IIV3 and PPV23+IIV3 demonstrated similar immunogenicity and safety in the elderly. PMID:28168172

  11. Information scanning and vaccine safety concerns among African American, Mexican American, and non-Hispanic White women.

    PubMed

    Moran, Meghan Bridgid; Frank, Lauren B; Chatterjee, Joyee S; Murphy, Sheila T; Baezconde-Garbanati, Lourdes

    2016-01-01

    A significant number of parents delay or refuse vaccinating their children. Incidental exposure to vaccine information (i.e., scanned information) may be an important contributor to anti-vaccine sentiment. This study examines the association between scanned information, trust in health information sources and vaccine safety concerns among African American, Mexican American, and non-Hispanic White women. Women (N=761) in Los Angeles County were sampled via random digit dial and surveyed regarding use of and trust in health information resources and vaccine safety concerns. Analyses indicate that the sources of information associated with vaccine safety concerns varied by ethnicity. Each ethnic group exhibited different patterns of association between trust in health information resources and vaccine safety concerns. Information scanning is associated with beliefs about vaccine safety, which may lead parents to refuse or delay vaccinating their children. These relationships vary by ethnicity. These findings help inform practitioners and policy makers about communication factors that influence vaccine safety concerns. Knowing these sources of information will equip practitioners to better identify women who may have been exposed to anti-vaccine messages and counter these beliefs with effective, vaccine-promoting messages via the most relevant information sources. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. Information scanning and vaccine safety concerns among African American, Mexican American, and non-Hispanic White women

    PubMed Central

    Moran, Meghan Bridgid; Frank, Lauren B.; Chatterjee, Joyee S.; Murphy, Sheila T.; Baezconde-Garbanati, Lourdes

    2015-01-01

    Objective A significant number of parents delay or refuse vaccinating their children. Incidental exposure to vaccine information (i.e., scanned information) may be an important contributor to anti-vaccine sentiment. This study examines the association between scanned information, trust in health information sources and vaccine safety concerns among African American, Mexican American, and non-Hispanic White women. Methods Women (N=761) in Los Angeles County were sampled via random digit dial and surveyed regarding use of and trust in health information resources and vaccine safety concerns. Results Analyses indicate that the sources of information associated with vaccine safety concerns varied by ethnicity. Each ethnic group exhibited different patterns of association between trust in health information resources and vaccine safety concerns. Conclusions Information scanning is associated with beliefs about vaccine safety, which may lead parents to refuse or delay vaccinating their children. These relationships vary by ethnicity. Practice Implications These findings help inform practitioners and policy makers about communication factors that influence vaccine safety concerns. Knowing these sources of information will equip practitioners to better identify women who may have been exposed to anti-vaccine messages and counter these beliefs with effective, vaccine-promoting messages via the most relevant information sources. PMID:26321294

  13. [Efficacy and safety of vaccination against hepatitis A and B in patients with chronic liver disease].

    PubMed

    de Artaza Varasa, Tomás; Sánchez Ruano, Juan José; García Vela, Almudena; Gómez Rodríguez, Rafael; Romero Gutiérrez, Marta; de la Cruz Pérez, Gema; Gómez Moreno, Ana Zaida; Carrobles Jiménez, José María

    2009-01-01

    Vaccination to protect against hepatitis A and B should be part of the routine management of patients with chronic liver disease (CLD). To evaluate the efficacy and safety of hepatitis A virus (HAV) and hepatitis B virus (HBV) vaccination in a group of patients with CLD and to assess the presence of factors predictive of response. We performed a prospective, single-center study in 194 patients (123 men, 71 women; mean age, 48.9+/-10.7 years) with CLD: 107 with chronic hepatitis (CH) and 87 with hepatic cirrhosis (HC), all Child-Pugh class A. The most frequent causes of CLD were HCV infection and alcohol. Patients negative for anti-HAV IgG received the HAV vaccination (1440 ELISA units in two doses) and those with negative HBV serology received the HBV vaccination ( three 20 microg doses). Patients with inadequate response to the latter vaccine received an additional double dose. Thirty patients received a combination vaccine (three doses). Sixty patients (31%) received the HAV vaccine and 150 (77%) patients received the HBV vaccine. Seroconversion was achieved by 91.6% of patients for HAV and by 57% of the patients for HBV. After the additional dose, the response increased to 74%. Efficacy was similar between CH and HC. HBV vaccination was less effective in HC than in CH and the seroconversion rate was significantly lower in patients with HC and previous decompensation. The combination vaccine (30 patients) was highly immunogenic. No adverse effects were registered. HAV vaccination has high efficacy in patients with CLD. Patients with HC respond weakly to HBV vaccination compared with those with CH and especially if there is prior decompensation. The combination vaccine seems particularly effective in patients with CLD. The three vaccines are safe.

  14. Safety and perception: What are the greatest enemies of HPV vaccination programmes?

    PubMed

    Bonanni, Paolo; Zanella, Beatrice; Santomauro, Francesca; Lorini, Chiara; Bechini, Angela; Boccalini, Sara

    2017-06-10

    Vaccines stimulate a person's immune system to produce an adequate reaction against a specific infectious agent; i.e. the person is protected from that disease without having to get it first. As vaccines are administrated to healthy subjects, they are held to the highest standards of safety. Regarding human papillomavirus (HPV) vaccines, at present three prophylactic vaccines are licensed (bivalent HPV 16/18, quadrivalent HPV 6/11/16/18 and the nonovalent HPV 6/11/16/18/31/33/45/52/58 vaccine). Pre- and post-licensure studies (i.e. not yet for nonovalent HPV vaccine) confirm that HPV vaccines are generally safe and well-tolerated, site injections symptoms are the most common adverse events (AEs) reported, and pain is the most frequently referred local symptom. Serious AEs are rare and not associated with severe sequelae, at least no vaccine-related deaths have occurred. Despite these scientific evidences, it is still difficult to explain to the population the importance of a good vaccination programme. There are many determinants for HPV vaccines hesitancy which represent a barrier that must be overcome in order to increase vaccine coverage, including psychological reactions, religious or cultural aspects, and fear of possible AEs (demyelinating diseases, Complex Regional Pain Syndrome - CRPS, or Postural Orthostatic Tachycardia Syndrome - POTS). A weak communication strategy which frequently suffers due to spread of unverified news by media and websites may lead to the failure of a vaccination programme. Such a situation happened in Japan (2013), due to which a great number of women remain vulnerable to HPV-related cancers. In order to resolve the issues around HPV vaccines acceptance, it is necessary to use good communication strategies. Multicomponent and dialogue-based interventions seem to be the most effective, especially if an adequate language is used, customized according to the vaccination programme target. Copyright © 2017 Elsevier Ltd. All rights

  15. Monitoring the safety of a smallpox vaccination program in the United States: report of the joint Smallpox Vaccine Safety Working Group of the advisory committee on immunization practices and the Armed Forces Epidemiological Board.

    PubMed

    Neff, John; Modlin, John; Birkhead, Guthrie S; Poland, Gregory; Robertson, Rose Marie; Sepkowitz, Kent; Yancy, Clyde; Gardner, Pierce; Gray, Gregory C; Maurer, Toby; Siegel, Jane; Guerra, Fernando A; Berger, Tim; Flanders, W Dana; Shope, Robert

    2008-03-15

    In December 2002, the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices and the Department of Defense Armed Forces Epidemiological Board formed a joint Smallpox Vaccine Safety Working Group (SVS WG) to provide independent safety oversight for smallpox vaccination safety-monitoring systems. From January 2003 through June 2004, the SVS WG reviewed individual and aggregate safety data on postvaccination adverse events. Serious adverse events were rare because of careful education, prevaccination screening, and strict attention to vaccination-site management. Recent vaccinees safely cared for high-risk patients, adhering to recommended site care. Human immunodeficiency virus-infected individuals without severe immunosuppression had uncomplicated vaccination reactions. Epidemiological studies supported a causal relationship between myocarditis and/or pericarditis and smallpox vaccination. Data supported neutrality regarding hypothesized causal associations between vaccination and dilated cardiomyopathy or ischemic cardiac disease. The SVS WG concurs with recommendations to defer from vaccination any person with >/=3 ischemic cardiac disease risk factors.

  16. [Candid#1 vaccine against Argentine hemorrhagic fever produced in Argentina. Immunogenicity and safety].

    PubMed

    Enria, Delia A; Ambrosio, Ana M; Briggiler, Ana M; Feuillade, María Rosa; Crivelli, Eleonora

    2010-01-01

    A clinical study in 946 human volunteers was done to compare Candid #1 vaccine manufactured in Argentina with the vaccine produced in USA that had been previously used. The efficacy was evaluated using immunogenicity measured by the detection of neutralizing antibodies as a subrogate marker. Safety was evaluated comparing the rate of adverse events. Both vaccines showed a comparable rate of seroconversion, slightly higher than the efficacy estimated from previous studies (95.5%). There were no severe adverse events related to the vaccines. The general events considered related to the vaccines were not clinically relevant and disappeared either spontaneously or with symptomatic treatment. Similar rates of adverse events (29.9% for the Argentine vaccine and 35.0% for the USA vaccine) were found for both vaccines. These included: headache, weakness, myalgias, mild low blood cell (< 4,000/mm(3)) and platelet (< 150,000/mm(3)) counts, nausea and/or vomiting, fever, retroocular pain, dizziness, microhematuria, low backache and exantema. These results indicate that the vaccine Candid#1 manufactured in Argentina is equivalent to the manufactured in USA. These results allowed the National Institute of Human Viral Diseases (INEVH) to register the vaccine produced locally under the National Regulatory Authority (ANMAT).

  17. A pilot program to improve vaccination status for hospitalized children.

    PubMed

    Pahud, Barbara; Clark, Shannon; Herigon, Joshua C; Sherman, Ashley; Lynch, Daryl A; Hoffman, Amber; Jackson, Mary Anne

    2015-01-01

    Screening of immunization status at each health care encounter is recommended to improve immunization coverage rates but is often limited to primary care practices. A pilot intervention study was performed to ascertain the immunization status of hospitalized children and determine if development of an immunization plan before discharge would improve the vaccination status for such children. On the basis of power calculations estimated to detect an increase in immunization status from 60% to 70% with 80% power, 356 randomly selected children were enrolled between March 6, 2012 and June 14, 2012. Immunization records were obtained, immunization status determined, and parent/guardian informed if catch-up dose(s) were needed. If parent requested vaccine dose(s), they were administered before discharge. Vaccination status was current per Advisory Committee on Immunization Practices guidelines in 73% of hospitalized children, and 27% children required catch-up dose(s) (200 doses for 95 children). Human papilloma virus vaccine (dose 1), varicella zoster vaccine (dose 2), and meningococcal conjugate vaccine were the most commonly identified dose(s) needed. Of those requiring catch-up dose(s), 25% were caught up, increasing vaccination status to 80% at 1-month post hospital discharge. This is the first study to determine the immunization status of hospitalized pediatric patients of all ages, including adolescents, providing new data on the immunization status of the inpatient pediatric population. A pilot intervention consisting of obtaining immunization records, determining immunization status, and discussing catch-up dose(s) before discharge resulted in improvement of immunization status, suggesting that the inpatient setting may be used along with many other national strategies to help address missed vaccination opportunities. Copyright © 2015 by the American Academy of Pediatrics.

  18. Improving patient safety by instructional systems design

    PubMed Central

    Battles, J B

    2006-01-01

    Education and training are important elements in patient safety, both as a potential contributing factor to risks and hazards of healthcare associated injury or harm and as an intervention to be used in eliminating or preventing such harm. All too often we have relied on training as the only interventions for patient safety without examining other alternatives or realizing that, in some cases, the training systems themselves are part of the problem. One way to ensure safety by design is to apply established design principles to education and training. Instructional systems design (ISD) is a systematic method of development of education and training programs for improved learner performance. The ISD process involves five integrated steps: analysis, development, design, implementation, and evaluation (ADDIE). The application of ISD using the ADDIE approach can eliminate or prevent education and training from being a contributing factor of health associated injury or harm, and can also be effective in preventing injury or harm. PMID:17142604

  19. Immunogenicity, effectiveness and safety of combined hepatitis A and B vaccine: a systematic literature review.

    PubMed

    Bakker, Marina; Bunge, Eveline M; Marano, Cinzia; de Ridder, Marc; De Moerlooze, Laurence

    2016-07-01

    Hepatitis A and B are two of the most common vaccine-preventable diseases and vaccination for Hepatitis A virus (HAV) and hepatitis B virus (HBV) is recommended for those at risk of contracting HAV and/or HBV through their occupation, travel or lifestyle. To describe the vaccine efficacy, immunogenicity, effectiveness and safety of the combined vaccine against hepatitis A and hepatitis B. A systematic review of the literature published between 1990 and 2015. Anti-HAV seropositivity rates ranged from 96.2% to 100% and anti-HBs seroprotection rates from 82% to 100%. Antibodies persisted up to 15 years and geometric mean concentration (GMC) remained above the seropositivity cut-off value for both. Anti-HAV and anti-HBs immune responses were lower in less immunocompetent individuals one month after completion of the immunization schedule. The safety profiles of Twinrix(TM) and monovalent hepatitis A and B vaccines were similar. The vaccine offers satisfactory long-term immunogenicity rates, expected duration of protection and safety profile similar to the monovalent hepatitis A or B vaccines.

  20. Examination of the safety of pediatric vaccine schedules in a non-human primate model: assessments of neurodevelopment, learning, and social behavior.

    PubMed

    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; Hewitson, Laura

    2015-06-01

    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. The objective of this study was to examine the safety of pediatric vaccine schedules in a non-human primate model. 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. 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. This comprehensive 5-year case-control study, which closely examined the effects of pediatric vaccines on early primate

  1. 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

  2. “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

  3. 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.

  4. The safety and efficacy of the oral rabies vaccine SAG2 in Indian stray dogs.

    PubMed

    Cliquet, F; Gurbuxani, J P; Pradhan, H K; Pattnaik, B; Patil, S S; Regnault, A; Begouen, H; Guiot, A L; Sood, R; Mahl, P; Singh, R; Meslin, F X; Picard, E; Aubert, M F A; Barrat, J

    2007-04-30

    India is one of the countries with the highest prevalence of human rabies throughout the world. Dogs are primarily responsible for rabies transmission. Among them, stray dogs play a major role in that country. Parenteral vaccination programmes are insufficient to eliminate rabies partly due to difficulties in establishing satisfactory immunisation coverage in the dog population in view of the high proportion of stray dogs. Oral vaccination may be a useful adjunct to parenteral vaccination by increasing dog vaccination coverage. Safety, immunogenicity and efficacy of Rabidog SAG2 bait were evaluated in Indian stray dogs in captivity. Safety of SAG2 was demonstrated by the absence of adverse clinical sign, salivary excretion and absence of replication of the vaccine strain in brain and salivary glands of 21 vaccinated dogs, even when immunodepressed. Efficacy was shown 109 days post-vaccination after challenge with a highly virulent street rabies virus which killed all five controls whereas all nine vaccinated dogs survived, despite the fact that only five out of nine had seroconverted before challenge.

  5. Safety of a modified-live combination vaccine against respiratory and reproductive diseases in pregnant cows.

    PubMed

    Ellsworth, Michael A; Brown, Martha J; Fergen, Brian J; Ficken, Martin D; Tucker, Cassius M; Bierman, Patrick; TerHune, Terry N

    2003-01-01

    A combination vaccine (Bovi-Shield FP4 + L5, Pfizer Animal Health) containing modified-live virus (MLV) components against bovine herpesvirus-1 (BHV-1), bovine viral diarrhea virus BVDV), parainfluenza virus-3 (PI3), bovine respiratory syncytial virus (BRSV), and inactivated cultures of Leptospira canicola, grippotyphosa, hardjo, icterohaemorrhagiae, and pomona was evaluated for safety in pregnant beef and dairy animals. Heifers vaccinated prebreeding with the minimum immunizing dose (lowest antigen level initiating immunizing effects) of the vaccine's MLV BHV-1 or BVDV components and during pregnancy (approximately 200 days of gestation) with vaccine containing 10x doses of the same BHV-1 and BVDV components delivered live, healthy calves that were determined to be serologically negative (titer less than 1:2) for neutralizing antibodies to BHV-1 and BVDV prior to nursing. Additionally, in three field safety studies, previously vaccinated cows and heifers that received a field dose (vaccine containing antigen levels required for commercial sale of the MLV combination vaccine during either the first, second, or third trimester of pregnancy had abortion rates similar to those of pregnant cows and heifers vaccinated during the same stage of pregnancy with sterile water diluent.

  6. Revaccination of Guinea Pigs With the Live Attenuated Mycobacterium tuberculosis Vaccine MTBVAC Improves BCG's Protection Against Tuberculosis.

    PubMed

    Clark, Simon; Lanni, Faye; Marinova, Dessislava; Rayner, Emma; Martin, Carlos; Williams, Ann

    2017-09-01

    The need for an effective vaccine against human tuberculosis has driven the development of different candidates and vaccination strategies. Novel live attenuated vaccines are being developed that promise greater safety and efficacy than BCG against tuberculosis. We combined BCG with the vaccine MTBVAC to evaluate whether the efficacy of either vaccine would be affected upon revaccination. In a well-established guinea pig model of aerosol infection with Mycobacterium tuberculosis, BCG and MTBVAC delivered via various prime-boost combinations or alone were compared. Efficacy was determined by a reduction in bacterial load 4 weeks after challenge. Efficacy data suggests MTBVAC-associated immunity is longer lasting than that of BCG when given as a single dose. Long and short intervals between BCG prime and MTBVAC boost resulted in improved efficacy in lungs, compared with BCG given alone. A shorter interval between MTBVAC prime and BCG boost resulted in improved efficacy in lungs, compared with BCG given alone. A longer interval resulted in protection equivalent to that of BCG given alone. These data indicate that, rather than boosting the waning efficacy of BCG, a vaccination schedule involving a combination of the 2 vaccines yielded stronger immunity to M. tuberculosis infection. This work supports development of MTBVAC use as a revaccination strategy to improve on the effects of BCG in vaccinated people living in tuberculosis-endemic countries.

  7. 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

  8. 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

  9. Safety and immunogenicity of Brucella abortus strain RB51 vaccine in cross bred cattle calves in India.

    PubMed

    Singh, Rashmi; Basera, Sanjay Singh; Tewari, Kamal; Yadav, Shweta; Joshi, Sumit; Singh, Brajesh; Mukherjee, Falguni

    2012-03-01

    Safety and immunogenicity of Brucella abortus RB51 vaccine has been evaluated in an organised dairy farm in India. All the cattle (r = 29) vaccinated with strain RB51 'responded' to the vaccine as demonstrated by iELISA using acetone killed strain RB51 antigen. The percentage responders at day 35, 60 and 90 post vaccination were 100%, 95% and 20%, respectively. Strain RB51 was able to elicit a good IFN-gamma response from vaccinated animals. The post-vaccination time point analysis indicated that the cumulative IFN-gamma response of whole blood from vaccinates stimulated with heat killed RB51 antigen was elicited in 80% of calves at 60 days post vaccination. Absence of strain RB51 in the secretions and excretion and lack of local or systemic reaction indicated the safety of the vaccine.

  10. Quality improvement initiative to reduce serious safety events and improve patient safety culture.

    PubMed

    Muething, Stephen E; Goudie, Anthony; Schoettker, Pamela J; Donnelly, Lane F; Goodfriend, Martha A; Bracke, Tracey M; Brady, Patrick W; Wheeler, Derek S; Anderson, James M; Kotagal, Uma R

    2012-08-01

    Many thousands of patients die every year in the United States as a result of serious and largely preventable safety events or medical errors. Safety events are common in hospitalized children. We conducted a quality improvement initiative to implement cultural and system changes with the goal of reducing serious safety events (SSEs) by 80% within 4 years at our large, urban pediatric hospital. A multidisciplinary SSE reduction team reviewed the safety literature, examined recent SSEs, interviewed internal leaders, and visited other leading organizations. Senior hospital leaders provided oversight, monitored progress, and helped to overcome barriers. Interventions focused on: (1) error prevention; (2) restructuring patient safety governance; (3) a new root cause analysis process and a common cause database; (4) a highly visible lessons learned program; and (5) specific tactical interventions for high-risk areas. Our outcome measures were the rate of SSEs and the change in patient safety culture. SSEs per 10000 adjusted patient-days decreased from a mean of 0.9 at baseline to 0.3 (P < .0001). The days between SSEs increased from a mean of 19.4 at baseline to 55.2 (P < .0001). After a worsening of patient safety culture outcomes in the first year of intervention, significant improvements were observed between 2007 and 2009. Our multifaceted approach was associated with a significant and sustained reduction of SSEs and improvements in patient safety culture. Multisite studies are needed to better understand contextual factors and the significance of specific interventions.

  11. Safety, Immunogenicity, and Surrogate Markers of Clinical Efficacy for Modified Vaccinia Ankara as a Smallpox Vaccine in HIV-Infected Subjects

    PubMed Central

    Greenberg, Richard N.; Overton, Edgar Turner; Haas, David W.; Frank, Ian; Goldman, Mitchell; von Krempelhuber, Alfred; Virgin, Garth; Bädeker, Nicole; Vollmar, Jens; Chaplin, Paul

    2013-01-01

    Background. Human immunodeficiency virus (HIV)–infected persons are at higher risk for serious complications associated with traditional smallpox vaccines. Alternative smallpox vaccines with an improved safety profile would address this unmet medical need. Methods. The safety and immunogenicity of modified vaccinia Ankara (MVA) was assessed in 91 HIV-infected adult subjects (CD4+ T-cell counts, ≥350 cells/mm3) and 60 uninfected volunteers. The primary objectives were to evaluate the safety of MVA and immunogenicity in HIV-infected and uninfected subjects. As a measure of the potential efficacy of MVA, the ability to boost the memory response in people previously vaccinated against smallpox was evaluated by the inclusion of vaccinia-experienced HIV-infected and HIV-uninfected subjects. Results. MVA was well tolerated and immunogenic in all subjects. Antibody responses were comparable between uninfected and HIV-infected populations, with only 1 significantly lower total antibody titer at 2 weeks after the second vaccination, while no significant differences were observed for neutralizing antibodies. MVA rapidly boosted the antibody responses in vaccinia-experienced subjects, supporting the efficacy of MVA against variola. Conclusions. MVA is a promising candidate as a safer smallpox vaccine, even for immunocompromised individuals, a group for whom current smallpox vaccines have an unacceptable safety profile. Clinical Trials Registration. NCT00189904. PMID:23225902

  12. Improvement in Herpes Zoster Vaccination in Patients with Rheumatoid Arthritis: A Quality Improvement Project.

    PubMed

    Sheth, Heena; Moreland, Larry; Peterson, Hilary; Aggarwal, Rohit

    2017-01-01

    To improve herpes zoster (HZ) vaccination rates in high-risk patients with rheumatoid arthritis (RA) being treated with immunosuppressive therapy. This quality improvement project was based on the pre- and post-intervention design. The project targeted all patients with RA over the age of 60 years while being treated with immunosuppressive therapy (not with biologics) seen in 13 rheumatology outpatient clinics. The study period was from July 2012 to June 2013 for the pre-intervention and February 2014 to January 2015 for the post-intervention phase. The electronic best practice alert (BPA) for HZ vaccination was developed; it appeared on electronic medical records during registration and medication reconciliation of the eligible patient by the medical assistant. The BPA was designed to electronically identify patient eligibility and to enable the physician to order the vaccine or to document refusal or deferral reason. Education regarding vaccine guidelines, BPA, vaccination process, and feedback were crucial components of the project interventions. The vaccination rates were compared using the chi-square test. We evaluated 1823 and 1554 eligible patients with RA during the pre-intervention and post-intervention phases, respectively. The HZ vaccination rates, reported as patients vaccinated among all eligible patients, improved significantly from the pre-intervention period of 10.1% (184/1823) to 51.7% (804/1554) during the intervention phase (p < 0.0001). The documentation rates (vaccine received, vaccine ordered, patient refusal, and deferral reasons) increased from 28% (510/1823) to 72.9% (1133/1554; p < 0.0001). The HZ infection rates decreased significantly from 2% to 0.3% (p = 0.002). Electronic identification of vaccine eligibility and BPA significantly improved HZ vaccination rates. The process required minimal modification of clinic work flow and did not burden the physician's time, and has the potential for self-sustainability and generalizability.

  13. Improved obstetric safety through programmatic collaboration.

    PubMed

    Goffman, Dena; Brodman, Michael; Friedman, Arnold J; Minkoff, Howard; Merkatz, Irwin R

    2014-01-01

    Healthcare safety and quality are critically important issues in obstetrics, and society, healthcare providers, patients and insurers share a common goal of working toward safer practice, and are continuously seeking strategies to facilitate improvements. To this end, 4 New York City voluntary hospitals with large maternity services initiated a unique collaborative quality improvement program. It was facilitated by their common risk management advisors, FOJP Service Corporation, and their professional liability insurer, Hospitals Insurance Company. Under the guidance of 4 obstetrics and gynecology departmental chairmen, consensus best practices for obstetrics were developed which included: implementation of evidence based protocols with audit and feedback; standardized educational interventions; mandatory electronic fetal monitoring training; and enhanced in-house physician coverage. Each institution developed unique safety related expertise (development of electronic documentation, team training, and simulation education), and experiences were shared across the collaborative. The collaborative group developed robust systems for audit of outcomes and documentation quality, as well as enforcement mechanisms. Ongoing feedback to providers served as a key component of the intervention. The liability carrier provided financial support for these patient safety innovations. As a result of the interventions, the overall AOI for our institutions decreased 42% from baseline (January-June 2008) to the most recently reviewed time period (July-December 2011) (10.7% vs 6.2%, p < 0.001). The Weighted Adverse Outcome Score (WAOS) also decreased during the same time period (3.9 vs 2.3, p = 0.001.) Given the improved outcomes noted, our unique program and the process by which it was developed are described in the hopes that others will recognize collaborative partnering with or without insurers as an opportunity to improve obstetric patient safety.

