[Human papillomavirus vaccine. Efficacy and safety].

Science.gov (United States)

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.

METHODS OF CONTROL DIPHTHERIA VACCINE SAFETY

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Isayenko Ye. Yu

2016-12-01

Full Text Available Vaccination success depends not only on the timely coverage of threatened contingents, but also on the quality of vaccines. Every day, the requirements for security guarantees vaccines and their use guarantees of security increases. For the fast, reliable and independent scientific assessment of vaccine safety issues, WHO in 1999 created the Global Advisory Committee on Vaccine Safety. To enhance the capacity of pharmaceutical supervision in relation to vaccines in 2012 it was developed the Global Vaccine Safety Initiative. The main directions of the Global Vaccine Safety programs are considered in this review. It’s noted more strict requirements of Ukrainian pharmaceutical industry to produce public immunization drugs regulated Supplements to the State Pharmacopoeia of Ukraine, in comparison with other countries. This review considered diphtheria vaccine safety monitoring in the process of production according to the recommendations of the World Health Organization (WHO, described a subcutaneous method for determining the specific toxicity of the combined purified toxoid, characterized an intracutaneous method of determining of the presence of diphtheria toxin in each sample of the combined purified toxoid, that additionally used by some manufacturers. The definition of diphtheria toxin in dilutions of purified toxoid is presented. This review considered diphtheria vaccine safety monitoring in the process of production according to the recommendations of the World Health Organization (WHO, described a subcutaneous method for determining the specific toxicity of the combined purified toxoid, characterized an intracutaneous method of determining of the presence of diphtheria toxin in each sample of the combined purified toxoid, that additionally used by some manufacturers. The definition of diphtheria toxin in dilutions of purified toxoid is presented. As methods for determination of diphtheria toxin must be able to detect even a small amount

Enhancing vaccine safety capacity globally: A lifecycle perspective

NARCIS (Netherlands)

R.T. Chen (Robert T.); T.T. Shimabukuro (Tom T.); D.B. Martin (David); P. Zuber (Patrick); D.M. Weibel (Daniel); M.C.J.M. Sturkenboom (Miriam)

2015-01-01

textabstractMajor 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

Detailed Safety Review of Anthrax Vaccine Adsorbed

National Research Council Canada - National Science Library

2001-01-01

To date, 18 human studies have assessed the safety of anthrax vaccination. These studies, some stretching back almost 50 years, reported adverse events after vaccination in varying degrees of detail...

The role of attitudes about vaccine safety, efficacy, and value in explaining parents' reported vaccination behavior.

Science.gov (United States)

Lavail, Katherine Hart; Kennedy, Allison Michelle

2013-10-01

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. A sample of parents with at least one child younger than 6 years (n = 376) was analyzed using data from the HealthStyles 2010 survey. Questions were grouped into block variables to create three confidence constructs: value, safety, and efficacy. Regression equations controlling for demographic characteristics were used to identify the confidence construct(s) that best predicted parents' self-reported vaccination decisions (accept all, some, or none of the recommended childhood vaccines). Among the three constructs evaluated, confidence in the value of vaccines, that is the belief that vaccines are important and vaccinating one's children is the right thing to do, was the best predictor of parents' vaccine decisions, F(2, 351) = 119.199, p parents' self-reported vaccine decisions. Confidence in the safety or efficacy of vaccines failed to account for additional significant variance in parent-reported vaccination behavior. Confidence in the value of vaccines is a helpful predictor of parent-reported vaccination behavior. Attitudinal constructs of confidence in the safety and efficacy of vaccines failed to account for additional significant variance in parents' vaccination behaviors. Future research should assess the role of vaccine knowledge and tangible barriers, such as access and cost, to further explain parents' vaccination behaviors.

Vaccination of health care workers for influenza: promote safety culture, not coercion.

Science.gov (United States)

Yassi, Annalee; Lockhart, Karen; Buxton, Jane A; McDonald, Isobel

2010-01-01

In British Columbia (BC), Canada, all health care facilities must have a written staff policy on influenza immunization that includes notice that non-immunized staff can be excluded from work without pay during an influenza outbreak in the facility. In light of this policy, our objectives were to explore the views of BC health care workers (HCWs) regarding how best to promote vaccine uptake. Long-term care, and acute and community health sites in three of six health regions were divided into thirds, according to their previous season's vaccine uptake rates, and the upper and lower thirds targeted. Ten focus groups were held. NVivo software (QSR International) and a separate editing style were used for analysis. Four dominant themes emerged: knowledge, communication, perceived punitive nature of workplace policy, and safety climate. HCWs across all focus groups noted that influenza campaign communications should include reinforcement of basic infection control, workplace health and healthy lifestyle choices that affect overall health. HCWs indicated that they wanted a workplace policy that is easy to understand, respectful of individual choice and not punitive. Our findings highlight the importance of comprehensive approaches, a message that has not appeared as strongly in previous literature. Focus group participants pointed out the importance of health and safety at work generally and felt that creating a healthy workplace culture is necessary to promoting vaccine uptake. Future vaccine promotion initiatives should be integrated into facility-wide workplace health campaigns and care taken to ensure that vaccination campaigns do not appear coercive to HCWs.

Responding to vaccine safety signals during pandemic influenza: a modeling study.

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Judith C Maro

Full Text Available Managing emerging vaccine safety signals during an influenza pandemic is challenging. Federal regulators must balance vaccine risks against benefits while maintaining public confidence in the public health system.We developed a multi-criteria decision analysis model to explore regulatory decision-making in the context of emerging vaccine safety signals during a pandemic. We simulated vaccine safety surveillance system capabilities and used an age-structured compartmental model to develop potential pandemic scenarios. We used an expert-derived multi-attribute utility function to evaluate potential regulatory responses by combining four outcome measures into a single measure of interest: 1 expected vaccination benefit from averted influenza; 2 expected vaccination risk from vaccine-associated febrile seizures; 3 expected vaccination risk from vaccine-associated Guillain-Barre Syndrome; and 4 expected change in vaccine-seeking behavior in future influenza seasons.Over multiple scenarios, risk communication, with or without suspension of vaccination of high-risk persons, were the consistently preferred regulatory responses over no action or general suspension when safety signals were detected during a pandemic influenza. On average, the expert panel valued near-term vaccine-related outcomes relative to long-term projected outcomes by 3:1. However, when decision-makers had minimal ability to influence near-term outcomes, the response was selected primarily by projected impacts on future vaccine-seeking behavior.The selected regulatory response depends on how quickly a vaccine safety signal is identified relative to the peak of the pandemic and the initiation of vaccination. Our analysis suggested two areas for future investment: efforts to improve the size and timeliness of the surveillance system and behavioral research to understand changes in vaccine-seeking behavior.

The Conceptual Framework for Ensuring Economic Safety of Corporate Integration Processes

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Gutsaliuk Oleksii M.

2016-08-01

Full Text Available The objective growth of the number of displays and influence of negative factors of threats from the environment actualizes the issue of ensuring economic safety of national economic entities. The article notes that simultaneously with counteracting threats enterprises are working for development, one form of which is the establishment of corporate structures and implementation of integration processes. It is proposed to ensure achieving the desired level of the corporate structure economic safety through optimizing the correlation of resources and competencies, skills and technologies for their use within the integrated logistics value chain. In this case it is the implementation of the integration process that serves as an instrument for achieving this optimal correlation, and the level of economic safety is considered as one of the optimization criteria. The system of authors’ hypotheses is taken as the basis for ensuring economic safety of the corporate integration process. Each of the hypotheses corresponds to a set of conceptual principles aimed at practical implementation of the proposed approaches. Within these conceptual principles the relationship between incentives and benefits of integration and the basis for ensuring their safety is presented, the differences between safety of functioning and safety of development are studied, the use of the methodology of logistics to harmonize the interests of participants of the corporate structure is justified, the relevance of applying the resource approach to manage the integration and development safety is proved. The graphical representation of causal relationships between the proposed conceptual principles allowed formalizing the subject area of studying corporate integration safety

Immunization safety review: influenza vaccines and neurological complications

National Research Council Canada - National Science Library

Stratton, Kathleen R

..., unlike other vaccines. The Immunization Safety Review committee reviewed the data on influenza vaccine and neurological conditions and concluded that the evidence favored rejection of a causal relationship...

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

Science.gov (United States)

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.

Methods for addressing "innocent bystanders" when evaluating safety of concomitant vaccines.

Science.gov (United States)

Wang, Shirley V; Abdurrob, Abdurrahman; Spoendlin, Julia; Lewis, Edwin; Newcomer, Sophia R; Fireman, Bruce; Daley, Matthew F; Glanz, Jason M; Duffy, Jonathan; Weintraub, Eric S; Kulldorff, Martin

2018-04-01

The need to develop methods for studying the safety of childhood immunization schedules has been recognized by the Institute of Medicine and Department of Health and Human Services. The recommended childhood immunization schedule includes multiple vaccines in a visit. A key concern is safety of concomitant (same day) versus separate day vaccination. This paper addresses a methodological challenge for observational studies using a self-controlled design to investigate the safety of concomitant vaccination. We propose a process for distinguishing which of several concomitantly administered vaccines is responsible for increased risk of an adverse event while adjusting for confounding due to relationships between effect modifying risk factors and concomitant vaccine combinations. We illustrate the approach by re-examining the known increase in risk of seizure 7 to 10 days after measles-mumps-rubella (MMR) vaccination and evaluating potential independent or modifying effects of other vaccines. Initial analyses suggested that DTaP had both an independent and potentiating effect on seizure. After accounting for the relationship between age at vaccination and vaccine combination, there was little evidence for increased risk of seizure with same day administration of DTaP and MMR; incidence rate ratio, 95% confidence interval 1.2 (0.9-1.6), P value = θ.226. We have shown that when using a self-controlled design to investigate safety of concomitant vaccination, it can be critically important to adjust for time-invariant effect modifying risk factors, such as age at time of vaccination, which are structurally related to vaccination patterns due to recommended immunization schedules. Copyright © 2018 John Wiley & Sons, Ltd.

EFFICACY AND SAFETY OF THE INFLUENZA VACCINE AMONG CHILDREN WITH DIFFERENT HEALTH CONDITIONS

OpenAIRE

M.G. Galitskaya

2007-01-01

Efficacy and safety of vaccine «Grippol» among children with different health status was analyzed. The most efficacy of the influenza vaccine revealed in the group of children with compromised health status, as well as in the group of allergic children. The safety of influenza vaccination was confirmed in children with different health conditions.Key words: children, vaccination, influenza, efficacy, safety.

ENSURING THE SAFETY OF ROAD TRANSPORTATION OF GOODS

Directory of Open Access Journals (Sweden)

Liudmila Nikolaevna Andronikova

2017-05-01

Full Text Available The article investigates Russian and foreign regulatory documents, governing the issues of cargo securing in road transport, and sets out recommendations to ensure the safety of road transportation of goods by means of their attachment.

SAFETY AND EFFICIENCY OF INACTIVATED OF SUBUNIT INFLUENZA VACCINE AT MASS VACCINATION OF CHILDREN

Directory of Open Access Journals (Sweden)

Yu.Z. Gendon

2007-01-01

Full Text Available The article considers the results of infantile mass vaccination with inactivated subunit influenza vaccine (Influvac. It shows that vaccination of 57–72% of children aged 3–17 from organized collectives residing in Mytishchi and Orekhovoczuevo districts of Moscow region was accompanied with nearly triple reduce of flu rates vs. Narofominsk and Odintsovo districts where vaccination was occasional (< 1% of children. The efficiency of the vaccination made 63,7%. Low reactogenicity of the influenza vaccine was recorded. Its convenient packing allows vaccination of large number of children in a short time. The article justifies the necessity of yearly vaccinations even in case of similarity of flu virus strain.Key words: children, mass vaccination, subunit flu vaccine, safety.

Intradermal influenza vaccination of healthy adults using a new microinjection system: a 3-year randomised controlled safety and immunogenicity trial

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Beran Jiri

2009-04-01

Full Text Available Abstract Background Intradermal vaccination provides direct and potentially more efficient access to the immune system via specialised dendritic cells and draining lymphatic vessels. We investigated the immunogenicity and safety during 3 successive years of different dosages of a trivalent, inactivated, split-virion vaccine against seasonal influenza given intradermally using a microinjection system compared with an intramuscular control vaccine. Methods In a randomised, partially blinded, controlled study, healthy volunteers (1150 aged 18 to 57 years at enrolment received three annual vaccinations of intradermal or intramuscular vaccine. In Year 1, subjects were randomised to one of three groups: 3 μg or 6 μg haemagglutinin/strain/dose of inactivated influenza vaccine intradermally, or a licensed inactivated influenza vaccine intramuscularly containing 15 μg/strain/dose. In Year 2 subjects were randomised again to one of two groups: 9 μg/strain/dose intradermally or 15 μg intramuscularly. In Year 3 subjects were randomised a third time to one of two groups: 9 μg intradermally or 15 μg intramuscularly. Randomisation lists in Year 1 were stratified for site. Randomisation lists in Years 2 and 3 were stratified for site and by vaccine received in previous years to ensure the inclusion of a comparable number of subjects in a vaccine group at each centre each year. Immunogenicity was assessed 21 days after each vaccination. Safety was assessed throughout the study. Results In Years 2 and 3, 9 μg intradermal was comparably immunogenic to 15 μg intramuscular for all strains, and both vaccines met European requirements for annual licensing of influenza vaccines. The 3 μg and 6 μg intradermal formulations were less immunogenic than intramuscular 15 μg. Safety of the intradermal and intramuscular vaccinations was comparable in each year of the study. Injection site erythema and swelling was more common with the intradermal route. Conclusion

Rotavirus vaccines

Science.gov (United States)

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

2014-01-01

Rotavirus is the leading cause of severe diarrhea among children 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

Neurovirulence safety testing of mumps vaccines--historical perspective and current status.

Science.gov (United States)

Rubin, S A; Afzal, M A

2011-04-05

Many live, attenuated viral vaccines are derived from wild type viruses with known neurovirulent properties. To assure the absence of residual neurotoxicity, pre-clinical neurovirulence safety testing of candidate vaccines is performed. For mumps virus, a highly neurotropic virus, neurovirulence safety testing is performed in monkeys. However, laboratory studies suggest an inability of this test to correctly discern among virus strains of varying neurovirulence potential in man, and, further, some vaccines found to be neuroattenuated in monkeys were later found to be neurovirulent in humans when administered in large numbers. Over the past decade, concerted efforts have been made to replace monkey-based neurovirulence safety testing with more informative, alternative methods. This review summarizes the current status of mumps vaccine neurovirulence safety testing and insights into models currently approved and those under development. Published by Elsevier Ltd.

EVALUATION OF REACTOGENICITY, SAFETY AND IMMUNOGENICITY OF INACTIVATED MONOVALENT VACCINE IN CHILDREN

Directory of Open Access Journals (Sweden)

A.N. Mironov

2010-01-01

Full Text Available NPO «Microgen» developed vaccine «PANDEFLU» — influenza inactivated subunit adsorbed monovalent vaccine, strain A/California/7/2009 (H1N1, for specific prophylaxis of pandemic influenza in different age groups of citizens. Reactogenicity, safety and immunogenicity were analyzed in a study of volunteers 18–60 years old. The article presents results of administration of vaccine «PANDEFLU» in children. The study performed in two clinical centers proves good tolerability, reactogenicity, safety and high immunogenicity of this vaccine.Key words: children, influenza, influenza virus А/H1N1, inactivated influenza vaccine, reactogenicity, safety, immunogenicity.(Voprosy sovremennoi pediatrii — Current Pediatrics. – 2010;9(4:106-109

Analyzing and strengthening the vaccine safety program in Manitoba.

Science.gov (United States)

Montalban, J M; Ogbuneke, C; Hilderman, T

2014-12-04

The emergence of a novel influenza A virus in 2009 and the rapid introduction of new pandemic vaccines prompted an analysis of the current state of the adverse events following immunization (AEFI) surveillance response in several provinces. To highlight aspects of the situational analysis of the Manitoba Health, Healthy Living and Seniors (MHHLS's) AEFI surveillance system and to demonstrate how common business techniques could be usefully applied to a provincial vaccine safety monitoring program. Situational analysis of the AEFI surveillance system in Manitoba was developed through a strengths-weaknesses-opportunities-threats (SWOT) analysis and informed by the National Immunization Strategy vaccine safety priorities. Strategy formulation was developed by applying the threats-opportunities-weaknesses-strengths (TOWS) matrix. Thirteen strategies were formulated that use strengths to either take advantage of opportunities or avoid threats, that exploit opportunities to overcome weaknesses, or that rectify weaknesses to circumvent threats. These strategies entailed the development of various tools and resources, most of which are either actively underway or completed. The SWOT analysis and the TOWS matrix enabled MHHLS to enhance the capacity of its vaccine safety program.

Safety of influenza vaccination in children with allergic diseases

OpenAIRE

Yang, Hyeon-Jong

2015-01-01

Global guidelines strongly recommend annual influenza vaccination in people age 6 months and older, particularly in asthmatic children. There is no doubt about the benefit of influenza vaccination in asthmatic children. However, some of the vaccine's components may elicit an IgE mediated hypersensitivity or disease exacerbation, including life-threatening events, in children with allergic diseases. As a result, concerns regarding the safety of the vaccine still continue today. The influenza v...

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

Science.gov (United States)

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.

Vaccine Pharmacovigilance: Adverse Effects Reported and the ...

African Journals Online (AJOL)

Routine utilization of vaccines during immunization in children is a tool in the reduction of childhood morbidity and mortality of infectious disease globally. This requires pharmacovigilance to ensure safety among the category of patients. Due to the exposure of new born to vaccine at birth, it became necessary to assess the ...

Safety and immunogenicity of TetractHib (a vaccine combining DTP ...

African Journals Online (AJOL)

The safety and immunogenicity of TETRActHIB (a vaccine combining diphtheria and tetanus toxoids-pertussis vaccine (DTP) with Haemophilus influenzae type b (Hib) conjugate vaccine (polyribosyl ribitol phosphate conjugated to tetanus protein) (PRP-T)) was assessed in 131 Cape Town infants immunised at 6, 10 and 14 ...

Analyzing and strengthening the vaccine safety program in Manitoba

Science.gov (United States)

Montalban, JM; Ogbuneke, C; Hilderman, T

2014-01-01

Background: The emergence of a novel influenza A virus in 2009 and the rapid introduction of new pandemic vaccines prompted an analysis of the current state of the adverse events following immunization (AEFI) surveillance response in several provinces. Objectives To highlight aspects of the situational analysis of the Manitoba Health, Healthy Living and Seniors (MHHLS’s) AEFI surveillance system and to demonstrate how common business techniques could be usefully applied to a provincial vaccine safety monitoring program. Method Situational analysis of the AEFI surveillance system in Manitoba was developed through a strengths-weaknesses-opportunities-threats (SWOT) analysis and informed by the National Immunization Strategy vaccine safety priorities. Strategy formulation was developed by applying the threats-opportunities-weaknesses-strengths (TOWS) matrix. Results Thirteen strategies were formulated that use strengths to either take advantage of opportunities or avoid threats, that exploit opportunities to overcome weaknesses, or that rectify weaknesses to circumvent threats. These strategies entailed the development of various tools and resources, most of which are either actively underway or completed. Conclusion The SWOT analysis and the TOWS matrix enabled MHHLS to enhance the capacity of its vaccine safety program. PMID:29769910

Safety and excellence--is regulation ensuring their achievement

International Nuclear Information System (INIS)

Levesque, R.J.A.

1992-01-01

Canada has a large, vigorous nuclear industry staffed by competent people, and a vigourous, independent regulatory agency similarly staffed. Nevertheless, there have been many signs over the last few years that the level of operating and engineering excellence needed to ensure a high level of safety was not being achieved in some key sections of the industry. Years of successful, accident-free operation - a hallmark of Canadian nuclear generating stations - are not by themselves a proof of adequate safety. Signs that the level of excellence is not being met in the nuclear reactor business have been seen, for example, in reviews of significant events, in the standard of generating documentation, and in the time taken to implement necessary design modifications. In the radioisotope business, the number of violations of licence conditions has been growing steadily, and there are an unacceptable number of workers exceeding regulatory dose limits. While many of these violations are minor in themselves, their prevalence suggests a degree of complacency has been developing which will be an enemy of excellence. Equally, the level of review, assessment, inspection and confirmatory research carried out in the past by the Atomic Energy Control Board (AECB) has been clearly inadequate. The paper discusses these and other examples of a lack of excellence, particularly in organization and management within its licensees and its effect on safety,. and identifies some of the performance indicators used. The paper also identifies some of the actions that are being taken by the AECB and the licensees to ensure an adequate level of safety is being maintained. The AECB is increasing, for example, its frequency of inspections in several industrial sectors and increasing its depth of safety review of nuclear generating stations

Immunization-Safety Monitoring Systems for the 2009 H1N1 Monovalent Influenza Vaccination Program

NARCIS (Netherlands)

Salmon, Daniel A.; Akhtar, Aysha; Mergler, Michelle J.; Vannice, Kirsten S.; Izurieta, Hector; Ball, Robert; Lee, Grace M.; Vellozzi, Claudia; Garman, Patrick; Cunningham, Francesca; Gellin, Bruce; Koh, Howard; Lurie, Nicole

The effort to vaccinate the US population against the 2009 H1N1 influenza virus hinged, in part, on public confidence in vaccine safety. Early in the vaccine program, >20% of parents reported that they would not vaccinate their children. Concerns about the safety of the vaccines were reported by

Safety of the yellow Fever vaccine: a retrospective study.

Science.gov (United States)

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

SAFETY OF CELL-DERIVED SUBUNIT ADJUVANTED INFLUENZA VACCINE FOR CHILDREN VACCINATION: DOUBLE-BLIND RANDOMIZED CLINICAL TRIAL

Directory of Open Access Journals (Sweden)

S.M. Kharit

2010-01-01

Full Text Available This article presents the safety data for cell-derived inactivated subunit adjuvanted influenza vaccine «Grippol Neo» in children 3–17 years old in comparison with reference egg-derived inactivated subunit vaccine «Grippol plus». Good test vaccine tolerability and high efficacy profile is demonstrated. Based on the results obtained vaccine «Grippol Neo» is recommended for mass influenza prophylaxis in pediatry, including National Immunization Schedule.Key words: children, influenza, vaccination, «Grippol Neo».(Voprosy sovremennoi pediatrii — Current Pediatrics. – 2010;9(4:44-49

Short and long-term safety of the 2009 AS03-adjuvanted pandemic vaccine.

Directory of Open Access Journals (Sweden)

Gaston De Serres

Full Text Available This study assessed the short and the long term safety of the 2009 AS03 adjuvanted monovalent pandemic vaccine through an active web-based electronic surveillance. We compared its safety profile to that of the seasonal trivalent inactivated influenza vaccine (TIV for 2010-2011.Health care workers (HCW vaccinated in 2009 with the pandemic vaccine (Arepanrix ® from GSK or HCW vaccinated in 2010 with the 2010-2011 TIV were invited to participate in a web-based active surveillance of vaccine safety. They completed two surveys the day-8 survey covered the first 7 days post-vaccination and the day-29 survey covered events occurring 8 to 28 days after vaccination. Those who reported a problem were called by a nurse to obtain details. The main outcome was the occurrence of a new health problem or the worsening of an existing health condition that resulted in a medical consultation or work absenteeism. For the pandemic vaccine, a six-month follow-up for the occurrence of serious adverse events (SAE was conducted. Among the 6242 HCW who received the pandemic vaccine, 440 (7% reported 468 events compared to 328 of the 7645 HCW (4.3% who reported 339 events after the seasonal vaccine. The 2009 pandemic vaccine was associated with significantly more local reactions than the 2010-2011 seasonal vaccine (1% vs. 0.03%, p<0.001. Paresthesia was reported by 7 HCW (0.1% after the pandemic vaccine but by none after the seasonal vaccine. For the pandemic vaccine, no clustering of SAE was found in the 6 month follow-up.The 2009 pandemic vaccine seems to have a good safety profile, similar to the 2010-2011 TIV, with the exception of local reactions. This surveillance was adequately powered to identify AE associated with an excess risk ≥1 per 1000 vaccinations but is insufficient to detect rare AE.ClinicalTrials.gov NCT01289418, NCT01318876.

Safety profile of the 9-valent HPV vaccine

DEFF Research Database (Denmark)

Moreira, Edson D; Block, Stan L; Ferris, Daron G

2016-01-01

OBJECTIVES: 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. METHODS: 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. RESULTS: The most common AEs (≥5%) experienced by 9vHPV vaccine recipients...

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

Directory of Open Access Journals (Sweden)

Moataz Alhaj

2016-01-01

Full Text Available 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.

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

Science.gov (United States)

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.

EVALUATION OF REACTOGENICITY, SAFETY AND IMMUNOGENICITY OF INACTIVATED MONOVALENT VACCINE IN CHILDREN

OpenAIRE

A.N. Mironov; A.A. Romanova; R.Ya. Meshkova; I.V. Fel’dblyum; N.V. Kupina; D.S. Bushmenkov; A.A. Tsaan

2010-01-01

NPO «Microgen» developed vaccine «PANDEFLU» — influenza inactivated subunit adsorbed monovalent vaccine, strain A/California/7/2009 (H1N1), for specific prophylaxis of pandemic influenza in different age groups of citizens. Reactogenicity, safety and immunogenicity were analyzed in a study of volunteers 18–60 years old. The article presents results of administration of vaccine «PANDEFLU» in children. The study performed in two clinical centers proves good tolerability, reactogenicity, safety ...

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

Science.gov (United States)

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

2017-10-27

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.

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

Science.gov (United States)

Tartof, Sara Yee; 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

2017-11-01

Quadrivalent meningococcal conjugate vaccine is recommended for children, adolescents and adults at increased risk of meningococcal disease. In 2011, MenACWY-CRM (Menveo, GSK, Siena, Italy) was approved for children 2-10 years of age in the United States. 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 prespecified events of interests (EOIs) and serious medically attended events (SMAEs) from inpatient or emergency settings up to 1 year after MenACWY-CRM vaccination. SMAEs were categorized by International Classification of Diseases, 9th revision 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 1 myasthenia gravis case underwent chart review which confirmed 1 incident asthma case occurring 237 days after concomitant vaccination with MenACWY-CRM and typhoid vaccine. Thirty-one children experienced SMAEs, most commonly because of 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.

Safety of the HPV Bivalent and Quadrivalent Vaccines During Pregnancy.

Science.gov (United States)

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.

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

Science.gov (United States)

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.

Ensuring the operational safety of finnish nuclear power plants

International Nuclear Information System (INIS)

Vuorinen, A.

1991-01-01

The Finnish nuclear energy programme has been successful both from the safety and economical point of view. These achievements are based on different factors which are discussed in the paper. Finnish Centre for Radiation and Nuclear Safety (STUK) has specified the technical requirements and procedures to be followed in the design, construction, commissioning and operation of NPPs in a series of guides. The guides are quite demanding and latest results of safety research and technical development are taken into account. Regulatory supervision of Finnish NPPs is comprehensive. As an example of this the regulatory inspection program for operational phase is presented. An important way to ensure operational safety of a NPP is to define a set of limits and conditions to identify limiting safety envelope for plant operation. Practices in Finland are reviewed in the paper. The strategy of Defence in Depth is amongst the fundamental principles of nuclear safety. Two corollary principles of defence of depth are accident prevention and accident mitigation. Means used in following these principles are discussed. (author)

Aerosol measles vaccination in macaques: Preclinical studies of immune responses and safety

NARCIS (Netherlands)

R.L. de Swart (Rik); T. Kuiken (Thijs); J. Fernandez-de Castro (Jorge); M.J. Papania (Mark); J.V. Bennett (John); J.L. Valdespino (José); P.D. Minor; C.L. Witham (Clyde); S. Yüksel (Selma); H.W. Vos (Helma); G. van Amerongen (Geert); A.D.M.E. Osterhaus (Albert)

2006-01-01

textabstractThe comparative efficacy and safety of measles vaccination via the aerosol route versus subcutaneous injection has not been fully resolved. We vaccinated cynomolgus monkeys (Macaca fascicularis) with the live-attenuated Edmonston-Zagreb measles virus (MV) vaccine and compared different

EFFICIENCY AND SAFETY OF VACCINATION AGAINST CHICKENPOX IN CHILDREN

Directory of Open Access Journals (Sweden)

A.G. Rumyantsev

2007-01-01

Full Text Available The article is dedicated to the problem of chicken pox in Russia and across the world, its social and economic aspects. The authors provides the modern information on the existing vaccines, their comparative efficacy in different age groups of the patients, as well as the patients from the high risk groups. The researchers reviewed the contraindications and restrictions against the immunization and analyzed the data on the safety and reactogenicity of the vaccine for the chicken pox prevention.Key words: chicken pox, vaccination, children.

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

Science.gov (United States)

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.

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

Science.gov (United States)

Amanna, Ian J.; Slifka, Mark K.

2016-01-01

Introduction 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. PMID:27267203

Safety and serologic response to a Haemonchus contortus vaccine in alpacas.

Science.gov (United States)

VanHoy, Grace; Carman, Michelle; Habing, Greg; Lakritz, Jeffrey; Hinds, C Austin; Niehaus, Andrew; Kaplan, Ray M; Marsh, Antoinette E

2018-03-15

Haemonchosis in camelids remains a challenging disease to treat, and prevention has become increasingly problematic due to widespread anthelmintic resistance. Barbervax ® is an adjuvanted vaccine containing natural H-11, H-gal-GP antigens obtained from Haemonchus contortus adults via a proprietary process and solubilized in Quil A. This vaccine is approved for use in Australia, after demonstrating its safety and efficacy in sheep and goats. There are no published studies evaluating Barbervax in other ruminants/pseudoruminants such as camelids which can be parasitized with H. contortus. The vaccine utilizes a mixture of the parasite gut mucosal membrane enzymes including H-gal-GP and H11, involved in digesting a blood meal from the host. This study monitored the safety profile of the Barbervax ® vaccine in a group of adolescent alpacas. Although designed into the original study of vaccine efficacy, the experimental infection with viable H. contortus third stage larvae could not be completed due to lack of detectable significant variation of infection following experimental challenge. Twelve alpacas (158 + 15 days) were randomized to vaccination with Barbervax ® or no treatment. Three doses of Barbervax ® were administered at 3 week intervals and investigators involved in animal monitoring and sample collection were blinded to the groupings. Clinical pathologic parameters were evaluated 7 days before vaccination, and 1 and 2 months post-vaccination. Daily clinical observations were made and specific observations regarding the injection site and rectal temperatures were monitored in each alpaca twice daily for 1 week following vaccination. Fecal egg counts, packed cell volume, and total protein were monitored following challenge with 1500 H. contortus larvae on days 42, 46, and 50. An increase in rectal temperature for a duration of 2 days (range 2-4 days) was observed post-vaccination. Vaccinated alpacas were lethargic for 2-3 days following vaccination

Immunogenicity and safety of a 13-valent pneumococcal conjugate vaccine administered to older infants and children naïve to pneumococcal vaccination.

Science.gov (United States)

Wysocki, Jacek; Brzostek, Jerzy; Szymański, Henryk; Tetiurka, Bogusław; Toporowska-Kowalska, Ewa; Wasowska-Królikowska, Krystyna; Sarkozy, Denise A; Giardina, Peter C; Gruber, William C; Emini, Emilio A; Scott, Daniel A

2015-03-30

Streptococcus pneumoniae infections are a major cause of morbidity and mortality in children vaccine (PCV13) has been developed and approved in many countries worldwide. Assess the safety and immunogenicity of PCV13 in healthy older infants and children naïve to previous pneumococcal vaccination. This was a phase 3, open-label, multicenter study conducted in Polish children (N=354) who were vaccinated according to 3 age-appropriate catch-up schedules: Group 1 (aged 7 to vaccine doses only; and Group 3 (aged 24 to vaccine, was determined for each vaccine serotype. In addition, antipolysaccharide immunoglobulin (Ig) G geometric mean concentrations (GMCs) were calculated. Safety assessments included systemic and local reactions, and adverse events. The proportion of immunological responders was ≥88% across groups for all serotypes. Antipolysaccharide IgG GMCs were generally similar across groups. Each schedule elicited immune response levels against all 13 serotypes comparable to or greater than levels previously reported in infants after a 3-dose series. The 3 catch-up schedules had similar tolerability and safety profiles; a trend was present towards greater local tenderness with increasing age and subsequent dose administration. Immunological responses and safety results support the use of PCV13 for catch-up schedules in older infants and children naïve to pneumococcal vaccination. Copyright © 2015. Published by Elsevier Ltd.

A New Method for the Evaluation of Vaccine Safety Based on Comprehensive Gene Expression Analysis

Directory of Open Access Journals (Sweden)

Haruka Momose

2010-01-01

Full Text Available For the past 50 years, quality control and safety tests have been used to evaluate vaccine safety. However, conventional animal safety tests need to be improved in several aspects. For example, the number of test animals used needs to be reduced and the test period shortened. It is, therefore, necessary to develop a new vaccine evaluation system. In this review, we show that gene expression patterns are well correlated to biological responses in vaccinated rats. Our findings and methods using experimental biology and genome science provide an important means of assessment for vaccine toxicity.

The safety and immunogenicity of influenza vaccine in children with asthma in Mexico.

Science.gov (United States)

Pedroza, Alvaro; Huerta, José G; Garcia, Maria de la Luz; Rojas, Arsheli; López-Martínez, Irma; Penagos, Martín; Franco-Paredes, Carlos; Deroche, Christele; Mascareñas, Cesar

2009-07-01

The morbidity and mortality associated with influenza is substantial in children with asthma. There are no available data on the safety and immunogenicity of influenza vaccine in children with asthma in Latin America. Furthermore, it is unclear if influenza vaccination may cause asthma exacerbations. We conducted a placebo-controlled trial to investigate the safety and immunogenicity of an inactivated trivalent split virus influenza vaccine in children with asthma in Mexico. We also measured the impact of influenza vaccination on pulmonary function tests in this population. The inactivated influenza vaccine was immunogenic and safe in terms of local and systemic side effects compared to placebo. We observed no significant impact on pulmonary function tests among vaccine recipients. Given the significant morbidity associated with influenza in children, strategies to promote increased influenza vaccination coverage in this high-risk group in Latin America and elsewhere are urgently needed.

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

Science.gov (United States)

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. Copyright © 2014 Elsevier Ltd. All rights reserved.

Yellow fever vaccination status and safety in hemodialysis patients.

Science.gov (United States)

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.

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

Science.gov (United States)

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

Immunogenicity and Safety of an Adjuvanted Herpes Zoster Subunit Vaccine Coadministered With Seasonal Influenza Vaccine in Adults Aged 50 Years or Older.

Science.gov (United States)

Schwarz, Tino F; Aggarwal, Naresh; Moeckesch, Beate; Schenkenberger, Isabelle; Claeys, Carine; Douha, Martine; Godeaux, Olivier; Grupping, Katrijn; Heineman, Thomas C; Fauqued, Marta Lopez; Oostvogels, Lidia; Van den Steen, Peter; Lal, Himal

2017-12-12

The immunogenicity and safety of an adjuvanted herpes zoster subunit (HZ/su) vaccine when coadministered with a quadrivalent seasonal inactivated influenza vaccine (IIV4) was investigated in a phase 3, open-label, randomized clinical trial in adults aged ≥50 years. Subjects were randomized 1:1 to receive either HZ/su (varicella zoster virus glycoprotein E; AS01B Adjuvant System) and IIV4 at day 0 followed by a second HZ/su dose at month 2 (coadministration group), or IIV4 at month 0 and HZ/su at months 2 and 4 (control group). The primary objectives were the HZ/su vaccine response rate in the coadministration group and the noninferiority of the antibody responses to HZ/su and IIV4 in the coadministration compared with the control group. Safety information was collected throughout the duration of the study. A total of 413 subjects were vaccinated in the coadministration group and 415 in the control group. The HZ/su vaccine response rate in the coadministration group was 95.8% (95% confidence interval, 93.3%-97.6%) and the anti-glycoprotein E GMCControl/Coadmin ratio was 1.08 (.97-1.20). The primary noninferiority objectives were met. No safety concerns were observed. No interference in the immune responses to either vaccine was observed when the vaccines were coadministered, and no safety concerns were identified. NCT01954251. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

The immunogenicity and safety of the new, Indonesian DTwP-HB-Hib vaccine compared to the DTwP/HB vaccine given with the Hib vaccine

Directory of Open Access Journals (Sweden)

Novilia Sjafri Bachtiar

2017-06-01

Full Text Available Background Haemophilus influenzae type b (Hib causes infection with predominant manifestations of pneumonia, meningitis, and other invasive diseases, occurring primarily in children aged under 2 years, particularly in infants.  The World Health Organization (WHO and Indonesian Technical Advisory Group for Immunization recommend to include the Hib vaccine into the national immunization program. The newly developed DTwP-HB-Hib combination vaccine is anticipated to be the preferred choice for Hib vaccine introduction; it is efficient, simple, and has higher coverage. Objective To evaluate the immunogenicity and safety of a new, combined Bio Farma DTwP-HB-Hib vaccine, compared to the registered Hib monovalent vaccine given simultaneously with the local DTwP-HB vaccine, when used as the primary vaccination of Indonesian infants. Methods A prospective, randomized, open-label, phase II study was conducted on the DTwP-HB-Hib vaccine compared to the Hib (registered vaccine given simultaneously with the DTwP-HB vaccine, in Bandung from July 2011 to January 2012. Infants were serially vaccinated at 6-11, 10-15, and 14-19 weeks. Serological assessments were done prior to the first vaccine dose and 28 days after the third dose. Safety was assessed from the time of first injection until 1 month after the last injection. Results Of 220 healthy infants enrolled, 211 completed the study, with 105 receiving the combined vaccine and 106 the two separate vaccines. All vaccines were well tolerated. No differences in rates of local and systemic reactions were seen between the two methods of administration. No serious adverse events were considered to be related to the vaccines. In the DTwP-HB-Hib primary-vaccination group, at least 98% of the infants reached protective levels of antibodies (seropositivity against the antigens employed in the vaccines while 96% in the control group. Conclusion The DTwP-HB-Hib combined vaccine is immunogenic and safe, as well as

Efficacy and Safety of the RTS,S/AS01 Malaria Vaccine during 18 Months after Vaccination

DEFF Research Database (Denmark)

Theander, Thor Grundtvig; Lusingu, John Peter Andrea

2014-01-01

BACKGROUND: A malaria vaccine could be an important addition to current control strategies. We report the safety and vaccine efficacy (VE) of the RTS,S/AS01 vaccine during 18 mo following vaccination at 11 African sites with varying malaria transmission. METHODS AND FINDINGS: 6,537 infants aged 6......-12 wk and 8,923 children aged 5-17 mo were randomized to receive three doses of RTS,S/AS01 or comparator vaccine. VE against clinical malaria in children during the 18 mo after vaccine dose 3 (per protocol) was 46% (95% CI 42% to 50%) (range 40% to 77%; VE, p... after vaccine dose 1 (intention to treat [ITT]) was 45% (95% CI 41% to 49%). VE against severe malaria, malaria hospitalization, and all-cause hospitalization was 34% (95% CI 15% to 48%), 41% (95% CI 30% to 50%), and 19% (95% CI 11% to 27%), respectively (ITT). VE against clinical malaria in infants...

Immunization Safety Review: Thimerosal - Containing Vaccines and Neurodevelopmental Disorders

National Research Council Canada - National Science Library

Stratton, Kathleen; Gable, Alicia; McCormick, Marie C

2001-01-01

In this report, the Immunization Safety Review committee examines the hypothesis of whether or not the use of vaccines containing the preservative thimerosal can cause neurodevelopmental disorders (NDDs...

Safety and immunogenicity of a candidate parvovirus B19 vaccine.

Science.gov (United States)

Bernstein, David I; El Sahly, Hana M; Keitel, Wendy A; Wolff, Mark; Simone, Gina; Segawa, Claire; Wong, Susan; Shelly, Daniel; Young, Neal S; Dempsey, Walla

2011-10-06

Parvovirus B19 is an important human pathogen causing erythema infectiosum, transient aplastic crisis in individuals with underlying hemolytic disorders and hydropsfetalis. We therefore evaluated a parvovirus B19 virus like particle (VLP) vaccine. The safety and immunogenicity of a 25 μg dose of parvovirus B19 recombinant capsid; 2.5 and 25 μg doses of the recombinant capsid given with MF59; and saline placebo were assessed in healthy adults. Because of 3 unexplained cutaneous events the study was halted after enrollment of 43 subjects and before any subject received their third scheduled dose. The rashes developed 5-9 days after the first or second injection and were seen in one placebo recipient (without an injection site lesion) and two vaccine recipients (with injection site reactions). No clear cause was established. Other safety evaluations revealed mostly injection site reactions that were mild to moderate with an increase in pain in subjects receiving vaccine and MF59. After dose 2 the majority of vaccine recipients developed ELISA and neutralizing antibody to parvovirus B19. Given the possible severe consequences of parvovirus B19 infection, further development of a safe and effective vaccine continues to be important. Copyright © 2011 Elsevier Ltd. All rights reserved.

BVDV vaccination in North America: risks versus benefits.

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Griebel, Philip J

2015-06-01

The control and prevention of bovine viral diarrhea virus (BVDV) infections has provided substantial challenges. Viral genetic variation, persistent infections, and viral tropism for immune cells have complicated disease control strategies. Vaccination has, however, provided an effective tool to prevent acute systemic infections and increase reproductive efficiency through fetal protection. There has been substantial controversy about the safety and efficacy of BVDV vaccines, especially when comparing killed versus modified-live viral (MLV) vaccines. Furthermore, numerous vaccination protocols have been proposed to protect the fetus and ensure maternal antibody transfer to the calf. These issues have been further complicated by reports of immune suppression during natural infections and following vaccination. While killed BVDV vaccines provide the greatest safety, their limited immunogenicity makes multiple vaccinations necessary. In contrast, MLV BVDV vaccines induce a broader range of immune responses with a longer duration of immunity, but require strategic vaccination to minimize potential risks. Vaccination strategies for breeding females and young calves, in the face of maternal antibody, are discussed. With intranasal vaccination of young calves it is possible to avoid maternal antibody interference and induce immune memory that persists for 6-8 months. Thus, with an integrated vaccination protocol for both breeding cows and calves it is possible to maximize disease protection while minimizing vaccine risks.

Establish Central Kitchen under HACCP Control in Food and Beverage Industry to Ensure Food Safety and Hygiene

Directory of Open Access Journals (Sweden)

Cuihua Qi

2014-04-01

Full Text Available In recent years, food safety and hygiene have been a social problem. So, it is worth studying in-depth that how to control the safety and hygiene of food and beverage. This paper proposes to establish central kitchens under HACCP control to ensure food safety and hygiene in the food and beverage industry. Considering the practical difficulties in the application of HACCP, this paper introduces the establishment of dishes HACCP system with some examples to give the reference of the food and beverage industry. Central kitchens have many advantages while HACCP is the golden standard to ensure food safety and hygiene, hence, it will ensure food safety and hygiene if both can be combined with in the use of food and beverage industry.

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

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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.

Live attenuated S. Typhimurium vaccine with improved safety in immuno-compromised mice.

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Balamurugan Periaswamy

Full Text Available 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.

Safety and immunogenicity of a live attenuated mumps vaccine

Science.gov (United States)

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

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

Science.gov (United States)

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

2018-01-01

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. PMID:27129416

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

Science.gov (United States)

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. Published by Elsevier Ltd.

Immunogenicity and Safety of the HZ/su Adjuvanted Herpes Zoster Subunit Vaccine in Adults Previously Vaccinated With a Live Attenuated Herpes Zoster Vaccine.

Science.gov (United States)

Grupping, Katrijn; Campora, Laura; Douha, Martine; Heineman, Thomas C; Klein, Nicola P; Lal, Himal; Peterson, James; Vastiau, Ilse; Oostvogels, Lidia

2017-12-12

Protection against herpes zoster (HZ) induced by the live attenuated zoster vaccine Zostavax (ZVL) wanes within 3-7 years. Revaccination may renew protection. We assessed whether (re)vaccination with the adjuvanted HZ subunit vaccine candidate (HZ/su) induced comparable immune responses in previous ZVL recipients and ZVL-naive individuals (HZ-NonVac). In an open-label, multicenter study, adults ≥65 years of age, vaccinated with ZVL ≥5 years previously (HZ-PreVac), were matched to ZVL-naive adults (HZ-NonVac). Participants received 2 doses of HZ/su 2 months apart. The primary objective of noninferiority of the humoral immune response 1 month post-dose 2 was considered demonstrated if the upper limit of the 95% confidence interval (CI) of the adjusted anti-glycoprotein E geometric mean concentration (GMC) ratio of HZ-NonVac over HZ-PreVac was <1.5. HZ/su cellular immunogenicity, reactogenicity, and safety were also assessed. In 430 participants, humoral immune response to HZ/su was noninferior in HZ-PreVac compared with HZ-NonVac (adjusted GMC ratio, 1.04 [95% CI, .92-1.17]). Cellular immunogenicity, reactogenicity, and safety appeared to be comparable between groups. HZ/su was well-tolerated, with no safety concerns raised within 1 month post-dose 2. HZ/su induces a strong immune response irrespective of prior vaccination with ZVL, and may be an attractive option to revaccinate prior ZVL recipients. NCT02581410. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Concomitant or sequential administration of live attenuated Japanese encephalitis chimeric virus vaccine and yellow fever 17D vaccine: randomized double-blind phase II evaluation of safety and immunogenicity.

Science.gov (United States)

Nasveld, Peter E; Marjason, Joanne; Bennett, Sonya; Aaskov, John; Elliott, Suzanne; McCarthy, Karen; Kanesa-Thasan, Niranjan; Feroldi, Emmanuel; Reid, Mark

2010-11-01

A randomized, double-blind, study was conducted to evaluate the safety, tolerability and immunogenicity of a live attenuated Japanese encephalitis chimeric virus vaccine (JE-CV) co-administered with live attenuated yellow fever vaccine (YF-17D strain; Stamaril®, Sanofi Pasteur) or administered successively. Participants (n = 108) were randomized to receive: YF followed by JE-CV 30 days later, JE followed by YF 30 days later, or the co-administration of JE and YF followed or preceded by placebo 30 days later or earlier. Placebo was used in a double-dummy fashion to ensure masking. Neutralizing antibody titers against JE-CV, YF-17D and selected wild-type JE strains was determined using a 50% serum-dilution plaque reduction neutralization test. Seroconversion was defined as the appearance of a neutralizing antibody titer above the assay cut-off post-immunization when not present pre-injection at day 0, or a least a four-fold rise in neutralizing antibody titer measured before the pre-injection day 0 and later post vaccination samples. There were no serious adverse events. Most adverse events (AEs) after JE vaccination were mild to moderate in intensity, and similar to those reported following YF vaccination. Seroconversion to JE-CV was 100% and 91% in the JE/YF and YF/JE sequential vaccination groups, respectively, compared with 96% in the co-administration group. All participants seroconverted to YF vaccine and retained neutralizing titers above the assay cut-off at month six. Neutralizing antibodies against JE vaccine were detected in 82-100% of participants at month six. These results suggest that both vaccines may be successfully co-administered simultaneously or 30 days apart.

New adjuvanted vaccines in pregnancy : what is known about their safety?

NARCIS (Netherlands)

Herberts, Carla; Melgert, Barbro; van der Laan, Jan Willem; Faas, Marijke

2010-01-01

The recent introduction of oil-in-water emulsions as adjuvants in several pandemic vaccines, such as the H1N1 vaccine, has challenged regulatory authorities to establish their safety in the general population, as well as in specific populations. Pregnant women were advised to be a target group for

Ensuring the operational safety of nuclear power plants with WWER reactors

International Nuclear Information System (INIS)

Shasharin, G.A.; Veretennikov, G.A.; Abagyan, A.A.; Lesnoj, S.A.

1984-01-01

At the start of 1983, 27 nuclear power producing units with reactor facilities of the WWER type were in operation in the Soviet Union and other countries. In 1982 the average load factor for nuclear power plants with WWER reactors was 73 per cent. There was not a single nuclear accident or even damage with any significant radiation consequences in the WWER reactors during the entire period of their operation. The most modern nuclear power plants with WWER-440 and WWER-1000 reactors meet all present-day international requirements. Safe operation of the plants is achieved by a variety of measures, the most important of which include: procedures for increasing the reliability of plant equipment and systems; ensuring exact compliance with plant operating instructions; ensuring reliable operation of plant safety systems; action directed towards maintaining the skills of plant personnel at a level adequate to ensure the taking of proper action during transient processes and accident situations. The paper discusses concrete steps for ensuring safe nuclear power plant operation along these lines. In particular, measures such as the following are described: the use of a system for collecting and processing information on equipment failures and defects; the development and introduction of methods of early defect diagnosis; the performance of complex testing of safety systems; the training of highly skilled personnel for nuclear power plants at educational combines and at teaching and training centres making use of simulators; arranging accident-prevention training and special instruction for personnel. (author)

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

Science.gov (United States)

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.

Parental Opinions and Attitudes about Children’s Vaccination Safety in Silesian Voivodeship, Poland

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Bogumiła Braczkowska

2018-04-01

Full Text Available Despite mandatory vaccinations in Poland, the final decision on vaccination in children is taken by their parents or legal guardians. Understanding parents’ attitudes and opinions regarding vaccinations is essential for planning and undertaking extensive and properly targeted educational actions aimed at preventing their hesitancy. In 2016, a cross-sectional study was conducted in the Silesian Voivodeship (Poland in 11 randomly selected educational institutions. The authors’ self-administered questionnaire contained 24 mixed-type questions. It was distributed among 3000 parents or legal guardians of children aged 6–13 years; prior consent of the relevant bioethics committee had been obtained. The response rate was 41.3% (N = 1239. Data were analysed using descriptive and analytical statistics, and focused on parental opinions regarding the safety of vaccines. Results of simple and multivariable analyses showed that perceived risk of adverse vaccine reaction (AVR, contraindications and perception of the qualification procedure for vaccination as substandard were significant factors associated with the rating of children’s vaccination as unsafe (p < 0.001. Respondents with a lower level of education, compared with those with higher, more often declared vaccinations to be safe (p = 0.03; however, results of multivariable analysis did not confirm that effect. AVR occurrence, finding of contraindication to vaccinations and perception of qualification procedure for vaccination were found to be the most important factors responsible for influencing general public opinions in the field of vaccination safety.

28 CFR 97.20 - Standards to ensure the safety of violent prisoners during transport.

Science.gov (United States)

2010-07-01

... physical safety of the prisoners during transport, including a first-aid kit and employees who are... transportation, where practicable; (f) Policies, practices, and procedures are in effect to ensure that female..., practices, and procedures are in effect to ensure that female guards are on duty to supervise the...

Rotavirus vaccines: safety, efficacy and public health impact.

Science.gov (United States)

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. © 2011 The Association for the Publication of the Journal of Internal Medicine.

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

Science.gov (United States)

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.

Post-authorization safety surveillance of a liquid pentavalent vaccine in Guatemalan children.

Science.gov (United States)

Asturias, Edwin J; Contreras-Roldan, Ingrid L; Ram, Malathi; Garcia-Melgar, Ana J; Morales-Oquendo, Vilma; Hartman, Katharina; Rauscher, Martina; Moulton, Lawrence H; Halsey, Neal A

2013-12-02

Combination vaccines have improved the efficiency of delivery of new vaccines in low and middle-income countries. Post-authorization monitoring of adverse events (AEs) after vaccination with a liquid pentavalent DTwP-HepB-Hib combination vaccine was conducted in Guatemalan infants. A prospective observational safety study of the incidence of medical attended events (MAEs) and serious adverse events (SAEs) in children who received pentavalent and oral polio vaccines at 2, 4 and 6 months of age was conducted in two clinics at the Institute of Guatemala. Parents were contacted by telephone after each dose. All outpatient, emergency department visits, and hospitalizations were monitored. A self-controlled analysis was conducted to determine if there was evidence of increased risk of MAEs or SAEs following vaccines as compared to control time windows. Of 3000 recruited infants, 2812 (93.7%) completed the third dose and 2805 (93.5%) completed follow-up. Ten AEs in eight infants, of which four SAEs in four infants, were classified as related to the vaccine. Thirteen deaths were reported due to common illnesses of infancy, and none were judged to be related to the vaccine. The mortality rate (4.4 per 1000) was lower than expected for the population. The incidence-rate-ratio for healthcare visits was lower in post-vaccination time windows than for control windows; after the first vaccine dose, the rate ratios for the risk periods of 0-1, 2-6, and 7-30 days post-vaccination were 0.3, 0.5, and 0.7, respectively (all statistically significantly different from the reference value of 1.0 for the 31-60 day control period). The liquid pentavalent vaccine was associated with lower rates of health care visits and not associated with increases in SAEs or hospitalizations. Systems can be set up in low to middle income countries to capture all health care visits to monitor the safety of new vaccines. Copyright © 2013 Elsevier Ltd. All rights reserved.

Importance of background rates of disease in assessment of vaccine safety during mass immunisation with pandemic H1N1 influenza vaccines

Science.gov (United States)

Black, Steven; Eskola, Juhani; Siegrist, Claire-Anne; Halsey, Neal; MacDonald, Noni; Law, Barbara; Miller, Elizabeth; Andrews, Nick; Stowe, Julia; Salmon, Daniel; Vannice, Kirsten; Izurieta, Hector S; Akhtar, Aysha; Gold, Mike; Oselka, Gabriel; Zuber, Patrick; Pfeifer, Dina; Vellozzi, Claudia

2010-01-01

Because of the advent of a new influenza A H1N1 strain, many countries have begun mass immunisation programmes. Awareness of the background rates of possible adverse events will be a crucial part of assessment of possible vaccine safety concerns and will help to separate legitimate safety concerns from events that are temporally associated with but not caused by vaccination. We identified background rates of selected medical events for several countries. Rates of disease events varied by age, sex, method of ascertainment, and geography. Highly visible health conditions, such as Guillain-Barré syndrome, spontaneous abortion, or even death, will occur in coincident temporal association with novel influenza vaccination. On the basis of the reviewed data, if a cohort of 10 million individuals was vaccinated in the UK, 21·5 cases of Guillain-Barré syndrome and 5·75 cases of sudden death would be expected to occur within 6 weeks of vaccination as coincident background cases. In female vaccinees in the USA, 86·3 cases of optic neuritis per 10 million population would be expected within 6 weeks of vaccination. 397 per 1 million vaccinated pregnant women would be predicted to have a spontaneous abortion within 1 day of vaccination. PMID:19880172

SAFETY AND IMMUNOLOGIC EFFICACY OF COMBINED IMMUNIZATION IN CHILDREN AGED 6—7 YEARS WITH VACCINES FROM THE NATIONAL CALENDAR OF PROPHYLACTICS VACCINES

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I. V. Konovalov

2013-01-01

Full Text Available We estimated the safety of the vaccination for prevention of influenza with Grippol® plus vaccine alongside with vaccination with combined preparations for the prevention of diphtheria and tetanus (Td and measles, rubella, mumps in children aged 6—7 years. We determined that combined immunization with the indicated vaccines proves good tolerability and low reactogenicity. Vaccine Grippol® Plus shows low reactogenicity , high immunologenicity and does not cause cross-suppression of antibodies in co-administration with other vaccines on vaccination calendar. Also concomitant vaccination with Grippol® plus and other vaccines does not inhibit the development of a specific immune response against influenza.

The role of hazard- and risk-based approaches in ensuring food safety

DEFF Research Database (Denmark)

Barlow, Susan M.; Boobis, Alan R.; Bridges, Jim

2015-01-01

action. Risk-based approaches allow consideration of exposure in assessing whether there may be unacceptable risks to health. Scope and approach The advantages and disadvantages of hazard- and risk-based approaches for ensuring the safety of food chemicals, allergens, ingredients and microorganisms were...

Radiation processing of minimally processed fruits and vegetables to ensure microbiological safety

International Nuclear Information System (INIS)

Bandekar, J.R.; Saroj, S.D.; Shashidhar, R.; Dhokane, V.S.; Hajare, S.N.; Nagar, V.; Sharma, A.

2009-01-01

Minimally processed fruits and vegetables are in demand as they offer ready rich source of nutrients and convenience to consumers. However, these products are often unsafe due to contamination with harmful pathogens. Therefore, a study was carried out to analyze microbiological quality of minimally processed fruits, vegetables and sprouts and to optimize radiation dose necessary to ensure safety of these commodities. Microbiological quality of these products was found to be poor. Decimal reduction dose (D 10 ) for Salmonella Typhimurium and Listeria monocytogenes in these minimally processed foods (MPF) were in the range of 164 to 588 Gy. Radiation processing with 2 kGy dose of gamma radiation resulted in 5 log reduction of S. Typhimurium and 4 log reduction of L. monocytogenes. The treatment did not significantly affect nutritional, organoleptic and textural properties. These results suggest that radiation processing can ensure safety of these products. (author)

Safety evaluation in mice of the childhood immunization vaccines from two south-eastern states of Nigeria

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Oli Angus Nnamdi

2015-02-01

Conclusions:: The vaccine samples tested were safe and did not affect the hematopoietic system adversely. The storage conditions of the vaccines in the States’ cold-chain stores had not compromised the safety of the vaccines.

Frequency of medically attended adverse events following tetanus and diphtheria toxoid vaccine in adolescents and young adults: a Vaccine Safety Datalink study

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Naleway Allison

2009-10-01

Full Text Available Abstract Background Local reactions are the most commonly reported adverse events following tetanus and diphtheria toxoid (Td vaccine and the risk of local reactions may increase with number of prior Td vaccinations. Methods To estimate the risk of medically attended local reactions following Td vaccination in adolescents and young adults we conducted a six-year retrospective cohort study assessing 436,828 Td vaccinations given to persons 9 through 25 years of age in the Vaccine Safety Datalink population from 1999 through 2004. Results Overall, the estimated risk of a medically attended local reaction was 3.6 events per 10,000 Td vaccinations. The lowest risk (2.8 events per 10,000 vaccinations was found in the 11 to 15 year old age group. In comparison with that group, the event risks were significantly higher in both the 9 to 10 and 21 to 25 year old age groups. The risk of a local reaction was significantly higher in persons who had received another tetanus and diphtheria toxoid containing vaccine (TDCV in the previous five years (incidence rate ratio, 2.9; 95% confidence interval, 1.2 to 7.2. Twenty-eight percent of persons with a local reaction to Td vaccine were prescribed antibiotics. Conclusion Medically attended local reactions were uncommon following Td vaccination. The risk of those reactions varied by age and by prior receipt of TDCVs. These findings provide a point of reference for future evaluations of the safety profile of newer vaccines containing tetanus or diphtheria toxoid.

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

Science.gov (United States)

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

In Vivo Safety Studies With SPBN GASGAS in the Frame of Oral Vaccination of Foxes and Raccoon Dogs Against Rabies

Directory of Open Access Journals (Sweden)

Steffen Ortmann

2018-05-01

Full Text Available In order to obtain Marketing Authorization for an oral rabies vaccine in the European Union, not only safety studies in the target species, red fox and raccoon dog, are required. Since baits are distributed unsupervised in the environment, specific safety studies in selected non-target species are compulsory. Furthermore, oral rabies vaccines are based on live, replication-competent viruses and thus distinct safety studies in the target species for such type of vaccines are also mandatory. Here, the results of these safety studies in target and selected non-target species for a 3rd generation oral rabies virus vaccine construct, SPBN GASGAS (Rabitec, are presented. The studies included the following species; red fox, raccoon dog, domestic dog, domestic cat, domestic pig, wild rodents. The following safety topics were investigated; overdose, repeated dose, dissemination, shedding, horizontal and vertical transmission. It was shown that SPBN GASGAS did not cause disease or any other adverse reaction in vaccinated animals and naïve contact animals. The vaccine did not disseminate within the host beyond the site of entry. No horizontal transmission was observed in wild rodents. In the target species, there was evidence that in a few cases horizontal transmission of vaccine virus could have occurred under these experimental conditions; most likely immediately after vaccine administration. The vaccine construct SPBN GASGAS meets therefore the latest revised minimal safety requirements as laid down in the European Pharmacopoeia.

Risk of venous thromboembolism following influenza vaccination in adults aged 50years and older in the Vaccine Safety Datalink.

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Vickers, Elizabeth R; McClure, David L; Naleway, Allison L; Jacobsen, Steven J; Klein, Nicola P; Glanz, Jason M; Weintraub, Eric S; Belongia, Edward A

2017-10-13

Influenza-like illness and inflammation are known risk factors for venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE). However, few studies have characterized the risk of VTE following influenza vaccination. We examined VTE risk after vaccination in adults 50years old and older within the Vaccine Safety Datalink (VSD). We used the self-controlled case series method to determine the risk of VTE among age-eligible adults who received influenza vaccine (with or without pandemic H1N1) and experienced a VTE during the months of September through December in 2007 through 2012. Presumptive VTE cases were identified among VSD participants using diagnostic codes, diagnostic tests, and oral anticoagulant prescription. Potential cases were validated by medical record review. The VTE incidence rate ratio was calculated among confirmed cases for the risk window 1 to 10days after vaccination relative to all other person-time from September through December. Of the 1,488 presumptive cases identified, 508 were reviewed, of which 492 (97%) were confirmed cases of VTE. The analysis included 396 incident, confirmed cases. Overall, there was no increased risk of VTE in the 1 to 10days after influenza vaccination (IRR=0.89, 95% CI 0.69-1.17) compared to the control period. Results were similar when all person-time was censored before vaccination. A post hoc analysis showed an increased risk among current tobacco smokers (IRR=2.57, 95% CI 1.06-6.23). No clustering of VTE was observed in the 1-42days after vaccination. Overall, there was no evidence that inactivated influenza vaccine was associated with VTE in adults ≥50years old. An increased risk was found among current smokers in a post hoc analysis. These findings are consistent with previous research and support the safety of annual vaccination in this population. Copyright © 2017 Elsevier Ltd. All rights reserved.

Immunogenicity and safety of concomitant administration of a combined hepatitis A/B vaccine and a quadrivalent meningococcal conjugate vaccine in healthy adults.

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Alberer, Martin; Burchard, Gerd; Jelinek, Tomas; Reisinger, Emil C; Meyer, Seetha; Forleo-Neto, Eduardo; Dagnew, Alemnew F; Arora, Ashwani Kumar

2015-01-01

This phase 3b randomized, open-label study evaluated the immunogenicity and safety of coadministration of a hepatitis A and/or B vaccine with a quadrivalent oligosaccharide meningococcal CRM197 -conjugate vaccine (MenACWY-CRM), in the context of an accelerated hepatitis A and/or B immunization schedule. A total of 252 healthy adult subjects were randomized to three groups to receive hepatitis A/B only (HepA/B), hepatitis A/B coadministered with MenACWY-CRM (HepA/B+MenACWY-CRM), or MenACWY-CRM only (MenACWY-CRM). Hepatitis A and/or B vaccination was administered in the form of a single booster dose or a primary three-dose series, depending on the hepatitis A and/or B vaccination history of subjects. Antibody responses to hepatitis A/B vaccination were assessed 1 month following the last hepatitis A and/or B dose. Serum bactericidal activity with human complement (hSBA) against meningococcal serogroups A, C, W-135, and Y was assessed 1 month post-MenACWY-CRM vaccination. Safety was monitored throughout the study. At 1 month following the final hepatitis A and/or B vaccination, concomitant administration of hepatitis A/B and MenACWY-CRM was non-inferior to administration of hepatitis A/B alone in terms of geometric mean concentrations of antibodies against the hepatitis A and B antigens. One month post-MenACWY-CRM vaccination, the percentages of subjects achieving hSBA titers ≥8 for serogroups A, C, W-135, and Y in the HepA/B+MenACWY-CRM group (76, 87, 99, and 94%, respectively) were comparable to those in the MenACWY-CRM group (67, 82, 96, and 88%, respectively). The percentages of subjects reporting adverse events (AEs) were similar across study groups and a majority of the reported AEs were mild to moderate in nature. There were no study vaccine-related serious AEs. MenACWY-CRM can be administered concomitantly with a hepatitis A and/or B vaccine in the context of an accelerated hepatitis A and/or B immunization schedule without increasing safety concerns

The role of hazard- and risk-based approaches in ensuring food safety

NARCIS (Netherlands)

Barlow, S.M.; Boobis, A.R.; Bridges, J.; Cockburn, A.; Dekant, W.; Hepburn, P.; Houben, G.F.; König, J.; Nauta, M.J.; Schuermans, J.; Bánáti, D.

2015-01-01

Background: Food legislation in the European Union and elsewhere includes both hazard- and risk-based approaches for ensuring safety. In hazard-based approaches, simply the presence of a potentially harmful agent at a detectable level in food is used as a basis for legislation and/or risk management

Effect of vaccine dose on the safety and immunogenicity of a candidate TB vaccine, MVA85A, in BCG vaccinated UK adults.

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Pathan, Ansar A; Minassian, Angela M; Sander, Clare R; Rowland, Rosalind; Porter, David W; Poulton, Ian D; Hill, Adrian V S; Fletcher, Helen A; McShane, Helen

2012-08-17

A non-randomised, open-label, Phase I safety and immunogenicity dose-finding study to assess the safety and immunogenicity of the candidate TB vaccine Modified Vaccinia virus Ankara expressing Antigen 85A (MVA85A) from Mycobacterium tuberculosis (MTB) in healthy adult volunteers previously vaccinated with BCG. Healthy BCG-vaccinated volunteers were vaccinated with either 1×10(7) or 1×10(8)PFU of MVA85A. All adverse events were documented and antigen specific T cell responses were measured using an ex vivo IFN-γ ELISPOT assay. Safety and immunogenicity were compared between the 2 dose groups and with a previous trial in which a dose of 5×10(7)PFU MVA85A had been administered. There were no serious adverse events recorded following administration of either 1×10(7) or 1×10(8)PFU of MVA85A. Systemic adverse events were more frequently reported following administration of 1×10(8)PFU of MVA85A when compared to either 5×10(7) or 1×10(7)PFU of MVA85A but were mild or moderate in severity and resolved completely within 7 days of immunisation. Antigen specific T cell responses as measured by the IFN-γ ELISPOT were significantly higher following immunisation in adults receiving 1×10(8)PFU compared to the 5×10(7) and 1×10(7) doses. Additionally, a broader range of Ag85A epitopes are detected following 1×10(8)PFU of MVA85A. A higher dose of 1×10(8)PFU of MVA85A is well-tolerated, increases the frequency of IFN-γ secreting T cells detected following immunisation and broadens the range of Ag85A epitopes detected. Copyright © 2012 Elsevier Ltd. All rights reserved.