  14. Creating effective leadership for improving patient safety.

    PubMed

    Mohr, Julie J; Abelson, Herbert T; Barach, Paul

    2002-01-01

    Leadership has emerged as a key theme in the rapidly growing movement to improve patient safety. Leading an organization that is committed to providing safer care requires overcoming the common traps in thinking about error, such as blaming individuals, ignoring the underlying systems factors, and blaming the bureaucracy of the organization. Leaders must address the system issues that are at work within their organizations to allow individual and organizational learning to occur.

  15. 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

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

    PubMed

    He, Yongqun

    2014-07-01

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

  17. An evaluation of the immunogenicity and safety of a new trivalent meningococcal polysaccharide vaccine.

    PubMed

    Chandramohan, Daniel; Hodgson, Abraham; Coleman, Paul; Baiden, Rita; Asante, Kwaku; Awine, Elizabeth; Owusu-Agyei, Seth; Boutriau, Dominique; Nelson, Christopher B; Greenwood, Brain

    2007-09-03

    The immunogenicity and safety of a meningococcal trivalent A/C/W135 polysaccharide vaccine was compared with that of a tetravalent A/C/Y/W135 polysaccharide vaccine in a randomised, double blind trial. The study included 360 adults, who received either a trivalent or tetravalent polysaccharide meningococcal vaccine. Antibody responses were determined by serum bactericidal antibody (rSBA) assays prior to vaccination and on day 28 and month 11 after vaccination. The percentage of participants in the trivalent vaccine group who had rSBA titres >or=8 on day 28 post-vaccination against serogroups A, C and W135 meningococci were 99, 98 and 91%, respectively. The corresponding figures in the tetravalent vaccine group were 99, 99 and 90%. The percentage of participants with various cut off levels of rSBA against serogroups A, W135 and C meningococci on day 28 and 11-month post-vaccination and the incidence of adverse events did not differ significantly between the two groups.

  18. 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

  19. 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.

  20. [Analysis of the immunological reconstitution, effectiveness and safety of vaccination in children with cancer].

    PubMed

    Kołtan, Sylwia; Kołtan, Andrzej; Grześk, Elzbieta; Debski, Robert; Wysocki, Mariusz

    2010-01-01

    The aim of this study was an assessment of immunologic reconstitution, efficiency and safety of vaccination performed in course of oncological treatment and after the therapy. 129 children aged 1 month-19,5 years with diagnosis of leukemia or lymphoma (74,4%) or a solid tumor (25,6%). Immune status was evaluated 6 months after cessation of treatment in order to plan active immunization. Effectiveness of vaccination against hepatitis B was performed too. PATIENTS who did not complete immunization against hepatitis B at the time of diagnosis continued vaccination according to the scheme 0-1-6 months, the others were given one doubled dose. In 90,7% patients complete immune reconstitution was observed and both mandatory and optional immunization was then resumed. In 5,4% of children vaccination with live vaccines was suspended due to moderate immune deficiencies. In 3,9% of patients severe immune deficiencies were diagnosed and vaccination was abandoned. At diagnosis of cancer double vaccine doses against hepatitis B were given to 94,6% of patients, while 5,4% continued standard vaccination scheme. After anticancer therapy anti-HBs titer >100 IU/ml was observed in 55%, 10-100 IU/ml in 26% and <10 IU/ml in 18,6% of patients. One case of HBV infection was noted. Neither adverse reactions after immunization nor life-threatening infections the patients were vaccinated against was noted. Our Immunization protocol adopted in the study seem to be efficient and safe.

  1. [Post-licensure passive safety surveillance of rotavirus vaccines: reporting sensitivity for intussusception].

    PubMed

    Pérez-Vilar, S; Díez-Domingo, J; Gomar-Fayos, J; Pastor-Villalba, E; Sastre-Cantón, M; Puig-Barberà, J

    2014-08-01

    The aims of this study were to describe the reports of suspected adverse events due to rotavirus vaccines, and assess the reporting sensitivity for intussusception. Descriptive study performed using the reports of suspected adverse events following rotavirus vaccination in infants aged less than 10 months, as registered in the Pharmacovigilance Centre of the Valencian Community during 2007-2011. The reporting rate for intussusception was compared to the intussusception rate in vaccinated infants obtained using the hospital discharge database (CMBD), and the regional vaccine registry. The adverse event reporting rate was 20 per 100,000 administered doses, with the majority (74%) of the reports being classified as non-serious. Fever, vomiting, and diarrhea were the adverse events reported more frequently. Two intussusception cases, which occurred within the first seven days post-vaccination, were reported as temporarily associated to vaccination. The reporting sensitivity for intussusception at the Pharmacovigilance Centre in the 1-7 day interval following rotavirus vaccination was 50%. Our results suggest that rotavirus vaccines have, in general, a good safety profile. Intussusception reporting to the Pharmacovigilance Centre shows sensitivity similar to other passive surveillance systems. The intussusception risk should be further investigated using well-designed epidemiological studies, and evaluated in comparison with the well-known benefits provided by these vaccines. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

  2. Inactivated yellow fever 17D vaccine: development and nonclinical safety, immunogenicity and protective activity.

    PubMed

    Monath, Thomas P; Lee, Cynthia K; Julander, Justin G; Brown, Alicja; Beasley, David W; Watts, Douglas M; Hayman, Edward; Guertin, Patrick; Makowiecki, Joseph; Crowell, Joseph; Levesque, Philip; Bowick, Gavin C; Morin, Merribeth; Fowler, Elizabeth; Trent, Dennis W

    2010-05-14

    In the last 10 years new concerns have arisen about safety of the live, attenuated yellow fever (YF) 17D vaccine, in particular viscerotropic adverse events, which have a case-fatality rate of 64%. A non-replicating cell culture-based vaccine would not cause these adverse events, and potentially could be used in persons with precautions or contraindications to use of the live vaccine, including age <9 months and >60 years, egg allergy, immune suppression, and pregnancy. We developed a whole virion vaccine from the 17D strain inactivated with beta-propiolactone, and adsorbed to aluminum hydroxide. The inactivated vaccine was highly immunogenic in mice, hamsters, and cynomolgus macaques. After a single dose in hamsters and macaques, neutralizing antibody titers were similar to those elicited by the live 17D vaccine (YF-VAX, Sanofi Pasteur). After two doses of inactivated vaccine, neutralizing antibody titers in hamsters were significantly higher than after a single dose of YF-VAX [geometric mean titer (GMT) 20,480 vs. 1940, respectively (P<0.001, ANOVA)]. Hamsters given a single dose or two doses of inactivated vaccine or a single dose of YF-VAX were fully protected against hepatitis, viremia, weight loss and death after challenge with YF virus (Jimenez strain). A clinical trial of the inactivated vaccine (XRX-001) has been initiated. Copyright 2010 Elsevier Ltd. All rights reserved.

  3. Safety and immunogenicity of the synthetic malaria vaccine SPf66 in a large field trial.

    PubMed

    Amador, R; Moreno, A; Murillo, L A; Sierra, O; Saavedra, D; Rojas, M; Mora, A L; Rocha, C L; Alvarado, F; Falla, J C

    1992-07-01

    In the first field trial with synthetic malaria vaccine SPf66 in a large population naturally exposed to malaria, 9957 persons greater than 1 year old and residing on the Colombian Pacific coast received three doses of the vaccine. To evaluate vaccine safety, clinical observations were made 30 min and 48 h after each immunization. There were no adverse reactions in 95.7% of cases. In the 4.3% of cases with adverse reactions, local induration and erythema were the most frequent. In a randomly selected group of vaccinees, anti-SPf66 antibody titers were measured after the third dose: 93% of the vaccinees raised antibodies to SPf66. Among these, 55% had titers greater than 1:1600. These results demonstrate the safety and immunogenicity of the SPf66 vaccine in a large field trial.

  4. 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.

  5. Development of improved vaccine cell lines against rotavirus

    PubMed Central

    Wu, Weilin; Orr-Burks, Nichole; Karpilow, Jon; Tripp, Ralph A.

    2017-01-01

    Rotavirus is a major cause of severe gastroenteritis among very young children. In developing countries, rotavirus is the major cause of mortality in children under five years old, causing up to 20% of all childhood deaths in countries with high diarrheal disease burden, with more than 90% of these deaths occurring in Africa and Asia. Rotavirus vaccination mimics the first infection without causing illness, thus inducing strong and broad heterotypic immunity against prospective rotavirus infections. Two live vaccines are available, Rotarix and RotaTeq, but vaccination efforts are hampered by high production costs. Here, we present a dataset containing a genome-wide RNA interference (RNAi) screen that identified silencing events that enhanced rotavirus replication. Evaluated against several rotavirus vaccine strains, hits were validated in a Vero vaccine cell line as well as CRISPR/Cas9 generated cells permanently and stably lacking the genes that affect RV replication. Knockout cells were dramatically more permissive to RV replication and permitted an increase in rotavirus replication. These data show a means to improve manufacturing of rotavirus vaccine. PMID:28248921

  6. Improving T cell responses to modified peptides in tumor vaccines.

    PubMed

    Buhrman, Jonathan D; Slansky, Jill E

    2013-03-01

    Immune recognition and elimination of cancerous cells is the primary goal of cancer immunotherapy. However, obstacles including immune tolerance and tumor-induced immunosuppression often limit beneficial immune responses. Vaccination is one proposed intervention that may help to overcome these issues and is an active area of study in cancer immunotherapy. Immunizing with tumor antigenic peptides is a promising, straight-forward vaccine strategy hypothesized to boost preexisting antitumor immunity. However, tumor antigens are often weak T cell agonists, attributable to several mechanisms, including immune self-tolerance and poor immunogenicity of self-derived tumor peptides. One strategy for overcoming these mechanisms is vaccination with mimotopes, or peptide mimics of tumor antigens, which alter the antigen presentation and/or T cell activation to increase the expansion of tumor-specific T cells. Evaluation of mimotope vaccine strategies has revealed that even subtle alterations in peptide sequence can dramatically alter antigen presentation and T cell receptor recognition. Most of this research has been performed using T cell clones, which may not be accurate representations of the naturally occurring antitumor response. The relationship between clones generated after mimotope vaccination and the polyclonal T cell repertoire is unclear. Our work with mimotopes in a mouse model of colon carcinoma has revealed important insights into these issues. We propose that the identification of mimotopes based on stimulation of the naturally responding T cell repertoire will dramatically improve the efficacy of mimotope vaccination.

  7. 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.; Folk, Martin J.; Nesbitt, Stephen A.

    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.

  8. 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.

  9. Safety of Quadrivalent Meningococcal Conjugate Vaccine in Children 2-10 Years.

    PubMed

    Tartof, Sara Y; Sy, Lina S; Ackerson, Bradley K; Hechter, Rulin C; Haag, Mendel; Slezak, Jeffrey M; Luo, Yi; Fischetti, Christine A; Takhar, Harp S; Miao, Yan; Solano, Zendi; Jacobsen, Steven J; Tseng, Hung-Fu

    2017-07-14

    Quadrivalent meningococcal conjugate vaccine is recommended for children, adolescents, and adults at increased risk of meningococcal disease. In 2011, MenACWY-CRM (Menveo, GSK) was approved for children aged 2-10 years in the U.S. Although no safety concerns arose from clinical trials, it remains important to monitor its safety in routine clinical settings. Kaiser Permanente Southern California members 2-10 years old who received MenACWY-CRM between September 2011 and September 2014 were included. Electronic health records were searched using a validated algorithm to identify 26 pre-specified events of interest (EOIs) and serious medically attended events (SMAEs) from inpatient or emergency settings up to one year following MenACWY-CRM vaccination. SMAEs were categorized by ICD-9 diagnostic categories. All events were reviewed to confirm the diagnosis and symptom onset date. The study was descriptive (NCT01452438); no statistical tests were performed. Among 387 vaccinated children, 327 with ≥6 months membership before vaccination were analyzed. Among EOIs, 9 asthma cases and one myasthenia gravis case underwent chart review which confirmed one incident asthma case occurring 237 days after concomitant vaccination with MenACWY-CRM and typhoid vaccine. Thirty-one children experienced SMAEs, most commonly due to unrelated injury and poisoning. The remaining events occurred sporadically after vaccination and most were unlikely related to vaccination based on medical record review. One incident EOI of asthma late in the 1-year observation period and sporadic distribution of SMAEs were observed. These data do not suggest safety concerns associated with MenACWY-CRM vaccination in children 2-10 years old.

  10. Safety of measles-containing vaccines in 1-year-old children.

    PubMed

    Klein, Nicola P; Lewis, Edwin; Fireman, Bruce; Hambidge, Simon J; Naleway, Allison; Nelson, Jennifer C; Belongia, Edward A; Yih, W Katherine; Nordin, James D; Hechter, Rulin C; Weintraub, Eric; Baxter, Roger

    2015-02-01

    All measles-containing vaccines are associated with several types of adverse events, including seizure, fever, and immune thrombocytopenia purpura (ITP). Because the measles-mumps-rubella-varicella (MMRV) vaccine compared with the separate measles-mumps-rubella (MMR) and varicella (MMR + V) vaccine increases a toddler's risk for febrile seizures, we investigated whether MMRV is riskier than MMR + V and whether either vaccine elevates the risk for additional safety outcomes. Study children were aged 12 to 23 months in the Vaccine Safety Datalink from 2000 to 2012. Nine study outcomes were investigated: 7 main outcomes (anaphylaxis, ITP, ataxia, arthritis, meningitis/encephalitis, acute disseminated encephalomyelitis, and Kawasaki disease), seizure, and fever. Comparing MMRV with MMR + V, relative risk was estimated by using stratified exact binomial tests. Secondary analyses examined post-MMRV or MMR + V risk versus comparison intervals; risk and comparison intervals were then contrasted for MMRV versus MMR+V. We evaluated 123,200 MMRV and 584,987 MMR + V doses. Comparing MMRV with MMR + V, risks for the 7 main outcomes were not significantly different. Several outcomes had few or zero postvaccination events. Comparing risk versus comparison intervals, ITP risk was higher after MMRV (odds ratio [OR]: 11.3 [95% confidence interval (CI): 1.9 to 68.2]) and MMR + V (OR: 10 [95% CI: 4.5 to 22.5]) and ataxia risk was lower after both vaccines (MMRV OR: 0.8 [95% CI: 0.5 to 1]; MMR + V OR: 0.8 [95% CI: 0.7 to 0.9]). Compared with MMR + V, MMRV increased risk of seizure and fever 7 to 10 days after vaccination. This study did not identify any new safety concerns comparing MMRV with MMR + V or after either the MMRV or the MMR + V vaccine. This study provides reassurance that these outcomes are unlikely after either vaccine. Copyright © 2015 by the American Academy of Pediatrics.

  11. 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

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

    PubMed

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

    2015-01-01

    %), 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. 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.

  13. 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.

  14. The first field trials of the chemically synthesized malaria vaccine SPf66: safety, immunogenicity and protectivity.

    PubMed

    Amador, R; Moreno, A; Valero, V; Murillo, L; Mora, A L; Rojas, M; Rocha, C; Salcedo, M; Guzman, F; Espejo, F

    1992-01-01

    This paper reports the results of the first field study performed to assess the safety, immunogenicity and protectivity of the synthetic malaria vaccine SPf66 directed against the asexual blood stages of Plasmodium falciparum. Clinical and laboratory tests were performed on all volunteers prior to and after each immunization, demonstrating that no detectable alteration was induced by the immunization process. The vaccines were grouped as high, intermediate or low responders according to their antibody titres directed against the SPf66 molecule. Two of the 185 (1.08%) SPf66-vaccinated and nine of the 214 (4.20%) placebo-vaccinated volunteers developed P. falciparum malaria. The efficacy of the vaccine was calculated as 82.3% against P. falciparum and 60.6% against Plasmodium vivax.

  15. Ensuring the quality, potency and safety of vaccines during preclinical development.

    PubMed

    Lebron, Jose A; Wolf, Jayanthi J; Kaplanski, Catherine V; Ledwith, Brian J

    2005-12-01

    There is an abundance of vaccines currently in development, with most of them exploring novel mechanisms, adjuvants and/or delivery systems not only for traditional prophylactic use, but also for therapeutic uses. As vaccines are generally administered to healthy individuals, ensuring their quality, potency and safety becomes crucial, especially prior to evaluation in humans. To ensure these key attributes, vaccine developers need to incorporate them as early in the development program as possible, starting in basic research and continuing through preclinical, clinical and postmarketing development. Fortunately for vaccine developers, ample guidance is available from various regulatory agencies to enlighten the long and arduous path of vaccine development. This review will highlight these regulatory expectations, and provide some clarity as to why they are in place.

  16. 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

  17. Technology and simulation to improve patient safety.

    PubMed

    Ghobrial, George M; Hamade, Youssef J; Bendok, Bernard R; Harrop, James S

    2015-04-01

    Improving the quality and efficiency of surgical techniques, reducing technical errors in the operating suite, and ultimately improving patient safety and outcomes through education are common goals in all surgical specialties. Current surgical simulation programs represent an effort to enhance and optimize the training experience, to overcome the training limitations of a mandated 80-hour work week, and have the overall goal of providing a well-balanced resident education in a society with a decreasing level of tolerance for medical errors. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Safety and immunogenicity of a novel quadrivalent meningococcal CRM-conjugate vaccine given concomitantly with routine vaccinations in infants.

    PubMed

    Klein, Nicola P; Reisinger, Keith S; Johnston, William; Odrljin, Tatjana; Gill, Christopher J; Bedell, Lisa; Dull, Peter

    2012-01-01

    In phase II studies, MenACWY-CRM elicited robust immunologic responses in young infants. We now present results from our pivotal phase III infant immunogenicity/safety study. In this open-label phase III study, we randomized full-term 2-month-old infants to 4 doses of MenACWY-CRM coadministered with routine vaccines at 2, 4, 6, and 12 months of age or with routine vaccines alone. We monitored for local and systemic reactions and serious adverse events among all study participants and evaluated for sufficiency of the immune responses to MenACWY-CRM through serum bactericidal activity assay with human complement. Bactericidal antibodies were present in 94% to 100% of subjects against each of the serogroups in MenACWY-CRM after the 4-dose series and were 67% to 97% after the first 3 doses. Geometric mean titers were higher after the fourth dose of MenACWY-CRM compared with a single dose of MenACWY-CRM at 12 months of age for all serogroups (range of ratios, 4.5-38). Responses to 3 doses of routine vaccines coadministered with MenACWY-CRM were noninferior to routine vaccinations alone, except for small differences in pneumococcal serotype 6B responses after dose 3 but not dose 4 and pertactin after dose 3. Inclusion of MenACWY-CRM did not affect the safety or reactogenicity profiles of the routine infant vaccine series. A 4-dose series of MenACWY-CRM was highly immunogenic and well tolerated in young infants, and it can be coadministered with routine infant vaccines. Substantial immunity was conferred after the first 3 doses administered at 2, 4, and 6 months of age.

  19. Safety and immunogenicity of a CRM or TT conjugated meningococcal vaccine in healthy toddlers.

    PubMed

    Bona, Gianni; Castiglia, Paolo; Zoppi, Giorgio; de Martino, Maurizio; Tasciotti, Annaelisa; D'Agostino, Diego; Han, Linda; Smolenov, Igor

    2016-06-17

    MenACWY-CRM (Menveo(®); GlaxoSmithKline) and MenACWY-TT (Nimenrix(®); Pfizer) are two meningococcal vaccines licensed in the European Union for use in both children and adults. While both vaccines target meningococcal serogroups A, C, W and Y, immunogenicity and reactogenicity of these quadrivalent meningococcal conjugate vaccines may differ due to differences in formulation processes and chemical structure. Yet data on the comparability of these two vaccines are limited. The reactogenicity and immunogenicity of one dose of either MenACWY-CRM or MenACWY-TT were evaluated in healthy toddlers aged 12-15 months. Immunogenicity was assessed using serum bactericidal antibody assays (SBA) with human (hSBA) and rabbit (rSBA) complement. A total of 202 children aged 12-15 months were enrolled to receive one dose of MenACWY-CRM or MenACWY-TT. Similar numbers of subjects reported solicited reactions within 7 days following either vaccination. Tenderness at the injection site was the most common local reaction. Systemic reactions reported were similar for both vaccines and mostly mild to moderate in severity: irritability, sleepiness and change in eating habits were most commonly reported. Immunogenicity at 1 month post-vaccination was generally comparable for both vaccines across serogroups. At 6 months post-vaccination antibody persistence against serogroups C, W, and Y was substantial for both vaccines, as measured by both assay methodologies. For serogroup A, hSBA titers declined in both groups, while rSBA titers remained high. Despite differences in composition, the MenACWY-CRM and MenACWY-TT vaccines have comparable reactogenicity and immunogenicity profiles. Immediate immune responses and short-term antibody persistence were largely similar between groups. Both vaccines were well-tolerated and no safety concerns were identified. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Efficacy, safety, and immunogenicity of a Vero-cell-culture-derived trivalent influenza vaccine: a multicentre, double-blind, randomised, placebo-controlled trial.

    PubMed

    Barrett, P Noel; Berezuk, Gregory; Fritsch, Sandor; Aichinger, Gerald; Hart, Mary Kate; El-Amin, Wael; Kistner, Otfried; Ehrlich, Hartmut J

    2011-02-26

    The use of cell-culture technologies for the manufacture of influenza vaccines might contribute to improved strain selection and robust vaccine supplies. We investigated the safety, immunogenicity, and protective efficacy of a Vero-cell-culture-derived influenza vaccine, and assessed the correlation between vaccine efficacy and haemagglutination inhibition antibody titre. In a double-blind, placebo-controlled, phase 3 trial undertaken in 36 centres in the USA, healthy adults (aged 18-49 years) were randomly assigned in a 1:1 ratio to one injection of either placebo or Vero-cell-culture-derived influenza vaccine during the 2008-09 season. Randomisation was done in blocks by use of the random number generator algorithm, and participants were allocated by use of a centralised telephone system. The primary objective was the efficacy of the vaccine in preventing cell-culture-confirmed influenza infection with viruses that were antigenically matched to one of the vaccine strains. Analysis was by intention to treat. The study is registered with ClinicalTrials.gov, number NCT00566345. 7250 participants were randomly assigned to vaccine (n=3626) and placebo (n=3624). 7236 were analysed for the primary outcome (n=3619 and n=3617, respectively). Overall protective efficacy for antigenically matched influenza infection was 78·5% (95% CI 60·8-88·2). The vaccine was well tolerated with no treatment-related serious adverse events. Adverse events were mainly mild and transient. An HI titre of at least 1:15 provided a reliable correlate of cell-culture-derived influenza vaccine-induced protection; no additional benefit was noted with titres greater than 1:30. The data indicate that existing correlates of protection afforded with egg-derived seasonal influenza vaccines also apply to this vaccine. Federal (US Government) funds from the Office for Preparedness and Response, Biomedical Advanced Research and Development Authority, under contract to DynPort Vaccine Company. Copyright

  1. Improving vaccine trials in infectious disease emergencies.

    PubMed

    Lipsitch, Marc; Eyal, Nir

    2017-07-14

    Unprecedented global effort is under way to facilitate the testing of countermeasures in infectious disease emergencies. Better understanding of the various options for trial design is needed in advance of outbreaks, as is preliminary global agreement on the most suitable designs for the various scenarios. What would enhance the speed, validity, and ethics of clinical studies of such countermeasures? Focusing on studies of vaccine efficacy and effectiveness in emergencies, we highlight three needs: for formal randomized trials-even in most emergencies; for individually randomized trials-even in many emergencies; and for six areas of innovation in trial methodology. These needs should inform current updates of protocols and roadmaps. Copyright © 2017, American Association for the Advancement of Science.

  2. 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

    2015-02-02

    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.

  3. Safety assessment of Madin Darby canine kidney cells as vaccine substrate.

    PubMed

    Medema, J K; Meijer, J; Kersten, A J; Horton, R

    2006-01-01

    Conventional influenza vaccines are manufactured using embryonated chicken eggs, a substrate with little flexibility and vulnerable to extraneous agents. Solvay Pharmaceuticals developed a production technology based on the continuous cell line Madin Darby Canine Kidney (MDCK) as vaccine cell substrate. A risk-based safety assessment of MDCK, with respect to tumorigenicity of intact cells and oncogenicity of cellular components, cellular DNA and adventitious agents, shows that this substrate is as safe as other substrates and therefore without increased risk to the vaccine recipient.

  4. [Characteristics of the clinical and immunologic safety of inactivated influenza vaccines in children undergoing multiple immunizations].

    PubMed

    Vasil'eva, R I; Merkur'eva, L A; Iatsenko, V G; Vasil'eva, A M; Shvager, M M

    1988-11-01

    In a strictly controlled epidemiological trial on 12,643 school children aged 11-14 years the reactogenic properties and safety of killed influenza chromatographic vaccine under the conditions of multiple immunization were studied. A single immunization dose of the vaccine (0.2 ml) contained the hemagglutinins of influenza viruses A/Philippines/82 (H3N3) and A/Kiev/59/79 (H1N1), 3.5 micrograms each. The preparation was introduced by means of a jet injector. The vaccine was shown to be clinically and immunologically safe under the conditions of the regular multiple immunization of children over the period of 4 years.

  5. An update on safety and immunogenicity of vaccines containing emulsion-based adjuvants.

    PubMed

    Fox, Christopher B; Haensler, Jean

    2013-07-01

    With the exception of alum, emulsion-based vaccine adjuvants have been administered to far more people than any other adjuvant, especially since the 2009 H1N1 influenza pandemic. The number of clinical safety and immunogenicity evaluations of vaccines containing emulsion adjuvants has correspondingly mushroomed. In this review, the authors introduce emulsion adjuvant composition and history before detailing the most recent findings from clinical and postmarketing data regarding the effects of emulsion adjuvants on vaccine immunogenicity and safety, with emphasis on the most widely distributed emulsion adjuvants, MF59® and AS03. The authors also present a summary of other emulsion adjuvants in clinical development and indicate promising avenues for future emulsion-based adjuvant development. Overall, emulsion adjuvants have demonstrated potent adjuvant activity across a number of disease indications along with acceptable safety profiles.