Predictive markers of safety and immunogenicity of adjuvanted vaccines.

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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.

Post-marketing safety surveillance for inactivated and live-attenuated Japanese encephalitis vaccines in China, 2008-2013.

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Wu, Wendi; Liu, Dawei; Li, Keli; Nuorti, J Pekka; Nohynek, Hanna M; Xu, Disha; Ye, Jiakai; Zheng, Jingshan; Wang, Huaqing

2017-06-22

Two types of Japanese encephalitis (JE) vaccines, inactivated JE vaccine (JE-I) and live-attenuated JE vaccine (JE-L), are available and used in China. In particular, one JE-L, produced by a domestic manufacturer in China, was prequalified by WHO in 2013. We assessed the safety of JE vaccines in China during 2008-2013 using the Chinese National Adverse Events Following Immunization Information System (CNAEFIS) data. We retrieved AEFI reporting data about JE vaccines from CNAEFIS, 2008-2013, examined demographic characteristics of AEFI cases, and used administrative data on vaccine doses as denominator to calculate and compare crude reporting rates. We also used disproportionality reporting analysis between JE-I and JE-L to assess potential safety signals. A total of 34,879 AEFIs related with JE-I and JE-L were reported, with a ratio of male to female as 1.3:1; 361 (1.0%) cases were classified as serious. JE vaccines were administered concurrently with one or more other vaccines in 13,592 (39.0%) of cases. The overall AEFI reporting rates were 214.4 per million vaccination doses for JE-L and 176.9 for JE-I (rate ratio [RR]: 1.2, 95% confidence interval [CI]: 1.1-1.3) in 2010-2013. Febrile convulsions (FC) following JE-I was found as a signal of disproportionate reporting (SDR). However, there was no significant difference between the reporting rates of FC of JE-I and JE-L (0.3 per million vaccination doses for JE-L, 0.4 for JE-I, p=0.05). While our analysis did not find apparent safety concern of JE vaccines in China, further study should consider JE-I vaccines and febrile convulsion, and taking more sensitive methods to detect signals. Copyright © 2017. Published by Elsevier Ltd.

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

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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.

Towards a Usability and Error "Safety Net": A Multi-Phased Multi-Method Approach to Ensuring System Usability and Safety.

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Kushniruk, Andre; Senathirajah, Yalini; Borycki, Elizabeth

2017-01-01

The usability and safety of health information systems have become major issues in the design and implementation of useful healthcare IT. In this paper we describe a multi-phased multi-method approach to integrating usability engineering methods into system testing to ensure both usability and safety of healthcare IT upon widespread deployment. The approach involves usability testing followed by clinical simulation (conducted in-situ) and "near-live" recording of user interactions with systems. At key stages in this process, usability problems are identified and rectified forming a usability and technology-induced error "safety net" that catches different types of usability and safety problems prior to releasing systems widely in healthcare settings.

Safety and immunogenicity of coadministering a combined meningococcal serogroup C and Haemophilus influenzae type b conjugate vaccine with 7-valent pneumococcal conjugate vaccine and measles, mumps, and rubella vaccine at 12 months of age.

Science.gov (United States)

Miller, Elizabeth; Andrews, Nick; Waight, Pauline; Findlow, Helen; Ashton, Lindsey; England, Anna; Stanford, Elaine; Matheson, Mary; Southern, Joanna; Sheasby, Elizabeth; Goldblatt, David; Borrow, Ray

2011-03-01

The coadministration of the combined meningococcal serogroup C conjugate (MCC)/Haemophilus influenzae type b (Hib) vaccine with pneumococcal conjugate vaccine (PCV7) and measles, mumps, and rubella (MMR) vaccine at 12 months of age was investigated to assess the safety and immunogenicity of this regimen compared with separate administration of the conjugate vaccines. Children were randomized to receive MCC/Hib vaccine alone followed 1 month later by PCV7 with MMR vaccine or to receive all three vaccines concomitantly. Immunogenicity endpoints were MCC serum bactericidal antibody (SBA) titers of ≥8, Hib-polyribosylribitol phosphate (PRP) IgG antibody concentrations of ≥0.15 μg/ml, PCV serotype-specific IgG concentrations of ≥0.35 μg/ml, measles and mumps IgG concentrations of >120 arbitrary units (AU)/ml, and rubella IgG concentrations of ≥11 AU/ml. For safety assessment, the proportions of children with erythema, swelling, or tenderness at site of injection or fever or other systemic symptoms for 7 days after immunization were compared between regimens. No adverse consequences for either safety or immunogenicity were demonstrated when MCC/Hib vaccine was given concomitantly with PCV and MMR vaccine at 12 months of age or separately at 12 and 13 months of age. Any small differences in immunogenicity were largely in the direction of a higher response when all three vaccines were given concomitantly. For systemic symptoms, there was no evidence of an additive effect; rather, any differences between schedules showed benefit from the concomitant administration of all three vaccines, such as lower overall proportions with postvaccination fevers. The United Kingdom infant immunization schedule now recommends that these three vaccines may be offered at one visit at between 12 and 13 months of age.

Safety and immunogenicity of a meningococcal B recombinant vaccine when administered with routine vaccines to healthy infants in Taiwan: A phase 3, open-label, randomized study.

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Chiu, Nan-Chang; Huang, Li-Min; Willemsen, Arnold; Bhusal, Chiranjiwi; Arora, Ashwani Kumar; Mojares, Zenaida Reynoso; Toneatto, Daniela

2018-01-16

Neisseria meningitidis is associated with high mortality and morbidity in infants and children worldwide. This phase 3 study (NCT02173704) evaluated safety and immunogenicity of a 4-component serogroup B recombinant meningococcal vaccine (4CMenB) co-administered with routine vaccines in Taiwanese infants. In total, 225 healthy infants were randomized (2 : 1 ) to receive 4CMenB and routine vaccines (4CMenB+Routine) or routine vaccines only (Routine group) at 2, 4, 6 and 12 months of age. Routine vaccines were diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b, 13-valent pneumococcal, hepatitis B, measles-mumps-rubella and varicella vaccines. Immune responses to 4CMenB components (factor H binding protein [fHbp], Neisserial adhesin A [NadA], porin A [PorA] and Neisseria heparin-binding antigen [NHBA]) were evaluated at 1 month post-primary and post-booster vaccination, using human serum bactericidal assay (hSBA). Reactogenicity and safety were also assessed. A sufficient immune response was demonstrated for fHbp, NadA and PorA, at 1 month post-primary and booster vaccination. In the 4CMenB+Routine group, hSBA titers ≥5 were observed in all infants for fHbp and NadA, in 79% and 59% of infants for PorA and NHBA, respectively, at 1 month post-primary vaccination and in 92-99% of infants for all antigens, at 1 month post-booster vaccination. In the 4CMenB+Routine group, hSBA geometric mean titers for all antigens increased post-primary (8.41-963) and post-booster vaccination (17-2315) compared to baseline (1.01-1.36). Immunogenicity of 4CMenB was not impacted by co-administration with routine pediatric vaccines in infants. Reactogenicity was slightly higher in the 4CMenB+Routine group compared with Routine group, but no safety concerns were identified.

Safety of a meningococcal group B vaccine used in response to two university outbreaks.

Science.gov (United States)

Duffy, Jonathan; Johnsen, Peter; Ferris, Mary; Miller, Mary; Leighton, Kevin; McGilvray, Mark; McNamara, Lucy; Breakwell, Lucy; Yu, Yon; Bhavsar, Tina; Briere, Elizabeth; Patel, Manisha

2017-03-31

To assess the safety of meningococcal group B (MenB)-4C vaccine. Undergraduates, dormitory residents, and persons with high-risk medical conditions received the MenB-4C vaccine two-dose series during mass vaccination clinics from 12/2013 through 11/2014. Adverse events (AEs) were identified by 15 minutes of observation postvaccination, spontaneous reports, surveys, and hospital surveillance. Causality was assessed for serious adverse events (SAEs). 16,974 persons received 31,313 MenB-4C doses. The incidence of syncope during the 15-minutes post-dose 1 was 0.88/1000 persons. 2% of participants spontaneously reported an AE (most common were arm pain and fever). 3 SAEs were suspected of being caused by the vaccine, including one case of anaphylaxis. Most AEs reported were nonserious and consistent with previous clinical trial findings. Measures to prevent injury from syncope and to treat anaphylaxis should be available wherever vaccines are administered. Our safety evaluation supports the use of MenB-4C in response to outbreaks.

Prevention of rotavirus gastroenteritis in infants and children: rotavirus vaccine safety, efficacy, and potential impact of vaccines

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Aruna Chandran

2010-07-01

Full Text Available Aruna Chandran1, Sean Fitzwater1, Anjie Zhen2, Mathuram Santosham11Department of International Health, Division of Health Systems, 2Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USAAbstract: Rotavirus infection is the most common cause of severe gastroenteritis globally, with greater than 86% of deaths occurring in low-income and middle-income countries. There are two rotavirus vaccines currently licensed in the United States and prequalified by the World Health Organization. RV1 is a monovalent attenuated human rotavirus strain, given orally in two doses. RV5 is a pentavalent human-bovine reassortant rotavirus vaccine, given orally in three doses. A third rotavirus vaccine, LLV, is a lamb rotavirus strain given orally as a single dose, which is currently available only in China. RV1 and RV5 have been shown to be highly efficacious in developed countries, and initial results from trials in Africa and Asia are promising as well. At least three other vaccines are in development, which are being developed by manufacturers of developing countries. Further studies are needed to clarify issues including administration of oral rotavirus vaccines with breastfeeding and other oral vaccines, and alterations in dosing schedule. Using new data on global diarrheal burden, rotavirus is estimated to cause 390,000 deaths in children younger than 5 years. Should rotavirus vaccines be introduced in the routine immunization programs of all countries, a potential of 170,000 deaths could be prevented annually. The largest impact on mortality would be seen in low-income and middle-income countries, despite poor immunization coverage and lower efficacy. Therefore, international efforts are needed to ensure that rotavirus vaccines reach the populations with highest burden of rotavirus disease.Keywords: vaccination, mortality, rotavirus, gastroenteritis

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

DEFF Research Database (Denmark)

Castellsagué, X; Giuliano, A R; Goldstone, S

2015-01-01

OBJECTIVES: 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 9v......HPV 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. METHODS: 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...

Does vaccination ensure protection? Assessing diphtheria and tetanus antibody levels in a population of healthy children

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Gowin, Ewelina; Wysocki, Jacek; Kałużna, Ewelina; Świątek-Kościelna, Bogna; Wysocka-Leszczyńska, Joanna; Michalak, Michał; Januszkiewicz-Lewandowska, Danuta

2016-01-01

Abstract Vaccination effectiveness is proven when the disease does not develop after a patient is exposed to the pathogen. In the case of rare diseases, vaccination effectiveness is assessed by monitoring specific antibody levels in the population. Such recurrent analyses allow the evaluation of vaccination programs. The primary schedule of diphtheria and tetanus vaccinations is similar in various countries, with differences mainly in the number and timing of booster doses. The aim of the study was to assess diphtheria and tetanus antibody concentrations in a population of healthy children. Diphtheria and tetanus antibody levels were analyzed in a group of 324 children aged 18 to 180 months. All children were vaccinated in accordance with the Polish vaccination schedule. Specific antibody concentrations greater than 0.1 IU/mL were considered protective against tetanus or diphtheria. Levels above 1.0 were considered to ensure long-term protection. Protective levels of diphtheria antibodies were found in 229 patients (70.46%), and of tetanus in 306 patients (94.15%). Statistically significant differences were found in tetanus antibody levels in different age groups. Mean concentrations and the percentage of children with high tetanus antibody titers increased with age. No similar correlation was found for diphtheria antibodies. High diphtheria antibody levels co-occurred in 72% of the children with high tetanus antibody levels; 95% of the children with low tetanus antibody levels had low levels of diphtheria antibodies. The percentage of children with protective diphtheria antibody levels is lower than that in the case of tetanus antibodies, both in Poland and abroad, but the high proportion of children without diphtheria protection in Poland is an exception. This is all the more puzzling when taking into account that Polish children are administered a total of 5 doses containing a high concentration of diphtheria toxoid, at intervals shorter than 5 years. The

Correlation of genetic variability with safety of mumps vaccine Urabe AM9 strain.

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Amexis, G; Fineschi, N; Chumakov, K

2001-08-15

The Urabe AM9 strain of mumps vaccine live is known for its genetic instability and some vaccines derived from this strain were withdrawn from the market due to an excessive number of vaccine-associated parotitis and meningitis cases. To identify the molecular basis of this instability, we determined complete nucleotide sequences of several stocks of the Urabe strain used for vaccine production by different manufacturers and of two clinical isolates from cases of vaccine-associated meningitis. In contrast to previously published studies relating the Lys335 --> Glu mutation in the viral HN gene with neurovirulence of mumps virus, we could not confirm any association of this mutation with the safety of mumps vaccine. Each of the three vaccine stocks studied had its own characteristic profile of mutations that was identified by cDNA sequencing and quantitated by mutant analysis by PCR and restriction enzyme cleavage. Determination of the mutational profile of mumps vaccine lots could allow vaccine manufacturers to characterize seed viruses and monitor the consistency of vaccine production to prevent emergence of virulent revertants.

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

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Birgit Schäfer

Full Text Available BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: 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.

Pre-Clinical Efficacy and Safety of Experimental Vaccines Based on Non-Replicating Vaccinia Vectors against Yellow Fever

Science.gov (United States)

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

Background 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. Methodology/Principal Findings 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 105 TCID50. 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. Conclusions/Significance 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. PMID:21931732

Safety and immunogenicity of a combined Tetanus, Diphtheria, recombinant acellular Pertussis vaccine (TdaP) in healthy Thai adults.

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Sirivichayakul, Chukiat; Chanthavanich, Pornthep; Limkittikul, Kriengsak; Siegrist, Claire-Anne; Wijagkanalan, Wassana; Chinwangso, Pailinrut; Petre, Jean; Hong Thai, Pham; Chauhan, Mukesh; Viviani, Simonetta

2017-01-02

An acellular Pertussis (aP) vaccine containing recombinant genetically detoxified Pertussis Toxin (PTgen), Filamentous Hemagglutinin (FHA) and Pertactin (PRN) has been developed by BioNet-Asia (BioNet). We present here the results of the first clinical study of this recombinant aP vaccine formulated alone or in combination with tetanus and diphtheria toxoids (TdaP). A phase I/II, observer-blind, randomized controlled trial was conducted at Mahidol University in Bangkok, Thailand in healthy adult volunteers aged 18-35 y. The eligible volunteers were randomized to receive one dose of either BioNet's aP or Tetanus toxoid-reduced Diphtheria toxoid-acellular Pertussis (TdaP) vaccine, or the Tdap Adacel® vaccine in a 1:1:1 ratio. Safety follow-up was performed for one month. Immunogenicity was assessed at baseline, at 7 and 28 d after vaccination. Anti-PT, anti-FHA, anti-PRN, anti-tetanus and anti-diphtheria IgG antibodies were assessed by ELISA. Anti-PT neutralizing antibodies were assessed also by CHO cell assay. A total of 60 subjects (20 per each vaccine group) were enrolled and included in the safety analysis. Safety laboratory parameters, incidence of local and systemic post-immunization reactions during 7 d after vaccination and incidence of adverse events during one month after vaccination were similar in the 3 vaccine groups. One month after vaccination, seroresponse rates of anti-PT, anti-FHA and anti-PRN IgG antibodies exceeded 78% in all vaccine groups. The anti-PT IgG, anti-FHA IgG, and anti-PT neutralizing antibody geometric mean titers (GMTs) were significantly higher following immunization with BioNet's aP and BioNet's TdaP than Adacel® (Pdiphtheria GMTs at one month after immunization were comparable in all vaccine groups. All subjects had seroprotective titers of anti-tetanus and anti-diphtheria antibodies at baseline. In this first clinical study, PTgen-based BioNet's aP and TdaP vaccines showed a similar tolerability and safety profile to Adacel

Safety Analysis for Pentavaccine Used in Premature Infants: Family Vaccination Centre’s Experiment

Directory of Open Access Journals (Sweden)

D. А. Novikova

2015-01-01

Full Text Available Combined vaccines containing non-cellular pertussis component and having low reactogenicity, increase vaccination coverage against controllable infections. However, the safety of vaccination in children dealing with health issues, as well as those having a history of premature infancy, requires additional research. The article presents reactogenicity analysis for the DTP-IPV/HIB pentavaccine during primary vaccination and revaccination of premature infants (n = 85, as well as vaccination of mature newborns (n = 1433 inoculated in accordance with the national Vaccination Calendar behind the schedule. The occurrence of post-vaccinal reactions in the premature infant group was the same as in the mature infant group and amounted to 41.2% and 45.0%; the occurrence of common reactions was 18.8% and 22.4%; local effects measured 25.8% and 27.9% respectively. Post-vaccinal reactions were either weak or moderate, not requiring treatment, and they would completely disappear by the end of the third post-vaccinal day. Simultaneous injection of pentavaccine and Hepatitis B vaccine and pneumococcal conjugate vaccine in children with a history of premature infancy, showed no influence during the post-vaccinal period. The reactogenicity of pentavaccine increased along with the vaccination ratio during the primary series of vaccinations. 

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

Directory of Open Access Journals (Sweden)

Ana Katherine Gonçalves

2014-11-01

Full Text Available 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.

Herpes zoster vaccine live: A 10 year review of post-marketing safety experience.

Science.gov (United States)

Willis, English D; Woodward, Meredith; Brown, Elizabeth; Popmihajlov, Zoran; Saddier, Patricia; Annunziato, Paula W; Halsey, Neal A; Gershon, Anne A

2017-12-19

Zoster vaccine is a single dose live, attenuated vaccine (ZVL) indicated for individuals ≥50 years-old for the prevention of herpes zoster (HZ). Safety data from clinical trials and post-licensure studies provided reassurance that ZVL is generally safe and well tolerated. The objective of this review was to provide worldwide post-marketing safety information following 10 years of use and >34 million doses distributed. All post-marketing adverse experience (AE) reports received worldwide between 02-May-2006 and 01-May-2016 from healthcare professionals following vaccination with ZVL and submitted to the MSD AE global safety database, were analyzed. A total of 23,556 AE reports, 93% non-serious, were reported. Local injection site reactions (ISRs), with a median time-to-onset of 2 days, were the most frequently reported AEs followed by HZ. The majority of HZ reports were reported within 2 weeks of vaccination and considered, based on time-to-onset, pathogenesis of HZ, and data from clinical trials, to be caused by wild-type varicella-zoster virus (VZV). HZ confirmed by PCR analysis to be VZV Oka/Merck vaccine-strain was identified in an immunocompetent individual 8 months postvaccination and in 4 immunocompromised individuals. Disseminated HZ was reported very rarely (marketing use, was favorable and consistent with that observed in clinical trials and post-licensure studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Safety and Immunogenicity of Coadministering a Combined Meningococcal Serogroup C and Haemophilus influenzae Type b Conjugate Vaccine with 7-Valent Pneumococcal Conjugate Vaccine and Measles, Mumps, and Rubella Vaccine at 12 Months of Age ▿

OpenAIRE

Miller, Elizabeth; Andrews, Nick; Waight, Pauline; Findlow, Helen; Ashton, Lindsey; England, Anna; Stanford, Elaine; Matheson, Mary; Southern, Joanna; Sheasby, Elizabeth; Goldblatt, David; Borrow, Ray

2010-01-01

The coadministration of the combined meningococcal serogroup C conjugate (MCC)/Haemophilus influenzae type b (Hib) vaccine with pneumococcal conjugate vaccine (PCV7) and measles, mumps, and rubella (MMR) vaccine at 12 months of age was investigated to assess the safety and immunogenicity of this regimen compared with separate administration of the conjugate vaccines. Children were randomized to receive MCC/Hib vaccine alone followed 1 month later by PCV7 with MMR vaccine or to receive all thr...

Ensuring microbiological safety of commercial eggs by gamma irradiation

International Nuclear Information System (INIS)

Hammad, A.A; Swailam, H.M.; Abd El-Rahim, E.A.; Shallan, M.A; Aly, W.F.

2009-01-01

Egg shell sanitizing practices are necessary to improve microbiological safety of fresh eggs. In this work, fifteen fresh eggs samples of each (balady, white and brown eggs) were collected from different local supermarkets to evaluate their microbiological quality. The results indicated that balady eggs were higher in microbial population in comparison with the two other varieties. Salmonella spp. was detected in 9 (60%) samples of balady eggs. The effect of gamma irradiation at dose of 0,2,3 and 4 kGy on microbiological quality of balady eggs during storage at 4± 1 deg c for 35 days as well as on total cholesterol , ph, and total carotenoids contents were also investigated. The results showed that irradiation at 3 kGy reduced total aerobic bacterial counts. Whereas completely eliminated coliform bacteria, E.coli and salmonella spp. Total cholesterol and total carotenoids were decreased in yolk egg. irradiation dose of 3 kGy were efficient and sufficient for ensuring safety, maintain quality and extend shelf-life of balady eggs

Consumer attitudes to vaccination of food-producing animals.

Science.gov (United States)

Scudamore, J M

2007-08-01

The 2001 outbreak of foot and mouth disease in the United Kingdom was unprecedented, with the need to develop a vaccination policy at the height of the epidemic. The extent of consumer concerns about eating products derived from vaccinated animals was unknown as survey results were equivocal. A recent survey on avian influenza reveals that the European public are well informed about the disease and its control, but over 50% of respondents would be reluctant to consume meat from vaccinated birds. There is little specific information available on consumer views about routine vaccination for other diseases. Their concerns appear to increase in an emergency situation when there is heightened awareness through the media. With the development of newer types of vaccines consumers will need more assurance about the safety and use of these products. This article examines these issues and makes practical recommendations for ensuring public confidence when emergency vaccination for disease control is proposed.

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

NARCIS (Netherlands)

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.

2017-01-01

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

Type I error probability spending for post-market drug and vaccine safety surveillance with binomial data.

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Silva, Ivair R

2018-01-15

Type I error probability spending functions are commonly used for designing sequential analysis of binomial data in clinical trials, but it is also quickly emerging for near-continuous sequential analysis of post-market drug and vaccine safety surveillance. It is well known that, for clinical trials, when the null hypothesis is not rejected, it is still important to minimize the sample size. Unlike in post-market drug and vaccine safety surveillance, that is not important. In post-market safety surveillance, specially when the surveillance involves identification of potential signals, the meaningful statistical performance measure to be minimized is the expected sample size when the null hypothesis is rejected. The present paper shows that, instead of the convex Type I error spending shape conventionally used in clinical trials, a concave shape is more indicated for post-market drug and vaccine safety surveillance. This is shown for both, continuous and group sequential analysis. Copyright © 2017 John Wiley & Sons, Ltd.

Efficacy, immunogenicity, and safety of a 9-valent human papillomavirus vaccine in Latin American girls, boys, and young women

OpenAIRE

Ángela María Ruiz-Sternberg; Edson D. Moreira, Jr; Jaime A. Restrepo; Eduardo Lazcano-Ponce; Robinson Cabello; Arnaldo Silva; Rosires Andrade; Francisco Revollo; Santos Uscanga; Alejandro Victoria; Ana María Guevara; Joaquín Luna; Manuel Plata; Claudia Nossa Dominguez; Edison Fedrizzi

2018-01-01

Background: A 9-valent human papillomavirus (HPV6/11/16/18/31/33/45/52/58; 9vHPV) vaccine was developed to expand coverage of the previously developed quadrivalent (HPV6/11/16/18; qHPV) vaccine. Methods: Efficacy, immunogenicity, and safety outcomes were assessed in Latin American participants enrolled in 2 international studies of the 9vHPV vaccine, including a randomized, double-blinded, controlled with qHPV vaccine, efficacy, immunogenicity, and safety study in young women aged 16–26 years...

The Immunogenicity and Safety of CYD-Tetravalent Dengue Vaccine (CYD-TDV) in Children and Adolescents: A Systematic Review.

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Agarwal, Raksheeth; Wahid, Mardiastuti H; Yausep, Oliver E; Angel, Sharon H; Lokeswara, Angga W

2017-01-01

to assess the immunogenicity and safety of CYD-tetravalent dengue vaccine (CYD-TDV) in children. comprehensive literature searches were conducted on various databases. Randomized-controlled trials on children with CYD-TDV as intervention were selected based on inclusion and exclusion criteria. Data extracted from selected trials included safety of vaccine and immunogenicity in terms of Geometric Mean Titres (GMT) of antibodies.   six clinical trials were selected based on preset criteria. GMT values were obtained using 50% Plaque Reduction Neutralization Test (PRNT) and safety was semi-quantitatively assessed based on adverse effects. Additional data processing was done to obtain a better understanding on the trends among the studies. The results showed that the groups vaccinated with CYD-TDV showed higher immunogenicity against dengue virus antigens than the control groups. Safety results were satisfactory in all trials, and most severe side effects were unrelated to the vaccine. CYD-TDV is both effective and safe for patients in endemic regions. This gives promise for further development and large-scale research on this vaccine to assess its efficacy in decreasing dengue prevalence, and its pervasive implementation in endemic countries, such as Indonesia.

Post-licensure safety monitoring of quadrivalent human papillomavirus vaccine in the Vaccine Adverse Event Reporting System (VAERS), 2009-2015.

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Arana, Jorge E; Harrington, Theresa; Cano, Maria; Lewis, Paige; Mba-Jonas, Adamma; Rongxia, Li; Stewart, Brock; Markowitz, Lauri E; Shimabukuro, Tom T

2018-03-20

The Food and Drug Administration (FDA) approved quadrivalent human papillomavirus vaccine (4vHPV) for use in females and males aged 9-26 years, since 2006 and 2009 respectively. We characterized reports to the Vaccine Adverse Event Reporting System (VAERS), a US spontaneous reporting system, in females and males who received 4vHPV vaccination. We searched VAERS for US reports of adverse events (AEs) following 4vHPV from January 2009 through December 2015. Signs and symptoms were coded using Medical Dictionary for Regulatory Activities (MedDRA). We calculated reporting rates and conducted empirical Bayesian data mining to identify disproportional reports. Clinicians reviewed available information, including medical records, and reports of selected pre-specified conditions. VAERS received 19,760 reports following 4vHPV; 60.2% in females, 17.2% in males, and in 22.6% sex was missing. Overall, 94.2% of reports were non-serious; dizziness, syncope and injection site reactions were commonly reported in both males and females. Headache, fatigue and nausea were commonly reported serious AEs. More than 60 million 4vHPV doses were distributed during the study period. Crude AE reporting rates were 327 reports per million 4vHPV doses distributed for all reports, and 19 per million for serious reports. Among 29 verified reports of death, there was no pattern of clustering of deaths by diagnosis, co-morbidities, age, or interval from vaccination to death. No new or unexpected safety concerns or reporting patterns of 4vHPV with clinically important AEs were detected. Safety profile of 4vHPV is consistent with data from pre-licensure trials and postmarketing safety data. Published by Elsevier Ltd.

Vaccines.gov

Science.gov (United States)

... Vaccine Safety Vaccines Work Vaccine Types Vaccine Ingredients Vaccines by Disease Chickenpox ... Typhoid Fever Whooping Cough (Pertussis) Yellow Fever Who and When Infants, Children, and Teens ...

Live attenuated influenza vaccine use and safety in children and adults with asthma.

Science.gov (United States)

Duffy, Jonathan; Lewis, Melissa; Harrington, Theresa; Baxter, Roger; Belongia, Edward A; Jackson, Lisa A; Jacobsen, Steven J; Lee, Grace M; Naleway, Allison L; Nordin, James; Daley, Matthew F

2017-04-01

Live attenuated influenza vaccine (LAIV) might increase the risk of wheezing in persons with asthma or children younger than 5 years with a history of recurrent wheezing. To describe the use and assess the safety of LAIV in persons with asthma in the Vaccine Safety Datalink population. We identified persons with asthma using diagnosis codes and medication records in 7 health care organizations over 3 influenza seasons (2008-2009 through 2010-2011) and determined their influenza vaccination rates. Using the self-controlled risk interval method, we calculated the incidence rate ratio of medically attended respiratory events in the 14 days after LAIV compared with 29 to 42 days after vaccination in persons 2 through 49 years old. In our population of 6.3 million, asthma prevalence was 5.9%. Of persons with asthma, approximately 50% received any influenza vaccine but less than 1% received LAIV. The safety study included 12,354 LAIV doses (75% in children; 93% in those with intermittent or mild persistent asthma). The incidence rate ratio for inpatient and emergency department visits for lower respiratory events (including asthma exacerbation and wheezing) was 0.98 (95% confidence interval 0.63-1.51) and the incidence rate ratio for upper respiratory events was 0.94 (95% confidence interval 0.48-1.86). The risk of lower respiratory events was similar for intermittent and mild persistent asthma, across age groups, and for seasonal trivalent LAIV and 2009 H1N1 pandemic monovalent LAIV. LAIV use in asthma was mostly in persons with intermittent or mild persistent asthma. LAIV was not associated with an increased risk of medically attended respiratory adverse events. Published by Elsevier Inc.

Safety and Efficacy Data on Vaccines and Immunization to Human Papillomavirus

Directory of Open Access Journals (Sweden)

Natalie Kash

2015-04-01

Full Text Available 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.

Unlicensed pharmaceutical preparations for clinical patient care: Ensuring safety.

Science.gov (United States)

de Wilde, Sofieke; de Jong, Maria G H; Le Brun, Paul P H; Guchelaar, Henk-Jan; Schimmel, Kirsten J M

2018-01-01

Most medicinal products dispensed to patients have marketing authorization (MA) to ensure high quality of the product, safety, and efficacy. However, in daily practice, to treat patients adequately, there is a medical need for drugs that do not hold MA. To meet this medical need, medicinal products are used in clinical care without MA (unlicensed), such as products prepared by (local) pharmacies: the pharmaceutical preparations. Three types of pharmaceutical preparations are distinguished: (i) reconstitution in excess of summary of product characteristics; (ii) adaptation of a licensed medicinal product (outside its official labeling); (iii) medicinal products from an active pharmaceutical ingredient. Although unlicensed, patients may expect the same quality for these unlicensed pharmaceutical preparations as for the licensed medicinal products. To assure this quality, a proper risk-benefit assessment and proper documentation in (centralized) patient registries and linking to a national pharmacovigilance database should be in place. Based on a risk assessment matrix, requirements for quality assurance can be determined, which has impact on the level of documentation of a pharmaceutical preparation. In this paper, the approach for good documentation including quality assurance and benefit-risk assessment will be discussed and possibilities for patient registries are described to make these crucial preparations available for regular patient care. KEY POINTS Ensuring pharmaceutical quality and performing a proper benefit-risk assessment will guarantee safe use of pharmaceutical preparations. Good documentation of (ultra-)orphan treatments can be collected in centralized patient registries and should be combined with existing information in (inter)national databases and self-reflection of patients. Linking patient registries to a centralized database for adverse drug events is highly recommended as it increases safety control of the (ultra) orphan pharmaceutical

Evaluating the safety and immunogenicity of yellow fever vaccines: a systematic review

Directory of Open Access Journals (Sweden)

Thomas RE

2015-04-01

Full Text Available Roger E Thomas Department of Family Medicine, G012 Health Sciences Center, University of Calgary Medical School, Calgary, AB, Canada Purpose: To review the safety and immunogenicity of yellow fever vaccines. Literature search: The Cochrane Library (including the Cochrane CENTRAL Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and the NHS Database of Abstracts of Reviews of Effects; MEDLINE; EMBASE; BIOSIS Previews; Global Health; CAB Abstracts; and the Lilacs Database of Latin American and Caribbean literature were searched for individual studies and systematic reviews through January 1, 2015. Results: Six yellow fever vaccines are currently produced, and they are effective against all seven yellow fever virus strains. There is a 99.2% homology of the genome sequences of the six current vaccines. Four systematic reviews identified very small numbers of serious adverse events. A systematic review (updated of all published cases identified 133 serious adverse events that met the Brighton Collaboration criteria: 32 anaphylactic, 42 neurologic (one death, 57 viscerotropic (25 deaths, and two of both neurologic and viscerotropic SAEs. The Sanofi Pasteur Global Pharmacovigilance database reported 276 million doses of Stamaril™ distributed worldwide and identified 12 reports of yellow fever vaccine-associated viscerotropic disease (YEL-AVD, 24 of yellow fever vaccine-associated neurologic disease (YEL-AND, and 33 reports of anaphylaxis (many already published. The Biomanguinhos manufacturer's database reported 110 million doses distributed worldwide between 1999 and 2009, and the rate of YEL-AND was estimated at 0.084/100,000 doses distributed and YEL-AVD at 0.02/100,000 doses distributed. Conclusion: Reports of serious adverse events are mostly from travelers from developed countries, and there is likely serious underreporting for developing countries. On the basis of the published reports, the yellow fever vaccines are

[Safety data of the new, reduced-dose influenza vaccine FluArt after its first season on the market].