  6. 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.

  7. Immunogenicity and safety of the 9-valent HPV vaccine in men.

    PubMed

    Castellsagué, X; Giuliano, A R; Goldstone, S; Guevara, A; Mogensen, O; Palefsky, J M; Group, T; Shields, C; Liu, K; Maansson, R; Luxembourg, A; Kaplan, S S

    2015-11-27

    This study was designed to evaluate the immunogenicity and tolerability of a prophylactic 9-valent HPV (types 6/11/16/18/31/33/45/52/58) VLP (9vHPV) vaccine in young men 16-26 years of age in comparison to young women 16-26 years of age (the population that was used to establish 9vHPV vaccine efficacy). Safety and immunogenicity data from this study will be used to bridge 9vHPV vaccine efficacy findings in 16-26 year old women to 16-26 year old men. This study enrolled 1106 heterosexual men (HM) and 1101 women who had not yet received HPV vaccination. In addition, 313 men having sex with men (MSM) were enrolled and were evaluated separately for immunogenicity because previous results showed that antibody responses to quadrivalent HPV (types 6/11/16/18) VLP (qHPV) vaccine were lower in MSM than in HM. All subjects were administered a 3-dose regimen (Day 1, Month 2, Month 6) of 9vHPV vaccine. Serum samples were collected for anti-HPV assays. Safety information was collected for ∼ 12 months. The geometric mean titers (GMTs) for HPV types 6, 11, 16, 18, 31, 33, 45, 52, and 58 for HM were non-inferior to those of women at Month 7. For all vaccine HPV types, Month 7 GMTs were numerically lower in MSM than in HM. Over 99.5% of subjects were seropositive at Month 7 for each vaccine HPV type. Administration of 9vHPV vaccine to both 16-26 year old men and women was generally well tolerated. These results support bridging the efficacy findings with 9vHPV vaccine in young women 16-26 years of age to men 16-26 years of age. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. 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

  9. 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.

  10. Safety, efficacy and immunogenicity evaluation of the SAG2 oral rabies vaccine in Formosan ferret badgers.

    PubMed

    Hsu, Ai-Ping; Tseng, Chun-Hsien; Barrat, Jacques; Lee, Shu-Hwae; Shih, Yu-Hua; Wasniewski, Marine; Mähl, Philippe; Chang, Chia-Chia; Lin, Chun-Ta; Chen, Re-Shang; Tu, Wen-Jane; Cliquet, Florence; Tsai, Hsiang-Jung

    2017-01-01

    Since 2013, rabies cases have been reported among Formosan ferret badgers in Taiwan, and they have been shown to be the major reservoirs for Taiwanese enzootics. To control and eradicate rabies, the authorities plan to implement a vaccination programme. Before distributing live vaccines in the field, this study assessed the safety, efficacy, and immunogenicity of SAG2 vaccine on ferret badgers by direct oral instillation. After application of 109 TCID50/dose, no virus was excreted into the oral cavity 1-7 days post-application, and safety was also satisfactorily verified over a 266-day period. Moreover, despite the low level of rabies virus neutralising antibodies induced after vaccination of a 108 TCID50/dose, the efficacy assessment revealed a 100% survival rate (15/15) of vaccinees and an 87.5% fatality rate (7/8) in control animals after a challenge on the 198th day post-vaccination. The immunisation and protection rates obtained more than 6 months after a single vaccination dose demonstrated that SAG2 is an ideal vaccine candidate to protect Formosan ferret badgers against rabies in Taiwan.

  11. 487 Safety of Sublingual Immunotherapy with Standardized Vaccines of Domestic Mites

    PubMed Central

    Alvarez, Mirta; Castro, Raúl; Gutierrez, Daniel; Labrada, Alexis; Enriquez, Irene; Ronquillo, Mercedes; Rodríguez, José; García, Iris

    2012-01-01

    Background Allergen-specific immunotherapy consists of administering gradually increasing doses of the allergen, to which the patient is sensitized, aiming at achieving tolerance to it and decreasing clinical symptoms. The sublingual immunotherapy (SLIT) was introduced as an alternative to subcutaneous route. Its use is being increased in the world and in Cuba, using standardized vaccines owing to greater safety. The objective of this study was to determine the safety of sublingual standardized vaccines of 3 domestic mite species (Valergen, Cuba) and its adverse events in allergic patients from the Calixto García University Hospital in Havana, as well as the frequency of its prescription. Methods Descriptive and cross sectional study design, which included 130 patients with treatment of SLIT with VALERGEN-DP (Dermatophagoides pteronyssinus), VALERGEN-DS (D. siboney) and VALERGEN-BT (Blomia tropicalis) (BIOCEN, Cuba), who attended the Allergy Service in the period January-September 2010. Age distribution: mean 19.6 years (range 1–75), 40.7 % was younger than 18 years. Results The multiallergen vaccine was the type of vaccine most used (63.8%). The most common allergen was D. pteronyssinus followed by B. tropicalis. 71.55% of administered allergens vaccines were in maintenance phase. We found 4 adverse events (3.1% of patients), all local, mild, and not requiring treatment or change of vaccination dosing schedule. Conclusions The Valergen vaccines by sublingual route are safe and well tolerated in Cuban allergic patients.

  12. Evaluation of synergistic effect of biodegradable polymeric nanoparticles and aluminum based adjuvant for improving vaccine efficacy.

    PubMed

    Bansal, Vivek; Kumar, Manoj; Dalela, Manu; Brahmne, H G; Singh, Harpal

    2014-08-25

    Aluminum based adjuvants have been used widely to induce long lasting protective immunity through vaccination. But reported incidences of toxicity and side effects of aluminum have raised concerns regarding their safety in childhood vaccines. The present study demonstrates the synergistic effect of admixture of polylactic acid-polyethylene glycol (PLA-PEG) based biodegradable nanoparticles (NPs) and aluminum phosphate as a potential adjuvant system using tetanus toxoid (TT) as a model antigen. The immunological activity of the admixture formulation was maintained up to 180 days of storage at 5 °C±3 °C. Percent adsorption/encapsulation of tetanus toxoid increased to nearly 90% in admixture formulation as compared to 55% in conventional vaccine. Admixture preparation (PLA-PEG-Al 0.2 mg-TT and PLA-Al 0.2 mg-TT) showed 80% and 50% survival respectively, even at 180 days as compared to 30% survival observed in the conventional tetanus vaccine. The present study established the feasibility to formulate a dosage form with improved efficacy and reduced aluminum concentration for vaccination. Copyright © 2014. Published by Elsevier B.V.

  13. 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

  14. Cancer Vaccines in Ovarian Cancer: How Can We Improve?

    PubMed Central

    Martin Lluesma, Silvia; Wolfer, Anita; Harari, Alexandre; Kandalaft, Lana E.

    2016-01-01

    Epithelial ovarian cancer (EOC) is one important cause of gynecologic cancer-related death. Currently, the mainstay of ovarian cancer treatment consists of cytoreductive surgery and platinum-based chemotherapy (introduced 30 years ago) but, as the disease is usually diagnosed at an advanced stage, its prognosis remains very poor. Clearly, there is a critical need for new treatment options, and immunotherapy is one attractive alternative. Prophylactic vaccines for prevention of infectious diseases have led to major achievements, yet therapeutic cancer vaccines have shown consistently low efficacy in the past. However, as they are associated with minimal side effects or invasive procedures, efforts directed to improve their efficacy are being deployed, with Dendritic Cell (DC) vaccination strategies standing as one of the more promising options. On the other hand, recent advances in our understanding of immunological mechanisms have led to the development of successful strategies for the treatment of different cancers, such as immune checkpoint blockade strategies. Combining these strategies with DC vaccination approaches and introducing novel combinatorial designs must also be considered and evaluated. In this review, we will analyze past vaccination methods used in ovarian cancer, and we will provide different suggestions aiming to improve their efficacy in future trials. PMID:28536377

  15. Therapeutic vaccine against DPP4 improves glucose metabolism in mice.

    PubMed

    Pang, Zhengda; Nakagami, Hironori; Osako, Mariana K; Koriyama, Hiroshi; Nakagami, Futoshi; Tomioka, Hideki; Shimamura, Munehisa; Kurinami, Hitomi; Takami, Yoichi; Morishita, Ryuichi; Rakugi, Hiromi

    2014-04-01

    The increasing prevalence of type 2 diabetes mellitus is associated with a significant economic burden. We developed a dipeptidyl peptidase 4 (DPP4)-targeted immune therapy to increase glucagon-like peptide 1 hormone levels and improve insulin sensitivity for the prevention and treatment of type 2 diabetes mellitus. Immunization with the DPP4 vaccine in C57BL/6J mice successfully increased DPP4 titer, inhibited plasma DPP4 activity, and induced an increase in the plasma glucagon-like peptide 1 level. Moreover, this elevated titer was sustained for 3 mo. In mice fed a high-fat diet, DPP4 vaccination resulted in improved postprandial glucose excursions and insulin sensitivity and, in the diabetic KK-A(y) and db/db mice strains, DPP4 vaccination significantly reduced glucose excursions and increased both plasma insulin and pancreatic insulin content. Importantly, T cells were not activated following challenge with DPP4 itself, which suggests that this vaccine does not induce cell-mediated autoimmunity. Additionally, no significant immune-mediated damage was detected in cells and tissues where DPP4 is expressed. Thus, this DPP4 vaccine may provide a therapeutic alternative for patients with diabetes.

  16. Methotrexate safety improvement in nursing home residents.

    PubMed

    Zarowitz, Barbara J; Erwin, W Gary; Ferris, Mindy; Losben, Nancy; Proud, Terri

    2012-01-01

    Improve the safety of methotrexate use in nursing home residents by reducing methotrexate errors. Concurrent cohort analysis. Long term care facilities. Residents who received methotrexate from January 1, 2007, to December 31, 2009. A 3-pronged approach involving modification to dispensing systems and practices, mandatory staff training, and measurement was implemented in June 2008 and monitored through December 2009. Software programming to the pharmacy operating systems occurred forcing a mandatory second clinical review of all methotrexate orders during the pharmacist verification process, before dispensing. Pharmacists were required to call and clarify orders that failed to fulfill prespecified safety criteria before approving the prescription for dispensing. All pharmacists were required to complete a brief, concise, focused, mandatory training program that emphasized the proper use, adverse effects, boxed warnings, appropriate dosing schedules, and new dispensing requirements for methotrexate. On a daily basis, methotrexate orders from the previous day were summarized and forwarded to a Clinical Intervention Center for analysis and measurement. Prescriptions that triggered preestablished safety concerns were triaged back to their respective pharmacies for verification or modification. The results of the Methotrexate Safety Program were measured by tracking the number of prescriptions filled, number of patients treated, number of sentinel events, and number of safety variances identified. All assigned pharmacists (n = 2293) completed the mandatory training between June and December 2008. In 2009, a total of 369 new employees completed the training. The prescriptions per year and patients treated per year remained comparable, whereas the number of sentinel events decreased from 3 in 2007 and 4 in 2008 to 0 following program implementation. The most prevalent variance was daily dosing of methotrexate when weekly was intended. The measurement process detected and

  17. [Evaluation on the effect of immunization and safety of live attenuated and inactivated hepatitis A vaccine in China].

    PubMed

    Li, Hui; Zhang, Xiao-shu; An, Jing

    2013-01-01

    To evaluate the safety of both domestic live attenuated and inactivated hepatitis A vaccines, and to provide reference for emergent vaccination after hepatitis A outbreaks. 493 children aged 6 - 9 with negative antibody to HAV (produced by Abbott) were randomly divided into four groups as vaccinated with domestic live attenuated hepatitis A vaccine (Group A), domestic inactivated hepatitis A vaccine (Group B), imported inactivated hepatitis A vaccine (Group C) and hepatitis B vaccine (Group D) respectively. Adverse events following the immunization were observed 30 minutes, 24, 48 and 72 hours after the vaccination, under double-blind method. The main AEFIs were: fever, local pain and scleroma but no other severe AEFIs were observed. The rates of AEFIs were 13.95% in Group A, 15.25% in group B, 16.80% in group C and 25.62% in group D, with no statistical differences between these groups (χ(2) = 6.953, P > 0.05). 2 weeks after the vaccination, the positive conversion rates of domestic live attenuated hepatitis A vaccine and domestic inactivated hepatitis A vaccine were 85.0% and 94.59% respectively. The rate of domestic inactivated hepatitis A vaccine reached 100% at 4 weeks after the vaccination. The antibody levels of HAV-IgG of Group A and B in 2, 4 and 12 weeks of vaccination and of Group C were higher than that of Group D. After 12 weeks of vaccination, the antibody level of group B became higher than it was Group C. There were no differences on safety among domestic live attenuated hepatitis A vaccine, domestic inactivated hepatitis A vaccine or imported inactivated hepatitis A vaccine under routine or emergency vaccination. All the vaccines showed satisfactory effects.

  18. 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.

  19. 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.

  20. New explosive detonator improves worksite safety

    SciTech Connect

    1996-12-01

    The industry has long been concerned about preventing unwanted detonation of explosives around work sites or downhole, because of inadvertent contact with stray electrical currents, impacts, heat, etc. To answer the challenge of developing a safer, more economical system to use in explosive perforating, cutting and severing jobs, Halliburton Energy Services has introduced the Rig Environment Detonator (RED). The new electroexplosive device utilizes semiconductor bridge technology and a special deflagration-to-detonation technique involving secondary, not primary, explosives. Three independent testing authorities in the US and the UK have recognized the improved safety of the system. Details of available conventional detonators ranging from the earliest blasting caps to very safe, but expensive, systems; design/testing of the new device; and case histories of its use are presented and illustrated in SPE paper 36637, ``Unique electrical detonator enhances safety in explosive operations: case histories``. This paper contains extracts from the SPE paper.

  1. [Improving patient safety through voluntary peer review].

    PubMed

    Kluge, S; Bause, H

    2015-01-01

    The intensive care unit (ICU) is one area of the hospital in which processes and communication are of primary importance. Errors in intensive care units can lead to serious adverse events with significant consequences for patients. Therefore quality and risk-management are important measures when treating critically ill patients. A pragmatic approach to support quality and safety in intensive care is peer review. This approach has gained significant acceptance over the past years. It consists of mutual visits by colleagues who conduct standardised peer reviews. These reviews focus on the systematic evaluation of the quality of an ICU's structure, its processes and outcome. Together with different associations, the State Chambers of Physicians and the German Medical Association have developed peer review as a standardized tool for quality improvement. The common goal of all stakeholders is the continuous and sustainable improvement in intensive care with peer reviews significantly increasing and improving communication between professions and disciplines. Peer reviews secure the sustainability of planned change processes and consequently lead the way to an improved culture of quality and safety.

  2. Safety of a live attenuated Erysipelothrix rhusiopathiae vaccine for swine.

    PubMed

    Neumann, Eric J; Grinberg, Alex; Bonistalli, Kathryn N; Mack, Hamish J; Lehrbach, Philip R; Gibson, Nicole

    2009-03-30

    Infection with Erysipelothrix rhusiopathiae has a significant economic impact on pig production systems worldwide. Both inactivated and attenuated vaccines are available to prevent development of clinical signs of swine erysipelas. The ability of a live attenuated E. rhusiopathiae strain to become persistently established in pigs after intranasal exposure and its potential to cause clinical signs consistent with swine erysipelas after being administered directly into the nasopharynx of healthy pigs was evaluated. Five, E. rhusiopathiae-negative pigs were vaccinated by deep intranasal inoculation then followed for 14 days. Nasal swabs were collected daily for 5 days and clinical observations were made daily for 14 days post-vaccination. Nasal swabs were cultured for E. rhusiopathiae with the intent of back-passaging any recovered organisms into subsequent replicates. No organism was recovered from nasal swabs in the first vaccination replicate. A second replicate including 10 pigs was initiated and followed in an identical manner to that described above. Again, no E. rhusiopathiae was recovered from any pigs. No pigs in either replicate showed any signs of clinical swine erysipelas. The live attenuated E. rhusiopathiae strain evaluated in this study did not appear to become persistently established in pigs post-vaccination, did not cause any local or systemic signs consistent with swine erysipelas, and was therefore unlikely to revert to a virulent state when used in a field setting.

  3. 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

  4. Safety and immunogenicity of the quadrivalent human papillomavirus vaccine in HIV-1-infected men.

    PubMed

    Wilkin, Timothy; Lee, Jeannette Y; Lensing, Shelly Y; Stier, Elizabeth A; Goldstone, Stephen E; Berry, J Michael; Jay, Naomi; Aboulafia, David; Cohn, David L; Einstein, Mark H; Saah, Alfred; Mitsuyasu, Ronald T; Palefsky, Joel M

    2010-10-15

    Human immunodeficiency virus type 1 (HIV-1)-infected men are at increased risk for anal cancer. Human papillomavirus (HPV) vaccination may prevent anal cancer caused by vaccine types. AIDS Malignancy Consortium Protocol 052 is a single-arm, open-label, multicenter clinical trial to assess the safety and immunogenicity of the quadrivalent HPV (types 6, 11, 16, and 18) vaccine in HIV-1-infected men. Men with high-grade anal intraepithelial neoplasia or anal cancer by history or by screening cytology or histology were excluded. Men received 0.5 mL intramuscularly at entry, week 8, and week 24. The primary end points were seroconversion to vaccine types at week 28, in men who were seronegative and without anal infection with the relevant HPV type at entry, and grade 3 or higher adverse events related to vaccination. There were no grade 3 or greater adverse events attributable to vaccination among the 109 men who received at least 1 vaccine dose. Seroconversion was observed for all 4 types: type 6 (59 [98%] of 60), type 11 (67 [99%] of 68), type 16 (62 [100%] of 62), and type 18 (74 [95%] of 78). No adverse effects on CD4 counts and plasma HIV-1 RNA levels were observed. The quadrivalent HPV vaccine appears safe and highly immunogenic in HIV-1-infected men. Efficacy studies in HIV-1-infected men are warranted. Clinical trials registration. NCT 00513526.

  5. Safety and Immunogenicity of the Quadrivalent Human Papillomavirus Vaccine in HIV-1-Infected Men

    PubMed Central

    Wilkin, Timothy; Lee, Jeannette Y.; Lensing, Shelly Y.; Stier, Elizabeth A.; Goldstone, Stephen E.; Berry, J. Michael; Jay, Naomi; Aboulafia, David; Cohn, David L.; Einstein, Mark H.; Saah, Alfred; Mitsuyasu, Ronald T.; Palefsky, Joel M.

    2011-01-01

    Background HIV-infected men are at increased risk for anal cancer. Human papillomavirus (HPV) vaccination may prevent anal cancer caused by vaccine types. Methods AIDS Malignancy Consortium Protocol 052 is a single-arm, open-label, multi-center clinical trial to assess the safety and immunogenicity of the quadrivalent HPV (types 6, 11, 16, 18) vaccine in HIV-infected men. Men with high-grade anal intraepithelial neoplasia or anal cancer by history or by screening cytology or histology were excluded. Men received 0.5 mL intramuscularly at entry, week 8, and 24. The primary endpoints were seroconversion to vaccine types at week 28, in men who were seronegative and without anal infection with the relevant HPV type at entry, and grade 3 or higher adverse events related to vaccination. Results There were no Grade 3 or greater adverse events attributable to vaccination among the 109 men who received at least one vaccine dose. Seroconversion was observed for all 4 types: type 6 (59/60, 98%), type 11 (67/68, 99%), type 16 (62/62, 100%), type 18 (74/78, 95%). No adverse effects on CD4 counts and plasma HIV-1 RNA were observed. Conclusions The quadrivalent HPV vaccine appears safe and highly immunogenic in HIV-infected men. Efficacy studies in HIV-infected men are warranted. PMID:20812850

  6. Safety, tolerability, and immunogenicity of a recombinant, genetically engineered, live-attenuated vaccine against canine blastomycosis.

    PubMed

    Wüthrich, Marcel; Krajaejun, Theerapong; Shearn-Bochsler, Valerie; Bass, Chris; Filutowicz, Hanna I; Legendre, Alfred M; Klein, Bruce S

    2011-05-01

    Blastomycosis is a severe, commonly fatal infection caused by the dimorphic fungus Blastomyces dermatitidis in dogs that live in the United States, Canada, and parts of Africa. The cost of treating an infection can be expensive, and no vaccine against this infection is commercially available. A genetically engineered live-attenuated strain of B. dermatitidis lacking the major virulence factor BAD-1 successfully vaccinates against lethal experimental infection in mice. Here we studied the safety, toxicity, and immunogenicity of this strain as a vaccine in dogs, using 25 beagles at a teaching laboratory and 78 foxhounds in a field trial. In the beagles, escalating doses of live vaccine ranging from 2 × 10⁴ to 2 × 10⁷ yeast cells given subcutaneously were safe and did not disseminate to the lung or induce systemic illness, but a dose of < 2 × 10⁶ yeast cells induced less fever and local inflammation. A vaccine dose of 10⁵ yeast cells was also well tolerated in vaccinated foxhounds who had never had blastomycosis; however, vaccinated dogs with prior infection had more local reactions at the vaccine site. The draining lymph node cells and peripheral blood lymphocytes from vaccinated dogs demonstrated gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), and granulocyte-macrophage colony-stimulating factor (GM-CSF) specifically in response to stimulation with Blastomyces antigens. Thus, the live-attenuated vaccine against blastomycosis studied here proved safe, well tolerated, and immunogenic in dogs and merits further studies of vaccine efficacy.

  7. Development of a mouse-adapted live attenuated influenza virus that permits in vivo analysis of enhancements to the safety of live attenuated influenza virus vaccine.

    PubMed

    Cox, Andrew; Baker, Steven F; Nogales, Aitor; Martínez-Sobrido, Luis; Dewhurst, Stephen

    2015-03-01

    The live attenuated influenza virus vaccine (LAIV) is preferentially recommended for use in persons 2 through 49 years of age but has not been approved for children under 2 or asthmatics due to safety concerns. Therefore, increasing safety is desirable. Here we describe a murine LAIV with reduced pathogenicity that retains lethality at high doses and further demonstrate that we can enhance safety in vivo through mutations within NS1. This model may permit preliminary safety analysis of improved LAIVs. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  8. Post-licensure safety surveillance study of routine use of quadrivalent meningococcal diphtheria toxoid conjugate vaccine.

    PubMed

    Hansen, J; Zhang, L; Klein, N P; Robertson, C A; Decker, M D; Greenberg, D P; Bassily, E; Baxter, R

    2017-09-20

    Menactra® vaccine (MenACWY-D) was licensed in the United States in 2005 for persons 11-55years of age. The aim of this study was to assess the safety of MenACWY-D administered as part of routine clinical care to patients at Kaiser Permanente Northern California (KPNC). This was an observational, retrospective study that included all KPNC members who received MenACWY-D during the study period. We monitored all vaccine recipients for non-elective hospitalizations, emergency department visits, and selected outcomes captured in the clinic setting (Bell's palsy, seizures, neuritis, Guillain-Barré syndrome, encephalopathy, encephalitis, epilepsy, transverse myelitis, multiple sclerosis, hypersensitivity reactions, idiopathic thrombocytopenic purpura, diabetes, arthritis, hemolytic anemia, collagen-vascular disease) through 6months after vaccination. Using vaccine recipients as their own controls, we calculated incidence rate ratios (IRRs) of outcomes during the post-vaccination risk interval and compared these with rates during a comparison interval more remote from vaccination. We also compared rates of outcomes in MenACWY-D recipients with those in matched controls who received selected vaccines in the prior year. We reviewed medical records for selected outcomes. From April 2005 through April 2006, 31,561 KPNC patients (>99% of whom were 11-55years of age) received MenACWY-D. Overall, there were 21 outcomes with significantly elevated IRRs and 44 outcomes with significantly reduced IRRs. Medical record review of outcomes with significantly elevated IRRs did not suggest any relationship with MenACWY-D. Two serious adverse events were considered possibly related to vaccination by the study investigator. This study did not detect any safety concerns following MenACWY-D and provides reassurance that MenACWY-D administered as part of routine care was not associated with unexpected safety risks. ClinicalTrials.gov Identifier is NCT00254995. Copyright © 2017. Published by

  9. Systematic review of human papillomavirus vaccine coadministration.

    PubMed

    Noronha, Alinea S; Markowitz, Lauri E; Dunne, Eileen F

    2014-05-13

    Human papillomavirus (HPV) vaccination is recommended in early adolescence, at an age when other vaccines are also recommended. Administration of multiple vaccines during one visit is an opportunity to improve uptake of adolescent vaccines. We conducted a systematic review of safety and immunogenicity of HPV vaccines coadministered with other vaccines. Our review included 9 studies, 4 of quadrivalent HPV vaccine and 5 of bivalent HPV vaccine; coadministered vaccines included: meningococcal conjugate, hepatitis A, hepatitis B, combined hepatitis A and B, tetanus, diphtheria, acellular pertussis, and inactivated poliovirus vaccines. Studies varied in methods of data collection and measurement of immunogenicity and safety. Noninferiority of immune response and an acceptable safety profile were demonstrated when HPV vaccine was coadministered with other vaccines.

  10. 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.