Science.gov (United States)

Vajó, Péter; Gyurján, Orsolya; Szabó, Ágnes Mira; Kalabay, László; Vajó, Zoltán; Torzsa, Péter

2017-12-01

The currently licensed seasonal influenza vaccines contain split, subunit or whole virions, typically in amounts of 15 µg hemagglutinin per virus strain for adult and up to 60 µg in elderly patients. The present study reports safety data of the newly licensed, reduced dose vaccine with 6 µg of hemagglutinin per strain produced by Fluart (Hungary) after its first season on the market. The main objective of enhanced safety surveillance was to detect a potential increase in reactogenicity and allergic events that is intrinsic to the product in near real-time in the earliest vaccinated cohorts. The study methods were based on the Interim guidance on enhanced safety surveillance for seasonal influenza vaccines in the EU by the European Medicines Agency. We used the Fisher exact test with 95% confidence intervals. We studied 587 patients and detected a total 24 adverse events, all of which have already been known during the licensing studies of the present vaccine. The frequencies of the adverse events were not different from what had been seen with the previously licensed 15 µg vaccine. Based on the results, the authors conclude that the new, reduced dose vaccine FluArt is safe and tolerable. Orv Hetil. 2017; 158(49): 1953-1959.

The role of emerging technologies to ensure the microbial safety of fresh produce, milk and eggs

Science.gov (United States)

This article reviews emerging techniques that are applied in the produce and dairy industry to ensure product safety. Microbial safety of produce, dairy and egg continues to be a major concern. According to Economic Research Service, USDA the cost of foodborne illnesses in the U.S. tops $15.6 billio...

Vaccines and Thimerosal

Science.gov (United States)

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

Usability Methods for Ensuring Health Information Technology Safety: Evidence-Based Approaches. Contribution of the IMIA Working Group Health Informatics for Patient Safety.

Science.gov (United States)

Borycki, E; Kushniruk, A; Nohr, C; Takeda, H; Kuwata, S; Carvalho, C; Bainbridge, M; Kannry, J

2013-01-01

Issues related to lack of system usability and potential safety hazards continue to be reported in the health information technology (HIT) literature. Usability engineering methods are increasingly used to ensure improved system usability and they are also beginning to be applied more widely for ensuring the safety of HIT applications. These methods are being used in the design and implementation of many HIT systems. In this paper we describe evidence-based approaches to applying usability engineering methods. A multi-phased approach to ensuring system usability and safety in healthcare is described. Usability inspection methods are first described including the development of evidence-based safety heuristics for HIT. Laboratory-based usability testing is then conducted under artificial conditions to test if a system has any base level usability problems that need to be corrected. Usability problems that are detected are corrected and then a new phase is initiated where the system is tested under more realistic conditions using clinical simulations. This phase may involve testing the system with simulated patients. Finally, an additional phase may be conducted, involving a naturalistic study of system use under real-world clinical conditions. The methods described have been employed in the analysis of the usability and safety of a wide range of HIT applications, including electronic health record systems, decision support systems and consumer health applications. It has been found that at least usability inspection and usability testing should be applied prior to the widespread release of HIT. However, wherever possible, additional layers of testing involving clinical simulations and a naturalistic evaluation will likely detect usability and safety issues that may not otherwise be detected prior to widespread system release. The framework presented in the paper can be applied in order to develop more usable and safer HIT, based on multiple layers of evidence.

Non-Replicating Adenovirus-Vectored Anthrax Vaccine

International Nuclear Information System (INIS)

Van Kampen, K. R.; Zhang, J.; Jex, E.; Tang, D. C.

2007-01-01

As bioterrorism is emerging as a national threat, it is urgent to develop a new generation of anthrax vaccines that can be rapidly produced and mass administered in an emergency setting. We have demonstrated that protective immunity against anthrax spores could be elicited in mice by intranasal administration of a non-replicating human adenovirus serotype 5 (Ad5)-derived vector encoding Bacillus anthracis protective antigen (PA) in a single-dose regimen. The potency of an Ad5 vector encoding PA was remarkably enhanced by codon optimization of the PA gene to match the tRNA pool found in human cells. This nasal vaccine can be mass-administered by non-medical personnel during a bioterrorist attack. In addition, replication-competent adenovirus (RCA)-free Ad5-vectored anthrax vaccines can be mass produced in PER.C6 cells in serum-free wave bioreactors and purified by column chromatography to meet a surge in demand. The non-replicating nature of this new generation of anthrax vaccine ensures an excellent safety profile for vaccines and the environment.(author)

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

Science.gov (United States)

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

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

Science.gov (United States)

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.

SAFETY OF COMBINED INJECTION OF VACCINES AGAINST HIB-INFECTION (the data on pilot project fulfilled in Murmansk region and Yaroslavl

Directory of Open Access Journals (Sweden)

S.M. Kharit

2009-01-01

Full Text Available The results of an observation of 288 children under the age 3–20 months old (46 healthy infants and 142 patients with allergic diseases, residual lesions of CNS, frequently ailing ones and infants with other pathologies, vaccinated and re-vaccinated with Hiberix and Infanrix in one syringe were analyzed. High safety of such method of injection allowed decreasing of injection load during the vaccination against hemophilic infection type b in infants. Common moderate reaction was detected in only one child (0,5%. Topical reactions were registered in 5,0% of vaccinated patients.Key words: children, hemophilic infection, vaccination, post-vaccinal period, safety.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2009;8(6:36-41

Efficacy and Safety of Vaccination in Pediatric Patients with Systemic Inflammatory Rheumatic Diseases: a systematic review of the literature.

Science.gov (United States)

Sousa, Sandra; Duarte, Ana Catarina; Cordeiro, Inês; Ferreira, Joana; Gonçalves, Maria João; Meirinhos, Tiago; Rocha, Teresa Martins; Romão, Vasco C; Santos, Maria José

2017-01-01

Children and adolescents with systemic rheumatic diseases have an increased risk of infections. Although some infections are vaccine-preventable, immunization among patients with juvenile rheumatic diseases is suboptimal, partly due to some doubts that still persist regarding its efficacy and safety in this patient population. To review the available evidence regarding the immunological response and the safety of vaccination in children and adolescents with systemic inflammatory rheumatic diseases (SIRD). A systematic review of the current literature until December 2014 using MEDLINE, EMBASE and abstracts from the American College of Rheumatology and European League Against Rheumatism congresses (2011-2014), complemented by hand search was performed. Eligible studies were identified and efficacy (seroprotection and/or seroconversion) and safety (reactions to vaccine and relapse of rheumatic disease) outcomes were extracted and summarized according to the type of vaccine. Twenty-eight articles concerning vaccination in pediatric patients with SIRDs were found, that included almost 2100 children and adolescents, comprising nearly all standard vaccinations of the recommended immunization schedule. Children with SIRDs generally achieved seroprotection and seroconversion; nevertheless, the antibody levels were often lower when compared with healthy children. Glucocorticoids and conventional disease-modifying anti-rheumatic drugs do not seem to significantly hamper the immune responses, whereas TNF inhibitors may reduce antibody production, particularly in response to pneumococcal conjugate, influenza, meningococcal C and hepatitis A vaccine. There were no serious adverse events, nor evidence of a relevant worsening of the underlying rheumatic disease. Concerning live attenuated vaccines, the evidence is scarce, but no episodes of overt disease were reported, even in patients under biological therapy. Existing literature demonstrates that vaccines are generally well

Efficacy and Safety of Vaccination in Pediatric Patients with Systemic Inflammatory Rheumatic Diseases: a systematic review of the literature

Directory of Open Access Journals (Sweden)

Sandra Sousa

2017-01-01

Full Text Available Introduction: Children and adolescents with systemic rheumatic diseases have an increased risk of infections. Although some infections are vaccine-preventable, immunization among patients with juvenile rheumatic diseases is suboptimal, partly due to some doubts that still persist regarding its efficacy and safety in this patient population. Objectives: To review the available evidence regarding the immunological response and the safety of vaccination in children and adolescents with systemic inflammatory rheumatic diseases (SIRD. Methods: A systematic review of the current literature until December 2014 using MEDLINE, EMBASE and abstracts from the American College of Rheumatology and European League Against Rheumatism congresses (2011-2014, complemented by hand search was performed. Eligible studies were identified and efficacy (seroprotection and/or seroconversion and safety (reactions to vaccine and relapse of rheumatic disease outcomes were extracted and summarized according to the type of vaccine. Results: Twenty-eight articles concerning vaccination in pediatric patients with SIRDs were found, that included almost 2100 children and adolescents, comprising nearly all standard vaccinations of the recommended immunization schedule. Children with SIRDs generally achieved seroprotection and seroconversion; nevertheless, the antibody levels were often lower when compared with healthy children. Glucocorticoids and conventional disease-modifying anti-rheumatic drugs do not seem to significantly hamper the immune responses, whereas TNF inhibitors may reduce antibody production, particularly in response to pneumococcal conjugate, influenza, meningococcal C and hepatitis A vaccine. There were no serious adverse events, nor evidence of a relevant worsening of the underlying rheumatic disease. Concerning live attenuated vaccines, the evidence is scarce, but no episodes of overt disease were reported, even in patients under biological therapy

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

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

2016-02-10

Vaccination of domestic animals has emerged as an alternative long-term strategy for the control of tuberculosis (TB). A trial under field conditions was conducted in a TB-free goat herd to assess the safety of the Mycobacterium bovis BCG vaccine. Eleven kids and 10 milking goats were vaccinated with BCG. Bacterial shedding and interferon gamma (IFN-γ) responses were monitored throughout the study. Comprehensive pathological examination and mycobacterial culture of target tissues were performed. BCG vaccine strain was only isolated from the draining lymph node of the injection site of a kid euthanized at week 8 post-vaccination. The remaining animals were euthanized at week 24. Six out of 20 showed small granulomas at the injection site. BCG shedding was not detected in either faeces or in milk throughout the study. All vaccinated kids showed BCG-induced IFN-γ responses at week 8 post-vaccination. BCG vaccination of goats showed no lack of biological safety for the animals, environment and public health, and local adverse reactions were negligible. Copyright © 2016 Elsevier Ltd. All rights reserved.

Use of Fixed Effects Models to Analyze Self-Controlled Case Series Data in Vaccine Safety Studies.

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Xu, Stanley; Zeng, Chan; Newcomer, Sophia; Nelson, Jennifer; Glanz, Jason

2012-04-19

Conditional Poisson models have been used to analyze vaccine safety data from self-controlled case series (SCCS) design. In this paper, we derived the likelihood function of fixed effects models in analyzing SCCS data and showed that the likelihoods from fixed effects models and conditional Poisson models were proportional. Thus, the maximum likelihood estimates (MLEs) of time-varying variables including vaccination effect from fixed effects model and conditional Poisson model were equal. We performed a simulation study to compare empirical type I errors, means and standard errors of vaccination effect coefficient, and empirical powers among conditional Poisson models, fixed effects models, and generalized estimating equations (GEE), which has been commonly used for analyzing longitudinal data. Simulation study showed that both fixed effect models and conditional Poisson models generated the same estimates and standard errors for time-varying variables while GEE approach produced different results for some data sets. We also analyzed SCCS data from a vaccine safety study examining the association between measles mumps-rubella (MMR) vaccination and idiopathic thrombocytopenic purpura (ITP). In analyzing MMR-ITP data, likelihood-based statistical tests were employed to test the impact of time-invariant variable on vaccination effect. In addition a complex semi-parametric model was fitted by simply treating unique event days as indicator variables in the fixed effects model. We conclude that theoretically fixed effects models provide identical MLEs as conditional Poisson models. Because fixed effect models are likelihood based, they have potentials to address methodological issues in vaccine safety studies such as how to identify optimal risk window and how to analyze SCCS data with misclassification of adverse events.

Translating self-persuasion into an adolescent HPV vaccine promotion intervention for parents attending safety-net clinics.

Science.gov (United States)

Baldwin, Austin S; Denman, Deanna C; Sala, Margarita; Marks, Emily G; Shay, L Aubree; Fuller, Sobha; Persaud, Donna; Lee, Simon Craddock; Skinner, Celette Sugg; Wiebe, Deborah J; Tiro, Jasmin A

2017-04-01

Self-persuasion is an effective behavior change strategy, but has not been translated for low-income, less educated, uninsured populations attending safety-net clinics or to promote human papillomavirus (HPV) vaccination. We developed a tablet-based application (in English and Spanish) to elicit parental self-persuasion for adolescent HPV vaccination and evaluated its feasibility in a safety-net population. Parents (N=45) of age-eligible adolescents used the self-persuasion application. Then, during cognitive interviews, staff gathered quantitative and qualitative feedback on the self-persuasion tasks including parental decision stage. The self-persuasion tasks were rated as easy to complete and helpful. We identified six question prompts rated as uniformly helpful, not difficult to answer, and generated non-redundant responses from participants. Among the 33 parents with unvaccinated adolescents, 27 (81.8%) reported deciding to get their adolescent vaccinated after completing the self-persuasion tasks. The self-persuasion application was feasible and resulted in a change in parents' decision stage. Future studies can now test the efficacy of the tablet-based application on HPV vaccination. The self-persuasion application facilitates verbalization of reasons for HPV vaccination in low literacy, safety-net settings. This self-administered application has the potential to be more easily incorporated into clinical practice than other patient education approaches. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

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

2012-09-07

In a randomized, placebo-controlled, monocenter, observer blinded study conducted in an area where dengue is endemic, we assessed the safety and immunogenicity of a recombinant, live, attenuated, tetravalent dengue vaccine candidate (CYD-TDV) in 2-11 year-olds with varying levels of pre-existing yellow-fever immunity due to vaccination 1-7 years previously. 199 children received 3 injections of CYD-TDV (months 0, 6 and 12) and 99 received placebo (months 0 and 6) or pneumococcal polysaccharide vaccine (month 12). One month after the third dengue vaccination, serotype specific neutralizing antibody GMTs were in the range of 178-190 (1/dil) (versus 16.7-38.1 in the control group), a 10-20 fold-increase from baseline, and 94% of vaccines were seropositive to all four serotypes (versus 39% in the control group). There were no vaccine-related SAEs. The observed reactogenicity profile was consistent with phase I studies, with severity grade 1-2 injection site pain, headache, malaise and fever most frequently reported and no increase after subsequent vaccinations. Virologically confirmed dengue cases were seen after completion of the 3 doses: 1 in the CYD-TDV group (N=199), and 3 in the control group (N=99). A 3-dose regimen of CYD-TDV had a good safety profile in 2-11 year olds with a history of YF vaccination and elicited robust antibody responses that were balanced against the four serotypes. Copyright © 2012 Elsevier Ltd. All rights reserved.

Field study on the safety and efficacy of intradermal versus intramuscular vaccination against Mycoplasma hyopneumoniae.

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Beffort, Lisa; Weiß, Christine; Fiebig, Kerstin; Jolie, Rika; Ritzmann, Mathias; Eddicks, Matthias

2017-09-30

The present study compares the safety and efficacy of a needle-free, intradermal Mycoplasma hyopneumoniae vaccine to an intramuscular one. 420 piglets (21+3 days of age) were randomly assigned to two vaccination groups (intradermal vaccination V1 (n=138), intramuscular vaccination V2 (n=144)) and one unvaccinated control group (CG, n=138). As safety parameters clinical observations, local injection site reactions (ISR) and rectal temperatures were assessed. Average daily weight gain (ADWG) and pneumonic lung lesions (LL) were measured as efficacy parameters. ISRs were minor in V1. After both vaccinations, no adverse impact on appetite was observed and mean rectal temperatures remained within physiological range. ADWG during the fattening period was significantly higher in vaccinated groups (V1: 913.4 g, V2: 924.5 g) compared with CG (875.6 g). No differences in ADWG were observed between V1 and V2. Vaccinated pigs had a significantly reduced mean extent of LL compared with CG. V1 was superior in reducing the extent and prevalence of LL compared with V2. These results reveal that a needle-free intradermal vaccination is safe and efficacious in reducing both the prevalence and extent of lung lesions, as well as in improving performance parameters, in a farrow-to-finish farm with a late onset of M hyopneumonia e infection. © 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.

Post-licensure safety surveillance for human papillomavirus-16/18-AS04-adjuvanted vaccine: more than 4 years of experience.

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Angelo, Maria-Genalin; Zima, Julia; Tavares Da Silva, Fernanda; Baril, Laurence; Arellano, Felix

2014-05-01

To summarise post-licensure safety surveillance over more than 4 years of routine use of the human papillomavirus-16/18-AS04-adjuvanted vaccine (HPV-16/18 vaccine: Cervarix®, GlaxoSmithKline, Belgium). We describe global post-licensure passive surveillance data based on routine pharmacovigilance from 18 May 2007 until 17 November 2011 and enhanced surveillance implemented during the 2-year national immunisation programme in the UK (school years 2008-2010). Spontaneous reports from countries worldwide showed a similar pattern for the most frequently reported adverse events after HPV-16/18 vaccination. No patterns or trends were observed for potential immune-mediated diseases after vaccination. Observed incidences of Bell's palsy and confirmed Guillain-Barré syndrome were within the expected range in the general population. Outcomes of pregnancy in women who were inadvertently exposed to HPV-16/18 vaccine during pregnancy, were in line with published reports for similar populations. Enhanced surveillance of adverse events in the UK triggered a review of cases of anaphylaxis, angioedema and syncope reports, leading to an update to the prescribing information. Collaborative partnerships between industry and national regulatory agencies facilitated rapid notification and transfer of safety information, allowing for rapid responses in the event of a safety signal of adverse event of concern. More than 4 years of post-licensure experience may provide confidence to providers and the public about the safety profile of HPV-16/18 vaccine in routine use. The safety profile appears to be consistent with pre-licensure data reporting that HPV-16/18 vaccine has an acceptable benefit-risk profile in adolescent girls and women. © 2014 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.

Safety and immunogenicity of meningococcal ACWY CRM197-conjugate vaccine in children, adolescents and adults in Russia.

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Ilyina, Natalia; Kharit, Susanna; Namazova-Baranova, Leila; Asatryan, Asmik; Benashvili, Mayya; Tkhostova, Elmira; Bhusal, Chiranjiwi; Arora, Ashwani Kumar

2014-01-01

Neisseria meningitidis is the leading cause of bacterial invasive infections in people aged safety of the quadrivalent meningococcal CRM197-conjugate vaccine MenACWY when administered to healthy Russian subjects aged 2 years and above. A total of 197 subjects were immunized with a single dose of the vaccine, and serogroup-specific serum bactericidal activity was measured pre and 1-month post-vaccination with human complement (hSBA) serum titers. Regardless of baseline serostatus, 1 month after a single dose of MenACWY-CRM197 85% (95%CI, 79-90%) of subjects showed serologic response against serogroup A, 74% (67-80%) against serogroup C, 60% (53-67%) against serogroup W, and 83% (77-88%) against serogroup Y. The percentage of subjects with hSBA titers ≥ 1:8 1 month after vaccination was 89% (83-93%) against serogroup A, 84% (78-89%) against serogroup C, 97% (93-99%) against serogroup W, and 88% (82-92%) against serogroup Y. Comparable results were obtained across all subjects: children (2 to 10 years), adolescents (11 to 17 years), and adults (≥18 years). The MenACWY-CRM197 vaccine showed an acceptable safety profile and was well tolerated across all age groups, with no serious adverse events or deaths reported during the study. In conclusion, a single dose of meningococcal MenACWY-CRM197 vaccine is immunogenic and has an acceptable safety profile, provides a broad protection against the most frequent epidemic serogroups, and is a suitable alternative to currently available unconjugated monovalent or bivalent polysaccharide vaccines in Russia.

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

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Barkhouse, Darryll A. [Department of Cancer Biology, 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Center for Neurovirology 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Faber, Milosz [Center for Neurovirology 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Department of Microbiology and Immunology 1020 Locust St., Jefferson Alumni Hall, Room 465, Philadelphia, PA 19107 (United States); Hooper, D. Craig, E-mail: douglas.hooper@jefferson.edu [Department of Cancer Biology, 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Department of Neurological Surgery, 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Center for Neurovirology 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States)

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.

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

International Nuclear Information System (INIS)

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

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

Science.gov (United States)

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

2017-08-24

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

Safety of currently licensed hepatitis B surface antigen vaccines in the United States, Vaccine Adverse Event Reporting System (VAERS), 2005-2015.

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Haber, Penina; Moro, Pedro L; Ng, Carmen; Lewis, Paige W; Hibbs, Beth; Schillie, Sarah F; Nelson, Noele P; Li, Rongxia; Stewart, Brock; Cano, Maria V

2018-01-25

Currently four recombinant hepatitis B (HepB) vaccines are in use in the United States. HepB vaccines are recommended for infants, children and adults. We assessed adverse events (AEs) following HepB vaccines reported to the Vaccine Adverse Event Reporting System (VAERS), a national spontaneous reporting system. We searched VAERS for reports of AEs following single antigen HepB vaccine and HepB-containing vaccines (either given alone or with other vaccines), from January 2005 - December 2015. We conducted descriptive analyses and performed empirical Bayesian data mining to assess disproportionate reporting. We reviewed serious reports including reports of special interest. VAERS received 20,231 reports following HepB or HepB-containing vaccines: 10,291 (51%) in persons 18 years; for 1485 (7.3%) age was missing. Dizziness and nausea (8.4% each) were the most frequently reported AEs following a single antigen HepB vaccine: fever (23%) and injection site erythema (11%) were most frequent following Hep-containing vaccines. Of the 4444 (22%) reports after single antigen HepB vaccine, 303 (6.8%) were serious, including 45 deaths. Most commonly reported cause of death was Sudden Infant Death Syndrome (197). Most common non-death serious reports following single antigen HepB vaccines among infants aged children aged 1-23 months; infections and infestation (8) among persons age 2-18 years blood and lymphatic systemic disorders; and general disorders and administration site conditions among persons age >18 years. Most common vaccination error following single antigen HepB was incorrect product storage. Review current U.S.-licensed HepB vaccines administered alone or in combination with other vaccines did not reveal new or unexpected safety concerns. Vaccination errors were identified which indicate the need for training and education of providers on HepB vaccine indications and recommendations. Published by Elsevier Ltd.

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

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Kenneth S Plante

Full Text Available 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 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.

Satisfactory safety and immunogenicity of MSP3 malaria vaccine candidate in Tanzanian children aged 12–24 months

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Segeja Method D

2009-07-01

Full Text Available Abstract Background Development and deployment of an effective malaria vaccine would complement existing malaria control measures. A blood stage malaria vaccine candidate, Merozoite Surface Protein-3 (MSP3, produced as a long synthetic peptide, has been shown to be safe in non-immune and semi-immune adults. A phase Ib dose-escalating study was conducted to assess the vaccine's safety and immunogenicity in children aged 12 to 24 months in Korogwe, Tanzania (ClinicalTrials.gov number: NCT00469651. Methods This was a double-blind, randomized, controlled, dose escalation phase Ib trial, in which children were given one of two different doses of the MSP3 antigen (15 μg or 30 μg or a control vaccine (Engerix B. Children were randomly allocated either to the MSP3 candidate malaria vaccine or the control vaccine administered at a schedule of 0, 1, and 2 months. Immunization with lower and higher doses was staggered for safety reasons starting with the lower dose. The primary endpoint was safety and reactogenicity within 28 days post-vaccination. Blood samples were obtained at different time points to measure immunological responses. Results are presented up to 84 days post-vaccination. Results A total of 45 children were enrolled, 15 in each of the two MSP3 dose groups and 15 in the Engerix B group. There were no important differences in reactogenicity between the two MSP3 groups and Engerix B. Grade 3 adverse events were infrequent; only five were detected throughout the study, all of which were transient and resolved without sequelae. No serious adverse event reported was considered to be related to MSP3 vaccine. Both MSP3 dose regimens elicited strong cytophilic IgG responses (subclasses IgG1 and IgG3, the isotypes involved in the monocyte-dependant mechanism of Plasmodium falciparum parasite-killing. The titers reached are similar to those from African adults having reached a state of premunition. Furthermore, vaccination induced seroconversion in

Safety and immunogenicity of therapeutic DNA vaccination in individuals treated with antiretroviral therapy during acute/early HIV-1 infection.

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Eric S Rosenberg

2010-05-01

Full Text Available An effective therapeutic vaccine that could augment immune control of HIV-1 replication may abrogate or delay the need for antiretroviral therapy. AIDS Clinical Trials Group (ACTG A5187 was a phase I/II, randomized, placebo-controlled, double-blinded trial to evaluate the safety and immunogenicity of an HIV-1 DNA vaccine (VRC-HVDNA 009-00-VP in subjects treated with antiretroviral therapy during acute/early HIV-1 infection. (clinicaltrials.gov NCT00125099Twenty healthy HIV-1 infected subjects who were treated with antiretroviral therapy during acute/early HIV-1 infection and had HIV-1 RNA<50 copies/mL were randomized to receive either vaccine or placebo. The objectives of this study were to evaluate the safety and immunogenicity of the vaccine. Following vaccination, subjects interrupted antiretroviral treatment, and set-point HIV-1 viral loads and CD4 T cell counts were determined 17-23 weeks after treatment discontinuation.Twenty subjects received all scheduled vaccinations and discontinued antiretroviral therapy at week 30. No subject met a primary safety endpoint. No evidence of differences in immunogenicity were detected in subjects receiving vaccine versus placebo. There were also no significant differences in set-point HIV-1 viral loads or CD4 T cell counts following treatment discontinuation. Median set-point HIV-1 viral loads after treatment discontinuation in vaccine and placebo recipients were 3.5 and 3.7 log(10 HIV-1 RNA copies/mL, respectively.The HIV-1 DNA vaccine (VRC-HIVDNA 009-00-VP was safe but poorly immunogenic in subjects treated with antiretroviral therapy during acute/early HIV-1 infection. Viral set-points were similar between vaccine and placebo recipients following treatment interruption. However, median viral load set-points in both groups were lower than in historical controls, suggesting a possible role for antiretroviral therapy in persons with acute or early HIV-1 infection and supporting the safety of

Ensuring Microbiological Safety of Fresh Eggs by Using Gamma Irradiation

International Nuclear Information System (INIS)

Hammad, A. A.; Swailam, H.M.; Aly, W. F.

2008-01-01

Egg shell sanitizing practices are necessary to improve microbiological safety of fresh eggs. In this work, fifteen fresh eggs samples of each (Balady, White and Brown eggs) were collected from different local supermarkets to evaluate their microbiological quality. The results indicated that Balady eggs were higher in microbial population in comparison with the two other varieties. Salmonella spp. was detected in 9 (60%) samples of Balady eggs. The effect of gamma irradiation at dose of 0, 2, 3 and 4 kGy on microbiological quality of Balady eggs during storage at 4±1 degree C for 35 days was studied. The effects of irradiation and storage on total cholesterol, and total carotenoids contents in Balady eggs were also investigated. The results showed that irradiation at 3 kGy reduced total aerobic bacterial counts. Coliform bacteria, E. coli and Salmonella spp. were completely eliminated. Total cholesterol and total carotenoids were decreased in yolk egg as a result of irradiation. Treated Balady eggs with irradiation dose of 3 kGy were efficient and sufficient for ensuring safety, maintain quality and extend shelf-life.

Safety of the novel influenza viral vector Brucella abortus vaccine in pregnant heifers

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Kaissar Tabynov

2016-01-01

Full Text Available ABSTRACT: The present study provides the first information about the safety of a new influenza viral vector vaccine expressing the Brucella ribosomal protein L7/L12 or Omp16 containing the adjuvant Montanide Gel01 in pregnant heifers. Immunization of pregnant heifers was conducted via the conjunctival (n=10 or subcutaneous (n=10 route using cross prime and booster vaccination schedules at an interval of 28 days. The vector vaccine was evaluated in comparison with positive control groups vaccinated with B. abortus S19 (n=10 or B. abortus RB51 (n=10 and a negative (PBS+Montanide Gel01; n=10 control group. Clinical studies, thermometry, assessment of local reactogenicity and observation of abortion showed that the vector vaccine via the conjunctival or subcutaneous route was completely safe for pregnant heifers compared to the commercial vaccines B. abortus S19 or B. abortus RB51. The only single adverse event was the formation of infiltration at the site of subcutaneous injection; this reaction was not observed for the conjunctival route.

Guideline for collection, analysis and presentation of safety data in clinical trials of vaccines in pregnant women

Science.gov (United States)

Jones, Christine E.; Munoz, Flor M.; Spiegel, Hans M.L.; Heininger, Ulrich; Zuber, Patrick L.F.; Edwards, Kathryn M.; Lambach, Philipp; Neels, Pieter; Kohl, Katrin S.; Gidudu, Jane; Hirschfeld, Steven; Oleske, James M.; Khuri-Bulos, Najwa; Bauwens, Jorgen; Eckert, Linda O.; Kochhar, Sonali; Bonhoeffer, Jan; Heath, Paul T.

2017-01-01

Vaccination during pregnancy is increasingly being used as an effective approach for protecting both young infants and their mothers from serious infections. Drawing conclusions from published studies in this area can be difficult because of the inability to compare vaccine trial results across different studies and settings due to the heterogeneity in the definitions of terms used to assess the safety of vaccines in pregnancy and the data collected in such studies. The guidelines proposed in this document have been developed to harmonize safety data collection in all phases of clinical trials of vaccines in pregnant women and apply to data from the mother, fetus and infant. Guidelines on the prioritization of the data to be collected is also provided to allow applicability in various geographic, cultural and resource settings, including high, middle and low-income countries. PMID:27481360

Safety of administering the canine melanoma DNA vaccine (Oncept) to cats with malignant melanoma - a retrospective study.

Science.gov (United States)

Sarbu, Luminita; Kitchell, Barbara E; Bergman, Philip J

2017-02-01

Objectives A xenogeneic human tyrosinase DNA vaccine was developed for treatment of dogs with oral malignant melanoma (Oncept; Merial). No studies have evaluated the safety or efficacy of this vaccine in cats. The purpose of this study was to evaluate the safety of the canine melanoma vaccine in cats diagnosed with melanoma. Methods Medical records were reviewed from cats diagnosed with malignant melanoma and treated with the canine melanoma DNA vaccine (Oncept). Data regarding signalment, melanoma location, treatments received, vaccine adverse effects and cause of death were collected. Results A total of 114 melanoma vaccines were administered to 24 cats. Seven cats (11.4%) had clinical adverse effects from a total of 13 vaccines classified as grade 1 or 2 based on the Veterinary Cooperative Oncology Group's common terminology criteria for adverse events v1.1. These included pain on vaccine administration, brief muscle fasciculation, transient inappetence, depression, nausea and mild increase in pigmentation at the injection site. Nineteen cats were deceased at study close. The most common cause of death was melanoma (14 cats). Hematological and biochemical changes were observed in six cats, five of which had concurrent disease or treatments that likely caused or greatly contributed to the laboratory abnormalities found. Therefore, these adverse events were considered unlikely to be caused by the melanoma vaccine. One cat had transient grade 1 hypoalbuminemia, which was possibly caused by the vaccination but not thoroughly evaluated. Conclusions and relevance The canine melanoma DNA vaccine can be safely administered to cats, with minimal risk of adverse effects.

Patterns of pneumococcal vaccination and revaccination in elderly and non-elderly adults: a Vaccine Safety Datalink study

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Belongia Edward A

2009-03-01

Full Text Available Abstract Background Pneumococcal polysaccharide vaccine (PPV is recommended for all adults 65 years of age and older and for younger adults with high-risk conditions. While data from national surveys provide information on the proportion of adults 65 years of age and older reporting ever receipt of PPV they do not collect more detailed information, such as age at vaccination or the total number of vaccinations received. In addition, there is relatively little information available on PPV coverage in younger adults with chronic conditions. To assess contemporary patterns of pneumococcal vaccination and revaccination of adults, we conducted a cross-sectional study of adults enrolled in medical care organizations (MCOs participating in the Vaccine Safety Datalink project. Methods The study population included 1.5 million adults 25 years of age and older enrolled in the four participating MCOs on December 1, 2006. PPVs administered to members of the study population prior to that date were identified from computerized immunization registries maintained by the MCOs. Results Among the general population of adults 25 through 64 years of age, vaccine coverage increased from 2% in the 25–29 year old age-group to 26% in the 60–64 year old age-group. In all age-groups, coverage was substantially higher in persons defined as having a chronic high risk condition. This was particularly true for diabetes mellitus, with vaccine coverage of over 50% in the lower age-groups and 75% in those 60–64 years of age. Among adults 65 years of age and older, 82% had received at least one PPV and 18% had received two or more PPVs. Conclusion We found higher levels of PPV coverage among adults 65 years of age and older and among younger adults with diabetes mellitus than reported by national surveys and for those groups PPV coverage approached the Healthy People 2010 national objectives. These results suggest that achieving those objectives for PPV is possible and

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

Science.gov (United States)

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.

The role of hazard- and risk-based approaches in ensuring food safety

OpenAIRE

Barlow, Susan M.; Boobis, Alan R.; Bridges, Jim; Cockburn, Andrew; Dekant, Wolfgang; Hepburn, Paul; Houben, Geert F.; König, Jürgen; Nauta, Maarten; Schuermans, Jeroen; Bánáti, Diána

2015-01-01

BackgroundFood legislation in the European Union and elsewhere includes both hazard- and risk-based approaches for ensuring safety. In hazard-based approaches, simply the presence of a potentially harmful agent at a detectable level in food is used as a basis for legislation and/or risk management action. Risk-based approaches allow consideration of exposure in assessing whether there may be unacceptable risks to health.Scope and approachThe advantages and disadvantages of hazard- and risk-ba...

Phase II, randomized, open, controlled study of AS03-adjuvanted H5N1 pre-pandemic influenza vaccine in children aged 3 to 9 years: follow-up of safety and immunogenicity persistence at 24 months post-vaccination.

Science.gov (United States)

Díez-Domingo, Javier; Baldó, José-María; Planelles-Catarino, Maria Victoria; Garcés-Sánchez, María; Ubeda, Isabel; Jubert-Rosich, Angels; Marès, Josep; Garcia-Corbeira, Pilar; Moris, Philippe; Teko, Maurice; Vanden Abeele, Carline; Gillard, Paul

2015-03-01

An AS03-adjuvanted H5N1 influenza vaccine elicited broad and persistent immune responses with an acceptable safety profile up to 6 months following the first vaccination in children aged 3-9 years. In this follow-up of the Phase II study, we report immunogenicity persistence and safety at 24 months post-vaccination in children aged 3-9 years. The randomized, open-label study assessed two doses of H5N1 A/Vietnam/1194/2004 influenza vaccine (1·9 μg or 3·75 μg hemagglutinin antigen) formulated with AS03A or AS03B (11·89 mg or 5·93 mg tocopherol, respectively). Control groups received seasonal trivalent influenza vaccine. Safety was assessed prospectively and included potential immune-mediated diseases (pIMDs). Immunogenicity was assessed by hemagglutination-inhibition assay 12 and 24 months after vaccination; cross-reactivity and cell-mediated responses were also assessed. (NCT00502593). The safety population included 405 children. Over 24 months, five events fulfilled the criteria for pIMDs, of which four occurred in H5N1 vaccine recipients, including uveitis (n = 1) and autoimmune hepatitis (n = 1), which were considered to be vaccine-related. Overall, safety profiles of the vaccines were clinically acceptable. Humoral immune responses at 12 and 24 months were reduced versus those observed after the second dose of vaccine, although still within the range of those observed after the first dose. Persistence of cell-mediated immunity was strong, and CD4(+) T cells with a TH 1 profile were observed. Two doses of an AS03-adjuvanted H5N1 influenza vaccine in children showed low but persistent humoral immune responses and a strong persistence of cell-mediated immunity, with clinically acceptable safety profiles up to 24 months following first vaccination. © 2014 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

Efficacy, immunogenicity, and safety of a 9-valent human papillomavirus vaccine in Latin American girls, boys, and young women.

Science.gov (United States)

Ruiz-Sternberg, Ángela María; Moreira, Edson D; Restrepo, Jaime A; Lazcano-Ponce, Eduardo; Cabello, Robinson; Silva, Arnaldo; Andrade, Rosires; Revollo, Francisco; Uscanga, Santos; Victoria, Alejandro; Guevara, Ana María; Luna, Joaquín; Plata, Manuel; Dominguez, Claudia Nossa; Fedrizzi, Edison; Suarez, Eugenio; Reina, Julio C; Ellison, Misoo C; Moeller, Erin; Ritter, Michael; Shields, Christine; Cashat, Miguel; Perez, Gonzalo; Luxembourg, Alain

2018-06-01

A 9-valent human papillomavirus (HPV6/11/16/18/31/33/45/52/58; 9vHPV) vaccine was developed to expand coverage of the previously developed quadrivalent (HPV6/11/16/18; qHPV) vaccine. Efficacy, immunogenicity, and safety outcomes were assessed in Latin American participants enrolled in 2 international studies of the 9vHPV vaccine, including a randomized, double-blinded, controlled with qHPV vaccine, efficacy, immunogenicity, and safety study in young women aged 16-26 years, and an immunogenicity and safety study in girls and boys aged 9-15 years. Participants (N=5312) received vaccination at Day 1, Month 2, and Month 6. Gynecological swabs were collected regularly in young women for cytological and HPV DNA testing. Serum was analyzed for HPV antibodies in all participants. Adverse events (AEs) were also monitored in all participants. The 9vHPV vaccine prevented HPV 31-, 33-, 45-, 52-, and 58-related high-grade cervical, vulvar, and vaginal dysplasia with 92.3% efficacy (95% confidence interval 54.4, 99.6). Anti-HPV6, 11, 16, and 18 geometric mean titers at Month 7 were similar in the 9vHPV and qHPV vaccination groups. Anti-HPV antibody responses following vaccination were higher among girls and boys than in young women. Most (>99%) 9vHPV vaccine recipients seroconverted for all 9 HPV types at Month 7. Antibody responses to the 9 HPV types persisted over 5 years. The most common AEs were injection-site related, mostly of mild to moderate intensity. The 9vHPV vaccine is efficacious, immunogenic, and well tolerated in Latin American young women, girls, and boys. These data support 9vHPV vaccination programs in Latin America, a region with substantial cervical cancer burden. Copyright © 2018 Merck Sharp & Dohme Corp., and The Authors. Published by Elsevier B.V. All rights reserved.

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

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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.

Addressing a Yellow Fever Vaccine Shortage - United States, 2016-2017.

Science.gov (United States)

Gershman, Mark D; Angelo, Kristina M; Ritchey, Julian; Greenberg, David P; Muhammad, Riyadh D; Brunette, Gary; Cetron, Martin S; Sotir, Mark J

2017-05-05

Recent manufacturing problems resulted in a shortage of the only U.S.-licensed yellow fever vaccine. This shortage is expected to lead to a complete depletion of yellow fever vaccine available for the immunization of U.S. travelers by mid-2017. CDC, the Food and Drug Administration (FDA), and Sanofi Pasteur are collaborating to ensure a continuous yellow fever vaccine supply in the United States. As part of this collaboration, Sanofi Pasteur submitted an expanded access investigational new drug (eIND) application to FDA in September 2016 to allow for the importation and use of an alternative yellow fever vaccine manufactured by Sanofi Pasteur France, with safety and efficacy comparable to the U.S.-licensed vaccine; the eIND was accepted by FDA in October 2016. The implementation of this eIND protocol included developing a systematic process for selecting a limited number of clinic sites to provide the vaccine. CDC and Sanofi Pasteur will continue to communicate with the public and other stakeholders, and CDC will provide a list of locations that will be administering the replacement vaccine at a later date.

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

Science.gov (United States)

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.

Ensuring the population living safety in the contaminated areas

Directory of Open Access Journals (Sweden)

S. I. Voronov

2016-01-01

Full Text Available The state policy of the Russian Federation to ensure population, living in the contaminated areas, life safety is implemented by means of federal programs.12 programs for overcoming the Chernobyl accident consequences, children’s population protection and housing provision for the Chernobyl accident liquidators are adopted and realized during this time. Total financing amount from the federal budget is more than 9,2 billion rubles. The main efforts are directed to create necessary infrastructure in settlements, development and deployment rehabilitation measures for agricultural lands and forests, creation of radiation situation monitoring systems, increase housekeeping safety culture in the contaminated territories, informational support and social and psychological rehabilitation of the population. Within the state programs are developing complex systems of a radiation situation monitoring in 12 subjects of the Russian Federation. Experts training for the outreach work with population, concerning radiation safety, increasing population knowledge level about radiation in a format of seminars, conferences, with use of online technologies is provided. The project on creation the uniform interdepartmental information system on overcoming radiation accidents aftermath, integrating the operating information systems of The Ministry of the Russian Federation for Civil Defence, Emergencies and Elimination of Consequences of Natural Disasters, Federal Service for Hydrometeorology and Environmental Monitoring, the Russian Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing and the Russian Academy of Sciences is realized.However, the problem of overcoming the radiation accidents aftermath remains relevant up to date.In 14 subjects of the Russian Federation there are territories contaminated by radioactive materials as a result of the Chernobyl accident where more than 1,5 million people live.

Vaccine quality and safety: Scrutinizing the reported 3-fold increase in adverse effects following immunization (Aefi) in India

OpenAIRE

Patil, Rajan R

2013-01-01

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.

Safety, immunogenicity and duration of immunity elicited by an inactivated bovine ephemeral fever vaccine.

Directory of Open Access Journals (Sweden)

Orly Aziz-Boaron

Full Text Available 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.

Safety of the malaria vaccine candidate, RTS,S/AS01E in 5 to 17 month old Kenyan and Tanzanian Children.

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John Lusingu

2010-11-01

Full Text Available The malaria vaccine candidate, RTS,S/AS01(E, showed promising protective efficacy in a trial of Kenyan and Tanzanian children aged 5 to 17 months. Here we report on the vaccine's safety and tolerability. The experimental design was a Phase 2b, two-centre, double-blind (observer- and participant-blind, randomised (1∶1 ratio controlled trial. Three doses of study or control (rabies vaccines were administered intramuscularly at 1 month intervals. Solicited adverse events (AEs were collected for 7 days after each vaccination. There was surveillance and reporting for unsolicited adverse events for 30 days after each vaccination. Serious adverse events (SAEs were recorded throughout the study period which lasted for 14 months after dose 1 in Korogwe, Tanzania and an average of 18 months post-dose 1 in Kilifi, Kenya. Blood samples for safety monitoring of haematological, renal and hepatic functions were taken at baseline, 3, 10 and 14 months after dose 1. A total of 894 children received RTS,S/AS01(E or rabies vaccine between March and August 2007. Overall, children vaccinated with RTS,S/AS01(E had fewer SAEs (51/447 than children in the control group (88/447. One SAE episode in a RTS,S/AS01(E recipient and nine episodes among eight rabies vaccine recipients met the criteria for severe malaria. Unsolicited AEs were reported in 78% of subjects in the RTS,S/AS01(E group and 74% of subjects in the rabies vaccine group. In both vaccine groups, gastroenteritis and pneumonia were the most frequently reported unsolicited AE. Fever was the most frequently observed solicited AE and was recorded after 11% of RTS,S/AS01(E doses compared to 31% of doses of rabies vaccine. The candidate vaccine RTS,S/AS01(E showed an acceptable safety profile in children living in a malaria-endemic area in East Africa. More data on the safety of RTS,S/AS01(E will become available from the Phase 3 programme.

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

Science.gov (United States)

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 (pvaccination, 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 (pvaccine administration (pchildren, 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. Copyright © 2015 Elsevier Ltd. All rights reserved.

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.

Science.gov (United States)

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 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. Copyright © 2014 Elsevier Ltd. All rights reserved.

Efficacy, immunogenicity, and safety of a 9-valent human papillomavirus vaccine in Latin American girls, boys, and young women

Directory of Open Access Journals (Sweden)

Ángela María Ruiz-Sternberg

2018-06-01

Full Text Available Background: A 9-valent human papillomavirus (HPV6/11/16/18/31/33/45/52/58; 9vHPV vaccine was developed to expand coverage of the previously developed quadrivalent (HPV6/11/16/18; qHPV vaccine. Methods: Efficacy, immunogenicity, and safety outcomes were assessed in Latin American participants enrolled in 2 international studies of the 9vHPV vaccine, including a randomized, double-blinded, controlled with qHPV vaccine, efficacy, immunogenicity, and safety study in young women aged 16–26 years, and an immunogenicity and safety study in girls and boys aged 9–15 years. Participants (N=5312 received vaccination at Day 1, Month 2, and Month 6. Gynecological swabs were collected regularly in young women for cytological and HPV DNA testing. Serum was analyzed for HPV antibodies in all participants. Adverse events (AEs were also monitored in all participants. Results: The 9vHPV vaccine prevented HPV 31-, 33-, 45-, 52-, and 58-related high-grade cervical, vulvar, and vaginal dysplasia with 92.3% efficacy (95% confidence interval 54.4, 99.6. Anti-HPV6, 11, 16, and 18 geometric mean titers at Month 7 were similar in the 9vHPV and qHPV vaccination groups. Anti-HPV antibody responses following vaccination were higher among girls and boys than in young women. Most (>99% 9vHPV vaccine recipients seroconverted for all 9 HPV types at Month 7. Antibody responses to the 9 HPV types persisted over 5 years. The most common AEs were injection-site related, mostly of mild to moderate intensity. Conclusions: The 9vHPV vaccine is efficacious, immunogenic, and well tolerated in Latin American young women, girls, and boys. These data support 9vHPV vaccination programs in Latin America, a region with substantial cervical cancer burden. Keywords: Human papillomavirus, Vaccine, Cervical cancer, Persistent infection, 9vHPV

Immunogenicity and safety of 13-valent pneumococcal conjugate vaccine in Mexico

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Maricruz Gutiérrez Brito

2013-06-01

Full Text Available OBJECTIVE: To assess the safety and immune responses induced by a 13-valent pneumococcal conjugate vaccine (PCV13 after immunization of infants in Mexico. METHODS: PCV13 was given with other routine childhood vaccinations to 225 infants in Mexico at ages 2, 4, 6, and 12 months. RESULTS: The proportions of subjects achieving immunoglobulin G (IgG concentrations ≥0.35 µg/mL after the infant series and toddler dose were ≥93.1% and ≥96.7%, respectively, for all 13 serotypes. The serotype-specific pneumococcal IgG geometric mean concentrations after the infant series and toddler dose ranged from 1.18 to 9.13 µg/mL and from 1.62 to 15.41 µg/mL, respectively. The most common local reaction and systemic event after each dose were tenderness and irritability, respectively. Most fever was mild; no fever >40.0°C (i.e., severe was reported. One subject withdrew because of Kawasaki disease 5 days after the first dose of vaccines, but this condition was not considered related to PCV13. CONCLUSIONS: Overall, PCV13 administered with routine pediatric vaccines was immunogenic and safe in healthy infants in Mexico.

CYD-TDV dengue vaccine: systematic review and meta-analysis of efficacy, immunogenicity and safety.

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Godói, Isabella Piassi; Lemos, Livia Lovato Pires; de Araújo, Vânia Eloisa; Bonoto, Braúlio Cesar; Godman, Brian; Guerra Júnior, Augusto Afonso

2017-03-01

Dengue virus (DENV) is a serious global health problem. CYD-TDC (Dengvaxia ® ) was the first vaccine to gain regulatory approval to try and address this problem. Summarize all available evidence on the immunogenicity, efficacy and safety of the CYD-TDV dengue vaccine. Meta-analysis and systematic review. The best and worst immunogenicity results were for DENV4 and DENV1, respectively. Vaccine efficacy of 60% was derived from studies with participants aged 2-16 years old, with DENV4 and DENV2 presenting the best and worst results, respectively. Erythema and swelling were more frequent with CYD-TDV. No differences were detected for systemic adverse events. CYD-TDV showed moderate efficacy in children and adolescents. From the immunogenicity results in adults, we can expect satisfactory efficacy from vaccination in this population.

The main ecological principles of ensuring safety of man and biosphere in the handling of radioactive wastes

International Nuclear Information System (INIS)

Kryshev, I.I.; Sazykina, T.G.

1999-01-01

This paper provides an assessment of ecological safety in the handling of radioactive wastes in the territory of Russia. The following problems are considered: the main sources of radioactive wastes and spent nuclear fuel; assessments of collective dose from the enterprises of the nuclear fuel cycle in Russia; and principles and criteria for ensuring ecological safety when handling radioactive wastes

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

Science.gov (United States)

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 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 (Pvaccine 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.

The safety of seasonal influenza vaccines in Australian children in 2013.

Science.gov (United States)

Wood, Nicholas J; Blyth, Chris C; Willis, Gabriela A; Richmond, Peter; Gold, Michael S; Buttery, Jim P; Crawford, Nigel; Crampton, Michael; Yin, J Kevin; Chow, Maria Yui Kwan; Macartney, Kristine

2014-11-17

To examine influenza vaccine safety in Australian children aged under 10 years in 2013. Active prospective surveillance study conducted with parents or carers of children who received influenza vaccine in outpatient clinics at six tertiary paediatric hospitals or from selected primary health care providers between 18 March and 19 July 2013. Parental-reported frequency of systemic reactions (fever, headache, nausea, abdominal symptoms, convulsions, rash, rigors and fatigue), injection site reactions (erythema, swelling and/or pain at the injection site), use of antipyretics or analgesics, and medical attendance or advice within 72 hours after vaccination. Of 981 children enrolled in the surveillance, 893 children aged 6 months to children received 1052 influenza vaccine doses. Fever was reported in 5.5% (95% CI, 4.1%-7.3%) and 6.5% (95% CI, 3.5%-10.9%) of children after Doses 1 and 2, respectively. One febrile convulsion occurred in a child with a known seizure disorder. Injection site reactions occurred in 21.2% (95% CI, 18.5%-24.1%) and 6.0% (95% CI, 3.1%-10.2%) after Doses 1 and 2, respectively; most were mild. Very few parents sought medical follow-up for their child's reaction: 22 (2.6%; 95% CI, 1.6%-3.9%) after Dose 1, and 11 (5.5%; 95% CI, 2.8%-9.6%) after Dose 2. These results are consistent with clinical trials and other observational studies of influenza vaccines currently registered for use in young children in Australia and can reassure parents and health care providers that influenza vaccination is safe and well tolerated.

Safety of a quadrivalent meningococcal serogroups A, C, W and Y conjugate vaccine (MenACWY-CRM) administered with routine infant vaccinations: results of an open-label, randomized, phase 3b controlled study in healthy infants.

Science.gov (United States)

Abdelnour, Arturo; Silas, Peter E; Lamas, Marta Raquel Valdés; Aragón, Carlos Fernándo Grazioso; Chiu, Nan-Chang; Chiu, Cheng-Hsun; Acuña, Teobaldo Herrera; Castrejón, Tirza De León; Izu, Allen; Odrljin, Tatjana; Smolenov, Igor; Hohenboken, Matthew; Dull, Peter M

2014-02-12

The highest risk for invasive meningococcal disease (IMD) is in infants aged CRM, a quadrivalent meningococcal conjugate vaccine, concomitantly administered with routine vaccinations to healthy infants. Two-month-old infants were randomized 3:1 to receive MenACWY-CRM with routine vaccines or routine vaccines alone at ages 2, 4, 6 and 12 months. Adverse events (AEs) that were medically attended and serious adverse events (SAEs) were collected from all subjects from enrollment through 18 months of age. In a subset, detailed safety data (local and systemic solicited reactions and all AEs) were collected for 7 days post vaccination. The primary objective was a non-inferiority comparison of the percentages of subjects with ≥1 severe systemic reaction during Days 1-7 after any vaccination of MenACWY-CRM plus routine vaccinations versus routine vaccinations alone (criterion: upper limit of 95% confidence interval [CI] of group difference CRM plus routine vaccines and 13% after routine vaccines alone (group difference 3.0% (95% CI -0.8, 6.4%). Although the non-inferiority criterion was not met, post hoc analysis controlling for significant center and group-by-center differences revealed that MenACWY-CRM plus routine vaccinations was non-inferior to routine vaccinations alone (group difference -0.1% [95% CI -4.9%, 4.7%]). Rates of solicited AEs, medically attended AEs, and SAEs were similar across groups. In a large multinational safety study, a 4-dose series of MenACWY-CRM concomitantly administered with routine vaccines was clinically acceptable with a similar safety profile to routine vaccines given alone. Copyright © 2013 Elsevier Ltd. All rights reserved.

WISE recommendations to ensure the safety of injections in diabetes.

Science.gov (United States)

Strauss, K

2012-01-01

Injections and fingersticks administered to patients with diabetes in health care settings present a risk of blood exposure to the injector as well as other workers in potential contact with sharps. Such exposures could lead to transmission of bloodborne pathogens such as hepatitis and HIV. A recent EU Directive requires that where such risks have been identified, processes and devices must be put in place to reduce or eliminate the risk. The aim of this paper is to provide formal guidelines on the application of this Directive to diabetes care settings. These evidence-based recommendations were written and vetted by a large group of international safety experts. A systematic literature search was conducted for all peer-reviewed studies and publications which bear on sharps safety in diabetes. Initially a group of experts reviewed this literature and drafted the recommendations. These were then presented for review, debate and revision to 57 experts from 14 countries at the WISE workshop in October, 2011. After the WISE meeting, the revised Recommendations were circulated electronically to attendees on three occasions, each time in a new iteration with revisions. Each recommendation was graded by the weight it should have in daily practice and by its degree of support in the medical literature. The topics covered include Risks of Sharps Injury and Muco-cutaneous Exposure, The EU Directive, Device Implications, Injection Technique Implications, Education and Training (Creating a "Safety Culture"), Value, Awareness and Responsibility. These safety recommendations provide practical guidance and fill an important gap in diabetes management. If followed, they should help ensure safe, effective and largely injury-free injections and fingersticks. They will serve as the roadmap for applying the new EU Directive to diabetes care. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Evaluation of C-reactive protein as an inflammatory biomarker in rabbits for vaccine nonclinical safety studies

NARCIS (Netherlands)

Destexhe, E.; Prinsen, M.K.; Schöll, I. van; Kuper, C.F.; Garçon, N.; Veenstra, S.; Segal, L.

2013-01-01

Introduction: Inflammatory reactions are one of the potential safety concerns that are evaluated in the framework of vaccine safety testing. In nonclinical studies, the assessment of the inflammation relies notably on the measurement of biomarkers. C-reactive protein (CRP) is an acute-phase plasma

[Safety and immunogenicity of a 7-valent pneumococcal conjugate vaccine (Prevenar) booster dose in healthy Chinese toddlers].

Science.gov (United States)

Li, Rong-cheng; Li, Feng-xiang; Li, Yan-ping

2009-06-01

To evaluate the safety and immunogenicity of the booster dose of 7 valent pneumococcal conjugate vaccine (PCV7) to the healthy Chinese toddlers who had received 3 primary doses. Four hundred and eighty-eight Chinese toddlers received a booster dose of PCV7 at age of 12-15 months following a primary series of the vaccine given at ages 3, 4, 5 months separately with Diphtheria Tetanus Acellular Pertussis Combined Vaccine (DTaP) in Group 1 or concurrently with DTaP in Group 2. Following the booster dose immunization, each subject was followed up for 30 days to observe the safety of the vaccine. Blood samples were taken from a subset of subjects prior and post 30 days the booster dose immunization to evaluate immunogenicity. A high proportion of subjects in Group 1 (89%) and Group 2 (91%) remained afebrile after the booster dose. Local reactions to the PCV7 booster dose were generally mild. For each serotype, the rise in GMC (post-/pre-vaccination) showed a statistically significant difference (P<0.0001) between both groups. PCV7 administered as a booster dose is generally safe, well tolerate, and immunogenic in healthy Chinese toddlers.

Ensuring the safety of surgical teams when managing casualties of a radiological dirty bomb.

Science.gov (United States)

Williams, Geraint; O'Malley, Michael; Nocera, Antony

2010-09-01

The capacity for surgical teams to ensure their own safety when dealing with the consequences caused by the detonation of a radiological dirty bomb is primarily determined by prior knowledge, familiarity and training for this type of event. This review article defines the associated radiological terminology with an emphasis on the personal safety of surgical team members in respect to the principles of radiological protection. The article also describes a technique for use of hand held radiation monitors and will discuss the identification and management of radiologically contaminated patients who may pose a significant danger to the surgical team. 2010 Elsevier Ltd. All rights reserved.

Exploring Facilitators and Barriers to Initiation and Completion of the Human Papillomavirus (HPV) Vaccine Series among Parents of Girls in a Safety Net System.

Science.gov (United States)

O'Leary, Sean T; Lockhart, Steven; Barnard, Juliana; Furniss, Anna; Dickinson, Miriam; Dempsey, Amanda F; Stokley, Shannon; Federico, Steven; Bronsert, Michael; Kempe, Allison

2018-01-23

Objective: To assess, among parents of predominantly minority, low-income adolescent girls who had either not initiated (NI) or not completed (NC) the HPV vaccine series, attitudes and other factors important in promoting the series, and whether attitudes differed by language preference. Design/Methods: From August 2013-October 2013, we conducted a mail survey among parents of girls aged 12-15 years randomly selected from administrative data in a Denver safety net system; 400 parents from each group (NI and NC) were targeted. Surveys were in English or Spanish. The response rate was 37% (244/660; 140 moved or gone elsewhere; 66% English-speaking, 34% Spanish-speaking). Safety attitudes of NIs and NCs differed, with 40% NIs vs. 14% NC's reporting they thought HPV vaccine was unsafe ( p HPV vaccine before, but now I am" (English-speaking, 23%, Spanish-speaking, 50%). Items rated as very important among NIs in the decision regarding vaccination included: more information about safety (74%), more information saying it prevents cancer (70%), and if they knew HPV was spread mainly by sexual contact (61%). Conclusions : Safety concerns, being unaware of the need for multiple doses, and low perceived risk of infection remain significant barriers to HPV vaccination for at-risk adolescents. Some parents' safety concerns do not appear until initial vaccination.

Trichinella diagnostics and control: Mandatory and best practices for ensuring food safety

DEFF Research Database (Denmark)

Gajadhar, A. A.; Pozio, E.; Gamble, H. R.

2009-01-01

Because of its role in human disease, there are increasing global requirements for reliable diagnostic and control methods for Trichinella in food animals to ensure meat safety and to facilitate trade. Consequently, there is a need for standardization of methods, programs, and best practices used...... in various porcine and equine pre- and post-slaughter programs, including farm or herd certification programs is also discussed. A brief review of the effectiveness of meat processing methods, such as freezing, cooking and preserving is provided. The importance of proper quality assurance and its application...

Sero-Surveillance to assess immunity to rubella and assessment of immunogenicity and safety of a single dose of rubella vaccine in school girls

Directory of Open Access Journals (Sweden)

Sharma Hitt

2010-01-01

Full Text Available Background: Rubella vaccination is not yet included in National Immunization Schedule in India. Serosurvey is frequently used to assess epidemiologic pattern of Rubella in a community. Serosurveys in different parts of India have found that 6-47% of women are susceptible for Rubella infection. The present serosurveillance was conducted in Jammu, India, in two public schools. Objective: To determine serological status of Rubella antibodies of school girls and assessment of immunogenicity and reactogenicity of Rubella immunization in seronegative girls. Materials and Methods: The current study was conducted to determine Rubella serostatus in peripubertal schoolgirls aged 11-18 years and also to assess immunogenicity and safety of Rubella vaccine (R-Vac of Serum Institute of India Ltd., Pune, in seronegative girls. For screening, pre-vaccination serum Rubella IgG antibodies were determined and to assess immunogenicity of the vaccine, post-vaccination IgG antibodies were compared with pre-vaccination levels. Safety assessment was done for a period of 8 weeks, post-vaccination. Results: A total of 90 (32.7% seronegative girls were vaccinated. All girls (100% became seropositive, post-vaccination. Clinically relevant and statistically significant increase in anti-Rubella IgG titres was observed. The adverse events were mild and self-limiting. Conclusions: R-Vac vaccine used in the study demonstrated an excellent safety and immunogenicity profile.

Framework conditions and requirements to ensure the technical functional safety of reprocessed medical devices.

Science.gov (United States)

Kraft, Marc

2008-09-03

Testing and restoring technical-functional safety is an essential part of medical device reprocessing. Technical functional tests have to be carried out on the medical device in the course of the validation of reprocessing procedures. These ensure (in addition to the hygiene tests) that the reprocessing procedure is suitable for the medical device. Functional tests are, however, also a part of reprocessing procedures. As a stage in the reprocessing, they ensure for the individual medical device that no damage or other changes limit the performance. When determining which technical-functional tests are to be carried out, the current technological standard has to be taken into account in the form of product-specific and process-oriented norms. Product-specific norms primarily define safety-relevant requirements. The risk management method described in DIN EN ISO 14971 is the basis for recognising hazards; the likelihood of such hazards arising can be minimised through additional technical-functional tests, which may not yet have been standardised. Risk management is part of a quality management system, which must be bindingly certified for manufacturers and processors of critical medical devices with particularly high processing demands by a body accredited by the competent authority.

Immunogenicity and Safety of a Trivalent Inactivated Influenza Vaccine in Children 6 Months to 17 Years of Age, Previously Vaccinated with an AS03-Adjuvanted A(H1N1)Pdm09 Vaccine: Two Open-label, Randomized Trials.

Science.gov (United States)

Vesikari, Timo; Richardus, Jan Hendrik; Berglund, Johan; Korhonen, Tiina; Flodmark, Carl-Erik; Lindstrand, Ann; Silfverdal, Sven Arne; Bambure, Vinod; Caplanusi, Adrian; Dieussaert, Ilse; Roy-Ghanta, Sumita; Vaughn, David W

2015-07-01

During the influenza pandemic 2009-2010, an AS03-adjuvanted A(H1N1)pdm09 vaccine was used extensively in children 6 months of age and older, and during the 2010-2011 influenza season, the A(H1N1)pdm09 strain was included in the seasonal trivalent inactivated influenza vaccine (TIV) without adjuvant. We evaluated the immunogenicity and safety of TIV in children previously vaccinated with the AS03-adjuvanted A(H1N1)pdm09 vaccine. Healthy children were randomized (1:1) to receive TIV or a control vaccine. Children were aged 6 months to 9 years (n = 154) and adolescents 10-17 years (n = 77) when they received AS03-adjuvanted A(H1N1)pdm09 vaccine at least 6 months before study enrolment. Hemagglutination inhibition (HI) and neutralizing antibody responses against the A(H1N1)pdm09 strain were evaluated before (day 0) and at day 28 and month 6 after study vaccination. Reactogenicity was assessed during the 7 day postvaccination period, and safety was assessed for 6 months. At day 0, >93.9% of all children had HI titers ≥1:40 for the A(H1N1)pdm09 strain, which increased to 100% at both day 28 and month 6 in the TIV group. Between days 0 and 28, HI antibody geometric mean titers against A(H1N1)pdm09 increased by 9-fold and 4-fold in children 6 months to 9 years of age and 10-17 years of age, respectively. AS03-adjuvanted A(H1N1)pdm09 vaccine-induced robust immune responses in children that persisted into the next season, yet were still boosted by TIV containing A(H1N1)pdm09. The reactogenicity and safety profile of TIV did not appear compromised by prior receipt of AS03-adjuvanted A(H1N1)pdm09 vaccine.

Safety and immunogenicity of a modified process hepatitis B vaccine in healthy neonates.

Science.gov (United States)

Minervini, Gianmaria; McCarson, Barbara J; Reisinger, Keith S; Martin, Jason C; Stek, Jon E; Atkins, Barbara M; Nadig, Karin B; Liska, Vladimir; Schödel, Florian P; Bhuyan, Prakash K

2012-02-14

A manufacturing process using a modified adjuvant was developed to optimize the consistency and immunogenicity for recombinant hepatitis B vaccine (control: RECOMBIVAX-HB™). This modified process hepatitis B vaccine (mpHBV), which was previously shown to have an acceptable safety and immunogenicity profile in young adults, has now been studied in newborn infants. Healthy 1-10-day-old neonates (N=566) received 3 intramuscular doses (5μg hepatitis B surface antigen [HBsAg] per dose) of either mpHBV or control at Day 1, and Months 1 and 6. Serum antibody to HBsAg (anti-HBs) was assayed at Month 7 (1 month Postdose 3). Anti-HBs geometric mean titers (GMTs) and seroprotection rates (SPRs) (% of subjects with an anti-HBs titer ≥10mIU/mL) were compared at Month 7. After each dose, injection-site adverse experiences (AEs) and axillary temperatures were recorded for 5 days; systemic AEs were recorded for Days 1-14. Month 7 SPR was 97.9% for the mpHBV group and 98.9% for the control. The GMT was 843.7mIU/mL for the mpHBV group and 670.1mIU/mL for the control. The GMT ratio (mpHBV/control) was 1.26 (95% confidence interval [CI]: 0.94, 1.69), meeting the prespecified non-inferiority criteria. The percentages of subjects reporting any AE, injection-site AEs, or systemic AEs were similar across the 2 vaccination groups. There were no serious AEs. The safety profile of mpHBV was comparable to that of the control vaccine. The geometric mean antibody titer for mpHBV was higher than control vaccine in this infant population, but the difference did not meet the predefined statistical criterion for superiority. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

Science.gov (United States)

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

2012-04-05

In the development of novel substrates used for production of human vaccines there has been significant progress made in recent years. Emerging and re-emerging infectious diseases like the recent porcine Influenza A virus (H1N1) pandemic necessitated the availability of unprecedented amounts of vaccines. In addition, the high demand for vaccines in the industrialised countries has also been paralleled by a steep increase in demand in developing countries. The manufacturing capability for viral vaccines produced in embryonated hen eggs and conventional/classical cell substrates, such as chicken embryo fibroblasts, has now reached its capacity limit. This constraint may be overcome by utilising other recognised cell substrates such as Madin Darby Canine Kidney (MDCK) (dog origin), Chinese Hamster Ovary (CHO) (hamster cells) or Vero cells (monkey origin) or as an alternative, introduce new cell substrates of human or avian origin. Using new cell substrates may prove to be a highly replication-proficient way of producing live viral vaccines such as Influenza A viruses. Despite some advantages, cell substrates may pose a small residual risk to humans since some of them are known to be tumourigenic in immunosuppressed animals. However, this residual risk should be considered acceptable by regulators. Safety testing requirements for cell substrates used in the manufacture of vaccines is mandated by published guidance from organisations such as World Health Organization (WHO), United States Food and Drug Administration (FDA), European Medicines Agency (EMA) and International Conferences on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human use (ICH) as well as requirements laid down in compendial monographs (Ph. Eur. and USP). This paper considers the guidance contained in these regulatory documents. In addition, the safety challenges and almost arbitrary risk-based classification of cell substrates used in the production of human

76 FR 32364 - Collaboration in Regulatory Science and Capacity To Advance Global Access to Safe Vaccines and...

Science.gov (United States)

2011-06-06

... project has the following goals: Contribute to the knowledge base of the current state of regulatory... in assuring the safety, efficacy and quality of vaccines. WHO is the directing and coordinating... scientific consultation and on international consensus and are intended to ensure the consistent quality and...