  11. Immunogenicity and Safety of a Live Attenuated Zoster Vaccine (ZOSTAVAX™) in Korean Adults.

    PubMed

    Choi, Won Suk; Choi, Jung-Hyun; Choi, Jun Yong; Eom, Joong Sik; Kim, Sang Il; Pai, Hyunjoo; Peck, Kyong Ran; Sohn, Jang Wook; Cheong, Hee Jin

    2016-01-01

    A live attenuated zoster vaccine (ZOSTAVAX™, Merck & Co., Inc.) was approved by the Korea Ministry of Food and Drug Safety in 2009. However, the immunogenicity and safety of the vaccine has not been assessed in Korean population. This is multi-center, open-label, single-arm study performed with 180 healthy Korean adults ≥ 50 yr of age. The geometric mean titer (GMT) and geometric mean fold rise (GMFR) of varicella zoster virus (VZV) antibodies were measured by glycoprotein enzyme-linked immunosorbent assay (gpELISA) at 4 weeks post-vaccination. Subjects were followed for exposure to varicella or herpes zoster (HZ), the development of any varicella/varicella-like or HZ/HZ-like rashes, and any other clinical adverse experiences (AEs) for 42 days post-vaccination. For the 166 subjects included in the per-protocol population, the GMT at Day 1 was 66.9. At 4 weeks post-vaccination, the GMT for this population was 185.4, with a GMFR of 2.8 (95% CI, 2.5-3.1). Of the 180 subjects vaccinated, 62.8% experienced ≥ 1 AE, with 53.3% of subjects reporting injection-site AEs. The most frequently reported injection-site AEs were erythema (45.0%) with the majority being mild in intensity. Overall, 44 (24.4%) subjects experienced ≥ 1 systemic AE, 10 (5.5%) subjects experienced a systemic vaccine-related AE, and 3 (1.7%) subjects experienced ≥ 1 serious AE not related to vaccine. No subjects reported a VZV-like rash. There was no subject of death and no subject discontinued due to an adverse event. A single dose of zoster vaccine induced VZV-specific gpELISA antibody response and was generally well-tolerated in healthy Korean adults ≥50 yr of age (registry at www.clinicaltrial.gov No. NCT01556451).

  12. 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

  13. Effect of Vaccine Administration Modality on Immunogenicity and Efficacy

    PubMed Central

    Zhang, Lu; Wang, Wei; Wang, Shixia

    2016-01-01

    Summary The many factors impacting the efficacy of a vaccine can be broadly divided into three categories: (1) features of the vaccine itself, including immunogen design, vaccine type, formulation, adjuvant, and dosing; (2) individual variations among vaccine recipients; and (3) 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

  14. Formal training in vaccine safety to address parental concerns not routinely conducted in U.S. pediatric residency programs.

    PubMed

    Williams, S Elizabeth; Swan, Rebecca

    2014-05-30

    To determine if U.S. pediatric residency programs provide formal training in vaccine safety to address parental vaccine concerns. An electronic survey was mailed to all members of the Association of Pediatric Program Directors (APPD) to assess (1) if U.S. pediatric residency programs were providing formal vaccine safety training, (2) the content and format of the training if provided, and (3) interest in a training module for programs without training. Two follow-up surveys were mailed at 2 week intervals. Responses to the survey were collected at 4 weeks following the last mailing and analyzed. Logistic regression was used to assess the impact of program size on the likelihood of vaccine safety training. Pearson's chi square was used to compare programs with and without formal vaccine safety training in 5 U.S. regions. The survey was sent to 199 APPD members; 92 completed the survey (response rate 46.2%). Thirty-eight respondents (41%) had formal training in vaccine safety for pediatric residents at their programs; 54 (59%) did not. Of those that did not, the majority (81.5%) were interested in formal vaccine safety training for their residents. Of all respondents, 78% agreed that training in vaccine safety was a high priority for resident education. Thirty-five percent of all respondents agreed that local parental attitudes about vaccines influenced the likelihood of formal vaccine safety training. Most pediatric residency programs surveyed do not include formal training on vaccine safety; yet, such training is supported by pediatric residency program directors as a priority for pediatric residents. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Building on Dendritic Cell Subsets to Improve Cancer Vaccines

    PubMed Central

    Palucka, Karolina; Ueno, Hideki; Zurawski, Gerard; Fay, Joseph; Banchereau, Jacques

    2010-01-01

    SUMMARY T cells can reject established tumors when adoptively transferred into patients, thereby demonstrating that the immune system can be harnessed for cancer therapy. However, such passive immunotherapy is unlikely to maintain memory T cells that might control tumor outgrowth on the long term. Active immunotherapy with vaccines has the potential to induce tumor-specific effector and memory T cells. Vaccines act through dendritic cells (DCs) which induce, regulate and maintain T cell immunity. Clinical trials testing first generation DC vaccines pulsed with tumor antigens provided a proof-of-principle that therapeutic immunity can be elicited. The increased knowledge of the DC system, including the existence of distinct DC subsets is leading to new trials which aim at improved immune and clinical outcomes. PMID:20226644

  16. Policy considerations for improving influenza vaccination rates among pregnant women.

    PubMed

    Mollard, Elizabeth K; Guenzel, Nicholas; Brown, Peggy A; Keeler, Heidi J; Cramer, Mary E

    2014-01-01

    Influenza exposure during pregnancy can cause severe health problems for both the mother and her offspring, including an increased risk of mortality. Influenza vaccination during all trimesters of pregnancy is safe and effective, and recommended by professional organizations such as the American College of Obstetrics and Gynecology. Despite these recommendations, the U.S. vaccination rates remain low in this high-risk population. A policy analysis based on the five-part method identified by Teitelbaum and Wilensky () addresses factors to consider in identifying the best voluntary policy options to improve the vaccination rates. The authors provide discussion of the background, landscape, and stakeholder interests and the pros and cons of two voluntary policy options to increase vaccination. The policy options include: (a) financial incentives for providers and (b) an education emphasis for providers and staff. The authors conclude that based on considerations of cost, provider preference, and practicality of implementation, a continuing educational intervention is the preferred policy venue to increase vaccination rates. © 2014 Wiley Periodicals, Inc.

  17. Quality Improvement Initiative to Reduce Serious Safety Events and Improve Patient Safety Culture

    PubMed Central

    Goudie, Anthony; Schoettker, Pamela J.; Donnelly, Lane F.; Goodfriend, Martha A.; Bracke, Tracey M.; Brady, Patrick W.; Wheeler, Derek S.; Kotagal, Uma R.

    2012-01-01

    BACKGROUND AND OBJECTIVE: Many thousands of patients die every year in the United States as a result of serious and largely preventable safety events or medical errors. Safety events are common in hospitalized children. We conducted a quality improvement initiative to implement cultural and system changes with the goal of reducing serious safety events (SSEs) by 80% within 4 years at our large, urban pediatric hospital. METHODS: A multidisciplinary SSE reduction team reviewed the safety literature, examined recent SSEs, interviewed internal leaders, and visited other leading organizations. Senior hospital leaders provided oversight, monitored progress, and helped to overcome barriers. Interventions focused on: (1) error prevention; (2) restructuring patient safety governance; (3) a new root cause analysis process and a common cause database; (4) a highly visible lessons learned program; and (5) specific tactical interventions for high-risk areas. Our outcome measures were the rate of SSEs and the change in patient safety culture. RESULTS: SSEs per 10 000 adjusted patient-days decreased from a mean of 0.9 at baseline to 0.3 (P < .0001). The days between SSEs increased from a mean of 19.4 at baseline to 55.2 (P < .0001). After a worsening of patient safety culture outcomes in the first year of intervention, significant improvements were observed between 2007 and 2009. CONCLUSIONS: Our multifaceted approach was associated with a significant and sustained reduction of SSEs and improvements in patient safety culture. Multisite studies are needed to better understand contextual factors and the significance of specific interventions. PMID:22802607

  18. [Vaccines against Herpes zoster: Effectiveness, safety, and cost/benefit ratio].

    PubMed

    Ferahta, Nabila; Achek, Imene; Dubourg, Julie; Lang, Pierre-Olivier

    2016-02-01

    A vaccination against herpes zoster and its complication is available in France since June 2015. Its exact benefit for public health is still controversial and its level of protection is not optimal. All those reasons seem to suggest a low acceptation rate from general practitioners. To evaluate the effectiveness, the safety, and the cost/benefit ratio of the vaccination against herpes zoster in people aged 50 year or over. Systematic review in Medline and PubMed with research by key words: "herpes zoster vaccine", "zoster vaccine" and "post herpetic neuralgia vaccine". Randomized and observational studies published in English and French language have been selected by two readers. On 1886 articles identified, 62 studies were included in this systematic review of which 21 randomized trials, 21 observational studies, and 17 medico-economic studies concerned the unadjuvanted vaccine. Considered studies showed an effectiveness of 50% against herpes zoster and 60% on post-herpetic neuralgia incidence of the unadjuvanted vaccine. Five randomized controlled studies were identified for the adjuvanted vaccine. The overall effectiveness of this vaccine was > 90% whatever the age of subjects including those over age 70 and 80. The medico-economic studies conducted in many countries have shown that vaccine policies were beneficial in individuals aged 60 years or over. Most of data of effectiveness, and tolerance result from 2 large controlled studies only (SPS and ZEST) for the unadjuvanted vaccine and only one for the adjuvanted vaccine. Despite controversy and few uncertainties, the vaccine significantly reduces herpes zoster and its complication incidence. In terms of public health objectives, it reduces the burden of the disease and has a positive medico-economic impact. Preliminary data concerning the adjuvanted vaccine, whilst very promising, are still too limited. Up to now, no group of people with particularly high risk of herpes zoster-related complication who will

  19. 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.

  20. "Communicate to vaccinate": the development of a taxonomy of communication interventions to improve routine childhood vaccination.

    PubMed

    Willis, Natalie; Hill, Sophie; Kaufman, Jessica; Lewin, Simon; Kis-Rigo, John; De Castro Freire, Sara Bensaude; Bosch-Capblanch, Xavier; Glenton, Claire; Lin, Vivian; Robinson, Priscilla; Wiysonge, Charles S

    2013-05-11

    Vaccination is a cost-effective public health measure and is central to the Millennium Development Goal of reducing child mortality. However, childhood vaccination coverage remains sub-optimal in many settings. While communication is a key feature of vaccination programmes, we are not aware of any comprehensive approach to organising the broad range of communication interventions that can be delivered to parents and communities to improve vaccination coverage. Developing a classification system (taxonomy) organised into conceptually similar categories will aid in: understanding the relationships between different types of communication interventions; facilitating conceptual mapping of these interventions; clarifying the key purposes and features of interventions to aid implementation and evaluation; and identifying areas where evidence is strong and where there are gaps. This paper reports on the development of the 'Communicate to vaccinate' taxonomy. The taxonomy was developed in two stages. Stage 1 included: 1) forming an advisory group; 2) searching for descriptions of interventions in trials (CENTRAL database) and general health literature (Medline); 3) developing a sampling strategy; 4) screening the search results; 5) developing a data extraction form; and 6) extracting intervention data. Stage 2 included: 1) grouping the interventions according to purpose; 2) holding deliberative forums in English and French with key vaccination stakeholders to gather feedback; 3) conducting a targeted search of grey literature to supplement the taxonomy; 4) finalising the taxonomy based on the input provided. The taxonomy includes seven main categories of communication interventions: inform or educate, remind or recall, teach skills, provide support, facilitate decision making, enable communication and enhance community ownership. These categories are broken down into 43 intervention types across three target groups: parents or soon-to-be-parents; communities, community

  1. Safety and Immunogenicity of a Tetravalent Live-Attenuated Dengue Vaccine in Flavivirus-Naive Infants

    PubMed Central

    Watanaveeradej, Veerachai; Simasathien, Sriluck; Nisalak, Ananda; Endy, Timothy P.; Jarman, Richard G.; Innis, Bruce L.; Thomas, Stephen J.; Gibbons, Robert V.; Hengprasert, Sumetha; Samakoses, Rudiwilai; Kerdpanich, Angkool; Vaughn, David W.; Putnak, J. Robert; Eckels, Kenneth H.; Barrera, Rafael De La; Mammen, Mammen P.

    2011-01-01

    A Phase I/II observer-blind, randomized, controlled trial evaluated the safety and immunogenicity of a dengue virus (DENV) vaccine candidate in healthy Thai infants (aged 12–15 months) without measurable pre-vaccination neutralizing antibodies to DENV and Japanese encephalitis virus. Fifty-one subjects received two doses of either DENV (N = 34; four received 1/10th dose) or control vaccine (N = 17; dose 1, live varicella; dose 2, Haemophilus influenzae type b). After each vaccine dose, adverse events (AEs) were solicited for 21 days, and non-serious AEs were solicited for 30 days; serious AEs (SAEs) were recorded throughout the study. Laboratory safety assessments were performed at 10 and 30 days; neutralizing antibodies were measured at 30 days. The DENV vaccine was well-tolerated without any related SAEs. After the second dose, 85.7% of full-dose DENV vaccinees developed at least trivalent and 53.6% developed tetravalent neutralizing antibodies ≥ 1:10 to DENV (control group = 0%). This vaccine candidate, therefore, warrants continued development in this age group (NCT00322049; clinicaltrials.gov). PMID:21813857

  2. Keen on teen vaccines: improvement of adolescent vaccine coverage in rural North Carolina.

    PubMed

    Chung, Richard J; Walter, Emmanuel B; Kemper, Alex R; Dayton, Amanda

    2015-05-01

    To improve adolescent immunization coverage in a rural North Carolina county. Adolescent immunization coverage rates in an intervention and four comparison counties were compared over 1 year. We introduced practice-based interventions in seven practices centering on immunization registry-driven recall of adolescents for immunizations with postcard reminders (Phase 1), and 6 months later employed nontargeted school-generated telephone reminders to parents of adolescents (Phase 2). Improvements in the intervention county among 11- to 12-year-olds occurred for first-dose human papillomavirus vaccine in both boys (overall change, 14.2%-32.1%) and girls (27.4%-43.4%) and the meningococcal vaccine (34.6%-49.4%). Improvements among adolescents 13-18 years were limited to human papillomavirus vaccine completion in boys (1.6%-4.2%). Improvements were greater during Phase 1 than Phase 2 and among younger adolescents. Coverage improvements in the comparison counties were smaller than those observed in the intervention county. A resource-light two-phase intervention led to modest improvements in immunization coverage, most notably in the largest adolescent practice in the county, and suggested potential for further gains, particularly among younger adolescents. Copyright © 2015 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  3. 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

  4. Safety and immunogenicity of a defined vaccine for the prevention of cutaneous leishmaniasis.

    PubMed

    Vélez, Iván D; Gilchrist, Katherine; Martínez, Sofía; Ramírez-Pineda, José R; Ashman, Jill A; Alves, Fabiana P; Coler, Rhea N; Bogatzki, Lisa Y; Kahn, Stuart J; Beckmann, Anna Marie; Cowgill, Karen D; Reed, Steven G; Piazza, Franco M

    2009-12-11

    Healthy Colombian adult volunteers with no history of leishmaniasis were evaluated for evidence of previous subclinical infection with Leishmania based on the Montenegro skin test (MST). Twelve MST-positive subjects were enrolled in an open-label, uncontrolled clinical trial (the "MST-positive trial") and received three injections of the LEISH-F1+MPL-SE vaccine (consisting of 10 microg recombinant Leishmania polyprotein LEISH-F1 antigen [TSA+LmSTI1+LeIF]+25 microg MPL-SE adjuvant). Sixty-eight MST-negative subjects were enrolled in a randomized, double-blind, controlled trial (the "MST-negative trial") and were randomly assigned to receive three injections of either the vaccine (n=34), 10 microg LEISH-F1 protein alone (n=17), or saline placebo (n=17). In both trials, the study injections were given subcutaneously on Days 0, 28, and 56, and subjects were followed for safety and immunological endpoints. The LEISH-F1+MPL-SE vaccine was safe and well tolerated in MST-positive and MST-negative subjects. In both trials, an IFN-gamma response to the LEISH-F1 antigen at Day 84 was observed in more than half of the vaccine recipients. In the MST-negative trial, the IFN-gamma response was significantly more frequent and of greater magnitude in vaccine recipients than in protein-alone or placebo recipients. An IgG antibody response to LEISH-F1 was observed in all vaccine recipients. In both trials, delayed-type hypersensitivity (DTH) to LEISH-F1 was observed in most of the vaccine recipients. In the MST-negative trial, DTH was significantly higher in vaccine than placebo recipients. These clinical trials of the first defined vaccine for leishmaniasis show that the LEISH-F1+MPL-SE vaccine is safe and immunogenic in healthy subjects with and without evidence of previous subclinical infection with Leishmania.

  5. Safety of Quadrivalent Meningococcal Conjugate Vaccine in 11- to 21-Year-Olds.

    PubMed

    Tseng, Hung-Fu; Sy, Lina S; Ackerson, Bradley K; Hechter, Rulin C; Tartof, Sara Y; Haag, Mendel; Slezak, Jeffrey M; Luo, Yi; Fischetti, Christine A; Takhar, Harp S; Miao, Yan; Cunnington, Marianne; Solano, Zendi; Jacobsen, Steven J

    2017-01-01

    Meningococcal conjugate vaccination is recommended in the United States. This study evaluates the safety of quadrivalent meningococcal conjugate vaccine in a cohort aged 11 to 21 years. This cohort study with self-controlled case-series analysis was conducted at Kaiser Permanente Southern California. Individuals receiving MenACWY-CRM, a quadrivalent meningococcal conjugate vaccine, during September 30, 2011 to June 30, 2013, were included. Twenty-six prespecified events of interest (EOIs), including neurologic, rheumatologic, hematologic, endocrine, renal, pediatric, and pediatric infectious disease EOIs, were identified through electronic health records 1 year after vaccination. Of these, 16 were reviewed by case review committees. Specific risk and comparison windows after vaccination were predefined for each EOI. The relative incidence (RI) and 95% confidence intervals (CIs) were estimated through conditional Poisson regression models, adjusted for seasonality. This study included 48 899 vaccinated individuals. No cases were observed in the risk window for 14 of 26 EOIs. The RI for Bell's palsy, a case review committee-reviewed EOI, was statistically significant (adjusted RI: 2.9, 95% CI: 1.1-7.5). Stratified analyses demonstrated an increased risk for Bell's palsy in subjects receiving concomitant vaccines (RI = 5.0, 95% CI = 1.4-17.8), and no increased risk for those without concomitant vaccine (RI = 1.1, 95% CI = 0.2-5.5). We observed a temporal association between occurrence of Bell's palsy and receipt of MenACWY-CRM concomitantly with other vaccines. The association needs further investigation as it could be due to chance, concomitant vaccination, or underlying medical history predisposing to Bell's palsy. Copyright © 2017 by the American Academy of Pediatrics.

  6. Serologic response and safety to vaccination against avian influenza using inactivated H5N2 vaccine in zoo birds.

    PubMed

    Lécu, Alexis; De Langhe, Christophe; Petit, Thierry; Bernard, Frédéric; Swam, Hanny

    2009-12-01

    Due to the spread of the H5N1 highly pathogenic strain of avian influenza virus across Europe, a preventive vaccination occurred in early 2006 among 135 French zoologic institutions. Approximately 25,000 birds were vaccinated with a H5N2 inactivated vaccine. Among them, 4,369 birds were monitored by members of Association Francophone des Vétérinaires de Parc Zoologique regarding safety issues of the vaccination protocol. A total of 1,686 blood samples were collected before the first injection (n = 255), at the time of booster (n = 463), 60 day after the booster (n = 514), and 180 day (n = 229) and 330 day (n = 217) after the initial injection. Thus, sera of 126 species representing 15 different avian orders were tested using the hemagglutinin inhibition assay to evaluate seroconversion and the long-term serologic profile of selected anti-H5 antibody. Safety was considered satisfactory in all orders, and there were no deleterious effects on large-volume injection/body weight ratio. After the second injection, 71% of the birds developed a titer > or =32, with a mean titer of 558. Titers then decreased in all birds, with 42% of the remaining birds having a titer > or =32 at day 180 and only 26% at day 330. Results demonstrated that a booster 42 days after initial vaccination was mandatory to raise the titer above 32, considered to be the protective level in poultry, and to increase the number of seroconverted birds. Differences in the serologic responses among the orders and species of birds were detected and could be linked with the variation of vaccine dose injected per body weight or with species-specific immune response. The protocol for additional campaigns will be adjusted for some bird orders through the increase of injected dose or a half yearly booster to sustain better titers over the year. Vaccination is a useful tool, together with biosecurity, that should always be used as a primary method of preventing and controlling avian influenza outbreaks.

  7. [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

    2016-01-01

    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

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

    PubMed

    Pellegrino, Paolo; Radice, Sonia; Clementi, Emilio

    2015-07-09

    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.

  9. 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.

  10. Immunogenicity, safety and tolerability of a bivalent human papillomavirus vaccine in adolescents with juvenile idiopathic arthritis.

    PubMed

    Esposito, Susanna; Corona, Fabrizia; Barzon, Luisa; Cuoco, Federica; Squarzon, Laura; Marcati, Giorgia; Torcoletti, Marta; Gambino, Monia; Palù, Giorgio; Principi, Nicola

    2014-11-01

    To evaluate the immunogenicity, safety and tolerability of the bivalent HPV vaccine in female patients with juvenile idiopathic arthritis (JIA). Twenty-one patients with JIA aged 12-25 years and 21 healthy controls were enrolled and received three doses of the bivalent HPV vaccine. All of the subjects were seronegative at baseline and seroconverted after the scheduled doses. The JIA patients showed significantly lower HPV16 neutralising antibody titres than controls 1 month after the administration of the third dose (p < 0.05), whereas no significant difference was observed in HPV18 neutralising antibody titres. Local and systemic reactions were similarly frequent in the patients and controls, and there were no significant changes in 27-joint juvenile arthritis disease activity score or laboratory tests. The bivalent HPV vaccine is safe in patients with stable JIA and regardless of the use of medications the vaccine assures an adequate degree of protection for a certain time.

  11. Further studies on autoclaved cercarial vaccine against schistosomiasis: safety, longevity and stability.

    PubMed

    Eissa, Maha M; Allam, Sonia R; El-Azzouni, Mervat Z; Maged, Hala R; Dessouky, Iman S

    2003-08-01

    The autoclaved cercarial vaccine (ACV) which is a special type of killed vaccine has been reported to induce experimental high level of homologous protective immunity. This study was to adjust the dose and to assess vaccine safety, longevity and stability as well as the possibility of transplacental transmission of immune response from pregnant mice to their offspring. The results showed that two doses of the lowest most effective concentration of ACV that achieved the high percentage reduction of worm burden is safe as demonstrated by absence of any local or systemic side effects, normal blood picture and normal liver and kidney function tests. ACV is stable when kept either at 4 degrees C for six months or at -35 degrees C for up to 12 months and it offered considerable duration of longevity. Offspring of vaccinated mothers didn't show any signs of protection against challenge infection.

  12. 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.

  13. Safety and immunogenicity of a single dose 23-valent pneumococcal polysaccharide vaccine in Russian subjects.

    PubMed

    Ciprero, Karen; Zykov, Kirill A; Briko, Nikolay I; Shekar, Tulin; Sterling, Tina M; Bitieva, Elizaveta; Stek, Jon E; Musey, Luwy

    2016-08-02

    Pneumococcal infection is a major cause of pneumonia, bacteremia, and meningitis. Incidence of pneumococcal disease (PD) varies worldwide. The 23-valent pneumococcal polysaccharide vaccine (PPV23) displays an acceptable safety profile and has been demonstrated cost-effective in reducing burden of PD.

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

    USDA-ARS?s Scientific Manuscript database

    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...

  15. Combining multiple healthcare databases for postmarketing drug and vaccine safety surveillance: why and how?

    PubMed

    Trifirò, G; Coloma, P M; Rijnbeek, P R; Romio, S; Mosseveld, B; Weibel, D; Bonhoeffer, J; Schuemie, M; van der Lei, J; Sturkenboom, M

    2014-06-01

    A growing number of international initiatives (e.g. EU-ADR, Sentinel, OMOP, PROTECT and VAESCO) are based on the combined use of multiple healthcare databases for the conduct of active surveillance studies in the area of drug and vaccine safety. The motivation behind combining multiple healthcare databases is the earlier detection and validation, and hence earlier management, of potential safety issues. Overall, the combination of multiple healthcare databases increases statistical sample size and heterogeneity of exposure for postmarketing drug and vaccine safety surveillance, despite posing several technical challenges. Healthcare databases generally differ by underlying healthcare systems, type of information collected, drug/vaccine and medical event coding systems and language. Therefore, harmonization of medical data extraction through homogeneous coding algorithms across highly different databases is necessary. Although no standard procedure is currently available to achieve this, several approaches have been developed in recent projects. Another main challenge involves choosing the work models for data management and analyses whilst respecting country-specific regulations in terms of data privacy and anonymization. Dedicated software (e.g. Jerboa) has been produced to deal with privacy issues by sharing only anonymized and aggregated data using a common data model. Finally, storage and safe access to the data from different databases requires the development of a proper remote research environment. The aim of this review is to provide a summary of the potential, disadvantages, methodological issues and possible solutions concerning the conduct of postmarketing multidatabase drug and vaccine safety studies, as demonstrated by several international initiatives.

  16. 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.

  17. 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

  18. Ongoing pharmacovigilance on vaccines.

    PubMed

    Santuccio, Carmela; Trotta, Francesco; Felicetti, Patrizia

    2015-02-01

    Vaccines have peculiar characteristics as well as their surveillance. Specific requirements, needs and challenges for the vaccine vigilance are discussed in the perspective to improve the whole system in order to guarantee a safer vaccine use and the keeping of the public confidence in vaccinations. Key elements for the routine safety monitoring, new regulations and some available tools are taken into account. Finally, the Italian experience is shortly described.

  19. Strategies for improved stability of Peste des Petits Ruminants Vaccine.

    PubMed

    Silva, Ana Carina; Carrondo, Manuel J T; Alves, Paula M

    2011-07-12

    The main focus of this work was the improvement of the stability of the current PPRV vaccine. First, new formulations based on the Tris buffer were tested, with and without the addition of sucrose and trehalose and compared with the formulation normally used to stabilize the vaccine, the Weybridge medium. The results show a virus half-life of 21 h at 37°C and 1 month at 4°C for the Tris/trehalose liquid formulation and, in the lyophilized form, the formulation was able to maintain the viral titer above the 1 × 10(4) TCID(50)/mL (>10 doses/mL) for at least 21 months at 4°C (0.6 log lost), 144 h at 37°C (0.6 log lost) and 120 h at 45°C (1 log lost). Secondly, a strategy based on culture medium composition manipulation aiming at improving the intrinsic PPRV vaccine stability was also evaluated. The addition of 25 mM fructose resulted in a higher virus production (1log increase) with higher stability (2.6-fold increase compared to glucose 25 mM) at 37°C. Increased concentrations of NaCl, improved virus release, reducing the cell-associated fraction of the virus produced. Moreover this harvesting strategy is scalable and more suitable for a larger scale production than the freeze/thaw cycles normally used. The information gathered in this work showed that it is possible for the PPRV vaccine to have adequate short-term stability at non-freezing temperatures to support manufacturing, short-term shipping and storage. The identification of a more stable formulation should significantly enhance the utility of the vaccine in the control of a PPRV outbreak.