Immunogenicity and safety of cell-derived MF59®-adjuvanted A/H1N1 influenza vaccine for children

Science.gov (United States)

Knuf, Markus; Leroux-Roels, Geert; Rümke, Hans; Rivera, Luis; Pedotti, Paola; Arora, Ashwani Kumar; Lattanzi, Maria; Kieninger, Dorothee; Cioppa, Giovanni Della

2015-01-01

Mass immunization of children has the potential to decrease infection rates and prevent the transmission of influenza. We evaluated the immunogenicity, safety, and tolerability of different formulations of cell-derived MF59-adjuvanted and nonadjuvanted A/H1N1 influenza vaccine in children and adolescents. This was a randomized, single-blind, multicenter study with a total of 666 healthy subjects aged 6 months–17 y in one of 3 vaccination groups, each receiving formulations containing different amounts of influenza A/H1N1 antigen with or without MF59. A booster trivalent seasonal MF59 vaccine was administered one year after primary vaccinations. Antibody titers were assessed by hemagglutination inhibition (HI) and microneutralization assays obtained on days 1, 22, 43, 366, and 387 (3 weeks post booster). Safety was monitored throughout the study. One vaccination with 3.75 μg of A/H1N1 antigen formulated with 50% MF59 (3.75_halfMF59) or 7.5 μg of A/H1N1 antigen formulated with 100% MF59 (7.5_fullMF59) induced an HI titer ≥1:40 in >70% of children in the 1–vaccinations with nonadjuvanted 15 μg A/H1N1 antigen were needed to achieve this response in the 1–children aged 6–11 months, 1 dose of 7.5_fullMF59 resulted in an HI titer ≥1:40 in >70% while 2 doses of 3.75_halfMF59 were required to achieve this result. All vaccines were well tolerated. Our findings support the immunogenicity and safety of the 3.75_halfMF59 (2 doses for children vaccine formulations for use in children and adolescents aged 6 months to 17 y The use of the 3.75_halfMF59 could have the benefit of antigen and adjuvant sparing, increasing the available vaccine doses allowing vaccination of more people. PMID:25621884

Parental concern about vaccine safety in Canadian children partially immunized at age 2: a multivariable model including system level factors.

Science.gov (United States)

MacDonald, Shannon E; Schopflocher, Donald P; Vaudry, Wendy

2014-01-01

Children who begin but do not fully complete the recommended series of childhood vaccines by 2 y of age are a much larger group than those who receive no vaccines. While parents who refuse all vaccines typically express concern about vaccine safety, it is critical to determine what influences parents of 'partially' immunized children. This case-control study examined whether parental concern about vaccine safety was responsible for partial immunization, and whether other personal or system-level factors played an important role. A random sample of parents of partially and completely immunized 2 y old children were selected from a Canadian regional immunization registry and completed a postal survey assessing various personal and system-level factors. Unadjusted odds ratios (OR) and adjusted ORs (aOR) were calculated with logistic regression. While vaccine safety concern was associated with partial immunization (OR 7.338, 95% CI 4.138-13.012), other variables were more strongly associated and reduced the strength of the relationship between concern and partial immunization in multivariable analysis (aOR 2.829, 95% CI 1.151-6.957). Other important factors included perceived disease susceptibility and severity (aOR 4.629, 95% CI 2.017-10.625), residential mobility (aOR 3.908, 95% CI 2.075-7.358), daycare use (aOR 0.310, 95% CI 0.144-0.671), number of needles administered at each visit (aOR 7.734, 95% CI 2.598-23.025) and access to a regular physician (aOR 0.219, 95% CI 0.057-0.846). While concern about vaccine safety may be addressed through educational strategies, this study suggests that additional program and policy-level strategies may positively impact immunization uptake.

Ensuring the safety of nuclear facilities located in large cities

International Nuclear Information System (INIS)

Ryazantsev, E.P.; Kolyadin, V.I.; Bylkin, B.K.; Zverkov, Yu.A.

2002-01-01

The problems of ensuring the safety of nuclear facilities and other facilities representing a radiation hazard (hereinafter referred to as 'nuclear facilities') which are located in large cities are considered in the light of the experience with the 'Kurchatov Institute' Russian Research Centre. The accumulation of substantial quantities of spent nuclear fuel and radwaste at the Centre was an inevitable consequence of the military and civilian nuclear research programmes which started there in 1943. A comprehensive programme has been developed for reducing the impact of ionizing radiation on the Centre's personnel, the population living near the Centre and the local environment. The authors describe the basic elements of a programme for decommissioning reactor facilities and eliminating spent fuel and radwaste storage sites and also describe how the programme is progressing. (author)

Safety and tolerability of cell culture-derived and egg-derived trivalent influenza vaccines in 3 to children and adolescents at risk of influenza-related complications.

Science.gov (United States)

Diez-Domingo, Javier; de Martino, Maurizio; Lopez, Jose Garcia-Sicilia; Zuccotti, Gian Vincenzo; Icardi, Giancarlo; Villani, Alberto; Moreno-Perez, David; Hernández, María Méndez; Aldeán, Javier Álvarez; Mateen, Ahmed Abdul; Enweonye, Igwebuike; de Rooij, Richard; Chandra, Richa

2016-08-01

This descriptive, non-comparative, phase III study evaluated the safety and tolerability of cell culture-derived (TIVc) and egg-derived (TIV) seasonal influenza vaccines in children at risk of influenza-related complications. Four hundred and thirty subjects were randomized 2:1 to TIVc or TIV. Subjects aged 3 to vaccinated, n=89) or two doses (if not previously vaccinated, n=124) of the study vaccines; the 9 to vaccination; safety was monitored for 6 months. After any vaccination, the most frequently reported solicited local adverse event (AE) was tenderness/pain (TIVc 44%, 66%, 53% and TIV 56%, 51%, 65% in the age groups 3 to vaccine-related serious AEs were noted. New onset of chronic disease was reported in ≤1% of subjects. TIVc and TIV had acceptable tolerability and similar safety profiles in at-risk children (NCT01998477). Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Immunogenicity and safety evaluation of bivalent types 1 and 3 oral poliovirus vaccine by comparing different poliomyelitis vaccination schedules in China: A randomized controlled non-inferiority clinical trial.

Science.gov (United States)

Qiu, Jingjun; Yang, Yunkai; Huang, Lirong; Wang, Ling; Jiang, Zhiwei; Gong, Jian; Wang, Wei; Wang, Hongyan; Guo, Shaohong; Li, Chanjuan; Wei, Shuyuan; Mo, Zhaojun; Xia, Jielai

2017-06-03

The type 2 component of the oral poliovirus vaccine is targeted for global withdrawal through a switch from the trivalent oral poliovirus vaccine (tOPV) to a bivalent oral poliovirus vaccine (bOPV). The switch is intended to prevent paralytic polio caused by circulating vaccine-derived poliovirus type 2. We aimed to assess the immunogenicity and safety profile of 6 vaccination schedules with different sequential doses of inactivated poliovirus vaccine (IPV), tOPV, or bOPV. A randomized controlled trial was conducted in China in 2015. Healthy newborn babies randomly received one of the following 6 vaccination schedules: cIPV-bOPV-bOPV(I-B-B), cIPV-tOPV-tOPV(I-T-T), cIPV-cIPV-bOPV(I-I-B), cIPV-cIPV-tOPV(I-I-T), cIPV-cIPV-cIPV(I-I-I), or tOPV-tOPV-tOPV(T-T-T). Doses were administered sequentially at 4-6 week intervals after collecting baseline blood samples. Patients were proactively followed up for observation of adverse events after the first dose and 30 days after all doses. The primary study objective was to investigate the immunogenicity and safety profile of different vaccine schedules, evaluated by seroconversion, seroprotection and antibody titer against poliovirus types 1, 2, and 3 in the per-protocol population. Of 600 newborn babies enrolled, 504 (84.0%) were included in the per-protocol population. For type 1 poliovirus, the differences in the seroconversion were 1.17% (95% CI = -2.74%, 5.08%) between I-B-B and I-T-T and 0.00% (95% CI: -6.99%, 6.99%) between I-I-B and I-I-T; for type 3 poliovirus, differences in the seroconversion were 3.49% (95% CI: -1.50%, 8.48%) between I-B-B and I-T-T and -2.32% (95% CI: -5.51%, 0.86%) between I-I-B and I-I-T. The non-inferiority conclusion was achieved in both poliovirus type 1 and 3 with the margin of -10%. Of 24 serious adverse events reported, no one was vaccine-related. The vaccination schedules with bOPV followed by one or 2 doses of IPV were recommended to substitute for vaccinations involving tOPV without

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

Directory of Open Access Journals (Sweden)

Mauricio Hernández-Ávila

2016-01-01

Full Text Available 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

Safety and immunogenicity of a live attenuated RSV vaccine in healthy RSV-seronegative children 5 to 24 months of age.

Directory of Open Access Journals (Sweden)

Elissa Malkin

Full Text Available Despite substantial morbidity associated with respiratory syncytial virus (RSV infection, there is no licensed vaccine. MEDI-559 is a live attenuated intranasal vaccine candidate being developed for prevention of lower respiratory illness due to RSV in young children. This randomized, placebo-controlled study evaluated safety of MEDI-559 in healthy, RSV-seronegative children. MEDI-559 or placebo was administered on 3 occasions, 2 months apart. Primary safety was based on solicited symptoms (SSs and adverse events (AEs collected for 28 days after each dose. Nasal wash samples were collected 3 times after each dose (days 7-10, 12-18, 28-34 and at sick visits. Serum was collected for measuring antibody immune responses to RSV prior to first vaccination and 28 days post final dose. Long-term safety was monitored for 365 days from first dose. SSs were mild and frequent (MEDI-559 84%; placebo 91%; most common SSs were runny/stuffy nose, cough, and irritability/fussiness. AEs occurred in 67% MEDI-559 and 57% placebo recipients: most common AE was upper respiratory tract infection (MEDI-559 35%; placebo 23%. Higher incidence of medically attended lower respiratory illness within 28 days after dosing occurred in the MEDI-559 arm compared to placebo (none associated with vaccine virus shedding. There was no evidence of enhanced RSV disease. Vaccine virus was detected only in MEDI-559 recipients; shedding occurred in 56%subjects, primarily post dose 1. A functional immune response was observed in 59% and 9% MEDI-559 and placebo recipients, respectively, by an RSV microneutralization assay. Vaccine take, assessed by proportion that shed vaccine-type virus or had a seroresponse against RSV, was seen in 95% MEDI-559 subjects. MEDI-559 is therefore biologically active and immunogenic in this seronegative pediatric population. Although the frequency of SSs and AEs was not considered clinically significant, the increase in medically attended lower respiratory

Predictors of intent to vaccinate against HPV/cervical cancer: a multi-ethnic survey of 769 parents in New Zealand.

Science.gov (United States)

Rose, Sally B; Lawton, Beverley A; Lanumata, Tolotea S; Hibma, Merilyn; Baker, Michael G

2012-02-24

To identify factors predictive of parents' intent to have their daughters' receive the HPV/cervical cancer vaccine. 3123 questionnaires were distributed to parents recruited from 14 socioeconomically diverse schools in 2008. Survey questions were structured around the health beliefs model. The main outcome measure was intent to seek vaccination for daughter(s). A quarter of parents completed questionnaires (769/3123). Two-thirds of respondents (67%) indicated they would want their daughter(s) to receive the vaccine, with no significant differences by ethnicity. Intent to vaccinate was significantly associated with having fewer negative views on vaccination (OR 0.47, 95%CI 0.37-0.59), having adequate information about the vaccine, perceiving HPV infection and cervical cancer as serious and likely to occur (OR 1.2, 95%CI 1.05-1.36), and considering efficacy and safety of the vaccine important (OR 1.17, 95%CI 1.06-1.28) (pHPV-related facts was lowest among Maori and Pacific parents (pparents were more likely to have concerns about vaccination impacting negatively on girls' sexual behaviour. Strategies will be needed to provide detailed information outlining HPV prevalence and consequences, vaccine safety and efficacy to ensure all parents and their daughters are adequately informed when deciding on vaccination.

Genetic and phenotypic characterization of manufacturing seeds for a tetravalent dengue vaccine (DENVax.

Directory of Open Access Journals (Sweden)

Claire Y-H Huang

Full Text Available We have developed a manufacturing strategy that can improve the safety and genetic stability of recombinant live-attenuated chimeric dengue vaccine (DENVax viruses. These viruses, containing the pre-membrane (prM and envelope (E genes of dengue serotypes 1-4 in the replicative background of the attenuated dengue-2 PDK-53 vaccine virus candidate, were manufactured under cGMP.After deriving vaccine viruses from RNA-transfected Vero cells, six plaque-purified viruses for each serotype were produced. The plaque-purified strains were then analyzed to select one stock for generation of the master seed. Full genetic and phenotypic characterizations of the master virus seeds were conducted to ensure these viruses retained the previously identified attenuating determinants and phenotypes of the vaccine viruses. We also assessed vector competence of the vaccine viruses in sympatric (Thai Aedes aegypti mosquito vectors.All four serotypes of master vaccine seeds retained the previously defined safety features, including all three major genetic loci of attenuation, small plaques, temperature sensitivity in mammalian cells, reduced replication in mosquito cell cultures, and reduced neurovirulence in new-born mice. In addition, the candidate vaccine viruses demonstrated greatly reduced infection and dissemination in Aedes aegypti mosquitoes, and are not likely to be transmissible by these mosquitoes. This manufacturing strategy has successfully been used to produce the candidate tetravalent vaccine, which is currently being tested in human clinical trials in the United States, Central and South America, and Asia.

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

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

2015-03-01

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

2-Year Efficacy, Immunogenicity, and Safety of Vigoo Enterovirus 71 Vaccine in Healthy Chinese Children: A Randomized Open-Label Study.

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Wei, Mingwei; Meng, Fanyue; Wang, Shiyuan; Li, Jingxin; Zhang, Yuntao; Mao, Qunying; Hu, Yuemei; Liu, Pei; Shi, Nianmin; Tao, Hong; Chu, Kai; Wang, Yuxiao; Liang, Zhenglun; Li, Xiuling; Zhu, Fengcai

2017-01-01

 This study evaluated the 2-year efficacy, immunogenicity, and safety of the Vigoo enterovirus 71 (EV71) vaccine.  In an initial phase 3 study, we randomly assigned healthy infants and children aged 6-35 months (ratio, 1:1) to receive 2 doses of either EV71 vaccine (5120 participants) or placebo (5125 participants) at days 0 and 28, and followed them for 12 months after vaccination. In this extended follow-up study, we continued to evaluate the efficacy, immunogenicity, and safety of the EV71 vaccine for up to 2 years.  Overall efficacy was 94.84% (95% confidence interval [CI], 83.53%-98.38%) during the 2-year follow-up period (P vaccine efficacy during the second year was 100.00% (95% CI, 84.15%-100.00%) against EV71-associated hand-foot-and-mouth disease (HFMD; P vaccine-related serious adverse events were recorded.  Two doses of Vigoo EV71 vaccine could provide sustained protection against EV71-associated HFMD in healthy Chinese children.  NCT01508247. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Does vaccination ensure protection? Assessing diphtheria and tetanus antibody levels in a population of healthy children: A cross-sectional study.

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Gowin, Ewelina; Wysocki, Jacek; Kałużna, Ewelina; Świątek-Kościelna, Bogna; Wysocka-Leszczyńska, Joanna; Michalak, Michał; Januszkiewicz-Lewandowska, Danuta

2016-12-01

Vaccination effectiveness is proven when the disease does not develop after a patient is exposed to the pathogen. In the case of rare diseases, vaccination effectiveness is assessed by monitoring specific antibody levels in the population. Such recurrent analyses allow the evaluation of vaccination programs. The primary schedule of diphtheria and tetanus vaccinations is similar in various countries, with differences mainly in the number and timing of booster doses. The aim of the study was to assess diphtheria and tetanus antibody concentrations in a population of healthy children.Diphtheria and tetanus antibody levels were analyzed in a group of 324 children aged 18 to 180 months. All children were vaccinated in accordance with the Polish vaccination schedule.Specific antibody concentrations greater than 0.1 IU/mL were considered protective against tetanus or diphtheria. Levels above 1.0 were considered to ensure long-term protection.Protective levels of diphtheria antibodies were found in 229 patients (70.46%), and of tetanus in 306 patients (94.15%). Statistically significant differences were found in tetanus antibody levels in different age groups. Mean concentrations and the percentage of children with high tetanus antibody titers increased with age. No similar correlation was found for diphtheria antibodies. High diphtheria antibody levels co-occurred in 72% of the children with high tetanus antibody levels; 95% of the children with low tetanus antibody levels had low levels of diphtheria antibodies.The percentage of children with protective diphtheria antibody levels is lower than that in the case of tetanus antibodies, both in Poland and abroad, but the high proportion of children without diphtheria protection in Poland is an exception. This is all the more puzzling when taking into account that Polish children are administered a total of 5 doses containing a high concentration of diphtheria toxoid, at intervals shorter than 5 years. The decrease in

Longitudinal study to assess the safety and efficacy of a live-attenuated SHIV vaccine in long term immunized rhesus macaques

International Nuclear Information System (INIS)

Yankee, Thomas M.; Sheffer, Darlene; Liu Zhengian; Dhillon, Sukhbir; Jia Fenglan; Chebloune, Yahia; Stephens, Edward B.; Narayan, Opendra

2009-01-01

Live-attenuated viruses derived from SIV and SHIV have provided the most consistent protection against challenge with pathogenic viruses, but concerns regarding their long-term safety and efficacy have hampered their clinical usefulness. We report a longitudinal study in which we evaluated the long-term safety and efficacy of ΔvpuSHIV PPC , a live virus vaccine derived from SHIV PPC . Macaques were administered two inoculations of ΔvpuSHIV PPC , three years apart, and followed for eight years. None of the five vaccinated macaques developed an AIDS-like disease from the vaccine. At eight years, macaques were challenged with pathogenic SIV and SHIV. None of the four macaques with detectable cellular-mediated immunity prior to challenge had detectable viral RNA in the plasma. This study demonstrates that multiple inoculations of a live vaccine virus can be used safely and can significantly extend the efficacy of the vaccine, as compared to a single inoculation, which is efficacious for approximately three years

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

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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.

An Ethical Justification for Expanding the Notion of Effectiveness in Vaccine Post-Market Monitoring: Insights from the HPV Vaccine in Canada.

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Komparic, Ana; Smith, Maxwell J; Thompson, Alison

2016-04-01

Health regulators must carefully monitor the real-world safety and effectiveness of marketed vaccines through post-market monitoring in order to protect the public's health and promote those vaccines that best achieve public health goals. Yet, despite the fact that vaccines used in collective immunization programmes should be assessed in the context of a public health response, post-market effectiveness monitoring is often limited to assessing immunogenicity or limited programmatic features, rather than assessing effectiveness across populations. We argue that post-market monitoring ought to be expanded in two ways to reflect a 'public health notion of post-market effectiveness', which incorporates normative public health considerations: (i) effectiveness monitoring should yield higher quality data and grant special attention to underrepresented and vulnerable populations; and (ii) the scope of effectiveness should be expanded to include a consideration of the various social factors that maximize (and minimize) a vaccine's effectiveness at the population level, paying particular attention to how immunization programmes impact related health gradients. We use the case of the human papillomavirus vaccine in Canada to elucidate how expanding post-market effectiveness monitoring is necessary to close the gap between clinical practice and public health, and to ensure that vaccines are effective in a morally relevant sense.

In a safety net population HPV4 vaccine adherence worsens as BMI increases.

Directory of Open Access Journals (Sweden)

Diane M Harper

Full Text Available Obesity adversely inhibits antibody response to vaccination. Three doses of HPV4 may or may not provide adequate long term protection against HPV 16/18 in obese females. The aim of this study was to determine whether adherence to HPV4 vaccination in a safety net population was reduced with increasing body mass index (BMI.We designed a historical prospective study evaluating the number and dates of HPV4 dosing that occurred from July 1, 2006 through October 1, 2009 by the demographic characteristics of the 10-26 year old recipient females. The defined dosing intervals were adapted from the literature and obesity categories were defined by the WHO.1240 females with BMI measurements received at least one dose of HPV4; 38% were obese (class I, II and III and 25% were overweight. Females with normal BMI received on-time triplet dosing significantly more often than did the obese class II and III females (30% vs. 18%, p<0.001. Obese class II/III females have a significant 45% less chance of completing the on-time triplet HPV4 series than normal women (OR = 0.55, 95% CI: 0.37, 0.83. Pregnancy history has a significant influence on BMI and HPV4 dosing compliance in this safety net population where 71% had been gravid. Hispanic females were less likely to complete HPV4 dosing regardless of BMI (aOR = 0.39, 95% CI: 0.16, 0.95.Obesity, as well as gravidity and Hispanic race, are risk factors for lack of HPV4 vaccine adherence among young females in a safety net population.

Rotavirus vaccine strain transmission by vaccinated infants in the foster home.

Science.gov (United States)

Miura, Hiroki; Kawamura, Yoshiki; Sugata, Ken; Koshiyama, Nozomi; Yoshikawa, Akiko; Komoto, Satoshi; Taniguchi, Koki; Ihira, Masaru; Yoshikawa, Tetsushi

2017-01-01

Previous studies have demonstrated the transmission of rotavirus vaccine strains from vaccinated children to nonvaccinated siblings. We sought to fully elucidate the safety of rotavirus (RV) vaccination in closed contact circumstance, such as the foster home for future assessment of the vaccine safety in an neonatal intensive care unit. Stool samples were collected from 4 RV vaccinated (160 samples) and 23 unvaccinated (766 samples) infants. RV viral RNA loads were measured using real-time reverse transcription polymerase chain reaction (RT-PCR). RV vaccine strain RNA was persistently detected in stool samples collected from the four vaccine recipients and one unvaccinated infant, but not in the stool samples collected from the 22 other unvaccinated infants. The unvaccinated infant who tested positive for the RV vaccine strain was vaccinated prior to enrollment in this study. The quantitative real-time RT-PCR data revealed a peak viral RNA load 1 week after vaccination followed by a gradual decrease. The current study suggests that RV vaccination may be safe in a close contact environment because there was limited transmission from RV vaccinated to unvaccinated infants. J. Med. Virol. 89:79-84, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Safety of a tetanus-diphtheria-acellular pertussis vaccine when used off-label in an elderly population.

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Tseng, Hung Fu; Sy, Lina S; Qian, Lei; Marcy, S Michael; Jackson, Lisa A; Glanz, Jason; Nordin, Jim; Baxter, Roger; Naleway, Allison; Donahue, James; Weintraub, Eric; Jacobsen, Steven J

2013-02-01

Published data on the safety of tetanus-diphtheria-acellular pertussis vaccine (Tdap) in persons aged ≥65 years are limited. This study aims to examine a large cohort of Tdap users ≥65 years for evidence of increased risk of adverse events following vaccination. A matched cohort study design and a self-controlled case series (SCCS) design were used. The study population was adults aged ≥65 years who received the Tdap or tetanus and diphtheria (Td) vaccine during 1 January 2006-31 December 2010 at 7 health maintenance organizations in the United States. Seven major groups of prespecified events were identified electronically by diagnostic codes. The study included 119 573 Tdap vaccinees and the same number of Td vaccinees. The results indicated that the risk of the prespecified events following Tdap was comparable to that following Td vaccination in this elderly population. There was a small increased rate of codes suggesting medically attended inflammatory or allergic events in 1-6 days following Tdap in the SCCS analysis (incidence rate ratio, 1.59 [95% confidence interval, 1.40-1.81]). Although there is a small increased risk of medically attended inflammatory or allergic events in 1-6 days following Tdap compared to other time periods, it is no more common than that following Td. This study provides empirical safety data suggesting that immunizing adults aged ≥65 years with Tdap to reduce the risk of pertussis in the elderly and their contacts should not have untoward safety consequences.

Ensuring the Environmental and Industrial Safety in Solid Mineral Deposit Surface Mining

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Trubetskoy, Kliment; Rylnikova, Marina; Esina, Ekaterina

2017-11-01

The growing environmental pressure of mineral deposit surface mining and severization of industrial safety requirements dictate the necessity of refining the regulatory framework governing safe and efficient development of underground resources. The applicable regulatory documentation governing the procedure of ore open-pit wall and bench stability design for the stage of pit reaching its final boundary was issued several decades ago. Over recent decades, mining and geomechanical conditions have changed significantly in surface mining operations, numerous new software packages and computer developments have appeared, opportunities of experimental methods of source data collection and processing, grounding of the permissible parameters of open pit walls have changed dramatically, and, thus, methods of risk assessment have been perfected [10-13]. IPKON RAS, with the support of the Federal Service for Environmental Supervision, assumed the role of the initiator of the project for the development of Federal norms and regulations of industrial safety "Rules for ensuring the stability of walls and benches of open pits, open-cast mines and spoil banks", which contribute to the improvement of economic efficiency and safety of mineral deposit surface mining and enhancement of the competitiveness of Russian mines at the international level that is very important in the current situation.

Safety and Immunogenicity of a Candidate Parvovirus B19 Vaccine

OpenAIRE

Bernstein, David I; El Sahly, Hana M; Keitel, Wendy A; Wolff, Mark; Simone, Gina; Segawa, Claire; Wong, Susan; Shelly, Daniel; Young, Neal S; Dempsey, Walla

2011-01-01

Parvovirus B19 is an important human pathogen causing erythema infectiosum, transient aplastic crisis in individuals with underlying hemolytic disorders and hydrops fetalis. We therefore evaluated a parvovirus B19 virus like particle (VLP) vaccine. The safety and immunogenicity of a 25 μg dose of parvovirus B19 recombinant capsid; 2.5 and 25 μg doses of the recombinant capsid given with MF59; and saline placebo were assessed in healthy adults. Because of 3 unexplained cutaneous events the stu...

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

Science.gov (United States)

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.

The safety of H1N1 vaccine in children in Saudi Arabia: a cohort study using modern technology in a developing country.

Science.gov (United States)

Aljadhey, Hisham; Alyabsi, Mesnad; Alrwisan, Adel; Alqahtani, Nasser; Almutairi, Reem; Al Tawil, Esraa; Adam, Mansour; Shakir, Saad; Aljeraisy, Majed; Al-Blowi, Ali; Alkhashan, Hesham; Albogami, Yasser; Murray, Michael D

2012-07-01

With its rapid introduction in 2009, concerns about the safety of the H1N1 vaccines have been raised. Data were especially limited on the pediatric safety of H1N1 vaccine in Saudi Arabia. The objectives of this study were to investigate the safety of the H1N1 vaccine (Pandemrix(®)) in children and examine the feasibility of obtaining information on possibly associated adverse reactions using mobile telephone contact with child caregivers. A cohort study was conducted in Riyadh, Saudi Arabia. Patients were included if they were aged between 6 and 18 years and had received one dose of the H1N1 vaccine. A control group involved children from the same school system who had not received the vaccine. Six months following vaccination, a clinical pharmacist called the caregiver of the child to ask about hospitalization, emergency room visits and events related to H1N1 vaccine administration using a standardized questionnaire. Caregivers of 372 school-age children were contacted. The response rate was 97% (n = 359). A total of 169 children who received at least one dose of the H1N1 vaccine were compared with 190 children in the control group who had not received the vaccine. Controlling for age, sex, education and use of medications, the odds ratio (OR) of hospitalization or emergency room visits for children within the 6 months after vaccination relative to the unvaccinated children was 1.25 (95% CI 0.47, 3.35). The risk of influenza-like symptoms was significantly reduced in vaccinated children compared with unvaccinated children (OR 0.63; 95% CI 0.41, 0.99). School-age children in Saudi Arabia who received the H1N1 vaccine did not have an increased risk of hospitalization or emergency room visits. Larger studies are needed to confirm these results. Proactive pharmacovigilance is important in assessing the safety of vaccines and other medications. It is feasible to collect information on adverse drug reactions using mobile telephones, a method that can be of benefit in

Immunogenicity and Safety of the New Inactivated Quadrivalent Influenza Vaccine Vaxigrip Tetra: Preliminary Results in Children ≥6 Months and Older Adults

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Emanuele Montomoli

2018-03-01

Full Text Available Since the mid-1980s, two lineages of influenza B viruses have been distinguished. These can co-circulate, limiting the protection provided by inactivated trivalent influenza vaccines (TIVs. This has prompted efforts to formulate quadrivalent influenza vaccines (QIVs, to enhance protection against circulating influenza B viruses. This review describes the results obtained from seven phase III clinical trials evaluating the immunogenicity, safety, and lot-to-lot consistency of a new quadrivalent split-virion influenza vaccine (Vaxigrip Tetra® formulated by adding a second B strain to the already licensed TIV. Since Vaxigrip Tetra was developed by means of a manufacturing process strictly related to that used for TIV, the data on the safety profile of TIV are considered supportive of that of Vaxigrip Tetra. The safety and immunogenicity of Vaxigrip Tetra were similar to those of the corresponding licensed TIV. Moreover, the new vaccine elicits a superior immune response towards the additional strain, without affecting immunogenicity towards the other three strains. Vaxigrip Tetra is well tolerated, has aroused no safety concerns, and is recommended for the active immunization of individuals aged ≥6 months. In addition, preliminary data confirm its immunogenicity and safety even in children aged 6–35 months and its immunogenicity in older subjects (aged 66–80 years.

Efficacy and safety of human papillomavirus vaccine for primary prevention of cervical cancer: A review of evidence from phase III trials and national programs

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Partha Basu

2013-01-01

Full Text Available The Human Papillomavirus (HPV vaccines have been widely introduced in the national immunization programs in most of the medium and high income countries following endorsement from national and international advisory bodies. HPV vaccine is unique and its introduction is challenging in many ways - it is the first vaccine developed to prevent any cancer, the vaccine is gender specific, it targets adolescent females who are difficult to reach by any health intervention programs. It is not unusual for such a vaccine to face scepticism and reservations not only from lay public but also from professionals in spite of the clinical trial results convincingly and consistently proving their efficacy and safety. Over the last few years millions of doses of the HPV vaccine have been administered round the world and the efficacy and safety data have started coming from the real life programs. A comprehensive cervical cancer control program involving HPV vaccination of the adolescent girls and screening of the adult women has been proved to be the most cost-effective approach to reduce the burden of cervical cancer. The present article discusses the justification of HPV vaccination in the backdrop of natural history of cervical cancer, the mechanism of action of the vaccines, efficacy and safety data from phase III randomized controlled trials as well as from the national immunization programs of various countries.

Decree of the Czech Labor Safety Office No. 263/1991 amending the Decree No. 76/1989 on ensuring safety of technical facilities in the nuclear power sector

International Nuclear Information System (INIS)

1995-01-01

Some provisions of the Decree of the Czech Labor Safety Office No. 76/1989 on ensuring safety of technical facilities in the nuclear power sector are amended, particularly in the field of construction activities, assembling, reconstruction and repair of nuclear power facilities. The Decree entered into force on 28 June 1991. (J.B.)

Safety and immunogenicity of a four-component meningococcal group B vaccine (4CMenB) and a quadrivalent meningococcal group ACWY conjugate vaccine administered concomitantly in healthy laboratory workers.

Science.gov (United States)

Findlow, Jamie; Bai, Xilian; Findlow, Helen; Newton, Emma; Kaczmarski, Ed; Miller, Elizabeth; Borrow, Ray

2015-06-26

Safety precautions for laboratory staff working with meningococci should primarily rely on laboratory procedures preventing exposure to aerosols containing viable meningococci. Despite this, vaccination is a key component of protection in the occupational setting. In the UK in 2009, there were no licensed vaccines for meningococcal capsular group B or conjugate vaccines for capsular groups A, C, W and Y. We therefore undertook a Phase II trial in laboratory workers to investigate the safety and immunogenicity of a four component group B vaccine (4CMenB) and a quadrivalent group A, C, W and Y conjugate vaccine (ACWY-CRM). Enrolment was open to staff aged 18-65 years at the Public Health Laboratory, Manchester who may have had a potential occupational exposure risk to meningococci. 4CMenB was administered at 0, 2 and 6 months in the non-dominant arm and ACWY-CRM concomitantly at 0 months in the dominant arm. Pre- and post-vaccination blood samples were taken and analysed by the serum bactericidal antibody (SBA) assay against A, C, W and Y strains and a panel of seven diverse group B strains. Diary cards were used to record any local and systemic reactions following each vaccination. In total, 38 staff were enrolled and received initial vaccinations with 31 completing the trial per protocol. Both vaccines were proven safe, with local reactogenicity being more commonly reported following 4CMenB than ACWY-CRM. High proportions of subjects had putative protective SBA titres pre-vaccination, with 61-84 and 61-87% protected against A, C, W and Y strains and diverse MenB strains, respectively. Post-vaccination, SBA titres increased with 95-100 and 90-100% of subjects with protective SBA titres against A, C, W and Y strains and diverse MenB strains, respectively. These data suggest that 4CMenB and ACWY-CRM are safe when administered concomitantly and have the potential to enhance protection for laboratory workers. www.clinicaltrials.gov identifier: NCT00962624. Crown

Radiation processing of leafy vegetables to ensure their microbial safety

International Nuclear Information System (INIS)

Khade, H.D.; Jain, M.P.; Satyendra, Gautam

2015-01-01

Leafy vegetables which are consumed in raw form such as spinach, coriander and mint were found to be heavily burdened with microbial load including presumptive coliform, an indicator of pathogenic contaminations. Total aerobic plate counts in fresh spinach, coriander and mint samples collected from different location of Mumbai and nearby cities were found to be in the order of ∼ 10 7 to ∼ 10 8 CFU/g. In these samples yeast and mould count was in the order of ∼10 5 CFU/g and presumptive coliform in the order of ∼ 10 4 to ∼10 5 CFU/g. As per USFDA coliform load in the food commodity should be nil. The finding thus indicates that these fresh vegetables are not safe for raw consumption. Hence there is utmost need of process which can ensure the safety by reducing their microbial load below permissible level (<10 4 CFU/gm) and coliform load to nil without affecting the appearance and quality of such produce. In this study gamma radiation was used for hygienization of leafy vegetables. The sample were first cleaned in potable water followed by sodium hypochlorite wash (200 ppm for 20 min), air dried, packed in styrofoam based tray, wrapped with cling film and radiation processed at 1 to 2.5 kGy and stored at 4 and 10℃ . Post irradiation microbiological analysis of radiation processed samples was carried out at in 2 kGy irradiated samples total plate count was below ∼10 3 CFU/g and presumptive coliform count was below detectable level. Yeast and mould count in these samples also reduced to below ∼ 10 3 CFU/g. Based on the study the following combination treatment can be given to raw leafy vegetables, washing with potable water (5 min) → sodium hypochlorite (200 ppm 20 min) wash → Air drying → Packaging in styrofoam based tray and wrapping with cling film → Irradiation at 2 kGy → storage at 4℃ . Besides ensuring safety the treatment also resulted in increased shelf life extension of the commodities up to 20 days. (author)

'Hesitant compliers': Qualitative analysis of concerned fully-vaccinating parents.

Science.gov (United States)

Enkel, Stephanie L; Attwell, Katie; Snelling, Thomas L; Christian, Hayley E

2017-10-11

Some parents are hesitant about vaccines and yet still vaccinate their children. Vaccine behaviours are not fixed and parents who are concerned but nonetheless adherent to standard schedules could switch to an unconventional schedule, delaying or cherry-picking vaccines. There is a need to better understand vaccine hesitancy in specific contexts, acknowledging cultural and geographical variation, to ensure interventions targeting hesitancy are well directed and received. To identify the behaviours, knowledge and attitudes of 'hesitant compliers' in Perth, Western Australia, nine one-on-one in-depth interviews were conducted with vaccinating parents of children (vaccination as important for themselves and their community, despite their limited knowledge of vaccine preventable diseases. Parents reported concerns about potential side effects, and worried about the safety of the measles-mumps-rubella (MMR) and seasonal influenza vaccines. Concerned about the role of anti-vaccination information in the community, some sought to isolate themselves from parents who did not vaccinate, although others were concerned that this could entrench non-vaccinators' behaviours. Parents' views were all underlaid by two pivotal 'vaccine-related events' that had occurred in the community: the severe injury of a baby from seasonal influenza vaccination in 2010, and the death of a baby from whooping cough in 2015. Parents interpreted pivotal vaccine-related events in the community as requiring them to take personal responsibility for vaccine decisions. Their reports of continued vaccine fears (evident in international studies in recent decades) demonstrate that vaccine scares have long lasting effects. With vaccine rates high and stable, current strategies appear to be have little impact on addressing parental vaccine concerns. Further research is required to determine the prevalence of hesitancy amongst vaccinating parents and identify critical points for intervention. Copyright © 2017

Safety and efficacy of influenza vaccination in systemic lupus erythematosus patients with quiescent disease

NARCIS (Netherlands)

Holvast, A; Huckriede, A; Wilschut, J; Horst, G; De Vries, JJC; Benne, CA; Kallenberg, CGM; Bijl, M

Objective: to assess the safety and efficacy of influenza vaccination in patients with systemic lupus erythematosus (SLE), and to evaluate the influence of immunosuppressive drugs on the immune response. Methods: SLE patients (n = 56) and healthy controls (n = 18) were studied. All patients had

Exploring Facilitators and Barriers to Initiation and Completion of the Human Papillomavirus (HPV Vaccine Series among Parents of Girls in a Safety Net System

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Sean T. O’Leary

2018-01-01

Full Text Available Objective: To assess, among parents of predominantly minority, low-income adolescent girls who had either not initiated (NI or not completed (NC the HPV vaccine series, attitudes and other factors important in promoting the series, and whether attitudes differed by language preference. Design/Methods: From August 2013–October 2013, we conducted a mail survey among parents of girls aged 12–15 years randomly selected from administrative data in a Denver safety net system; 400 parents from each group (NI and NC were targeted. Surveys were in English or Spanish. Results: The response rate was 37% (244/660; 140 moved or gone elsewhere; 66% English-speaking, 34% Spanish-speaking. Safety attitudes of NIs and NCs differed, with 40% NIs vs. 14% NC’s reporting they thought HPV vaccine was unsafe (p < 0.0001 and 43% NIs vs. 21% NCs that it may cause long-term health problems (p < 0.001. Among NCs, 42% reported they did not know their daughter needed more shots (English-speaking, 20%, Spanish-speaking 52% and 39% reported that “I wasn’t worried about the safety of the HPV vaccine before, but now I am” (English-speaking, 23%, Spanish-speaking, 50%. Items rated as very important among NIs in the decision regarding vaccination included: more information about safety (74%, more information saying it prevents cancer (70%, and if they knew HPV was spread mainly by sexual contact (61%. Conclusions: Safety concerns, being unaware of the need for multiple doses, and low perceived risk of infection remain significant barriers to HPV vaccination for at-risk adolescents. Some parents’ safety concerns do not appear until initial vaccination.

Efficacy and safety of a combined Porcine Circovirus and Mycoplasma hyopneumoniae vaccine in finishing pigs

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Maarten Witvliet

2015-01-01

Full Text Available The safety and protective efficacy of a new one dose combination vaccine containing Porcine Circovirus type 2 (PCV2 and M. hyopneumoniae antigens – Porcilis® PCV M Hyo - was evaluated in laboratory studies and under field conditions. Vaccination resulted in a moderate temperature increase on the day of vaccination and mild systemic and local reactions were found in only a low percentage of the vaccinated pigs. The local reactions observed were small (max. 2 cm and transient (max. 1 day. In short term (onset of immunity and long term (duration of immunity challenge studies with the individual pathogens, the vaccine significantly reduced the PCV2 load in lymphoid tissue and lungs and M. hyopneumoniae-induced lung lesions. In a placebo-controlled field trial on a farm where both PCV2 and M. hyopneumoniae were present, vaccination of piglets at 3 weeks of age resulted in a reduction of PCV2 viremia and shedding and lower lung lesion scores at slaughter. In addition, a positive effect on the average daily weight gain (+ 34 g/day in the finishing phase was observed. It can therefore be concluded that this new ready to use combination vaccine is safe and efficacious against PCV2 and M. hyopneumoniae single and combined infections.

Safety comparison of four types of rabies vaccines in patients with WHO category II animal exposure: An observation based on different age groups.

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Peng, Jun; Lu, Sha; Zhu, Zhenggang; Zhang, Man; Hu, Quan; Fang, Yuan

2016-11-01

To evaluate the safeties of 4 types of rabies vaccines for patients with WHO category II animal exposure, especially in different age groups.A total of 4000 patients with WHO category II animal exposure were randomly divided into 4 vaccine groups, and were respectively given with Vaccines A, B, C, and D. And subjects in each vaccine group were divided into 4 age groups (≤5, 5-18, 19-60, and ≥60-year-old groups). Then adverse events (including local and systemic ones) were recorded and compared. Consequently, except for Vaccine B, patients under the age of 5 in Groups A, C, and D suffered from more adverse reactions than those in other age groups. Furthermore, for the children aged less than 5 years, incidence of adverse events following administration of Vaccine B, with the dose of 0.5 mL and production of bioreactor systems, was significantly lower than Vaccines A and D.Our data showed that rabies vaccines with smaller doses and more advanced processing techniques are of relatively high safety for the patients, especially for the young children.

WHO informal consultation on quality, safety and efficacy specifications for live attenuated rotavirus vaccines Mexico City, Mexico, 8-9 February 2005.

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Wood, David

2005-12-01

Rotavirus vaccines are at an advanced stage of development but there are as yet no WHO recommendations on production and quality control to provide regulatory guidance. A meeting of experts was convened by WHO and PAHO/AMRO to review the scientific basis for production and quality control of rotavirus vaccines, and to discuss specific measures to assure the safety and efficacy of rotavirus vaccines. The meeting was attended by 25 experts from 14 countries, drawn from academia, public health, national regulatory authorities and vaccine producers. It was agreed that existing guidance for other live virus vaccines provides a very good basis for product characterization, especially for source materials and control of production. The basis for attenuation of current vaccines or vaccine candidates is not known but, at least for the vaccines based on the Jennerian approach of using animal (bovine) rotaviruses, is likely to be multigenic. The risk of intussusception in humans is influenced by genetic background and age. Recent analyzes of large vaccine safety trials found that certain strains of vaccine virus were not associated with intussusception, although in these trials the first dose of vaccine was not administered to children over 3 months of age. Since age is a risk factor for intussusception, this may suggest that early delivery of the first dose of vaccine is desirable. However, maternal antibodies may mitigate against early delivery of the first vaccine dose. Factors which could affect vaccine efficacy or safety include strain diversity, malnutrition, other enteric infections, parasitic infection or immune suppression. It was concluded that data from clinical trials conducted in one part of the world would not necessarily be predictive of vaccine efficacy in other places. It was agreed that in nonclinical evaluations there was a need to use oral dosing for toxicity studies and, because rotavirus is non-neurovirulent, that there was no need for an animal

Safety and immunogenicity of yellow fever 17D vaccine in adults receiving systemic corticosteroid therapy: an observational cohort study.

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Kernéis, Solen; Launay, Odile; Ancelle, Thierry; Iordache, Laura; Naneix-Laroche, Véronique; Méchaï, Frédéric; Fehr, Thierry; Leroy, Jean-Philippe; Issartel, Bertrand; Dunand, Jean; van der Vliet, Diane; Wyplosz, Benjamin; Consigny, Paul-Henri; Hanslik, Thomas

2013-09-01

To assess the safety and immunogenicity of live attenuated yellow fever (YF) 17D vaccine in adults receiving systemic corticosteroid therapy. All adult travelers on systemic corticosteroid therapy who had received the YF17D vaccine in 24 French vaccination centers were prospectively enrolled and matched with healthy controls (1:2) on age and history of YF17D immunization. Safety was assessed in a self-administered standardized questionnaire within 10 days after immunization. YF-specific neutralizing antibody titers were measured 6 months after vaccination in patients receiving corticosteroids. Between July 2008 and February 2011, 102 vaccine recipients completed the safety study (34 receiving corticosteroids and 68 controls). The median age was 54.9 years (interquartile range [IQR] 45.1-60.3 years) and 45 participants had a history of previous YF17D immunization. The median time receiving corticosteroid therapy was 10 months (IQR 1-67 months) and the prednisone or equivalent dosage was 7 mg/day (IQR 5-20). Main indications were autoimmune diseases (n = 14), rheumatoid arthritis (n = 9), and upper respiratory tract infections (n = 8). No serious adverse event was reported; however, patients receiving corticosteroids reported more frequent moderate/severe local reactions than controls (12% and 2%, respectively; relative risk 8.0, 95% confidence interval 1.4-45.9). All subjects receiving corticosteroids who were tested (n = 20) had neutralizing antibody titers >10 after vaccination. After YF17D immunization, moderate/severe local reactions may be more frequent in patients receiving systemic corticosteroid therapy. Immunogenicity seems satisfactory. Large-scale studies are needed to confirm these results. Copyright © 2013 by the American College of Rheumatology.

Report: EPA Should Assess Needs and Implement Management Controls to Ensure Effective Incorporation of Chemical Safety Research Products

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Report #17-P-0294, June 23, 2017. With management controls that ensure the collaborative development of research products and prioritize chemical safety research needs, the EPA would be better able to conduct faster chemical risk assessments.

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.

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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.

Sudden Infant Death Syndrome (SIDS) and Vaccines

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

Challenges in conducting post-authorisation safety studies (PASS): A vaccine manufacturer's view.

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Cohet, Catherine; Rosillon, Dominique; Willame, Corinne; Haguinet, Francois; Marenne, Marie-Noëlle; Fontaine, Sandrine; Buyse, Hubert; Bauchau, Vincent; Baril, Laurence

2017-05-25

Post-authorisation safety studies (PASS) of vaccines assess or quantify the risk of adverse events following immunisation that were not identified or could not be estimated pre-licensure. The aim of this perspective paper is to describe the authors' experience in the design and conduct of twelve PASS that contributed to the evaluation of the benefit-risk of vaccines in real-world settings. We describe challenges and learnings from selected PASS of rotavirus, malaria, influenza, human papillomavirus and measles-mumps-rubella-varicella vaccines that assessed or identified potential or theoretical risks, which may lead to changes to risk management plans and/or to label updates. Study settings include the use of large healthcare databases and de novo data collection. PASS methodology is influenced by the background incidence of the outcome of interest, vaccine uptake, availability and quality of data sources, identification of the at-risk population and of suitable comparators, availability of validated case definitions, and the frequent need for case ascertainment in large databases. Challenges include the requirement for valid exposure and outcome data, identification of, and access to, adequate data sources, and mitigating limitations including bias and confounding. Assessing feasibility is becoming a key step to confirm that study objectives can be met in a timely manner. PASS provide critical information for regulators, public health agencies, vaccine manufacturers and ultimately, individuals. Collaborative approaches and synergistic efforts between vaccine manufacturers and key stakeholders, such as regulatory and public health agencies, are needed to facilitate access to data, and to drive optimal study design and implementation, with the aim of generating robust evidence. Copyright © 2017 GSK Biologicals SA. Published by Elsevier Ltd.. All rights reserved.

Safety of human papillomavirus vaccines: a review

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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 ra...

Safety Overview of a Recombinant Live-Attenuated Tetravalent Dengue Vaccine: Pooled Analysis of Data from 18 Clinical Trials.

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Sophia Gailhardou

2016-07-01

Full Text Available A recombinant live attenuated tetravalent dengue vaccine (CYD-TDV has been shown to be efficacious in preventing virologically-confirmed dengue disease, severe dengue disease and dengue hospitalization in children aged 2-16 years in Asia and Latin America. We analyzed pooled safety data from 18 phase I, II and III clinical trials in which the dengue vaccine was administered to participants aged 2-60 years, including long-term safety follow-up in three efficacy trials. The participants were analyzed according to their age at enrollment. The percentage of participants aged 2-60 years reporting ≥1 solicited injection-site or systemic reactions was slightly higher in the CYD-TDV group than in the placebo group. The most common solicited injection-site reactions were pain. Headache and malaise were the most common solicited systemic reactions. In both groups 0.3% of participants discontinued for safety reasons. The most common unsolicited adverse events were injection-site reactions, gastrointestinal disorders, and infections. Reactogenicity did not increase with successive doses of CYD-TDV. The frequency and nature of SAEs occurring within 28 days of any dose were similar in the CYD-TDV and placebo groups and were common medical conditions that could be expected as a function of age. Baseline dengue virus serostatus did not appear to influence the safety profile. No vaccine-related anaphylactic reactions, neurotropic events or viscerotropic events were reported. In year 3 after dose 1, an imbalance for dengue hospitalization, including for severe dengue, observed in participants aged <9 years in the CYD-TDV group compared with the placebo group was not observed for participants aged ≥9 years. In Year 4, this imbalance in participants aged <9 years was less marked, giving an overall lower risk of dengue hospitalization or severe dengue from dose 1 to Year 4 in the CYD-TDV group. These results have contributed to the definition of the target

Pooled analysis of large and long-term safety data from the human papillomavirus-16/18-AS04-adjuvanted vaccine clinical trial programme

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Angelo, Maria-Genalin; David, Marie-Pierre; Zima, Julia; Baril, Laurence; Dubin, Gary; Arellano, Felix; Struyf, Frank

2014-01-01

Purpose The purpose of this study is to further evaluate the safety of the human papillomavirus (HPV)-16/18-AS04-adjuvanted vaccine (HPV-16/18-vaccine Cervarix®, GlaxoSmithKline, Belgium) through a pooled analysis of data from 42 completed/ongoing clinical studies. Methods Unsolicited adverse events (AEs) were reported for 30 days after each dose. Medically significant conditions, serious AEs (SAEs), potential immune-mediated diseases (pIMDs) and pregnancy outcomes were captured until study completion. Events leading to subject withdrawal were reviewed. Relative risks compared incidences of spontaneous abortion and pIMDs in controlled studies. Results Thirty one thousand one hundred seventy-three adolescent girls/women received HPV-16/18-vaccine alone (HPV group), 2166 received HPV-16/18-vaccine coadministered with another vaccine and 24 241 were controls. Mean follow-up was 39 months (range 0–113.3). Incidences of unsolicited AEs reported within 30 days after any dose were similar between HPV and Control groups (30.8%/29.7%). During the entire study period, reports of medically significant conditions (25.0%/28.3%) and SAEs (7.9%/9.3%) were also similarly distributed between groups. Deaths were rare: HPV (alone/coadministered) n = 25, controls n = 20 (n = 18 in blinded groups). pIMDs within 1 year were reported by 0.2% of HPV-16/18 vaccinees and controls. For each pIMD event category, no increased relative risks were reported for HPV-16/18 vaccinees versus controls. Coadministration did not change the overall safety profile. Pregnancy outcomes and withdrawal rates were similar between groups. Conclusions Analysis of safety data arising from 57 580 subjects and 96 704 HPV-16/18-vaccine doses shows that the incidences and distribution of AEs were similar among HPV-16/18-vaccine recipients and controls. No new safety signals were identified. The data confirm previous findings that HPV-16/18-vaccine has an acceptable benefit-risk profile in adolescent girls and

Thermostable cross-protective subunit vaccine against Brucella species.

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Cherwonogrodzky, John W; Barabé, Nicole D; Grigat, Michelle L; Lee, William E; Poirier, Robert T; Jager, Scott J; Berger, Bradley J

2014-12-01

A subunit vaccine candidate was produced from Brucella suis 145 (biovar 4; expressing both the A antigen of Brucella abortus and the M antigen of Brucella melitensis). The preparation consisted mostly of polysaccharide (PS; >90% [wt/wt]; both cell-associated PS and exo-PS were combined) and a small amount of protein (1 to 3%) with no apparent nucleic acids. Vaccinated mice were protected (these had a statistically significant reduction in bacterial colonization compared to that of unvaccinated controls) when challenged with representative strains of three Brucella species most pathogenic for humans, i.e., B. abortus, B. melitensis, and B. suis. As little as 1 ng of the vaccine, without added adjuvant, protected mice against B. suis 145 infection (5 × 10(5) CFU), and a single injection of 1 μg of this subunit vaccine protected mice from B. suis 145 challenge for at least 14 months. A single immunization induced a serum IgG response to Brucella antigens that remained elevated for up to 9 weeks. The use of heat (i.e., boiling-water bath, autoclaving) in the vaccine preparation showed that it was thermostable. This method also ensured safety and security. The vaccine produced was immunogenic and highly protective against multiple strains of Brucella and represents a promising candidate for further evaluation. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

EXPERIENCE OF APPLICATION AND SAFETY ASSESSMENT OF THE 13-VALENT PNEUMOCOCCAL CONJUGATE VACCINE IN UNDER-5 CHILDREN

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M. V. Fedoseenko

2014-01-01

Full Text Available Compulsory use of the 7-valent pneumococcal conjugate vaccine in the framework of national pediatric immunization schedules of the developed countries resulted in significant decrease in the prevalence of the pneumococcal infections induced by the vaccinal serotypes. However, a growth in prevalence of the pneumonia and acute otitis media caused by non-vaccinal strains has also been observed. This required introduction of a new 13-valent pneumococcal conjugate vaccine with a wider range of pneumococcal population coverage. The experience of application accumulated in various countries (2010 onwards and results of the authors’ observations indicate high safety of the 13-valent pneumococcal conjugate vaccine for both healthy under-5 children and patients with various medical issues. The article presents results of the 13-valent pneumococcal conjugate vaccination tolerance assessment. The study involved 110 children from 2 months to 5 years of age. In most cases immunization concurred with other pediatric vaccines. The incidence of local reactions in vaccinated children did not exceed 33%, of generalized reactions – 11%. The authors observed a comparable incidence of side reactions in both virtually healthy children and children with various medical issues.

Immunogenicity and Safety of Yellow Fever Vaccine (Stamaril) When Administered Concomitantly With a Tetravalent Dengue Vaccine Candidate in Healthy Toddlers at 12-13 Months of Age in Colombia and Peru: A Randomized Trial.

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López, Pio; Lanata, Claudio F; Zambrano, Betzana; Cortés, Margarita; Andrade, Teresa; Amemiya, Isabel; Terrones, Cynthia; Gil, Ana I; Verastegui, Hector; Marquez, Viviana; Crevat, Denis; Jezorwski, John; Noriega, Fernando

2016-10-01

Dengue and yellow fever (YF) viruses are closely related members of the Flaviviridae family. Given the inherent similarities between the YF vaccine and dengue vaccine (CYD-TDV) candidate, it is possible that the latter could interfere with the response to the licensed YF vaccine when coadministered. In this randomized, observer-blind, controlled, phase III trial, conducted in Colombia and Peru, 787 toddlers were administered YF vaccine concomitantly with CYD-TDV (group 1) or placebo (group 2), followed by CYD-TDV after 6 and 12 months. YF and dengue neutralizing antibody titers were determined using a 50% plaque reduction neutralization test. Noninferiority was demonstrated if the lower limit of the 2-sided 95% confidence interval of the difference in seroconversion rates [(YF + CYD-TDV) - YF alone] was greater than -10%. The safety of both vaccines was also assessed. Concomitant administration of YF with either CYD-TDV or placebo yielded YF seroconversion rates of 100.0% and 99.7%, respectively. The difference in YF seroconversion rates between the 2 groups was 0.33% (95% confidence interval:0.98; 1.87), demonstrating that the immune response against YF administered concomitantly with CYD-TDV was noninferior to YF administered with placebo. After 2 injections of CYD-TDV, the percentage of participants with dengue titres ≥10 (1/dil) for the 4 dengue serotypes were 91.2%-100% for group 1 and 97.2%-100% in group 2. There were no safety concerns during the study period. Concomitant administration of YF vaccine with CYD-TDV has no relevant impact on the immunogenicity or safety profile of the YF vaccine.

Post-marketing safety surveillance conducted in Korea (2008-2013) following the introduction of the rotavirus vaccine, RIX4414 (Rotarix™).

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Shin, Son Moon; Kim, Chun Soo; Karkada, Naveen; Liu, Aixue; Jayadeva, Girish; Han, Htay Htay

2016-10-02

According to regulations from the Ministry of Food and Drug Safety in Korea, additional safety information on the use of Rotarix™ vaccine (RIX4414; GSK, Belgium) in ≥3000 evaluable Korean infants was required following vaccine registration. In order to comply with these regulations, we conducted a 6-year open, non-comparative, multicenter post-marketing surveillance (NCT00750893). During this time, the original lyophilized vaccine formulation of RIX4414 was replaced by a liquid formulation. Healthy infants aged ≥6 weeks were enrolled and given 2 doses of the RIX4414 vaccine, separated by an interval of ≥4 weeks. The overall incidence of adverse events (AEs) (expected and unexpected) was then assessed for up to 30 days along with the incidence of serious adverse events (SAEs). Adverse drug reactions (ADRs: any AE whose causality to the drug could not be ruled out) were identified. A total of 3040 children (mean age: 9.55 weeks) were analyzed. One or more expected AE was experienced by 30.5% infants and 8.6% had an ADR. The most commonly seen expected AE was irritability (14.0%). One or more unexpected AE was seen in 32.5% infants and 3.1% experienced an ADR. The most commonly seen unexpected AE was upper respiratory tract infection (8.7%). Of 34 SAEs recorded in 24 subjects, none were related to vaccination. We conclude that this 6-year surveillance showed both formulations of RIX4414 to have acceptable safety profiles when administered to Korean infants according to local prescribing recommendations and current clinical practice.

Immunogenicity and safety of yellow fever vaccine among 115 HIV-infected patients after a preventive immunisation campaign in Mali.

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Sidibe, Mariam; Yactayo, Sergio; Kalle, Abdoulaye; Sall, Amadou A; Sow, Samba; Ndoutabe, Modjirom; Perea, William; Avokey, Fenella; Lewis, Rosamund F; Veit, Olivia

2012-07-01

The immune response to yellow fever (YF) vaccine and its safety among HIV-infected individuals living in YF endemic areas is not well understood. Following a national YF preventive immunisation campaign in Mali in April 2008, we assessed the immunogenicity and safety of 17D yellow fever vaccine (17DV) among HIV-infected patients in two HIV treatment centres in Bamako, Mali, by testing for neutralising antibodies and identifying serious adverse events following immunisation (AEFI). A YF neutralisation titre (NT) of 1:≥20 was considered to be adequate and protective. A serious AEFI included hospitalisation, any life-threatening condition, or death, occurring within 30 days following 17DV administration. Of 115 HIV-infected patients who reported having received 17DV, 110 (96%) were on combination antiretroviral therapy and 83 patients were tested for neutralising antibodies. Around the time of vaccination, median CD4 cell count was 389 cells/mm(3) (IQR 227-511cells/mm(3)); HIV-RNA was undetectable in 24 of 46 patients tested. Seventy-six (92%) of 83 participants had adequate immune titres 9 months after the immunisation campaign. Previous vaccination or flavivirus exposure could contribute to this finding. No serious AEFI was found in the 115 participants. In this small series, YF vaccine appeared to be immunogenic with a favourable safety profile in HIV-infected patients on antiretroviral therapy. Higher CD4 cell counts and suppressed HIV-RNA were associated with the presence of an adequate immune titre and higher NTs. Copyright © 2012 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

Immunogenicity and safety assessment of a trivalent, inactivated split influenza vaccine in Korean children: Double-blind, randomized, active-controlled multicenter phase III clinical trial.

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Han, Seung Beom; Rhim, Jung-Woo; Shin, Hye Jo; Lee, Soo Young; Kim, Hyun-Hee; Kim, Jong-Hyun; Lee, Kyung-Yil; Ma, Sang Hyuk; Park, Joon Soo; Kim, Hwang Min; Kim, Chun Soo; Kim, Dong Ho; Choi, Young Youn; Cha, Sung-Ho; Hong, Young Jin; Kang, Jin Han

2015-01-01

A multicenter, double-blind, randomized, active-control phase III clinical trial was performed to assess the immunogenicity and safety of a trivalent, inactivated split influenza vaccine. Korean children between the ages of 6 months and 18 y were enrolled and randomized into a study (study vaccine) or a control vaccine group (commercially available trivalent, inactivated split influenza vaccine) in a 5:1 ratio. Antibody responses were determined using hemagglutination inhibition assay, and post-vaccination immunogenicity was assessed based on seroconversion and seroprotection rates. For safety assessment, solicited local and systemic adverse events up to 28 d after vaccination and unsolicited adverse events up to 6 months after vaccination were evaluated. Immunogenicity was assessed in 337 and 68 children of the study and control groups. In the study vaccine group, seroconversion rates against influenza A/H1N1, A/H3N2, and B strains were 62.0% (95% CI: 56.8-67.2), 53.4% (95% CI: 48.1-58.7), and 54.9% (95% CI: 48.1-60.2), respectively. The corresponding seroprotection rates were 95.0% (95% CI: 92.6-97.3), 93.8% (95% CI: 91.2-96.4), and 95.3% (95% CI: 93.0-97.5). The lower 95% CI limits of the seroconversion and seroprotection rates were over 40% and 70%, respectively, against all strains. Seroconversion and seroprotection rates were not significantly different between the study and control vaccine groups. Furthermore, the frequencies of adverse events were not significantly different between the 2 vaccine groups, and no serious vaccination-related adverse events were noted. In conclusion, the study vaccine exhibited substantial immunogenicity and safety in Korean children and is expected to be clinically effective.

Safety of 13-valent pneumococcal conjugate vaccine in infants and children: meta-analysis of 13 clinical trials in 9 countries.

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Thompson, Allison; Gurtman, Alejandra; Patterson, Scott; Juergens, Christine; Laudat, France; Emini, Emilio A; Gruber, William C; Scott, Daniel A

2013-10-25

Meta-analyses enable summarization and interpretation of data across clinical trials. When applied to safety data they allow for detection of rare events. Recently, a 13-valent pneumococcal conjugate vaccine (PCV13) was approved in multiple countries worldwide for routine immunization of infants and young children. This meta-analysis was conducted to identify potentially clinically important rare safety events associated with PCV13. To summarize the safety of PCV13 compared with 7-valent pneumococcal conjugate vaccine (PCV7) administered to infants and toddlers. A meta-analysis was performed of integrated safety data from 13 infant studies (PCV13 n=4729 and PCV7 n=2760) conducted in 9 North American, European, and Asian countries. Local reactions at the vaccine injection site and systemic events were collected for 4-7 days after each dose into electronic diaries. Adverse events (AEs) were collected after each vaccination. Overall, rates of local reactions after any dose of the infant series were similar between PCV13 and PCV7 groups: tenderness (46.7% vs 44.8%, respectively); swelling (28.5% vs 26.9%); and redness (36.4% vs 33.9%). After the toddler dose, tenderness was significantly higher among PCV7 subjects than PCV13 subjects (54.4% vs 48.8%; P=0.005). Frequencies of fever (≥38°C) were similar in both groups and mostly mild (≤39°C); incidence of moderate fever (>39°C to ≤40°C) with PCV13 was ≤2.8% after any infant dose and 5.0% after the toddler dose, compared with ≤2.6% and 7.3%, respectively, with PCV7. Fever >40°C was uncommon in both groups. Frequencies of decreased appetite, irritability, and sleep disturbances were similar in both groups. AEs were the types of conditions and symptoms expected in infants and children, and clinically significant differences between vaccine groups were not observed. PCV13 has a favorable safety profile similar to that of PCV7, a vaccine for which there is >10 years clinical experience. Copyright © 2013

Influvac, a trivalent inactivated subunit influenza vaccine.

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Zuccotti, Gian Vincenzo; Fabiano, Valentina

2011-01-01

Influenza represents a major sanitary and socio-economic burden and vaccination is universally considered the most effective strategy for preventing the disease and its complications. Traditional influenza vaccines have been on the market since the late 1940s, with million of doses administered annually worldwide, and demonstrated a substantial efficacy and safety. The trivalent inactivated subunit vaccine has been available for more than 25 years and has been studied in healthy children, adults and the elderly and in people affected by underlying chronic medical conditions. We describe vaccine technology focusing on subunit vaccine production procedures and mode of action and provide updated information on efficacy and safety available data. A review of efficacy and safety data in healthy subjects and in high risk populations from major sponsor- and investigator-driven studies. The vaccine showed a good immunogenicity and a favorable safety profile in all target groups. In the panorama of actually available influenza vaccines, trivalent inactivated subunit vaccine represents a well-established tool for preventing flu and the associated complications.