  20. 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

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

    PubMed

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

    2012-01-01

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

  2. Improving pneumococcal vaccination rates of medical inpatients in urban Nepal using quality improvement measures

    PubMed Central

    Bock, Allison; Chintamaneni, Kathan; Rein, Lisa; Frazer, Tifany; Kayastha, Gyan; MacKinney, Theodore

    2016-01-01

    Streptococcus pneumoniae infection is associated with high morbidity and mortality in low income countries. In Nepal, there is a high lung disease burden and incidence of pneumonia due to multiple factors including indoor air pollution, dust exposure, recurrent infections, and cigarette smoking. Despite the ready availability of effective pneumococcal vaccines (PNV), vaccine coverage rates remain suboptimal globally. Quality Improvement (QI) principles could be applied to improve compliance, but it is a virtually new technology in Nepal. This QI study for Patan Hospital sought to introduce the concept of QI there, to measure the baseline pneumococcal vaccination rate of qualifying adult patients discharged from the medical wards and to assess reasons for non-vaccination. QI interventions were instituted to improve this rate, measuring the effectiveness of QI methods to produce the desired outcomes using the Model for Improvement, Plan-Do-Study-Change (PDSA) methodology. In the three week baseline assessment, 2 out of 81 (2%) eligible patients recalled ever receiving a prior pneumococcal vaccine; 68 (84%) unvaccinated patients responded that they were not asked or were unaware of the PNV. After the QI interventions, the pneumococcal vaccination rate significantly increased to 42% (23/56, p<0.001). Post-intervention, the leading reason for non-vaccination was cost (20%, 11/56). Only 5 (9%) unvaccinated patients were not asked or were unaware of the PNV, a significant change in that process outcome from baseline (p<0.001). Quality improvement measures were effective in increasing pneumococcal vaccination rates, despite the limited familiarity with QI methods at this major teaching hospital. QI techniques may be useful in this and other efforts to improve quality in resource-limited settings, without great cost. PMID:27933153

  3. [Antiviral vaccines].

    PubMed

    Girard, M

    1999-01-01

    Vaccination has been successful in controlling numerous diseases in man and animals. Smallpox has been eradicated and poliomyelitis is on the verge of being eradicated. The traditional immunization arsenal includes vaccines using live, attenuated, and inactivated organisms. DNA recombinant technology has added two new types of vaccines, i.e. subunit vaccines based on purified antigens produced by genetic engineering in bacterial, yeast, or animal-cell cultures and live recombinant vaccines based on attenuated bacterial or viral vectors. Currently the best known examples of these new vaccines are those using poxvirus vectors (vaccinia virus, canarypox virus, or fowlpox virus) but new vectors are under development. Another application for genetic engineering in the field of vaccinology is the development of DNA vaccines using naked plasmid DNA. This technique has achieved remarkable results in small rodents but its efficacy, safety, and feasibility in man has yet to be demonstrated. Numerous studies are now under way to improve the process. In the field of synthetic vaccines, lipopeptides have shown promise for induction of cell immune response. Development of vaccines for administration by the oral or nasal route may one day revolutionize vaccination techniques. However, effective vaccines against hepatitis C and HIV have stalled in the face of the complexity and pathophysiology of these diseases. These are the greatest challenges confronting scientists at the dawn of the new millennium.

  4. 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.

  5. 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.

  6. Efficacy and safety studies on an inactivated vaccine against bluetongue virus serotype 2.

    PubMed

    Di Emidio, B; Nicolussi, P; Patta, C; Ronchi, G F; Monaco, F; Savini, G; Ciarelli, A; Caporale, V

    2004-01-01

    An inactivated vaccine was produced from an Italian field isolate of bluetongue virus serotype 2 (BTV-2) with a titre of 10(7.8)TCID50/ml. The virus was purified through a molecular cut cassette membrane, inactivated with beta-propriolactone and emulsified with ISA 206 (Seppic) adjuvant. The vaccine was then tested for sterility, toxicity and safety in laboratory and target animals according to European Pharmacopoeia standards. Immunogenicity was assessed by inoculating subcutaneously 10 sheep and 10 goats each with 2 ml of the vaccine and 10 bovines each with 5 ml of the vaccine. A booster dose was inoculated after 14 days and no side-effects were reported following vaccination. Fourteen days after the booster dose, all vaccinated animals developed virus neutralising (VN) bluetongue (BT) antibody titres that on day 60 post vaccination ranged between 1/20 and 1/1 280. After one year, goats still had high VN antibody titres. Sheep were challenged 138 days after vaccination by subcutaneously inoculating 1 ml of 10(5.6)TCID50/ml of an Italian field isolate of BTV serotype 2; four unvaccinated animals were also inoculated and used as controls. Starting from day 6 post challenge, control animals developed a fever, with temperature ranging from 39.9 degrees C to 40.6 degrees C and lasting 48 h on average. BTV-2 was also isolated from the blood of control animals between days 4 and 20 post challenge. Conversely, neither fever nor viraemia were detected in the vaccinated animals that were challenged. A new trial with a larger number of animals, including all target species, has been planned and is in progress.

  7. Safety of the Pandemic H1N1 Influenza Vaccine among Pregnant U.S. Military Women and Their Newborns

    DTIC Science & Technology

    2013-03-01

    Naval Health Research Center Safety of the Pandemic H1N1 Influenza Vaccine among Pregnant Women and Their Newborns Ava M.S. Conlin Anna...Safety of the Pandemic H1N1 Influenza Vaccine Among Pregnant U.S. Military Women and Their Newborns Ava Marie S. Conlin, DO, MPH, Anna T. Bukowinski...with either the pandemic H1N1 vaccine between October 2009 and June 2010 or with seasonal influenza vaccine between October 2008 and June 2009. Rates of

  8. A Single Vaccination with an Improved Nonspreading Rift Valley Fever Virus Vaccine Provides Sterile Immunity in Lambs

    PubMed Central

    Oreshkova, Nadia; van Keulen, Lucien; Kant, Jet; Moormann, Rob J. M.; Kortekaas, Jeroen

    2013-01-01

    Rift Valley fever virus (RVFV) is an important pathogen that affects ruminants and humans. Recently we developed a vaccine based on nonspreading RVFV (NSR) and showed that a single vaccination with this vaccine protects lambs from viremia and clinical signs. However, low levels of viral RNA were detected in the blood of vaccinated lambs shortly after challenge infection. These low levels of virus, when present in a pregnant ewe, could potentially infect the highly susceptible fetus. We therefore aimed to further improve the efficacy of the NSR vaccine. Here we report the expression of Gn, the major immunogenic protein of the virus, from the NSR genome. The resulting NSR-Gn vaccine was shown to elicit superior CD8 and CD4-restricted memory responses and improved virus neutralization titers in mice. A dose titration study in lambs revealed that the highest vaccination dose of 106.3 TCID50/ml protected all lambs from clinical signs and viremia. The lambs developed neutralizing antibodies within three weeks after vaccination and no anamnestic responses were observed following challenge. The combined results suggest that sterile immunity was achieved by a single vaccination with the NSR-Gn vaccine. PMID:24167574

  9. Shedding of Live Vaccine Virus, Comparative Safety, and Influenza-Specific Antibody Responses after Administration of Live Attenuated and Inactivated Trivalent Influenza Vaccines to HIV-Infected Children

    PubMed Central

    Levin, Myron J.; Song, Lin-Ye; Fenton, Terrence; Nachman, Sharon; Patterson, Julie; Walker, Robert; Kemble, George; Allende, Maria; Hultquist, Micki; Yi, Tingting; Nowak, Barbara; Weinberg, Adriana

    2008-01-01

    HIV-infected children (n = 243), ≥5 to <18 years old, receiving stable antiretroviral therapy, were stratified by immunologic status and randomly assigned to receive intranasal live attenuated influenza vaccine (LAIV) or intramuscular trivalent inactivated influenza vaccine (TIV). The safety profile after LAIV or TIV closely resembled the previously reported tolerability to these vaccines in children without HIV infection. Post-vaccination hemagglutination inhibition (HAI) antibody responses and shedding of LAIV virus were also similar, regardless of immunological stratum, to antibody responses and shedding previously reported for children without HIV infection. LAIV should be further evaluated for a role in immunizing HIV-infected children. PMID:18597900

  10. Comparative safety study of three inactivated BTV-8 vaccines in sheep and cattle under field conditions.

    PubMed

    Gethmann, J; Hüttner, K; Heyne, H; Probst, C; Ziller, M; Beer, M; Hoffmann, B; Mettenleiter, T C; Conraths, F J

    2009-06-24

    After massive epidemics of bluetongue disease in 2006 and 2007, Germany has started a compulsory vaccination program against bluetongue virus serotype 8 (BTV-8). Since the available vaccines had not yet been registered and only limited data were available on their performance, a safety study was conducted with three different inactivated monovalent vaccines under consideration for use in Germany. A total of 1007 sheep and 893 cattle were vaccinated and subsequently compared with 638 control animals (324 sheep and 314 cattle). During the study, all animals remained in good health condition. After the initial immunisation, only local swellings were observed in a small number of animals. Following revaccination, several sheep developed more distinct local reactions and a temporary rise in body temperature. Severe systemic reactions were not detected in any of the study groups. Among cattle, neither fever, nor a decrease in milk production and only temporary low-grade local reactions were observed. Overall, our results demonstrate a high level of safety of all vaccines tested.

  11. Safety and immunogenicity of a baculovirus-expressed hemagglutinin influenza vaccine: a randomized controlled trial.

    PubMed

    Treanor, John J; Schiff, Gilbert M; Hayden, Frederick G; Brady, Rebecca C; Hay, C Mhorag; Meyer, Anthony L; Holden-Wiltse, Jeanne; Liang, Hua; Gilbert, Adam; Cox, Manon

    2007-04-11

    A high priority in vaccine research is the development of influenza vaccines that do not use embryonated eggs as the substrate for vaccine production. To determine the dose-related safety, immunogenicity, and protective efficacy of an experimental trivalent influenza virus hemagglutinin (rHA0) vaccine produced in insect cells using recombinant baculoviruses. Randomized, double-blind, placebo-controlled clinical trial at 3 US academic medical centers during the 2004-2005 influenza season among 460 healthy adults without high-risk indications for influenza vaccine. Participants were randomly assigned to receive a single injection of saline placebo (n = 154); 75 microg of an rHA0 vaccine containing 15 microg of hemagglutinin from influenza A/New Caledonia/20/99(H1N1) and influenza B/Jiangsu/10/03 virus and 45 microg of hemagglutinin from influenza A/Wyoming/3/03(H3N2) virus (n = 153); or 135 microg of rHA0 containing 45 microg of hemagglutinin each from all 3 components (n = 153). Serum samples were taken before and 30 days following immunization. Primary safety end points were the rates and severity of solicited and unsolicited adverse events. Primary immunogenicity end points were the rates of 4-fold or greater increases in serum hemagglutinin inhibition antibody to each of the 3 vaccine strains before and 28 days after inoculation. The prespecified primary efficacy end point was culture-documented influenza illness, defined as development of influenza-like illness associated with influenza virus on a nasopharyngeal swab. Rates of local and systemic adverse effects were low, and the rates of systemic adverse effects were not different in either vaccine group than in the placebo group. Hemagglutinin inhibition antibody responses to the H1 component were seen in 3% of placebo, 51% of 75-microg vaccine, and 67% of 135-microg vaccine recipients, while responses to B were seen in 4% of placebo, 65% of 75-microg vaccine, and 92% of 135-microg vaccine recipients. Responses

  12. [Vaccination programmes].

    PubMed

    Varela, M Carmen

    2009-01-01

    Immunization is a highly cost-effective intervention that saves many lives. Its objective is to control and eliminate vaccine-preventable diseases (when the characteristics of the disease and the vaccine make it possible), resulting in improvements in the health of the population. In Spain, the first vaccination schedule was introduced in 1975 and currently coverages > 95% are achieved in children aged < 2 years of age. Before deciding to introduce a vaccination programme in a community or country, a series of aspects should be considered, including the disease burden in the population, the effectiveness and safety of the vaccine, the changes in the dynamics of the infection when the vaccine is introduced, the cost-effectiveness of the vaccine, the theoretical potential of elimination/eradication of the disease and the existence of other preventive or therapeutic measures. Once the programme has been introduced it should be subject to evaluation, considering aspects such as the coverage, effectiveness, safety and the impact on the population. This work defines different vaccination strategies for three diseases for which efficacious and safe vaccines are available: hepatitis A, influenza and varicella.

  13. A self-affirmation exercise does not improve intentions to vaccinate among parents with negative vaccine attitudes (and may decrease intentions to vaccinate)

    PubMed Central

    Ebbs, Jacob B.; Onunkwo, Adaobi K.; Sage, L. Mariah

    2017-01-01

    Two studies investigated the effectiveness of a self-affirmation exercise on vaccine safety beliefs and intent to vaccinate future children. In Study 1, a sample of 585 parents with at least one child under the age of 18 in the home participated through Amazon’s MTurk. Participants were randomly assigned to one of four conditions in a 2 x 2 design. Participants read either correcting information refuting a link between the measles, mumps, and rubella (MMR) vaccine and autism or a control passage about bird feeding. Additionally, participants either completed a self-affirmation exercise where they reflected on their personal values or in a control condition in which they reflected on least-personally-important values that might be important to others. Participants exposed to the correcting information were less likely to believe that vaccines cause serious side effects, but no less likely to believe that the MMR vaccine causes autism. For parents with initially positive vaccine attitudes, there was no effect of condition on intent to vaccinate a future child. For parents with initially negative vaccine attitudes, self-affirmation was ineffective in the presence of correcting information and resulted in less intention to vaccinate in the absence of correcting information. This effect was partially replicated in Study 2 (N = 576), which provided no correcting information but otherwise followed the same procedure as Study 1. PMID:28704520

  14. A self-affirmation exercise does not improve intentions to vaccinate among parents with negative vaccine attitudes (and may decrease intentions to vaccinate).

    PubMed

    Reavis, Rachael D; Ebbs, Jacob B; Onunkwo, Adaobi K; Sage, L Mariah

    2017-01-01

    Two studies investigated the effectiveness of a self-affirmation exercise on vaccine safety beliefs and intent to vaccinate future children. In Study 1, a sample of 585 parents with at least one child under the age of 18 in the home participated through Amazon's MTurk. Participants were randomly assigned to one of four conditions in a 2 x 2 design. Participants read either correcting information refuting a link between the measles, mumps, and rubella (MMR) vaccine and autism or a control passage about bird feeding. Additionally, participants either completed a self-affirmation exercise where they reflected on their personal values or in a control condition in which they reflected on least-personally-important values that might be important to others. Participants exposed to the correcting information were less likely to believe that vaccines cause serious side effects, but no less likely to believe that the MMR vaccine causes autism. For parents with initially positive vaccine attitudes, there was no effect of condition on intent to vaccinate a future child. For parents with initially negative vaccine attitudes, self-affirmation was ineffective in the presence of correcting information and resulted in less intention to vaccinate in the absence of correcting information. This effect was partially replicated in Study 2 (N = 576), which provided no correcting information but otherwise followed the same procedure as Study 1.

  15. Ginseng extract in aluminium hydroxide adjuvanted vaccines improves the antibody response of pigs to porcine parvovirus and Erysipelothrix rhusiopathiae.

    PubMed

    Rivera, E; Daggfeldt, A; Hu, S

    2003-01-10

    Ginseng, the dry extract prepared from the Panax ginseng C.A. Mayer-root contain immunomodulators named ginsenosides, which in the pig enhance the antibody response to viral and bacterial antigens. The enhancing effect of ginseng was demonstrated vaccinating pigs against porcine parvovirus (PPV) and Erysipelothrix rhusiopathiae infections, using commercially available vaccines. The potency of the licensed, aluminium hydroxide adjuvanted; vaccines were compared with those supplemented with ginseng. The antibody response to PPV was measured by the haemagglutination inhibition (HI) test whereas the mouse potency test and ELISA evaluated the immune response to E. rhusiopathiae. Antibodies to the 64-66 kDa glycoprotein of the E. rhusiopathiae were demonstrated by immunoblotting. The qualitative antibody responses were evaluated by means of ELISA(s) using monoclonal antibodies to swine IgG1 and IgG2. The addition of 2mg ginseng per vaccine dose, potentiate the antibody response of the commercial vaccines without altering their safety. Significantly higher (P<0.001) antibody titres were achieved to both PPV and to E. rhusiopathiae by the supplementation with ginseng. Aluminium hydroxide adjuvanted vaccines favoured the production of IgG1 antibodies. Interestingly, the vaccines supplemented with ginseng favoured IgG2. The vaccines used in the evaluations varied in their immunogenic potency. However, after the addition of ginseng the less immunogenic vaccine proved to be as potent as the better one without ginseng. Thus, the use of ginseng as a co-adjuvant provides a simple, safe and cheap alternative for improving the potency of aluminium hydroxide adjuvanted vaccines.

  16. Safety and tolerability of bivalent HPV vaccine: an Italian post-licensure study.

    PubMed

    Gasparini, Roberto; Bonanni, Paolo; Levi, Miriam; Bechini, Angela; Boccalini, Sara; Tiscione, Emilia; Amicizia, Daniela; Lai, Piero Luigi; Sulaj, Klodiana; Patria, Antonio Giuseppe; Panatto, Donatella

    2011-01-01

    One of the most important scientific discoveries of the last century was that persistent infection by some types of HPV is a precondition for the development of cervical cancer. The oncogenic types of HPV are also associated with other tumours (vaginal, vulvar and anal carcinomas, tumours of the head and neck, urethra and penis). Two preventive vaccines are currently available (Cervarix and Gardasil). Both have shown very good efficacy, safety and tolerability profiles. Nonetheless, extensive vaccination requires long-term monitoring of safety and tolerability. The aim of our study was to evaluate the safety and tolerability of the bivalent vaccine Cervarix in Italy. Every participant in the study completed a questionnaire after each dose of vaccine received, with a view to recording adverse events during the first 7 days after vaccination. We registered local (pain, redness, swelling) and systemic symptoms (fever, headache, myalgia, fatigue, arthralgia, itching, gastrointestinal disorders, rash and urticaria). A total of 4,643 subjects were recruited. In all, 7,107 questionnaires were collected: 3,064 after the first dose, 2,367 after the second and 1,676 after the third. No serious adverse events were observed. The most frequent local symptom was pain at the injection site, while fatigue, headache and myalgia were the most common systemic reactions. Pain was reported more frequently after the first dose than after the others, while all the other local and general symptoms were reported most frequently after the third dose. Almost all of the local and general reactions proved to be of negligible intensity and duration and required no medical intervention. Our results show better tolerability of the vaccine in comparison with the data from some controlled clinical studies and from other surveillance programmes conducted internationally. That tolerability proved to be better than in clinical studies could be explained by the absence of the typical apprehension felt

  17. Evaluating the value proposition for improving vaccine thermostability to increase vaccine impact in low and middle-income countries.

    PubMed

    Karp, Christopher L; Lans, Deborah; Esparza, José; Edson, Eleanore B; Owen, Katey E; Wilson, Christopher B; Heaton, Penny M; Levine, Orin S; Rao, Raja

    2015-07-09

    The need to keep vaccines cold in the face of high ambient temperatures and unreliable access to electricity is a challenge that limits vaccine coverage in low and middle-income countries (LMICs). Greater vaccine thermostability is generally touted as the obvious solution. Despite conventional wisdom, comprehensive analysis of the value proposition for increasing vaccine thermostability has been lacking. Further, while significant investments have been made in increasing vaccine thermostability in recent years, no vaccine products have been commercialized as a result. We analyzed the value proposition for increasing vaccine thermostability, grounding the analysis in specific vaccine use cases (e.g., use in routine immunization [RI] programs, or in campaigns) and in the broader context of cold chain technology and country level supply chain system design. The results were often surprising. For example, cold chain costs actually represent a relatively small fraction of total vaccine delivery system costs. Further, there are critical, vaccine use case-specific temporal thresholds that need to be overcome for significant benefits to be reaped from increasing vaccine thermostability. We present a number of recommendations deriving from this analysis that suggest a rational path toward unlocking the value (maximizing coverage, minimizing total system costs) of increased vaccine thermostability, including: (1) the full range of thermostability of existing vaccines should be defined and included in their labels; (2) for new vaccines, thermostability goals should be addressed up-front at the level of the target product profile; (3) improving cold chain infrastructure and supply chain system design is likely to have the largest impact on total system costs and coverage in the short term-and will influence the degree of thermostability required in the future; (4) in the long term, there remains value in monitoring the emergence of disruptive technologies that could remove the

  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. Improving Global Access to New Vaccines: Intellectual Property, Technology Transfer, and Regulatory Pathways

    PubMed Central

    2014-01-01

    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:25211753

  20. [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.

  1. 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.

  2. Safety Profile of the 9-Valent HPV Vaccine: A Combined Analysis of 7 Phase III Clinical Trials.

    PubMed

    Moreira, Edson D; Block, Stan L; Ferris, Daron; Giuliano, Anna R; Iversen, Ole-Erik; Joura, Elmar A; Kosalaraksa, Pope; Schilling, Andrea; Van Damme, Pierre; Bornstein, Jacob; Bosch, F Xavier; Pils, Sophie; Cuzick, Jack; Garland, Suzanne M; Huh, Warner; Kjaer, Susanne K; Qi, Hong; Hyatt, Donna; Martin, Jason; Moeller, Erin; Ritter, Michael; Baudin, Martine; Luxembourg, Alain

    2016-08-01

    The overall safety profile of the 9-valent human papillomavirus (9vHPV) vaccine was evaluated across 7 Phase III studies, conducted in males and females (nonpregnant at entry), 9 to 26 years of age. Vaccination was administered as a 3-dose regimen at day 1, and months 2 and 6. More than 15 000 subjects received ≥1 dose of 9vHPV vaccine. In 2 of the studies, >7000 control subjects received ≥1 dose of quadrivalent HPV (qHPV) vaccine. Serious and nonserious adverse events (AEs) and new medical conditions were recorded throughout the study. Subjects testing positive for pregnancy at day 1 were not vaccinated; those who became pregnant after day 1 were discontinued from further vaccination until resolution of the pregnancy. Pregnancies detected after study start (n = 2950) were followed to outcome. The most common AEs (≥5%) experienced by 9vHPV vaccine recipients were injection-site AEs (pain, swelling, erythema) and vaccine-related systemic AEs (headache, pyrexia). Injection-site AEs were more common in 9vHPV vaccine than qHPV vaccine recipients; most were mild-to-moderate in intensity. Discontinuations and vaccine-related serious AEs were rare (0.1% and <0.1%, respectively). Seven deaths were reported; none were considered vaccine related. The proportions of pregnancies with adverse outcome were within ranges reported in the general population. The 9vHPV vaccine was generally well tolerated in subjects aged 9 to 26 years with an AE profile similar to that of the qHPV vaccine; injection-site AEs were more common with 9vHPV vaccine. Its additional coverage and safety profile support widespread 9vHPV vaccination. Copyright © 2016 by the American Academy of Pediatrics.

  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.

  4. 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

  5. Efficacy and safety of an inactivated vaccine against Salmonid alphavirus (family Togaviridae).

    PubMed

    Karlsen, Marius; Tingbø, Terje; Solbakk, Inge-Tom; Evensen, Øystein; Furevik, Anette; Aas-Eng, Anne

    2012-08-17

    Pancreas disease (PD) in salmonid fish is caused by an infection with Salmonid alphavirus (SAV) and remains as one of the major health problems in the European fish farming industry. Sequence studies have revealed a genetic diversity among viral strains. A subtype of SAV (SAV3) is causing an epizootic in farmed salmonids in Norway. Here we evaluate efficacy and safety of an inactivated virus vaccine based on ALV405, a strain of SAV3 that was isolated from Norwegian salmon. The vaccine provided an average relative percent survival (RPS) of 98.5 in an intraperitoneal challenge model, and induced nearly total protection against PD in a cohabitant challenge model. It provided significant protection against SAV-induced mortality also in a field trial under industrial conditions. Local reactions seen as melanization and adhesions in the visceral cavity were less severe than those induced by two commercial vaccines. Finally, we demonstrated that the protection is not impaired when the ALV405 antigen is combined with other viral or bacterial antigens in a polyvalent vaccine. The results confirm that efficient and safe protection against SAV infection and development of PD is possible using an inactivated virus vaccine, both alone and as a component in a polyvalent vaccine.

  6. A genomics-based approach to assessment of vaccine safety and immunogenicity in children.

    PubMed

    White, Olivia J; McKenna, Katherine L; Bosco, Anthony; H J van den Biggelaar, Anita; Richmond, Peter; Holt, Patrick G

    2012-02-27

    Immune responses to vaccines in infants and young children are typically Th2-biased, giving rise to concerns regarding potential atopy-like side effects, and antagonism of Th1-associated sterilising immunity. Conventional immunological methodology has limited capacity to effectively address these problems because of the inherent complexity of the immune responses involved. In the present study, we sought to develop an unbiased systems biology approach to elucidate superficially similar Th2-associated responses to paediatric vaccines and allergens, and to differentiate between them via gene coexpression network analysis. We demonstrate below that in immune responses to the diptheria/acellular pertussis/tetanus and pneumococcal polysaccharide conjugate vaccines, potentially antagonistic Th1-/IFN-associated and Th2-associated gene networks coexist in an apparent state of dynamic equilibrium, whereas in Th2-dominant allergen-specific responses of atopics the Th1 and IFN networks are respectively disrupted and downregulated. Capacity to detect and interpret these covert differences between responses to vaccines and allergens relies on the use of sophisticated algorithms that underpin coexpression network analysis, which identify genes that function co-ordinately in complex pathways. This methodology has significant potential to identify covert interactions between inflammatory pathways triggered by vaccination, and as such may be a useful tool in prediction of vaccine safety/efficacy.

  7. Safety and preliminary evidence of biological efficacy of a mammaglobin-A DNA vaccine in patients with stable metastatic breast cancer

    PubMed Central

    Tiriveedhi, Venkataswarup; Tucker, Natalia; Herndon, John; Li, Lijin; Sturmoski, Mark; Ellis, Matthew; Ma, Cynthia; Naughton, Michael; Lockhart, A. Craig; Gao, Feng; Fleming, Timothy; Goedegebuure, Peter; Mohanakumar, Thalachallour; Gillanders, William E.

    2014-01-01

    Purpose Mammaglobin-A (MAM-A) is overexpressed in 40–80% of primary breast cancers. We initiated a phase 1 clinical trial of a MAM-A DNA vaccine to evaluate its safety and biological efficacy. Experimental Design Breast cancer patients with stable metastatic disease were eligible for enrollment. Safety was monitored with clinical and laboratory assessments. The CD8 T cell response was measured by ELISPOT, flow cytometry, and cytotoxicity assays. Progression-free survival was described using the Kaplan-Meier product limit estimator. Results Fourteen subjects have been treated with the MAM-A DNA vaccine and no significant adverse events have been observed. Eight of fourteen subjects were HLA-A2+, and the CD8 T cell response to vaccination was studied in detail. Flow cytometry demonstrated a significant increase in the frequency of MAM-A-specific CD8 T cells following vaccination (0.9 ± 0.5% vs. 3.8 ± 1.2%, p < 0.001), and ELISPOT analysis demonstrated an increase in the number of MAM-A-specific IFN-γ-secreting T cells (41 ± 32 vs. 215 ± 67 spm, p < 0.001). Although this study was not powered to evaluate progression-free survival, preliminary evidence suggests that subjects treated with the MAM-A DNA vaccine had improved progression-free survival compared to subjects who met all eligibility criteria, were enrolled in the trial, but were not vaccinated because of HLA phenotype. Conclusion The MAM-A DNA vaccine is safe, capable of eliciting MAM-A-specific CD8 T cell responses, and preliminary evidence suggests improved progression-free survival. Additional studies are required to define the potential of the MAM-A DNA vaccine for breast cancer prevention and/or therapy. PMID:25451106

  8. Improving the safety features of general practice computer systems.

    PubMed

    Avery, Anthony J; Savelyich, Boki S P; Teasdale, Sheila

    2003-01-01

    General practice computer systems already have a number of important safety features. However, there are problems in that general practitioners (GPs) have come to rely on hazard alerts when they are not foolproof. Furthermore, GPs do not know how to make best use of safety features on their systems. There are a number of solutions that could help to improve the safety features of general practice computer systems and also help to improve the abilities of healthcare professionals to use these safety features.

  9. 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.

  10. Quadrivalent human papillomavirus (HPV) vaccine: a review of safety, efficacy, and pharmacoeconomics.

    PubMed

    Pomfret, T C; Gagnon, J M; Gilchrist, A T

    2011-02-01

    The introduction of vaccines has lead to a significant reduction in morbidity and mortality from diseases such as measles, rubella and poliomyelitis, as well as the eradication of smallpox (Ertl HC, Xiang Z (1996) The Journal of Immunology, 156, 3579-3582). A recent vaccine approved by the Food and Drug Administration (FDA) is the recombinant quadrivalent human papillomavirus (HPV) vaccine (Merck, Gardasil®). Concerns raised with this preventive measure include safety and efficacy issues as well as the financial implications. Furthermore, the use of the vaccine in women outside the currently approved age ranges and in adolescent boys and men has also been a source of debate. A review of two licensed HPV vaccines (Gardasil, Merck and Cervarix, GalxoSmithKline) in the light of these issues. Literature searches were conducted using the MEDLINE (1966-December 2008) and PubMed databases in addition to the Centers for Disease Control and Prevention website. Bibliographies of selected references were also evaluated for relevant articles. Published guidelines and press releases were utilized as were the manufacturer's package inserts. The collection of information for this review was limited to the most recently available human data. The HPV quadrivalent vaccine has been effective in the management of HPV by preventing vaccine subtype-related persistent infection and precancerous lesions as evidenced by numerous clinical trials. It is also regarded as a generally safe and well-tolerated vaccine, based on an assessment of reported adverse events submitted through governmental databases and analyzed by independent researchers. The majority of adverse events were non-serious and the vaccine has not been conclusively implicated with serious events. The FDA continues to focus on routine post-marketing surveillance monitoring of reported adverse events. The bivalent vaccine has also been shown to be effective in reported trials. Its adverse effect profile also appears

  11. Vaccination of piglets at 1 week of age with an inactivated Mycoplasma hyopneumoniae vaccine reduces lung lesions and improves average daily gain in body weight.

    PubMed

    Wilson, Stephen; Van Brussel, Leen; Saunders, Gillian; Taylor, Lucas; Zimmermann, Lisa; Heinritzi, Karl; Ritzmann, Mathias; Banholzer, Elisabeth; Eddicks, Matthias

    2012-12-14

    The field efficacy and safety of a single-dose inactivated Mycoplasma hyopneumoniae vaccine, Suvaxyn MH-One, was evaluated in 4-5-day-old piglets on a commercial farm with a history of Mycoplasma disease in Southern Germany. The piglets were injected intramuscularly with the vaccine or saline (control group) and raised under commercial conditions to slaughter weight. The efficacy of the vaccine was determined by comparing the lung lesions associated with infection by M. hyopneumoniae in control and vaccinated pigs post mortem. In this analysis the vaccinated pigs had the lower mean percentage lung lesion at 5% compared to 9% in controls. Of the vaccinated pigs 52.3% were shown to have low levels of lung lesions between 0% and 5% and no more than 5.4% were shown to have levels above 20%. In contrast, the pigs administered saline showed 36.5% in the lower category (0-5%), while 18.3% showed lesions greater than 20%. There were significant differences in the mean body weight of pigs at the final two weight measurements at approximately 21 weeks and 26 weeks of age, with those receiving Suvaxyn MH-One being on average 5 kg heavier at each time point. There was also a significant increase in average daily gain in the vaccinated animals compared to the control group, particularly in the period from vaccination to the final two body weight measurements on day 138 and 166, from weaning at day 28 to the final two body measurements and from mid-way during finishing at day 84 to the final two body weight measurements. Vaccination had no adverse impact on appetite, although small numbers of vaccinated and control pigs did show mild signs of coughing, sneezing, respiratory distress or depression. There was no adverse impact on rectal temperatures and no signs of injection site reactions during the course of the study. We can conclude that vaccination with Suvaxyn MH-One to pigs at less than 1 week of age is effective in reducing lung lesions resulting from M. hyopneumoniae and

  12. 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

    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.

  13. Safety and immunogenicity of a 9-valent HPV vaccine in females 12-26 years of age who previously received the quadrivalent HPV vaccine.

    PubMed

    Garland, Suzanne M; Cheung, Tak-Hong; McNeill, Shelly; Petersen, Lone Kjeld; Romaguera, Josefina; Vazquez-Narvaez, Jorge; Bautista, Oliver; Shields, Christine; Vuocolo, Scott; Luxembourg, Alain

    2015-11-27

    To assess the safety and immunogenicity of the investigational 9-valent (6/11/16/18/31/33/45/52/58) HPV (9vHPV) vaccine in prior recipients of a 3-dose regimen of quadrivalent (6/11/16/18) HPV (qHPV) vaccine. V503-006 was a randomized, double-blinded, safety/tolerability and immunogenicity study of the 9vHPV vaccine in females 12-26 years of age who were previously vaccinated with qHPV vaccine. Subjects were randomized in a 2:1 ratio to receive 3 doses of 9vHPV vaccine (n=618) or saline placebo (n=306) at day 1, month 2, and month 6. Systemic, injection-site and serious adverse experiences (AEs) were monitored. Serum samples were collected at day 1, month 2, and month 7. Anti-HPV 6/11/16/18/31/33/45/52/58 titers were measured using the 9-valent HPV competitive Luminex Immunoassay (cLIA). The frequency of injection-site AEs (days 1-5 following any vaccination) was higher in the 9vHPV vaccine group than in the placebo group (91.1% and 43.9%, respectively). The frequencies of vaccine-related systemic AEs (days 1-15 following any vaccination) were generally comparable between the 2 groups (30.6% in the 9vHPV vaccine group, and 25.9% in the placebo group). One vaccine-related serious AE was reported in each of the 9vHPV vaccine and placebo groups. Few subjects (9vHPV=0.5%; placebo=0%) discontinued due to an AE. At 4 weeks post-dose 3, over 98% of subjects in the 9vHPV vaccine group were seropositive for HPV types 31/33/45/52/58, with marked elevations in cLIA geometric mean titers (GMTs) to these HPV types. Anti-HPV 31/33/45/52/58 GMTs were lower than in subjects administered 9vHPV vaccine who had not previously received qHPV vaccine (based on cross-study analyses); the clinical significance of this difference is unknown. Administration of a 3-dose regimen of 9vHPV vaccine to adolescent girls and young women 12-26 years of age who are prior qHPV vaccine recipients is highly immunogenic with respect to HPV types 31/33/45/52/58 and generally well tolerated. Copyright

  14. Safety and immunogenicity of typhoid fever and yellow fever vaccines when administered concomitantly with quadrivalent meningococcal ACWY glycoconjugate vaccine in healthy adults.

    PubMed

    Alberer, Martin; Burchard, Gerd; Jelinek, Tomas; Reisinger, Emil; Beran, Jiri; Hlavata, Lucie Cerna; Forleo-Neto, Eduardo; Dagnew, Alemnew F; Arora, Ashwani K

    2015-01-01

    Compact and short pre-travel immunization schedules, which include several vaccinations in a single visit, are desirable for many travelers. However, concomitant vaccination could potentially compromise immunogenicity and/or safety of the individual vaccines and, therefore, possible vaccine interferences should be carefully assessed. This article discusses the immunogenicity and safety of travel vaccines for typhoid fever (TF) and yellow fever (YF), when administered with or without a quadrivalent meningococcal glycoconjugate ACWY-CRM vaccine (MenACWY-CRM). Healthy adults (18-≤60 years) were randomized to one of three vaccine regimens: TF + YF + MenACWY-CRM (group I; n = 100), TF + YF (group II; n = 101), or MenACWY-CRM (group III; n = 100). Immunogenicity at baseline and 4 weeks post-vaccination (day 29) was assessed by serum bactericidal assay using human complement (hSBA), enzyme-linked immunosorbent assay (ELISA), or a neutralization test. Adverse events (AEs) and serious adverse events (SAEs) were collected throughout the study period. Non-inferiority of post-vaccination geometric mean concentrations (GMCs) and geometric mean titers (GMTs) was established for TF and YF vaccines, respectively, when given concomitantly with MenACWY-CRM vaccine versus when given alone. The percentages of subjects with seroprotective neutralizing titers against YF on day 29 were similar in groups I and II. The antibody responses to meningococcal serogroups A, C, W-135, and Y were within the same range when MenACWY-CRM was given separately or together with TF and YF vaccines. The percentage of subjects reporting AEs was the same for TF and YF vaccines with or without MenACWY-CRM vaccine. There were no reports of SAEs or AEs leading to study withdrawals. These data provide evidence that MenACWY-CRM can be administered with typhoid Vi polysaccharide vaccine and live attenuated YF vaccine without compromising antibody responses stimulated by the

  15. Safety of the trivalent, cold-adapted influenza vaccine (CAIV-T) in children.

    PubMed

    Piedra, Pedro A

    2002-04-01

    The trivalent, cold-adapted influenza vaccine (CAIV-T, FluMist, Aviron, Mountain View, CA) is a live attenuated influenza virus vaccine that is administered by nasal spray. CAIV-T is efficacious in preventing influenza virus infection. The vaccine was submitted to the Food and Drug Administration for licensure in healthy children and adults. Universal immunization is being considered in children, and an effective vaccine with minimal adverse reactions is thus required. The published studies on the safety of CAIV-T in children reviewed in this article were clinical trials sponsored by the National Institutes of Health (NIH) conducted in children from 1975 to 1991, clinical trials from 1991 to 1993 sponsored by a cooperative agreement between NIH and Wyeth-Ayerst Research, and clinical trials from 1995 to the present sponsored by a cooperative agreement between NIH and Aviron. Safety assessments included the occurrence of: 1) specific influenza-like symptoms, unexpected symptoms, and use of medications within the first 10 days after vaccination; 2) acute illness and use of medication within 11 to 42 days postvaccination; 3) serious adverse events and rare events within 42 days after vaccination; 4) healthcare utilization within 14 days after vaccination; and 5) acute respiratory symptoms with annual sequential vaccine doses. CAIV-T was safe and well-tolerated. Transient, mild respiratory symptoms were observed in a minority (10%-15%) of children and primarily with the first CAIV-T dose. Vomiting and abdominal pain occurred in fewer than 2 percent of CAIV-T recipients. The gastrointestinal symptoms were mild and of short duration. An excess of illness or use of medication was not observed after the 10th day of vaccination. Sequential annual doses of CAIV-T were well-tolerated and not associated with increased reactogenicity. CAIV-T did not cause an increase in healthcare utilization. Thus CAIV-T is safe in healthy children and should complement the use of inactivated

  16. The safety and immunogenicity of Quadrivalent HPV (qHPV) vaccine in systemic lupus erythematosus.

    PubMed

    Dhar, J Patricia; Essenmacher, Lynnette; Dhar, Renee; Magee, Ardella; Ager, Joel; Sokol, Robert J

    2017-05-09

    This study evaluated the safety and immunogenicity of qHPV vaccine in SLE. Subjects: 34 women ages 19-50years (yrs.) with mild to moderate SLE & minimally active or inactive SLE received qHPV vaccine at the standard dosing schedule. active SLE disease (SELENA-SLEDAI>2), history of severe SLE disease, deep venous thrombosis, on >400mg/day of hydroxychloroquine, on >15mg/day of prednisone, or active infections. Patients were monitored for adverse events (AE), SLE flare, generation of thrombogenic antibodies and thrombosis. Antibody (Ab) levels to HPV 6, 11, 16 & 18 were measured by HPV competitive Luminex Immunoassay and Geometric Mean Titers (GMTs) were calculated for each HPV type. Seroconversion was assessed for those seronegative at baseline. The women in the study: African-American (79%), mean age=38.1years, mean age at diagnosis of SLE=28.6years, 35.3% had a history of smoking, 91% had 4 or more sexual partners, 50% had a history of sexually transmitted diseases, and 27.3% used condoms on a regular basis. Vaccine site reactions (VSRs) occurred in 62%, all mild. Ninety-seven percent experienced at least 1 non vaccine adverse event (nvAE) with a total of 493 nvAEs in 33 patients, of which 90% were mild and none were related to vaccine or SLE. There were 9 serious AEs, none were related to vaccine or SLE, all resolved. No patient experienced an SLE flare, thrombosis, or generation of thrombogenic antibodies. Seroconversion rate was 100% with mean GMTs comparable to Gardasil® package insert data. In this SLE vaccine study, qHPV vaccine was generally safe, well tolerated, and highly immunogenic. This clinical trial is registered on Clinical Trials.gov under number, NCT01741012 and was conducted under the FDA IND BB14113. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Randomized trial to compare the safety and immunogenicity of CSL Limited's 2009 trivalent inactivated influenza vaccine to an established vaccine in United States children.

    PubMed

    Brady, Rebecca C; Hu, Wilson; Houchin, Vonda G; Eder, Frank S; Jackson, Kenneth C; Hartel, Gunter F; Sawlwin, Daphne C; Albano, Frank R; Greenberg, Michael

    2014-12-12

    A trivalent inactivated influenza vaccine (CSL's TIV, CSL Limited) was licensed under USA accelerated approval regulations for use in persons≥18 years. We performed a randomized, observer-blind study to assess the safety and immunogenicity of CSL's TIV versus an established US-licensed vaccine in a population≥6 months to <18 years of age. Subjects were stratified as follows: Cohort A (≥6 months to <3 years); Cohort B (≥3 years to <9 years); and Cohort C (≥9 years to <18 years). The subject's age and influenza vaccination history determined the dosing regimen (one or two vaccinations). Subjects received CSL's TIV (n=739) or the established vaccine (n=735) in the autumn of 2009. Serum hemagglutination-inhibition titers were determined pre-vaccination and 30 days after the last vaccination. No febrile seizures or other vaccine-related SAEs were reported. After the first vaccination for Cohorts A and B, respectively, the relative risks of fever were 2.73 and 2.32 times higher for CSL's TIV compared to the established vaccine. Irritability and loss of appetite (for Cohort A) and malaise (for Cohort B) were also significantly higher for CSL's TIV compared to the established vaccine. Post-vaccination geometric mean titers (GMTs) for CSL's TIV versus the established vaccine were 385.49 vs. 382.45 for H1N1; 669.13 vs. 705.61 for H3N2; and 100.65 vs. 93.72 for B. CSL's TIV demonstrated immunological non-inferiority to the established vaccine in all cohorts.

  18. Research on vaccines during pregnancy: protocol design and assessment of safety.

    PubMed

    Munoz, Flor M; Sheffield, Jeanne S; Beigi, Richard H; Read, Jennifer S; Swamy, Geeta K; Jevaji, Indira; Rasmussen, Sonja A; Edwards, Kathryn M; Fortner, Kimberly B; Patel, Shital M; Spong, Catherine Y; Ault, Kevin; Heine, R Philips; Nesin, Mirjana

    2013-09-13

    The Division of Microbiology and Infectious Diseases at the National Institute of Allergy and Infectious Diseases, National Institutes of Health organized a series of conferences, entitled "Enrolling Pregnant Women in Clinical Trials of Vaccines and Therapeutics", to discuss study design and the assessment of safety in clinical trials conducted in pregnant women. A panel of experts was charged with developing guiding principles for the design of clinical trials and the assessment of safety of vaccines during pregnancy. Definitions and a grading system to evaluate local and systemic reactogenicity, adverse events, and other events associated with pregnancy and delivery were developed. The purpose of this report is to provide investigators interested in vaccine research in pregnancy with a basic set of tools to design and implement maternal immunization studies which may be conducted more efficiently using consistent definitions and grading of adverse events to allow the comparison of safety reports from different trials. These guidelines and safety assessment tools may be modified to meet the needs of each particular protocol based on evidence collected as investigators use them in clinical trials in different settings and share their findings and expertise.

  19. Improved formulation and lyophilization cycle for rBCG vaccine.

    PubMed

    Jin, Tom H; Nguyen, Lisa; Qu, Tianli; Tsao, Eric

    2011-06-24

    To improve the conventional BCG vaccine in cake appearance and integrity, a new formulation with corresponding freeze drying cycle was developed for a recombinant BCG vaccine. The new formulation contains mannitol as a bulking agent, and trehalose, sucrose and sodium glutamate as stabilizers. The formulation and freeze drying cycle were tested with different super cooling rates and secondary drying temperatures, with or without an annealing process. Thermodynamic behavior was characterized using differential scanning calorimetry (DSC). Varying the secondary drying temperature and presence/absence of an annealing step caused marked differences in cake thermodynamic profiles irrespective of different cooling rates. The annealing process allowed efficient crystallization of the mannitol. Failure to crystallize the bulking agent had the potential to depress the Tg' and compromise storage stability in the final lyophile by crystallizing from the solid during storage, even when the secondary drying temperature was as high as 40°C. The improved formulation and freeze drying cycle resulted in good recovery of 53.2% during lyophilization and a higher survival rate of 61.7% in an accelerated stability study than the conventional BCG formulation and cycle. In summary, full crystallization was necessary for the mannitol bulking formulation. The freeze dried rBCG vials obtained using the formulation and drying cycle developed here met the requirements of BCG vaccine in good cake appearance, high viability post freeze drying and heat stability during storage. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. A Pre-Clinical Safety Evaluation of SBP (HBsAg-Binding Protein) Adjuvant for Hepatitis B Vaccine.

    PubMed

    Wang, Jingbo; Su, Caixia; Liu, Rui; Liu, Baoxiu; Khan, Inam Ullah; Xie, Jun; Zhu, Naishuo

    2017-01-01

    Although adjuvants are a common component of many vaccines, there are few adjuvants licensed for use in humans due to concerns about their toxic effects. There is a need to develop new and safe adjuvants, because some existing vaccines have low immunogenicity among certain patient groups. In this study, SBP, a hepatitis B surface antigen binding protein that was discovered through screening a human liver cDNA expression library, was introduced into hepatitis B vaccine. A good laboratory practice, non-clinical safety evaluation was performed to identify the side effects of both SBP and SBP-adjuvanted hepatitis B vaccine. The results indicate that SBP could enhance the HBsAg-specific immune response, thus increasing the protection provided by the hepatitis B vaccine. The safety data obtained here warrant further investigation of SBP as a vaccine adjuvant.

  1. A Pre-Clinical Safety Evaluation of SBP (HBsAg-Binding Protein) Adjuvant for Hepatitis B Vaccine

    PubMed Central

    Wang, Jingbo; Su, Caixia; Liu, Rui; Liu, Baoxiu; Khan, Inam Ullah; Xie, Jun; Zhu, Naishuo

    2017-01-01

    Although adjuvants are a common component of many vaccines, there are few adjuvants licensed for use in humans due to concerns about their toxic effects. There is a need to develop new and safe adjuvants, because some existing vaccines have low immunogenicity among certain patient groups. In this study, SBP, a hepatitis B surface antigen binding protein that was discovered through screening a human liver cDNA expression library, was introduced into hepatitis B vaccine. A good laboratory practice, non-clinical safety evaluation was performed to identify the side effects of both SBP and SBP-adjuvanted hepatitis B vaccine. The results indicate that SBP could enhance the HBsAg-specific immune response, thus increasing the protection provided by the hepatitis B vaccine. The safety data obtained here warrant further investigation of SBP as a vaccine adjuvant. PMID:28103328

  2. 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

  3. Immunogenicity and safety of a quadrivalent meningococcal polysaccharide CRM conjugate vaccine in infants and toddlers.

    PubMed

    Tregnaghi, Miguel; Lopez, Pio; Stamboulian, Daniel; Graña, Gabriela; Odrljin, Tatjana; Bedell, Lisa; Dull, Peter M

    2014-09-01

    This phase III study assessed the safety and immunogenicity of MenACWY-CRM, a quadrivalent meningococcal conjugate vaccine, administered with routine vaccines starting at 2 months of age. Healthy infants received MenACWY-CRM in a two- or three-dose primary infant series plus a single toddler dose. In addition, a two-dose toddler catch-up series was evaluated. Immune responses to MenACWY-CRM were assessed for serum bactericidal activity with human complement (hSBA). Reactogenicity and safety results were collected systematically. After a full infant/toddler series or two-dose toddler catch-up series, MenACWY-CRM elicited immune responses against the four serogroups in 94-100% of subjects. Noninferiority of the two- versus three-dose MenACWY-CRM infant dosing regimen was established for geometric mean titers for all serogroups. Following the three-dose infant primary series, 89-98% of subjects achieved an hSBA ≥ 8 across all serogroups. Immune responses to concomitant routine vaccines given with MenACWY-CRM were noninferior to responses to routine vaccines alone, except for pertactin after the two-dose infant series. Noninferiority criteria were met for all concomitant antigens after the three-dose infant series. MenACWY-CRM vaccination regimens in infants and toddlers were immunogenic and well tolerated. No clinically meaningful effects of concomitant administration with routine infant and toddler vaccines were observed. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. Immunogenicity, safety and tolerability of inactivated trivalent influenza vaccine in overweight and obese children.

    PubMed

    Esposito, Susanna; Giavoli, Claudia; Trombetta, Claudia; Bianchini, Sonia; Montinaro, Valentina; Spada, Anna; Montomoli, Emanuele; Principi, Nicola

    2016-01-02

    Obesity may be a risk factor for increased hospitalization and deaths from infections due to respiratory pathogens. Additionally, obese patients appear to have impaired immunity after some vaccinations. To evaluate the immunogenicity, safety and tolerability of an inactivated trivalent influenza vaccine (TIV) in overweight and obese children, 28 overweight/obese pediatric patients and 23 healthy normal weight controls aged 3-14 years received a dose of TIV. Four weeks after vaccine administration, significantly higher seroprotection rates against the A/H1N1 strain were observed among overweight/obese children compared with normal weight controls (p<0.05). Four months after vaccination, similar or slightly higher seroconversion and seroprotection rates against the A/H1N1 and A/H3N2 strains were detected in overweight/obese than in normal weight children, whereas significantly higher rates of seroconversion and seroprotection against the B strain were found in overweight/obese patients than in normal weight controls (p<0.05 for seroconversion and seroprotection). Geometric mean titers (GMTs) and fold increase against B strains were significantly higher in overweight/obese patients than in normal weight controls 4 months after vaccine administration (p<0.01 for GMT values and p<0.05 for fold increase). The frequency of local and systemic reactions was similar between the groups, and there were no serious adverse events. The results of this study indicate that in overweight and obese children, antibody response to TIV administration is similar or slightly higher than that evidenced in normal weight subjects of similar age and this situation persists for at least 4 months after vaccine administration in the presence of a favorable safety profile.

  5. Prospective safety monitoring of Haemophilus influenzae type b and heptavalent pneumococcal conjugate vaccines in Kagoshima, Japan.

    PubMed

    Nishi, Junichiro; Tokuda, Koichi; Imuta, Naoko; Minami, Taketsugu; Kawano, Yoshifumi

    2013-01-01

    Haemophilus influenzae type b (Hib) conjugate vaccine (PRP-T) and heptavalent pneumococcal conjugate vaccine (PCV7) were introduced in Japan in December 2008 and February 2010, respectively. The concurrent administration of these vaccines is routinely performed worldwide. However, the safety of the simultaneous administration of these vaccines has not been fully evaluated in Japan, because it has rarely been performed thus far. We conducted a 2-year prospective, observational, multicenter study on PRP-T and PCV7 safety from February 2009 through January 2011 in 29 facilities located in Kagoshima Prefecture, Japan. Objective severe adverse events included anaphylactoid reaction, encephalitis/encephalopathy, neurological events, severe focal reactions, systemic eruption/urticaria, fever above 39℃ within 2 days after inoculation, and other complications requiring hospitalization. The incidences of these events for PRP-T and PCV7 administration were 0.68% (76/11,197) and 0.92% (28/3,049), respectively. No deaths or subsequent complications were reported during the course of the study. There was no significant difference in the incidence of severe adverse events between the single and co-administration groups for both vaccines: PRP-T, 0.55% (31/5,662) versus 0.81% (45/5,535; P = 0.11); PCV7, 0.88% (11/1,247) versus 0.94% (17/1,802; P = 0.86). These results suggest that the simultaneous administration of vaccines including PRP-T and/or PCV7 does not increase the incidence of severe adverse events in Japanese children.

  6. Safety and immunogenicity of a live attenuated mumps vaccine: a phase I clinical trial.

    PubMed

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

    2014-01-01

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

  7. Safety, Tolerability and Immunogenicity of Pentavalent Rotavirus Vaccine Manufactured by a Modified Process.

    PubMed

    Martinón-Torres, Federico; Greenberg, David; Varman, Meera; Killar, John A; Hille, Darcy; Strable, Erica L; Stek, Jon E; Kaplan, Susan S

    2017-04-01

    Rotavirus is the leading cause of severe diarrhea in infants and young children. The current formulation of pentavalent rotavirus vaccine (RV5) must be stored refrigerated at 2-8°C. A modified formulation of RV5 (RV5mp) has been developed with stability at 37°C for 7 days and an expiry extended to 36 months when stored at 2-8°C. This study (ClinicalTrials.gov identifier: NCT01600092; EudraCT number: 2012-001611-23) evaluated the safety, tolerability and immunogenicity of RV5mp versus the currently marketed RV5 in infants. To maintain blinding, both vaccine formulations were stored refrigerated at 2-8°C for the duration of the study. Immunogenicity endpoints were (1) serum neutralizing antibody titers to human rotavirus serotypes G1, G2, G3, G4 and P1A[8] and (2) proportion of subjects with a ≥3-fold rise from baseline for serum neutralizing antibody to human rotavirus serotypes G1, G2, G3, G4 and P1A[8] and serum antirotavirus immunoglobulin A. The RV5mp group (n = 505) and RV5 group (n = 509) had comparable safety profiles. There were no deaths and no vaccine-related serious adverse events in this study. With respect to immunogenicity, RV5mp was noninferior compared with RV5. Serum neutralizing antibody responses by country and breast-feeding status were generally consistent with the overall results. RV5mp enhances storage requirements while maintaining the immunogenicity and safety profile of the currently licensed RV5. A vaccine that is stable at room temperature may be more convenient for vaccinators, particularly in places where the cold chain is unreliable, and ultimately will permit more widespread use.

  8. Safety and Immunogenicity of an Anti-Zika Virus DNA Vaccine - Preliminary Report.

    PubMed

    Tebas, Pablo; Roberts, Christine C; Muthumani, Kar; Reuschel, Emma L; Kudchodkar, Sagar B; Zaidi, Faraz I; White, Scott; Khan, Amir S; Racine, Trina; Choi, Hyeree; Boyer, Jean; Park, Young K; Trottier, Sylvie; Remigio, Celine; Krieger, Diane; Spruill, Susan E; Bagarazzi, Mark; Kobinger, Gary P; Weiner, David B; Maslow, Joel N

    2017-10-04

    Background Although Zika virus (ZIKV) infection is typically self-limiting, other associated complications such as congenital birth defects and the Guillain-Barré syndrome are well described. There are no approved vaccines against ZIKV infection. Methods In this phase 1, open-label clinical trial, we evaluated the safety and immunogenicity of a synthetic, consensus DNA vaccine (GLS-5700) encoding the ZIKV premembrane and envelope proteins in two groups of 20 participants each. The participants received either 1 mg or 2 mg of vaccine intradermally, with each injection followed by electroporation (the use of a pulsed electric field to introduce the DNA sequence into cells) at baseline, 4 weeks, and 12 weeks. Results The median age of the participants was 38 years, and 60% were women; 78% were white, and 22% black; in addition, 30% were Hispanic. At the interim analysis at 14 weeks (i.e., after the third dose of vaccine), no serious adverse events were reported. Local reactions at the vaccination site (e.g., injection-site pain, redness, swelling, and itching) occurred in approximately 50% of the participants. After the third dose of vaccine, binding antibodies (as measured on enzyme-linked immunosorbent assay) were detected in all the participants, with geometric mean titers of 1642 and 2871 in recipients of 1 mg and 2 mg of vaccine, respectively. Neutralizing antibodies developed in 62% of the samples on Vero-cell assay. On neuronal-cell assay, there was 90% inhibition of ZIKV infection in 70% of the serum samples and 50% inhibition in 95% of the samples. The intraperitoneal injection of postvaccination serum protected 103 of 112 IFNAR knockout mice (bred with deletion of genes encoding interferon-α and interferon-β receptors) (92%) that were challenged with a lethal dose of ZIKV-PR209 strain; none of the mice receiving baseline serum survived the challenge. Survival was independent of the neutralization titer. Conclusions In this phase 1, open-label clinical

  9. Immunogenicity and safety of an inactivated trivalent split influenza virus vaccine in young children with recurrent wheezing.

    PubMed

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

    2013-06-01

    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.

  10. Pre-clinical efficacy and safety of experimental vaccines based on non-replicating vaccinia vectors against yellow fever.

    PubMed

    Schäfer, Birgit; Holzer, Georg W; Joachimsthaler, Alexandra; Coulibaly, Sogue; Schwendinger, Michael; Crowe, Brian A; Kreil, Thomas R; Barrett, P Noel; Falkner, Falko G

    2011-01-01

    Currently existing yellow fever (YF) vaccines are based on the live attenuated yellow fever virus 17D strain (YFV-17D). Although, a good safety profile was historically attributed to the 17D vaccine, serious adverse events have been reported, making the development of a safer, more modern vaccine desirable. A gene encoding the precursor of the membrane and envelope (prME) protein of the YFV-17D strain was inserted into the non-replicating modified vaccinia virus Ankara and into the D4R-defective vaccinia virus. Candidate vaccines based on the recombinant vaccinia viruses were assessed for immunogenicity and protection in a mouse model and compared to the commercial YFV-17D vaccine. The recombinant live vaccines induced γ-interferon-secreting CD4- and functionally active CD8-T cells, and conferred full protection against lethal challenge already after a single low immunization dose of 10(5) TCID(50). Surprisingly, pre-existing immunity against wild-type vaccinia virus did not negatively influence protection. Unlike the classical 17D vaccine, the vaccinia virus-based vaccines did not cause mortality following intracerebral administration in mice, demonstrating better safety profiles. The non-replicating recombinant YF candidate live vaccines induced a broad immune response after single dose administration, were effective even in the presence of a pre-existing immunity against vaccinia virus and demonstrated an excellent safety profile in mice.

  11. 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.

  12. An update on safety studies of SAD B19 rabies virus vaccine in target and non-target species.

    PubMed Central

    Vos, A.; Neubert, A.; Aylan, O.; Schuster, P.; Pommerening, E.; Müller, T.; Chivatsi, D. C.

    1999-01-01

    SAD B19 is an attenuated vaccine virus for oral vaccination of carnivores against rabies. The safety of SAD B19 was investigated in 16 animal species by different routes of administration. During the observation period all animals given the vaccine virus, irrespective of the route of administration, did not show any clinical signs of rabies, with the exception of certain rodent species. In these animals a low residual pathogenicity was observed, however transmission of the vaccine virus to control animals was not demonstrable. No vaccine virus could be detected in the saliva of the six mammal species examined. Furthermore, the genetical stability was shown for SAD B19 through passaging in neural tissue of dogs, foxes and mice. From the results presented here on innocuity and stability, it can be concluded that SAD B19 rabies vaccine is suitable for oral vaccination campaigns for carnivores against rabies. PMID:10487653

  13. Alternative methods to compare safety of live-attenuated respiratory Newcastle disease vaccines in young chicks.

    PubMed

    Malo, Aris; de Wit, Sjaak; Swart, Wim A J M; Cook, Jane K A

    2017-09-02

    The work reported here is an initial attempt to find an alternative method by which the safety of live-attenuated Newcastle disease virus (NDV) vaccines for the respiratory tract of young chickens can be assessed. The current recommended methods involve either the subjective assessment of respiratory signs, or raise ethical concerns, as in the case of the intracerebral pathogenicity index. The two methods considered here were the use of tracheal organ cultures to assess the level of ciliostasis which the vaccines caused to the ciliated epithelium of the trachea and the incorporation of a pathogenic strain of Escherichia coli in the inoculum in order to induce colibacillosis. Both methods were successful in confirming the safety of the two vaccines. However, these results are only preliminary and more studies need to be performed to determine whether one or both methods have potential, either to replace the existing statutory tests, or provide a test which might be useful during the development stages of a new live-attenuated NDV vaccine. © British Veterinary Association (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  14. Immunogenicity and safety of a CRM-conjugated meningococcal ACWY vaccine administered concomitantly with routine vaccines starting at 2 months of age.

    PubMed

    Nolan, Terry M; Nissen, Michael D; Naz, Aftab; Shepard, Julie; Bedell, Lisa; Hohenboken, Matthew; Odrljin, Tatjana; Dull, Peter M

    2014-01-01

    Infants are at the highest risk for meningococcal disease and a broadly protective and safe vaccine is an unmet need in this youngest population. We evaluated the immunogenicity and safety of a 4-dose infant/toddler regimen of MenACWY-CRM given at 2, 4, 6, and 12 months of age concomitantly with pentavalent diphtheria-tetanus-acellular pertussis-Hemophilus influenzae type b-inactivated poliovirus-combination vaccine (DTaP-IPV/Hib), hepatitis B vaccine (HBV), 7- or 13-valent conjugate pneumococcal vaccine (PCV), and measles, mumps, and rubella vaccine (MMR). Four doses of MenACWY-CRM induced hSBA titers ≥8 in 89%, 95%, 97%, and 96% of participants against serogroups A, C, W-135, and Y, respectively. hSBA titers ≥8 were present in 76-98% of participants after the first 3 doses. A categorical linear analysis incorporating vaccine group and study center showed responses to routine vaccines administered with MenACWY-CRM were non-inferior to routine vaccines alone, except for seroresponse to the pertussis antigen fimbriae. The reactogenicity profile was not affected when MenACWY-CRM was administered concomitantly with routine vaccines. MenACWY-CRM administered with routine concomitant vaccinations in young infants was well tolerated and induced highly immunogenic responses against each of the serogroups without significant interference with the immune responses to routine infant vaccinations. Healthy 2 month old infants were randomized to receive MenACWY-CRM with routine vaccines (n = 258) or routine vaccines alone (n = 271). Immunogenicity was assessed by serum bactericidal assay using human complement (hSBA). Medically attended adverse events (AEs), serious AEs (SAEs) and AEs leading to study withdrawal were collected throughout the study period.

  15. Immunogenicity and safety of a CRM-conjugated meningococcal ACWY vaccine administered concomitantly with routine vaccines starting at 2 months of age

    PubMed Central

    Nolan, Terry M; Nissen, Michael D; Naz, Aftab; Shepard, Julie; Bedell, Lisa; Hohenboken, Matthew; Odrljin, Tatjana; Dull, Peter M

    2014-01-01

    Background: Infants are at the highest risk for meningococcal disease and a broadly protective and safe vaccine is an unmet need in this youngest population. We evaluated the immunogenicity and safety of a 4-dose infant/toddler regimen of MenACWY-CRM given at 2, 4, 6, and 12 months of age concomitantly with pentavalent diphtheria-tetanus-acellular pertussis-Hemophilus influenzae type b-inactivated poliovirus-combination vaccine (DTaP-IPV/Hib), hepatitis B vaccine (HBV), 7- or 13-valent conjugate pneumococcal vaccine (PCV), and measles, mumps, and rubella vaccine (MMR). Results: Four doses of MenACWY-CRM induced hSBA titers ≥8 in 89%, 95%, 97%, and 96% of participants against serogroups A, C, W-135, and Y, respectively. hSBA titers ≥8 were present in 76–98% of participants after the first 3 doses. A categorical linear analysis incorporating vaccine group and study center showed responses to routine vaccines administered with MenACWY-CRM were non-inferior to routine vaccines alone, except for seroresponse to the pertussis antigen fimbriae. The reactogenicity profile was not affected when MenACWY-CRM was administered concomitantly with routine vaccines. Conclusion: MenACWY-CRM administered with routine concomitant vaccinations in young infants was well tolerated and induced highly immunogenic responses against each of the serogroups without significant interference with the immune responses to routine infant vaccinations. Methods: Healthy 2 month old infants were randomized to receive MenACWY-CRM with routine vaccines (n = 258) or routine vaccines alone (n = 271). Immunogenicity was assessed by serum bactericidal assay using human complement (hSBA). Medically attended adverse events (AEs), serious AEs (SAEs) and AEs leading to study withdrawal were collected throughout the study period. PMID:24220326

  16. 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. © RSNA, 2015.

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

    PubMed

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

    2015-11-01

    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.

  19. Despite small improvement, black nursing home residents remain less likely than whites to receive flu vaccine.

    PubMed

    Cai, Shubing; Feng, Zhanlian; Fennell, Mary L; Mor, Vincent

    2011-10-01

    Vaccination is a key deterrent to influenza and its related complications and outcomes, including hospitalization and death. Using 2006-09 data, we found a small improvement in vaccination rates among nursing home residents, particularly for blacks. Nonetheless, overall vaccination rates remained well below the 90 percent target for high-quality care, and black nursing home residents remained less likely to be vaccinated than whites. Blacks were less likely to be vaccinated than were whites in the same facility and were more likely to live in facilities with lower vaccination rates. Blacks were also more likely to be noted as refusing vaccination. Strategies are needed to ensure that facilities offer vaccination to all residents and to make vaccination more acceptable to black residents and their families.

  20. Current status and future directions of post-marketing vaccine safety monitoring with focus on USA and Europe.

    PubMed

    Bonhoeffer, Jan; Black, Steve; Izurieta, Hector; Zuber, Patrick; Sturkenboom, Miriam

    2012-09-01

    Vaccine safety research is a key component of public health programs. Regulatory agencies need to be able to make informed decisions. Public health authorities need to respond to vaccine concerns before they turn into large scale scares reducing vaccine uptake and derailing immunization programs. Several post-licensure vaccine safety monitoring systems have been established in the USA and Europe, and methods such as rapid cycle analysis have been developed for real-time detection and analysis of safety issues. Accurate and reliable vaccine product testing and monitoring requires high quality data of populations of 100 million and above depending on the frequency of the event, vaccine coverage, and the time pressure during which data need to be generated. This requires post-licensure safety studies utilizing large linked population based databases of exposure and outcomes. Harmonized methods for development and linkage of these databases across countries need to be further developed, validated and implemented. Concerted action between the US and Europe could move vaccine safety monitoring to today's level of requirements globally and should be pursued.

  1. 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

  2. Safety and Immunogenicity of a Live-Attenuated Junin (Argentine Hemorrhagic Fever) Vaccine in Rhesus Macaques

    DTIC Science & Technology

    1993-01-01

    virus from animals in every dose group. vetted 1-2.5 weeks after initial virus recovery. That the viruses recovered were Junin virus is certain: all...wild-type strains (LI 1.25). When vivo neutralization and virus clearance are com- we used this system to examine viruses recovered plex and multi...Fredertcktfarniand Abstract. The safety and immunogenicity of Candid #1. a live-attenuated Junin- virus vaccine, were evaluated in rhesus macaques. Candid #1 was

  3. Active immunotherapy for cancer patients using tumor lysate pulsed dendritic cell vaccine: a safety study.

    PubMed

    Ovali, E; Dikmen, T; Sonmez, M; Yilmaz, M; Unal, A; Dalbasti, T; Kuzeyli, K; Erturk, M; Omay, S B

    2007-06-01

    Cancer vaccine therapy represents a promising therapeutical option. Consistently, with these new treatment strategies, the use of dendritic cell vaccines is becoming increasingly widespread and currently in the forefront for cancer treatment. The purpose of this study was to evaluate the feasibility and safety of tumor lysate-pulsed dendritic cell (DC) vaccine in patients with advanced cancers. For this purpose, eighteen patients with relapsed or refractory cancer were vaccinated with peripheral monocyte-derived DCs generated with GM-CSF and IL-4, and pulsed consequently with 100 microg/ml of tumor lysate before maturation in culture in the presence of IL-1beta, PGE2 and TNF alpha for two days. The first two vaccinations were given intradermally every two weeks while further injections were given monthly. Tumor lysate-pulsed dendritic cell injections were well-tolerated in all patients with no more than grade 1 injection-related toxicity. Local inflammatory response was mainly erythematous which subsided in 48 hrs time. No end organ toxicity or autoimmune toxicity was identified. Clinical responses observed in our study were satisfactory for a phase I clinical study. We observed 4 (22%) objective clinical responses. These responses are significantly correlated with delayed type hypersensitivity testing (DTH) (p < 0.01). The results showed that this active immunotherapy is feasible, safe, and may be capable of eliciting immune responses against cancer.

  4. Immunogenicity and safety of recombinant rabies viruses used for oral vaccination of stray dogs and wildlife.

    PubMed

    Faber, M; Dietzschold, B; Li, J

    2009-08-01

    Rabies is a zoonotic disease and stray dogs, wild carnivores and bats are the natural reservoirs of rabies. Oral immunization with live vaccines is the only practical approach to eradicate rabies in free ranging terrestrial animals. We have developed the double glycoprotein (G) rabies virus (RV) variant SPBNGAS-GAS that has great promise to be used as a live-attenuated vaccine. Oral immunization of rodents and several target animal species with this double G RV variant resulted in the induction of protective immunity, superior to that induced by a single RV G variant (SPBNGAS). The high oral efficacy of SPBNGAS-GAS is likely because of its increased ability to infect monocytes or immature dendritic cells (DCs), thereby inducing their conversion into mature DCs. Furthermore, infection of DCs with the double G variant resulted in a strong up-regulation of the expression of genes related to the NFjB signalling pathway including IFN-α and IFN-β, which might underlie the protection conferred by this live RV vaccine. A potential problem associated with the use of live RVs for oral vaccination could rest in the possibility of reversion to the pathogenic phenotype because of the high mutation rate characteristic for all RNA viruses. In this respect, the presence of a second non-pathogenic G gene decreases considerably the risk of reversion to the pathogenic phenotype because a nonpathogenic G is dominant over a pathogenic G in determining the pathogenicity of the double G RV variant. Because of its excellent efficacy and safety, the SPBNGAS-GAS vaccine may provide a distinct advantage over other live RV vaccine in its ability to vaccinate a broad range of mammalian species.

  5. Leadership, safety climate, and continuous quality improvement: impact on process quality and patient safety.

    PubMed

    McFadden, Kathleen L; Stock, Gregory N; Gowen, Charles R

    2015-01-01

    Successful amelioration of medical errors represents a significant problem in the health care industry. There is a need for greater understanding of the factors that lead to improved process quality and patient safety outcomes in hospitals. We present a research model that shows how transformational leadership, safety climate, and continuous quality improvement (CQI) initiatives are related to objective quality and patient safety outcome measures. The proposed framework is tested using structural equation modeling, based on data collected for 204 hospitals, and supplemented with objective outcome data from the Centers for Medicare and Medicaid Services. The results provide empirical evidence that a safety climate, which is connected to the chief executive officer's transformational leadership style, is related to CQI initiatives, which are linked to improved process quality. A unique finding of this study is that, although CQI initiatives are positively associated with improved process quality, they are also associated with higher hospital-acquired condition rates, a measure of patient safety. Likewise, safety climate is directly related to improved patient safety outcomes. The notion that patient safety climate and CQI initiatives are not interchangeable or universally beneficial is an important contribution to the literature. The results confirm the importance of using CQI to effectively enhance process quality in hospitals, and patient safety climate to improve patient safety outcomes. The overall pattern of findings suggests that simultaneous implementation of CQI initiatives and patient safety climate produces greater combined benefits.

  6. Leadership, safety climate, and continuous quality improvement: impact on process quality and patient safety.

    PubMed

    McFadden, Kathleen L; Stock, Gregory N; Gowen, Charles R

    2014-10-01

    Successful amelioration of medical errors represents a significant problem in the health care industry. There is a need for greater understanding of the factors that lead to improved process quality and patient safety outcomes in hospitals. We present a research model that shows how transformational leadership, safety climate, and continuous quality improvement (CQI) initiatives are related to objective quality and patient safety outcome measures. The proposed framework is tested using structural equation modeling, based on data collected for 204 hospitals, and supplemented with objective outcome data from the Centers for Medicare and Medicaid Services. The results provide empirical evidence that a safety climate, which is connected to the chief executive officer's transformational leadership style, is related to CQI initiatives, which are linked to improved process quality. A unique finding of this study is that, although CQI initiatives are positively associated with improved process quality, they are also associated with higher hospital-acquired condition rates, a measure of patient safety. Likewise, safety climate is directly related to improved patient safety outcomes. The notion that patient safety climate and CQI initiatives are not interchangeable or universally beneficial is an important contribution to the literature. The results confirm the importance of using CQI to effectively enhance process quality in hospitals, and patient safety climate to improve patient safety outcomes. The overall pattern of findings suggests that simultaneous implementation of CQI initiatives and patient safety climate produces greater combined benefits.

  7. Importance of Vaccine Safety in Children with Chronic Conditions--Experience at the Scientific Centre for Children's Health in Moscow, Russia.

    PubMed

    Grechukha, Tatiana A; Galitskaya, Marina G; Namazova-Baranova, Leyla S

    2015-01-01

    The risk of severe disease outcomes and complications of infectious diseases remains markedly increased in children and adolescents with chronic conditions. Specialized pediatric healthcare aims to improve quality of life in this high-risk group. One of the most important measures to achieve this goal is to improve immunization rates in this vulnerable population. This article aims to provide insight into models for the integration of infectious disease prevention into specialized healthcare for children with chronic conditions, by the example of the Department of Vaccines and Disease Prevention in Children with Chronic Conditions in Moscow, Russian Federation. The article highlights the importance of vaccine safety and effectiveness research in children with chronic conditions. Useful strategies for the optimization of vaccination rates in this population are presented, along with suggestions for the development of individual immunization schedules for different disease conditions.

  8. Vaccine adverse event text mining system for extracting features from vaccine safety reports.

    PubMed

    Botsis, Taxiarchis; Buttolph, Thomas; Nguyen, Michael D; Winiecki, Scott; Woo, Emily Jane; Ball, Robert

    2012-01-01

    To develop and evaluate a text mining system for extracting key clinical features from vaccine adverse event reporting system (VAERS) narratives to aid in the automated review of adverse event reports. Based upon clinical significance to VAERS reviewing physicians, we defined the primary (diagnosis and cause of death) and secondary features (eg, symptoms) for extraction. We built a novel vaccine adverse event text mining (VaeTM) system based on a semantic text mining strategy. The performance of VaeTM was evaluated using a total of 300 VAERS reports in three sequential evaluations of 100 reports each. Moreover, we evaluated the VaeTM contribution to case classification; an information retrieval-based approach was used for the identification of anaphylaxis cases in a set of reports and was compared with two other methods: a dedicated text classifier and an online tool. The performance metrics of VaeTM were text mining metrics: recall, precision and F-measure. We also conducted a qualitative difference analysis and calculated sensitivity and specificity for classification of anaphylaxis cases based on the above three approaches. VaeTM performed best in extracting diagnosis, second level diagnosis, drug, vaccine, and lot number features (lenient F-measure in the third evaluation: 0.897, 0.817, 0.858, 0.874, and 0.914, respectively). In terms of case classification, high sensitivity was achieved (83.1%); this was equal and better compared to the text classifier (83.1%) and the online tool (40.7%), respectively. Our VaeTM implementation of a semantic text mining strategy shows promise in providing accurate and efficient extraction of key features from VAERS narratives.

  9. Improved coverage and timing of childhood vaccinations in two post-Soviet countries, Armenia and Kyrgyzstan.

    PubMed

    Schweitzer, A; Krause, G; Pessler, F; Akmatov, M K

    2015-08-19

    Timing of childhood vaccinations has received close attention in many countries. Little is known about the trends in correctly timed vaccination in former Soviet countries. We examined trends in vaccination coverage and correct timing of vaccination in two post-Soviet countries, Armenia and Kyrgyzstan, and analyzed factors associated with delayed vaccinations. We used data from the Demographic and Health Surveys; the surveys were conducted in 2000 (n = 1726), 2005 (n = 1430) and 2010 (n = 1473) in Armenia and in 1997 (n = 1127) and 2012 (n = 4363) in Kyrgyzstan. We applied the Kaplan-Meier method to estimate age-specific vaccination coverage with diphtheria, tetanus and pertussis (DTP) vaccine and a measles-containing vaccine (MCV). A Cox proportional hazard regression with shared frailty was used to examine factors associated with delayed vaccinations. Vaccination coverage for all three doses of the DTP vaccine increased in Armenia from 92 % in 2000 to 96 % in 2010. In Kyrgyzstan, DTP coverage was 96 % and 97 % in 1997 and 2012, respectively. Vaccination coverage for MCV increased from 89 % (Armenia, 2000) and 93 % (Kyrgyzstan, 1997) to 97 % (Armenia, 2010) and 98 % (Kyrgyzstan, 2012). The proportion of children with correctly timed vaccinations increased over time for all examined vaccinations in both countries. For example, the proportion of children in Armenia with correctly timed first DTP dose (DTP1) increased from 46 % (2000) to 66 % (2010). In Kyrgyzstan, the proportion of correctly timed DTP1 increased from 75 % (1997) to 87 % (2012). In Armenia, delays in the third DTP dose (DTP3) and MCV vaccinations were less likely to occur in the capital, whereas in Kyrgyzstan DTP3 and MCV start was delayed in the capital compared to other regions of the country. Also, in Armenia living in urban areas was associated with delayed vaccinations. Vaccination coverage and timing of vaccination improved over the last years in both countries. Further

  10. Impact of unfounded vaccine safety concerns on the nationwide measles-rubella immunization campaign, Georgia, 2008.

    PubMed

    Khetsuriani, N; Imnadze, P; Baidoshvili, L; Jabidze, L; Tatishili, N; Kurtsikashvili, G; Lezhava, T; Laurent, E; Martin, R

    2010-09-07

    Vaccine safety fears following media reports of adverse events led to low (50.3%) coverage in a supplementary measles-rubella immunization campaign in Georgia in 2008. Review of adverse events associated with the campaign identified 432 reports (<0.1% of ∼ 493,000 vaccinees) including 338 (78.2%) cases of syncope. There were no deaths. Causality assessment was performed for 79 cases perceived by providers as severe and with clinical details available. Conditions likely caused by the vaccine were identified in 13 (16.5%) cases (allergic and local reactions, thrombocytopenia). Thirty-seven (46.8%) cases had symptoms consistent with syncope or anxiety attack; 36 (97.3%) of them were initially misdiagnosed as anaphylactic shock/allergies/"postvaccinal reactions". Twenty-nine (36.7%) cases had coincidental illnesses. Safety fears were unfounded and exaggerated by media reports and providers' difficulties in recognizing syncope/anxiety attacks. Risk communication strategies to address perceived vaccine safety concerns are urgently needed to ensure that the goal of measles and rubella elimination in the European Region of the World Health Organization is met.

  11. Evaluating the safety of a rotavirus vaccine: the REST of the story

    PubMed Central

    Kuter, Barbara J; Dallas, Michael J; Heaton, Penny

    2008-01-01

    The Rotavirus Efficacy and Safety Trial (REST) was a blinded, placebo-controlled study of the live pentavalent human-bovine vaccine, RotaTeq® (Merck & Co. Inc., West Point, PA). REST was noteworthy because its primary objective was to evaluate the safety of RotaTeq® with regard to intussusception, a rare intestinal illness that occurs with a background incidence of approximately 50 cases per 100 000 infant years. The study involved approximately 70 000 infants at over 500 study sites in 11 countries. The study demonstrated that the risk of intussusception was similar in vaccine and placebo recipients and that the vaccine prevented rotavirus gastroenteritis, ameliorated the severity of disease in those who had any disease, and substantially reduced rotavirus-associated hospitalizations and other health care contacts. This report provides an in-depth review of the background, statistical and regulatory considerations, and execution of REST. We describe the rationale and methods used for sample size, continuous safety monitoring, group sequential design, and detailed study execution. The results of the study have been reported elsewhere. The design and conduct of this study may serve as a useful model for planning other future large-scale clinical trials, especially those evaluating uncommon adverse events. PMID:18375651

  12. Improving safety culture through the health and safety organization: a case study.

    PubMed

    Nielsen, Kent J

    2014-02-01

    International research indicates that internal health and safety organizations (HSO) and health and safety committees (HSC) do not have the intended impact on companies' safety performance. The aim of this case study at an industrial plant was to test whether the HSO can improve company safety culture by creating more and better safety-related interactions both within the HSO and between HSO members and the shop-floor. A quasi-experimental single case study design based on action research with both quantitative and qualitative measures was used. Based on baseline mapping of safety culture and the efficiency of the HSO three developmental processes were started aimed at the HSC, the whole HSO, and the safety representatives, respectively. Results at follow-up indicated a marked improvement in HSO performance, interaction patterns concerning safety, safety culture indicators, and a changed trend in injury rates. These improvements are interpreted as cultural change because an organizational double-loop learning process leading to modification of the basic assumptions could be identified. The study provides evidence that the HSO can improve company safety culture by focusing on safety-related interactions. © 2013. Published by Elsevier Ltd and National Safety Council.

  13. Improvement in attitudes toward influenza vaccination in medical students following an integrated curricular intervention.

    PubMed

    Afonso, Nelia; Kavanagh, Maurice; Swanberg, Stephanie

    2014-01-16

    Vaccination of health care workers (HCW) reduces transmission of influenza among patients, yet uptake of vaccination remains low. If vaccination education is integrated into the early medical school curriculum, will student attitudes toward the vaccine change? The objectives of the study were to: (1) Determine influenza vaccination rates among entering medical students; (2) Assess the attitudes toward influenza vaccination; (3) Evaluate the effects of a multifaceted educational intervention on attitudes to vaccination. Entering medical students were surveyed before and after an intervention at the beginning of the influenza season. This intervention provided by an inter-professional team, included education about influenza, importance of vaccination for HCWs, followed by vaccination administration practice, and ended with students vaccinating consenting classmates. The pre-intervention surveys and intervention were completed by 124 of 125 (99%) students. Pre-intervention survey revealed 60 (48%) of students had been previously vaccinated. Of the vaccinated students 91% had been recommended vaccination by their healthcare provider compared to 43% of non-vaccinated students. More positive attitudes were noted in the vaccinated students compared to non-vaccinated students: importance of vaccination (p<0.01); HCWs should be vaccinated (p<0.01); recommendation of vaccine to family and friends (p<0.01). 97 (78%) students completed post-intervention surveys. Significant improvement in these attitudes was noted post-intervention compared to pre-intervention: importance of vaccination 93% versus 71% (p<0.01); HCWs should be vaccinated 95% versus 83% (p<0.01); recommendation to family and friends 93% versus 73% (p<0.01); comfort with vaccine counseling 92% versus 41%; comfort with vaccine administration 84% versus 22% (p<0.01). Educating medical students and promoting the importance of vaccination early in a medical student's career using such an intervention is relatively

  14. Immunogenicity, Safety and Antibody Persistence of a Booster Dose of Quadrivalent Meningococcal ACWY-tetanus Toxoid Conjugate Vaccine Compared with Monovalent Meningococcal Serogroup C Vaccine Administered Four Years After Primary Vaccination Using the Same Vaccines.

    PubMed

    Vesikari, Timo; Forsten, Aino; Bianco, Veronique; Van der Wielen, Marie; Miller, Jacqueline M

    2015-12-01

    We evaluated safety, immunogenicity and antibody persistence of meningococcal serogroups A, C, W and Y tetanus toxoid conjugate vaccine (MenACWY-TT) booster vaccination 4 years after priming of toddlers. This phase III, open-label, controlled study in Finland (NCT00955682) enrolled children previously randomized (3:1) at 12-23 months (NCT00474266) to receive 1 dose of MenACWY-TT or MenC conjugate vaccine (MenC-CRM197). Serum bactericidal antibody titers using rabbit (rSBA, cut-off 1:8) and human complement (hSBA, cut-off 1:8) were assessed at year 3 and 4 after priming and 1 month and 1 year after administration of a booster dose of the same vaccine given for primary vaccination. Reactogenicity and safety were assessed, and vaccination-related serious adverse events were recorded from the time of primary vaccination. Before booster (year 4), 74.1%, 40.4%, 49.3% and 58.2% of MenACWY-TT-recipients retained rSBA titers ≥1:8 for serogroups A, C, W and Y, respectively; 28.8%, 73.2%, 80.6% and 65.4% retained hSBA ≥1:8. Percentages for the MenC-CRM group were 35.6% (rSBA-MenC) and 46.9% (hSBA-MenC). After MenACWY-TT booster, ≥99.5% had rSBA ≥1:8 and hSBA ≥1:8 for each serogroup. After MenC-CRM197 booster, all children had rSBA-MenC ≥1:8 and hSBA-MenC ≥1:8. At year 5, percentages above the cut-off were ≥97.4% (rSBA) and ≥95.5% (hSBA) in MenACWY-TT-vaccinees for each serogroup. The MenACWY-TT booster dose had a clinically acceptable safety profile. No vaccine-related serious adverse events were reported. There was evidence of antibody persistence 4 years after toddlers were primed with MenACWY-TT. Booster vaccination induced robust immune responses for all serogroups with an acceptable safety profile.

  15. [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. Copyright © 2015 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.

  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.

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

    PubMed Central

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

    2016-01-01

    ABSTRACT 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

  18. 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).

  19. Improving tractor safety warnings: readability is missing.

    PubMed

    Tebeaux, E

    2010-07-01

    Research on tractor safety has not focused on user manuals. This study focuses on tractor operator manuals, specifically safety warnings, selected from the files of the Tractor Test facility at University of Nebraska-Lincoln. Analysis of many common warnings, based on readability and legibility research, shows that many warnings contain excessive information, confusing visuals and safety icons, poor document design, and illegible typefaces. The result is unreadable warnings that do not communicate quickly and correctly, and discourage readers rather than clarify critical information. Many tractor operator warnings are cluttered, "over-written," and contain information needed to protect the manufacturer rather than to inform operators. What is needed is a careful analysis and revision of many safety warnings with the goal of encouraging operators to read the warnings and follow their message.

  20. 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...

  1. 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...

  2. Immunogenicity and safety of measles-mumps-rubella vaccine delivered by disposable-syringe jet injector in healthy Brazilian infants: a randomized non-inferiority study.

    PubMed

    de Menezes Martins, Reinaldo; Curran, Birute; Maia, Maria de Lourdes Sousa; Ribeiro, Maria das Graças Tavares; Camacho, Luiz Antonio Bastos; da Silva Freire, Marcos; Yamamura, Anna Maya Yoshida; Siqueira, Marilda Mendonça; Lemos, Maria Cristina F; de Albuquerque, Elizabeth Maciel; von Doellinger, Vanessa dos Reis; Homma, Akira; Saganic, Laura; Jarrahian, Courtney; Royals, Michael; Zehrung, Darin

    2015-03-01

    This study aimed to determine if immunogenicity to measles-mumps-rubella vaccine delivered to infants via a disposable-syringe jet injector (DSJI) was non-inferior to that administered by needle and syringe (NS). Vaccination safety was evaluated, as were the use, performance, and acceptability of each delivery method. The DSJI was the PharmaJet 2009 generation-1 device (G1) and the vaccine was measles-mumps-rubella vaccine from Bio-Manguinhos. Five hundred eighty-two healthy Brazilian infants were randomized to receive vaccine via G1 or NS. Seroconversion rates against measles and mumps viruses in the G1 treatment group did not meet non-inferiority criteria when compared with the NS group; however, responses in the G1 group to rubella virus were non-inferior to those of NS vaccinees. Most adverse events were mild or moderate. Crying after injection was more frequent in the NS group, and local skin reactions were more common in the G1 group. Five serious adverse events were judged causally unrelated to treatment and all resolved. Parents/guardians expressed a strong preference for G1 over NS for their children. Vaccinators found the G1 easy to use but noted incomplete vaccine delivery in some cases. Although the G1 has been superseded by an updated device, our results are important for the continued improvement and evaluation of DSJIs, which have the potential to overcome many of the challenges and risks associated with needle-based injections worldwide. Recommendations for future DSJI clinical studies include rigorous training of vaccinators, quantitative measurement of wetness on the skin following injection, and regular monitoring of device and vaccinator performance. Copyright © 2014. Published by Elsevier Inc.

  3. Phase 3 trial evaluating the immunogenicity, safety, and tolerability of manufacturing scale 13-valent pneumococcal conjugate vaccine.

    PubMed

    Gadzinowski, Janusz; Albrecht, Piotr; Hasiec, Barbara; Konior, Ryszard; Dziduch, Jerzy; Witor, Anita; Mellelieu, Tracey; Tansey, Susan P; Jones, Thomas; Sarkozy, Denise; Emini, Emilio A; Gruber, William C; Scott, Daniel A

    2011-04-05

    13-valent pneumococcal conjugate vaccine (PCV13) includes polysaccharide conjugates from six pneumococcal serotypes in addition to those in the licensed 7-valent vaccine, thereby offering expanded protection against pneumococcal disease. The phase 3 trial reported here was conducted per a regulatory requirement to evaluate the immunogenicity, safety, and tolerability of two lots of the final PCV13 formulation that differed with respect to production scale but not the manufacturing process. The anti-pneumococcal polysaccharide immunogenicity and safety/tolerability were found to be similar between the two PCV13 vaccine lots.

  4. Randomized controlled field trial to assess the immunogenicity and safety of rift valley fever clone 13 vaccine in livestock.

    PubMed

    Njenga, M Kariuki; Njagi, Leonard; Thumbi, S Mwangi; Kahariri, Samuel; Githinji, Jane; Omondi, Eunice; Baden, Amy; Murithi, Mbabu; Paweska, Janusz; Ithondeka, Peter M; Ngeiywa, Kisa J; Dungu, Baptiste; Donadeu, Meritxell; Munyua, Peninah M

    2015-03-01

    Although livestock vaccination is effective in preventing Rift Valley fever (RVF) epidemics, there are concerns about safety and effectiveness of the only commercially available RVF Smithburn vaccine. We conducted a randomized controlled field trial to evaluate the immunogenicity and safety of the new RVF Clone 13 vaccine, recently registered in South Africa. In a blinded randomized controlled field trial, 404 animals (85 cattle, 168 sheep, and 151 goats) in three farms in Kenya were divided into three groups. Group A included males and non-pregnant females that were randomized and assigned to two groups; one vaccinated with RVF Clone 13 and the other given placebo. Groups B included animals in 1st half of pregnancy, and group C animals in 2nd half of pregnancy, which were also randomized and either vaccinated and given placebo. Animals were monitored for one year and virus antibodies titers assessed on days 14, 28, 56, 183 and 365. In vaccinated goats (N = 72), 72% developed anti-RVF virus IgM antibodies and 97% neutralizing IgG antibodies. In vaccinated sheep (N = 77), 84% developed IgM and 91% neutralizing IgG antibodies. Vaccinated cattle (N = 42) did not develop IgM antibodies but 67% developed neutralizing IgG antibodies. At day 14 post-vaccination, the odds of being seropositive for IgG in the vaccine group was 3.6 (95% CI, 1.5 - 9.2) in cattle, 90.0 (95% CI, 25.1 - 579.2) in goats, and 40.0 (95% CI, 16.5 - 110.5) in sheep. Abortion was observed in one vaccinated goat but histopathologic analysis did not indicate RVF virus infection. There was no evidence of teratogenicity in vaccinated or placebo animals. The results suggest RVF Clone 13 vaccine is safe to use and has high (>90%) immunogenicity in sheep and goats but moderate (> 65%) immunogenicity in cattle.

  5. Improving Patient Safety Event Reporting Among Residents and Teaching Faculty

    PubMed Central

    Louis, Michelle Y.; Hussain, Lala R.; Dhanraj, David N.; Khan, Bilal S.; Jung, Steven R.; Quiles, Wendy R.; Stephens, Lorraine A.; Broering, Mark J.; Schrand, Kevin V.; Klarquist, Lori J.

    2016-01-01

    Background: A June 2012 site visit report from the Accreditation Council for Graduate Medical Education Clinical Learning Environment Review revealed that residents and physicians at TriHealth, Inc., a large, nonprofit independent academic medical center serving the Greater Cincinnati area in Ohio, had an opportunity to improve their awareness and understanding of the hospital's system for reporting patient safety concerns in 3 areas: (1) what constitutes a reportable patient safety event, (2) who is responsible for reporting, and (3) how to use the hospital's current reporting system. Methods: To improve the culture of patient safety, we designed a quality improvement project with the goal to increase patient safety event reporting among residents and teaching faculty. An anonymous questionnaire assessed physicians' and residents' attitudes and experience regarding patient safety event reporting. An educational intervention was provided in each graduate medical education program to improve knowledge and skills related to patient safety event reporting, and the anonymous questionnaire was distributed after the intervention. We compared the responses to the preintervention and postintervention questionnaires and tracked monthly patient safety event reports for 1 year postintervention. Results: The number of patient safety event reports increased following the educational intervention; however, we saw wide variability in reporting per month. On the postintervention questionnaire, participants demonstrated improved knowledge and attitudes toward patient safety event reporting. Conclusion: The goal of this unique project was to increase patient safety event reporting by both residents and teaching faculty in 6 residency programs through education. We achieved this goal through an educational intervention tailored to the institution's new event reporting system delivered to each residency program. We clearly understand that improvements in quality and patient safety

  6. Improving the safety and quality of cancer care.

    PubMed

    Burke, Harry B

    2017-02-15

    The cancer community is increasingly interested in improving its safety and quality. Improvement will be driven by the expansion of safety and quality research and by a commitment to publish studies that advance high-quality, safe cancer care. Cancer 2017;123:549-550. © 2016 American Cancer Society. © 2016 American Cancer Society.

  7. 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 ...

  8. Vaccines.gov

    MedlinePlus

    ... Statements Vaccine Approvals Features: News & Video Free Resources Vaccines are safe, effective, and save lives. Find answers ... by science, on vaccine safety. Are your child’s vaccines up to date? Getting all recommended vaccines on ...

  9. [Study of reactogenicity, safety and immunogenicity of inactivated virosomal split influenza vaccine "Grifor" during phase I clinical trial].

    PubMed

    Zverev, V V; Korovkin, S A; Mironov, A N; Mel'nikov, S Ia; Mikhaĭlova, N A; Kostinov, M P; Dyldina, N V; Zhirova, S N

    2009-01-01

    Phase I clinical trial of inactivated virosomal split influenza vaccine "Grifor" was conducted in the Mechnikov Research Institute of Vaccines and Sera as accredited base for such trials. Forty healthy volunteers (males and females) aged 18 - 50 years consented to participate in the trial. Reactogenicity, safety, and immunogenicity of new Russian influenza vaccine were assessed. Analysis of obtained results showed that there was evidence of safety and low reactogenicity of the vaccine as well as of its high immunogenic characteristics, which satisfied both the EMEA's Committee for Proprietal Medicinal Products criteria and requirements of Federal Service for Surveillance for Protection of Consumers Rights and Human Welfare (MU 3.3.2.1758-03) for inactivated influenza vaccines.

  10. Comparison of the immunogenicity and safety of two different brands of Salmonella typhi Vi capsular polysaccharide vaccine.

    PubMed

    Sabitha, P; Prabha Adhikari, M R; Chowdary, Abhijit; Prabhu, Malathi; Soofi, Mohammad; Shetty, Meenakshi; Kamath, Asha; Lokaranjan, S S; Bangera, S S

    2004-04-01

    The recent emergence of multi-drug-resistant Salmonella strains highlights the need for better preventive measures, including vaccination. Safe and immunologic vaccines have been developed based on purified Vi polysaccharide. To compare the immune response elicited by two different brands of Salmonella Vi capsular polysaccharide vaccine (ViCPS). Double blind, randomized (3:1), controlled, parallel, phase III study was conducted at two centres in India to compare the safety and immunogenicity of Typbar, the investigational vaccine with an already marketed vaccine "X", in healthy subjects aged between 12 -25 years. A sample size of 184 subjects was calculated. Subjects were randomly distributed in two groups, immunized with single dose of Typbar or Vaccine "X". Serum samples were taken before 7 days and 4 weeks after immunization for the determination of antibodies to Vi polysaccharide, by ELISA method. Safety was assessed by physical examination, laboratory parameters before and after vaccination and by monitoring adverse events. The geometric mean antibody titre (GMT) 4 weeks after vaccination was compared from respective pre-vaccination values by Wilcoxon signed rank test. Geometric mean of antibody levels before and after immunization and the ratio between them (Mann-Whitney test), the Seroconversion rates (Z test of proportions) and the adverse events (Fisher's exact test and Chi square test), were compared between two groups. P value < 0.05 was considered statistically significant. P values and 95% confidence intervals were estimated in two-tailed fashion. 153 subjects (Typbar =116 and Vaccine "X" =37) were studied. 71.6% (95% CI=63.4%-79.8%) and 75.7% (95% CI=64.9% - 89.5%) were the seroconversion rates with Typbar and vaccine "X" respectively. The GMT values for Vi antibodies induced after Typbar and vaccine "X" were 10.23 Typbar and 13.46 mg/mL respectively and these values showed high significance when compared to their respective pre-immunization GMT

  11. Safety and immunogenicity of a novel cold-adapted modified-live equine influenza virus vaccine.

    PubMed

    Tabynov, K; Kydyrbayev, Z; Ryskeldinova, S; Assanzhanova, N; Kozhamkulov, Y; Inkarbekov, D; Sansyzbay, A

    2014-11-01

    To design and evaluate the safety and immunogenicity of a modified-live vaccine to prevent equine influenza virus (EIV) infection based on the novel reassortant cold-adapted strain A/HK/Otar/6:2/2010. Surface proteins (HA, NA) from the wild-type strain A/equine/Otar/764/2007 (H3N8) and internal proteins (PB2, PB1, PA, NP, M, NS) from the attenuated cold-adapted donor strain A/Hong Kong/1/68/162/35CA (H3N2) were included in the vaccine. Horses were administered 10(9.2) EID50 /mL of the modified-live vaccine or saline solution using a nasal spray. The clinical condition of the animals was assessed throughout the study and nasopharyngeal swabs were collected for virus titration. Two yearlings in each group were euthanased on day 5 post vaccination (PV) for histological examination and measurement of viral titres in the organs. Serum samples and nasal secretions were collected to evaluate serological response. Lymphoproliferation after restimulation in vitro was determined to evaluate cell-mediated immunity. To evaluate the protective capacity of the vaccine, the yearlings in both groups were challenged with the wild-type virus at 28 days PV and their clinical condition and serological response was evaluated. Nasal swabs were collected to assess viral shedding from the upper respiratory tract. Single intranasal administration of a modified-live EIV vaccine caused no adverse effects and vaccinated yearlings and pregnant mares did not form detectable levels of antibodies by days 7, 14 and 28 PV, as indicated by the HI reaction and ELISA. Secretory antibodies could be detected on day 7 and reached maximal levels on day 14 PV. In vitro studies showed that the yearlings and pregnant mares both formed a cell-mediated immune response by day 14 PV. The vaccine protected yearlings against challenge with wild-type virus. We conclude that single intranasal administration of the modified-live EIV vaccine was safe in the yearlings and pregnant mares that we treated, and was

  12. Adalimumab long-term safety: infections, vaccination response and pregnancy outcomes in patients with rheumatoid arthritis

    PubMed Central

    Burmester, Gerd R; Landewé, Robert; Genovese, Mark C; Friedman, Alan W; Pfeifer, Nathan D; Varothai, Nupun A; Lacerda, Ana P

    2017-01-01

    Background Adalimumab has been used in patients with moderately to severely active rheumatoid arthritis (RA) for over 10 years and has a well-established safety profile across multiple indications. Objective To update adverse events (AEs) of special interest from global adalimumab clinical trials in patients with RA. Methods This analysis includes 15 132 patients exposed to adalimumab in global RA clinical trials. AEs of interest included overall infections, laboratory abnormalities and AEs associated with influenza vaccination. Pregnancy outcome data were collected from the Adalimumab Pregnancy Registry. Results Serious infections and tuberculosis occurred at a rate of 4.7 and 0.3 events/100 patient-years, respectively. Two patients experienced hepatitis B reactivation. No significant laboratory abnormalities were reported with adalimumab-plus-methotrexate compared with placebo-plus-methotrexate. Influenza-related AEs occurred in 5% of vaccinated patients compared with 14% of patients not vaccinated during the study. Relative risk of major birth defects and spontaneous abortions in adalimumab-exposed women were similar between that of unexposed women with RA and healthy women. Conclusions This analysis confirms and expands the known safety profile of adalimumab and reports no additional safety risk of laboratory abnormalities, hepatitis B reactivation and pregnancy outcomes, including spontaneous abortions and birth defects. The benefits of influenza vaccination are reinforced. Trial registration numbers NCT00195663, NCT00195702, NCT00448383, NCT00049751, NCT00234845, NCT00650390, NCT00235859, NCT00647920, NCT00649545, NCT00647491, NCT00649922, NCT00538902, NCT00420927, NCT00870467, NCT00650156, NCT00647270, NCT01185288, NCT01185301. PMID:27338778

  13. Adalimumab long-term safety: infections, vaccination response and pregnancy outcomes in patients with rheumatoid arthritis.

    PubMed

    Burmester, Gerd R; Landewé, Robert; Genovese, Mark C; Friedman, Alan W; Pfeifer, Nathan D; Varothai, Nupun A; Lacerda, Ana P

    2017-02-01

    Adalimumab has been used in patients with moderately to severely active rheumatoid arthritis (RA) for over 10 years and has a well-established safety profile across multiple indications. To update adverse events (AEs) of special interest from global adalimumab clinical trials in patients with RA. This analysis includes 15 132 patients exposed to adalimumab in global RA clinical trials. AEs of interest included overall infections, laboratory abnormalities and AEs associated with influenza vaccination. Pregnancy outcome data were collected from the Adalimumab Pregnancy Registry. Serious infections and tuberculosis occurred at a rate of 4.7 and 0.3 events/100 patient-years, respectively. Two patients experienced hepatitis B reactivation. No significant laboratory abnormalities were reported with adalimumab-plus-methotrexate compared with placebo-plus-methotrexate. Influenza-related AEs occurred in 5% of vaccinated patients compared with 14% of patients not vaccinated during the study. Relative risk of major birth defects and spontaneous abortions in adalimumab-exposed women were similar between that of unexposed women with RA and healthy women. This analysis confirms and expands the known safety profile of adalimumab and reports no additional safety risk of laboratory abnormalities, hepatitis B reactivation and pregnancy outcomes, including spontaneous abortions and birth defects. The benefits of influenza vaccination are reinforced. NCT00195663, NCT00195702, NCT00448383, NCT00049751, NCT00234845, NCT00650390, NCT00235859, NCT00647920, NCT00649545, NCT00647491, NCT00649922, NCT00538902, NCT00420927, NCT00870467, NCT00650156, NCT00647270, NCT01185288, NCT01185301. Published by the BMJ Publishing Group Limi