Immunogenicity and safety of a multicomponent meningococcal serogroup B vaccine in healthy adolescents in Korea--A randomised trial.

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Lee, Hoan Jong; Choe, Young June; Hong, Young-Jin; Kim, Kyung-Hyo; Park, Su Eun; Kim, Yun-Kyung; Oh, Chi-Eun; Lee, Hyunju; Song, Hyoyoung; Bock, Hans; Casula, Daniela; Bhusal, Chiranjiwi; Arora, Ashwani Kumar

2016-02-24

Neisseria meningitidis serogroup B is a significant cause of septicaemia and meningitis worldwide. This phase 3 randomised, controlled study assessed the immunogenicity and safety of a multicomponent meningococcal serogroup B vaccine, 4CMenB, in healthy Korean adolescents. 264 adolescents (11-17 years old) were randomised to receive two doses, one month apart, of 4CMenB or control vaccines [placebo followed by one dose of a quadrivalent meningococcal ACWY glycoconjugate vaccine (MenACWY-CRM)]. Immunogenicity was evaluated by serum bactericidal assay with human complement (hSBA) against three serogroup B test strains specific for individual vaccine antigens (fHbp, NadA or PorA P1.4), and by enzyme-linked immunosorbent assay (ELISA) against the NHBA antigen. Solicited reactions and adverse events (AEs) were assessed. One month post-second vaccination, 98%, 97%, and 97% of subjects in the 4CMenB group achieved hSBA titres ≥ 4 against the fHbp, NadA and PorA test strains, respectively, while percentages in the Control group were comparable to baseline (27%, 16%, and 17%, respectively). Geometric mean ELISA concentrations (GMCs) against NHBA increased 52-fold relative to baseline in the 4CMenB group, while there was no substantial increase in GMCs in the Control group (1.05-fold). Frequencies of solicited reactions after any vaccination were higher in the 4CMenB group than in the Control group, although most reactions were of short duration and mild to moderate intensity. There were no vaccine-related serious AEs. Two doses of 4CMenB induced robust immune responses against the vaccine antigens and were well tolerated, with no safety concerns identified, in Korean adolescents (NCT01973218). Copyright © 2016 Elsevier Ltd. All rights reserved.

Geneva-Seattle collaboration in support of developing country vaccine manufacturing.

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Stevenson, Michael A

2018-04-01

Vaccines were once produced almost exclusively by state-supported entities. While they remain essential tools for public health protection, the majority of the world's governments have allowed industry to assume responsibility for this function. This is significant because while the international harmonisation of quality assurance standards have effectively increased vaccine safety, they have also reduced the number of developing country vaccine producers, and Northern multinational pharmaceutical companies have shown little interest in offering the range of low-priced products needed in low and middle-income-country contexts. This article examines how public-private collaboration is relevant to contemporary efforts aimed at strengthening developing country manufacturers' capacity to produce high-quality, low-priced vaccines. Specifically, it casts light on the important and largely complimentary roles of the World Health Organization, The Bill and Melinda Gates Foundation, and the Seattle-based non-profit PATH, in this process. The take away message is that external support remains critical to ensuring that developing country vaccine manufacturers have the tools needed to produce for both domestic and global markets, and the United Nations supply chain, and collaboration at the public-private interface is driving organisational innovation focused on meeting these goals.

Safety, immunogenicity, and efficacy of the ML29 reassortant vaccine for Lassa fever in small non-human primates✩

Science.gov (United States)

Lukashevich, Igor S.; Carrion, Ricardo; Salvato, Maria S.; Mansfield, Keith; Brasky, Kathleen; Zapata, Juan; Cairo, Cristiana; Goicochea, Marco; Hoosien, Gia E.; Ticer, Anysha; Bryant, Joseph; Davis, Harry; Hammamieh, Rasha; Mayda, Maria; Jett, Marti; Patterson, Jean

2008-01-01

A single injection of ML29 reassortant vaccine for Lassa fever induces low, transient viremia, and low or moderate levels of ML29 replication in tissues of common marmosets depending on the dose of the vaccination. The vaccination elicits specific immune responses and completely protects marmosets against fatal disease by induction of sterilizing cell-mediated immunity. DNA array analysis of human peripheral blood mononuclear cells from healthy donors exposed to ML29 revealed that gene expression patterns in ML29-exposed PBMC and control, media-exposed PBMC, clustered together confirming safety profile of the ML29 in non-human primates. The ML29 reassortant is a promising vaccine candidate for Lassa fever. PMID:18692539

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

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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

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

Science.gov (United States)

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

2014-12-01

Mammaglobin-A (MAM-A) is overexpressed in 40% to 80% of primary breast cancers. We initiated a phase I clinical trial of a MAM-A DNA vaccine to evaluate its safety and biologic efficacy. Patients with breast cancer 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 (PFS) was described using the Kaplan-Meier product limit estimator. Fourteen subjects have been treated with the MAM-A DNA vaccine and no significant adverse events have been observed. Eight of 14 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 after vaccination (0.9% ± 0.5% vs. 3.8% ± 1.2%; P cells (41 ± 32 vs. 215 ± 67 spm; P cell responses, and preliminary evidence suggests improved PFS. Additional studies are required to define the potential of the MAM-A DNA vaccine for breast cancer prevention and/or therapy. ©2014 American Association for Cancer Research.

Post-licensure, phase IV, safety study of a live attenuated Japanese encephalitis recombinant vaccine in children in Thailand.

Science.gov (United States)

Chotpitayasunondh, Tawee; Pruekprasert, Pornpimol; Puthanakit, Thanyawee; Pancharoen, Chitsanu; Tangsathapornpong, Auchara; Oberdorfer, Peninnah; Kosalaraksa, Pope; Prommalikit, Olarn; Tangkittithaworn, Suwimon; Kerdpanich, Phirangkul; Techasaensiri, Chonnamet; Korejwo, Joanna; Chuenkitmongkol, Sunate; Houillon, Guy

2017-01-05

Japanese encephalitis is a mosquito-borne viral disease endemic in most countries in Asia. A recombinant live, attenuated Japanese encephalitis virus vaccine, JE-CV, is licensed in 14 countries, including Thailand, for the prevention of Japanese encephalitis in adults and children. This was a prospective, phase IV, open-label, multicentre, safety study of JE-CV conducted from November 2013 to April 2015, to evaluate rare serious adverse events (AEs). JE-CV was administered to 10,000 healthy children aged 9months to vaccination. Serious AEs (SAEs), including AEs of special interest, up to 60days after administration were evaluated. Immediate Grade 3 systemic AEs up to 30min after JE-CV administration were also described. The median age of participants was 1.1years in Group 1 and 3.8years in Group 2. SAEs were reported in 204 (3.0%) participants in Group 1 and 59 (1.9%) participants in Group 2. Among a total of 294 SAEs in 263 participants, only three events occurring in two participants were considered related to vaccination. All three cases were moderate urticaria, none of which met the definition of AEs of special interest for hypersensitivity. AEs of special interest were reported in 28 (0.4%) participants in Group 1 and 4 (0.1%) participants in Group 2; none were considered related to vaccination. Febrile convulsion was the most frequently reported AE of special interest: 25 (0.4%) participants in Group 1; and 2 (vaccination. Our study did not identify any new safety concerns with JE-CV and confirms its good safety profile. This study was registered on www.clinicaltrials.gov (NCT01981967; Universal Trial Number: U1111-1127-7052). Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

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

2016-05-05

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

Safety and tolerability of 13-valent pneumococcal conjugate vaccine in the elderly

Science.gov (United States)

Durando, Paolo; Rosselli, Roberto; Cremonesi, Ilaria; Orsi, Andrea; Albanese, Erika; Barberis, Ilaria; Paganino, Chiara; Trucchi, Cecilia; Martini, Mariano; Marensi, Lorenzo; Turello, Valter; Study Group, the Ligurian Pneumococcal; Bregante, Alessandro; Cacciani, Roberto; Iudici, Rocco; La Marca, Diego; Pedano, Leonardo; Petrucci, Amadio Franco; Santolini, Maria; Sbisà, Valentina; Zacconi, Monica

2014-01-01

Background In September 2011 the European Medical Agency authorized the use of 13-valent pneumococcal conjugate vaccine (PCV13) in adults aged ≥50 years. The same occurred in the US in December 2011 when the Food and Drug Administration approved the use of PCV13 in the same target age-group with indication for the prevention of invasive pneumococcal diseases and community acquired pneumonia sustained by the serotypes contained in the vaccine. The Liguria Region, in Italy, implemented in 2013 an active and free of charge immunization strategy with PCV13 among adults affected by specific risk conditions and the elderly aged ≥70 years. Methods An observational study was performed in order to assess the safety and tolerability of PCV13 among elderly dwelling in the metropolitan area of Genoa, the capital city of Liguria Region. Eligible subjects, who received PCV13 following the public health immunization campaign at the Local Health Unit 3 of Genoa, provided a written informed consent to take part in the study. Eight-hundred-seventy-one subjects were enrolled between October 2013 and May 2014: all were monitored by qualified healthcare personnel for at least 30 min after vaccination at the outpatient clinics, in order to assess any possible sudden reaction. The occurrence of a series of local and systemic solicited reactions and of any unsolicited Adverse Events (AEs) was monitored using a self-administered clinical diary and by regular phone contacts up to 14 and 21 d following immunization, respectively. Moreover, a 6-months follow-up following vaccination was planned in order to monitor Severe Adverse Events (SAEs). Results No sudden reaction occurred in vaccinees at the outpatient clinics. Pain (27.4%) was the most frequent reaction reported by subjects at the injection site, while new muscle pain (13.6%), fatigue (10.7%), and headache (9.9%) resulted the most common systemic reactions. Rates of the main reactions reported in this on-field study resulted

U. S. Department of energy actions to ensure nuclear safety at its nuclear facilities in response to lessons being learned from the Fukushima dacha accident

Energy Technology Data Exchange (ETDEWEB)

Chung, Dae; O' Brien, James [U. S. Department of Energy, Washington (United States)

2012-03-15

The U. S. Department of Energy (DOE) has established a rigorous nuclear safety regulatory infrastructure for the protection of workers, the public, and the environment. An essential part of this infrastructure is a safety culture that promotes organizational learning and includes a commitment to safety by senior leaders that is demonstrated through their actions and behaviors. The tragic Fukushima Dacha accident presented an important challenge for DOE leaders to demonstrate a robust safety culture by critically examining the Department' s regulatory infrastructure and its implementation to ensure that appropriate safety provisions were in place. This paper discusses the actions DOE has taken to date in this regard and further planned action to ensure safety at DOE facilities in light of lessons being learned from the Fukushima Dacha accident.

U. S. Department of energy actions to ensure nuclear safety at its nuclear facilities in response to lessons being learned from the Fukushima dacha accident

International Nuclear Information System (INIS)

Chung, Dae; O'Brien, James

2012-01-01

The U. S. Department of Energy (DOE) has established a rigorous nuclear safety regulatory infrastructure for the protection of workers, the public, and the environment. An essential part of this infrastructure is a safety culture that promotes organizational learning and includes a commitment to safety by senior leaders that is demonstrated through their actions and behaviors. The tragic Fukushima Dacha accident presented an important challenge for DOE leaders to demonstrate a robust safety culture by critically examining the Department' s regulatory infrastructure and its implementation to ensure that appropriate safety provisions were in place. This paper discusses the actions DOE has taken to date in this regard and further planned action to ensure safety at DOE facilities in light of lessons being learned from the Fukushima Dacha accident

Immunogenicity and safety of an inactivated hepatitis A vaccine when coadministered with Diphtheria-tetanus-acellular pertussis and haemophilus influenzae type B vaccines in children 15 months of age.

Science.gov (United States)

Trofa, Andrew F; Klein, Nicola P; Paul, Ian M; Michaels, Marian G; Goessler, Mary; Chandrasekaran, Vijayalakshmi; Blatter, Mark

2011-09-01

This study (NCT00197236) evaluated the safety and immunogenicity of a hepatitis A virus (HAV) vaccine when coadministered with diphtheria-tetanus-acellular pertussis (DTaP) and Haemophilus influenzae type b (Hib) vaccines in children 15 months of age. This was an open-labeled, multicenter study with healthy subjects enrolled and randomized (1:1:1) into 3 treatment groups. A total of 394 subjects received the first study vaccinations at 15 months of age. Group HAV (N = 135) received 2 doses of HAV vaccine 6 to 9 months apart. Group HAV+DTaP+Hib (N = 127) received HAV vaccine coadministered with DTaP and Hib vaccines and the second dose of HAV vaccine, 6 to 9 months later. Group DTaP+Hib→HAV (N = 132) received the DTaP and Hib vaccines at 15 months of age, followed by HAV vaccine 30 days later and the second dose of HAV vaccine 7 to 10 months after the DTaP+Hib vaccines. Immune responses were evaluated before the first study vaccination and 30 days after each vaccine dose. Solicited, unsolicited, and serious adverse events were collected. After 2 doses of the HAV vaccine, all subjects in the 3 groups were seropositive. The geometric mean concentration of anti-HAV antibodies ranged between 1625.1 and 1904.4 mIU/mL. Coadministration of the 3 vaccines did not impact immunogenicity of the HAV, DTaP, or Hib vaccines. Vaccines were well tolerated in all groups. A 2-dose schedule of HAV vaccine was well tolerated and immunogenic when administered to children starting at 15 months of age. Immune responses to the DTaP or Hib vaccines were similar whether they were administered alone or were coadministered with the HAV vaccine.

Introduction of the system of hazard analysis critical control point to ensure the safety of irradiated food

International Nuclear Information System (INIS)

Sajet, A.S.

2014-01-01

Hazard Analysis Critical Control Point (HACCP) is a preventive system for food safety. It identifies safety risks faced by food. Identified points are controlled ensuring product safety. Because of presence of many of the pathogenic microorganisms and parasites in food which caused cases of food poisoning and many diseases transmitted through food, the current methods of food production could not prevent food contamination or prevent the growth of these pathogens completely because of being a part of the normal flora in the environment. Irradiation technology helped to control diseases transmitted through food, caused by pathological microorganisms and parasites present in food. The application of a system based on risk analysis as a means of risk management in food chain, demonstrated the importance of food irradiation. (author)

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.

Science.gov (United States)

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…

Safety and immunogenicity of live-attenuated Japanese encephalitis SA 14-14-2 vaccine co-administered with measles vaccine in 9-month-old infants in Sri Lanka.

Science.gov (United States)

Wijesinghe, Pushpa Ranjan; Abeysinghe, M R Nihal; Yoksan, Sutee; Yao, Yafu; Zhou, Benli; Zhang, Lei; Yaich, Mansour; Neuzil, Kathleen M; Victor, John C

2014-08-20

To facilitate introduction of live attenuated SA 14-14-2 Japanese encephalitis vaccine (LJEV) into the National Immunization Programme of Sri Lanka, we evaluated the safety and immunogenicity of co-administration of LJEV and measles vaccine at 9 months of age. Serum immune responses were evaluated post-vaccination on days 28, 180, and 365 using JE neutralization test and anti-measles IgG ELISA. 278 infants received one dose of LJEV and measles vaccine. Of these, 257 were eligible for the per-protocol analysis. On Day 0, 14 infants (5.5%) were seropositive for JE, but none were seropositive for measles. At Day 28, seropositivity rates were 90.7% (95% CI, 86.4-93.9%) for JE and 84.8% (95% CI, 79.8-89.0%) for measles. The geometric mean titer for JE neutralizing antibodies was 111 (95% CI, 90-135), and the geometric mean concentration (GMC) for anti-measles IgG was 375 mI U/mL (95% CI, 351-400 mI U/mL). Over the next year, JE neutralizing antibody responses declined only slightly, with seropositivity at 87.4% (95% CI, 82.6-91.2%) at Day 365. In contrast, measles antibody levels continued to increase over time. Seropositivity for anti-measles IgG reached 97.2% (95% CI, 94.4-98.9%) at Day 365, and the GMC rose to 1202 mI U/mL (95% CI, 1077-1341 mI U/mL). Co-administration of LJEV and measles vaccine was also safe. Most adverse reactions were mild, and no serious adverse events were related to study vaccinations. The safety and immunogenicity of LJEV co-administered with measles vaccine in Sri Lankan infants is similar to that seen in other populations, and our results support use of LJEV at 9 months of age. Live SA 14-14-2 vaccine is now prequalified by the WHO for use in infants in Asia, and other countries may wish to introduce LJEV to combat this devastating disease. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Law 19.056. It dictate rules to ensure the protection and radiation safety of people, goods and environment

International Nuclear Information System (INIS)

2013-01-01

The objective of this law is to ensure the protection and radiation safety of personnel occupationally exposed, the public in general and the environment from the effects of ionizing radiation as well as avoid risks of contamination in radiactive sources, physical facilities and means of transport

Safety and immunogenicity of an AMA-1 malaria vaccine in Malian adults: results of a phase 1 randomized controlled trial.

Directory of Open Access Journals (Sweden)

Mahamadou A Thera

2008-01-01

Full Text Available The objective was to evaluate the safety, reactogenicity and immunogenicity of the AMA-1-based blood-stage malaria vaccine FMP2.1/AS02A in adults exposed to seasonal malaria.A phase 1 double blind randomized controlled dose escalation trial was conducted in Bandiagara, Mali, West Africa, a rural town with intense seasonal transmission of Plasmodium falciparum malaria. The malaria vaccine FMP2.1/AS02A is a recombinant protein (FMP2.1 based on apical membrane antigen-1 (AMA-1 from the 3D7 clone of P. falciparum, adjuvanted with AS02A. The comparator vaccine was a cell-culture rabies virus vaccine (RabAvert. Sixty healthy, malaria-experienced adults aged 18-55 y were recruited into 2 cohorts and randomized to receive either a half dose or full dose of the malaria vaccine (FMP2.1 25 microg/AS02A 0.25 mL or FMP2.1 50 microg/AS02A 0.5 mL or rabies vaccine given in 3 doses at 0, 1 and 2 mo, and were followed for 1 y. Solicited symptoms were assessed for 7 d and unsolicited symptoms for 30 d after each vaccination. Serious adverse events were assessed throughout the study. Titers of anti-AMA-1 antibodies were measured by ELISA and P. falciparum growth inhibition assays were performed on sera collected at pre- and post-vaccination time points. Transient local pain and swelling were common and more frequent in both malaria vaccine dosage groups than in the comparator group. Anti-AMA-1 antibodies increased significantly in both malaria vaccine groups, peaking at nearly 5-fold and more than 6-fold higher than baseline in the half-dose and full-dose groups, respectively.The FMP2.1/AS02A vaccine had a good safety profile, was well-tolerated, and was highly immunogenic in malaria-exposed adults. This malaria vaccine is being evaluated in Phase 1 and 2 trials in children at this site.

A novel rabies vaccine based-on toll-like receptor 3 (TLR3) agonist PIKA adjuvant exhibiting excellent safety and efficacy in animal studies

Energy Technology Data Exchange (ETDEWEB)

Zhang, Yi [Yisheng Biopharma. Co., Ltd., Beijing (China); Zhang, Shoufeng [Academy of Military Medical Sciences, Changchun (China); Li, Wei [National Center for Safety Evaluation of Drugs, Beijing (China); Hu, Yuchi; Zhao, Jinyan [Beijing Institute for Drug Control, Beijing (China); Liu, Fang; Lin, Haixiang; Liu, Yuan; Wang, Liliang; Xu, Shu [Yisheng Biopharma. Co., Ltd., Beijing (China); Hu, Rongliang, E-mail: ronglianghu@hotmail.com [Academy of Military Medical Sciences, Changchun (China); Shao, Hui, E-mail: hui.shao@yishengbio.com [Yisheng Biopharma. Co., Ltd., Beijing (China); Li, Lietao, E-mail: lietao.li@gmail.com [Yisheng Biopharma. Co., Ltd., Beijing (China)

2016-02-15

Vaccination alone is not sufficiently effective to protect human from post-exposure rabies virus infection due to delayed generation of rabies virus neutralizing antibodies and weak cellular immunity. Therefore, it is vital to develop safer and more efficacious vaccine against rabies. PIKA, a stabilized chemical analog of double-stranded RNA that interacts with TLR3, was employed as adjuvant of rabies vaccine. The efficacy and safety of PIKA rabies vaccine were evaluated. The results showed that PIKA rabies vaccine enhanced both humoral and cellular immunity. After viral challenge, PIKA rabies vaccine protected 70–80% of animals, while the survival rate of non-adjuvant vaccine group (control) was 20–30%. According to the results of toxicity tests, PIKA and PIKA rabies vaccine are shown to be well tolerated in mice. Thus, this study indicates that PIKA rabies vaccine is an effective and safe vaccine which has the potential to develop next-generation rabies vaccine and encourage the start of clinical studies. - Highlights: • Vaccination alone is not effective to protect human from rabies virus infection due to delayed generation of rabies virus neutralizing antibodies (RVNA) and weak cellular immunity. • Therefore, it is vital to develop safer and more efficacious vaccine against rabies. PIKA, a stabilized chemical analog of double-stranded RNA that interacts with TLR3, was employed as an adjuvant of rabies vaccine. • The efficacy and safety of PIKA rabies vaccine was evaluated in mice. • The results showed that PIKA rabies vaccine enhanced both humoral and cellular immunity. • After viral challenge, PIKA rabies vaccine protected 70–80% of animals, while the survival rate of non-adjuvant vaccine group was only 20–30%. • According to the results of toxicity tests, PIKA and PIKA rabies vaccine are shown to be well tolerated in mice. • Thus, this study indicates that PIKA rabies vaccine is an effective and safe vaccine which has the potential to

A novel rabies vaccine based-on toll-like receptor 3 (TLR3) agonist PIKA adjuvant exhibiting excellent safety and efficacy in animal studies

International Nuclear Information System (INIS)

Zhang, Yi; Zhang, Shoufeng; Li, Wei; Hu, Yuchi; Zhao, Jinyan; Liu, Fang; Lin, Haixiang; Liu, Yuan; Wang, Liliang; Xu, Shu; Hu, Rongliang; Shao, Hui; Li, Lietao

2016-01-01

Vaccination alone is not sufficiently effective to protect human from post-exposure rabies virus infection due to delayed generation of rabies virus neutralizing antibodies and weak cellular immunity. Therefore, it is vital to develop safer and more efficacious vaccine against rabies. PIKA, a stabilized chemical analog of double-stranded RNA that interacts with TLR3, was employed as adjuvant of rabies vaccine. The efficacy and safety of PIKA rabies vaccine were evaluated. The results showed that PIKA rabies vaccine enhanced both humoral and cellular immunity. After viral challenge, PIKA rabies vaccine protected 70–80% of animals, while the survival rate of non-adjuvant vaccine group (control) was 20–30%. According to the results of toxicity tests, PIKA and PIKA rabies vaccine are shown to be well tolerated in mice. Thus, this study indicates that PIKA rabies vaccine is an effective and safe vaccine which has the potential to develop next-generation rabies vaccine and encourage the start of clinical studies. - Highlights: • Vaccination alone is not effective to protect human from rabies virus infection due to delayed generation of rabies virus neutralizing antibodies (RVNA) and weak cellular immunity. • Therefore, it is vital to develop safer and more efficacious vaccine against rabies. PIKA, a stabilized chemical analog of double-stranded RNA that interacts with TLR3, was employed as an adjuvant of rabies vaccine. • The efficacy and safety of PIKA rabies vaccine was evaluated in mice. • The results showed that PIKA rabies vaccine enhanced both humoral and cellular immunity. • After viral challenge, PIKA rabies vaccine protected 70–80% of animals, while the survival rate of non-adjuvant vaccine group was only 20–30%. • According to the results of toxicity tests, PIKA and PIKA rabies vaccine are shown to be well tolerated in mice. • Thus, this study indicates that PIKA rabies vaccine is an effective and safe vaccine which has the potential to

Safety and effectiveness assessment of 2011-2012 seasonal influenza vaccine produced in China: a randomized trial.

Science.gov (United States)

Jing-Xia, Gao; Yu-Liang, Zhao; Jin-Feng, Liu; Shu-Zhen, Liu; Guo-Yang, Liao; Qi, Li

2017-11-01

This study evaluated the effectiveness and safety of the egg-based, trivalent, inactivated split influenza vaccine produced by the Institute of Medical Biology, Chinese Academy of Medical Sciences, Peking Union Medical College, China. From March 2012 through May 2012, we enrolled a total of 1390 healthy volunteers between the ages of 3 and 80 years in a randomized clinical trial at the Hebei Disease Control Center Vaccine Clinical Evaluation Center. For all subjects, body part adverse reactions and whole-body adverse reactions were observed 30 min, 6 h, and 1-7 days' post-inoculation. If no severe adverse effects were observed 7 days' post-vaccination, the local and systemic reactions of preliminary test participants were recorded until day 28. There was no placebo group in this study. Blood samples were taken for serological testing before vaccination and 28 days' post-vaccination. Twenty-eight days after vaccination, the seroconversion rates of experimental and control groups were H1N1 75.3% and 75.7%, H3N2 75.8% and 71.8%, B 70.7% vs. 69.4%, (P > 0.05). The antibody Geometric Mean Titer（GMT）of experimental and control groups were H1N1 (179.7, 182.4), H3N2 (584.0, 445.7), B (201.4,191.6). The protection rate of experimental and control groups was not statistically significant (H1N1: 86% vs. 87%, H3N2: 99% vs. 98%, B: 98% vs. 98%). Also, 95% confidence intervals of the protection rate difference between the experimental and the control group were H1N1: -0.1% (-4.1,3.8) %, H3N2: 0.3% (-1.0,1.7) % and B: 0.2% (-1.5,1.9) %; confidence intervals exceeded the limit of -5%. The rates of adverse reactions between experimental and control groups were 6.3% and 7.7% in local response reactions, and 19.5% and 18.0% in systemic reactions. Three hundred and twenty-seven adverse events (AEs) in 1200 (27.76%) subjects were reported within 28 d after vaccination. No serious adverse events occurred during the study. The experimental vaccine three-antibody protection

Use of animals for toxicology testing is necessary to ensure patient safety in pharmaceutical development.

Science.gov (United States)

Mangipudy, Raja; Burkhardt, John; Kadambi, Vivek J

2014-11-01

There is an active debate in toxicology literature about the utility of animal testing vis-a-vis alternative in vitro paradigms. To provide a balanced perspective and add to this discourse it is important to review the current paradigms, explore pros and cons of alternatives, and provide a vision for the future. The fundamental goal of toxicity testing is to ensure safety in humans. In this article, IQ Consortium DruSafe, while submitting the view that nonclinical testing in animals is an important and critical component of the risk assessment paradigm in developing new drugs, also discusses its views on alternative approaches including a roadmap for what would be required to enhance the utilization of alternative approaches in the safety assessment process. Copyright © 2014 Elsevier Inc. All rights reserved.

Safety of live attenuated influenza vaccine in atopic children with egg allergy.

Science.gov (United States)

Turner, Paul J; Southern, Jo; Andrews, Nick J; Miller, Elizabeth; Erlewyn-Lajeunesse, Michel

2015-08-01

Live attenuated influenza vaccine (LAIV) is an intranasal vaccine recently incorporated into the United Kingdom immunization schedule. However, it contains egg protein and, in the absence of safety data, is contraindicated in patients with egg allergy. Furthermore, North American guidelines recommend against its use in asthmatic children. We sought to assess the safety of LAIV in children with egg allergy. We performed a prospective, multicenter, open-label, phase IV intervention study involving 11 secondary/tertiary centers in the United Kingdom. Children with egg allergy (defined as a convincing clinical reaction to egg within the past 12 months and/or >95% likelihood of clinical egg allergy as per published criteria) were recruited. LAIV was administered under medical supervision, with observation for 1 hour and telephone follow-up 72 hours later. Four hundred thirty-three doses were administered to 282 children with egg allergy (median, 4.9 years; range, 2-17 years); 115 (41%) had experienced prior anaphylaxis to egg. A physician's diagnosis of asthma/recurrent wheezing was noted in 67%, and 51% were receiving regular preventer therapy. There were no systemic allergic reactions (upper 95% CI for population, 1.3%). Eight children experienced mild self-limiting symptoms, which might have been due an IgE-mediated allergic reaction. Twenty-six (9.4%; 95% CI for population, 6.2% to 13.4%) children experienced lower respiratory tract symptoms within 72 hours, including 13 with parent-reported wheeze. None of these episodes required medical intervention beyond routine treatment. In contrast to current recommendations, LAIV appears to be safe for use in children with egg allergy. Furthermore, the vaccine appears to be well tolerated in children with a diagnosis of asthma or recurrent wheeze. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Immunogenicity, safety and reactogenicity of a booster dose of the 10-valent pneumococcal Nontypeable H. influenzae Protein D conjugate vaccine coadministered with DTPa-IPV-Hib in Dutch children

NARCIS (Netherlands)

Van Den Bergh, Menno R.; Spijkerman, Judith; François, Nancy; Swinnen, Kristien; Borys, Dorota; Schuerman, Lode; Veenhoven, Reinier H.; Sanders, Elisabeth A M

2016-01-01

Background: Immune responses and safety profiles may be affected when vaccines are coadministered. We evaluated the immunogenicity, safety and reactogenicity of a booster dose of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D-conjugate (PHiD-CV; Synflorix GSK Vaccines) and

Support for immunization registries among parents of vaccinated and unvaccinated school-aged children: a case control study

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Pan William KY

2006-09-01

Full Text Available Abstract Background Immunizations have reduced childhood vaccine preventable disease incidence by 98–100%. Continued vaccine preventable disease control depends on high immunization coverage. Immunization registries help ensure high coverage by recording childhood immunizations administered, generating reminders when immunizations are due, calculating immunization coverage and identifying pockets needing immunization services, and improving vaccine safety by reducing over-immunization and providing data for post-licensure vaccine safety studies. Despite substantial resources directed towards registry development in the U.S., only 48% of children were enrolled in a registry in 2004. Parental attitudes likely impact child participation. Consequently, the purpose of this study was to assess the attitudes of parents of vaccinated and unvaccinated school-aged children regarding: support for immunization registries; laws authorizing registries and mandating provider reporting; opt-in versus opt-out registry participation; and financial worth and responsibility of registry development and implementation. Methods A case control study of parents of 815 children exempt from school vaccination requirements and 1630 fully vaccinated children was conducted. Children were recruited from 112 elementary schools in Colorado, Massachusetts, Missouri, and Washington. Surveys administered to the parents, asked about views on registries and perceived utility and safety of vaccines. Parental views were summarized and logistic regression models compared differences between parents of exempt and vaccinated children. Results Surveys were completed by 56.1% of respondents. Fewer than 10% of parents were aware of immunization registries in their communities. Among parents aware of registries, exempt children were more likely to be enrolled (65.0% than vaccinated children (26.5% (p value = 0.01. A substantial proportion of parents of exempt children support immunization

Safety and immunogenicity of an AMA1 malaria vaccine in Malian children: results of a phase 1 randomized controlled trial.

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Mahamadou A Thera

2010-02-01

Full Text Available The objective was to evaluate the safety and immunogenicity of the AMA1-based malaria vaccine FMP2.1/AS02(A in children exposed to seasonal falciparum malaria.A Phase 1 double blind randomized controlled dose escalation trial was conducted in Bandiagara, Mali, West Africa, a rural town with intense seasonal transmission of Plasmodium falciparum malaria. The malaria vaccine FMP2.1/AS02(A is a recombinant protein (FMP2.1 based on apical membrane antigen 1 (AMA1 from the 3D7 clone of P. falciparum, formulated in the Adjuvant System AS02(A. The comparator vaccine was a cell-culture rabies virus vaccine (RabAvert. One hundred healthy Malian children aged 1-6 years were recruited into 3 cohorts and randomized to receive either 10 microg FMP2.1 in 0.1 mL AS02(A, or 25 microg FMP2.1 in 0.25 mL AS02(A, or 50 microg FMP2.1 50 microg in 0.5 mL AS02(A, or rabies vaccine. Three doses of vaccine were given at 0, 1 and 2 months, and children were followed for 1 year. Solicited symptoms were assessed for 7 days and unsolicited symptoms for 30 days after each vaccination. Serious adverse events were assessed throughout the study. Transient local pain and swelling were common and more frequent in all malaria vaccine dosage groups than in the comparator group, but were acceptable to parents of participants. Levels of anti-AMA1 antibodies measured by ELISA increased significantly (at least 100-fold compared to baseline in all 3 malaria vaccine groups, and remained high during the year of follow up.The FMP2.1/AS02(A vaccine had a good safety profile, was well-tolerated, and induced high and sustained antibody levels in malaria-exposed children. This malaria vaccine is being evaluated in a Phase 2 efficacy trial in children at this site.ClinicalTrials.gov NCT00358332 [NCT00358332].

Laser facilitates vaccination

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Ji Wang

2016-01-01

Full Text Available Development of novel vaccine deliveries and vaccine adjuvants is of great importance to address the dilemma that the vaccine field faces: to improve vaccine efficacy without compromising safety. Harnessing the specific effects of laser on biological systems, a number of novel concepts have been proposed and proved in recent years to facilitate vaccination in a safer and more efficient way. The key advantage of using laser technology in vaccine delivery and adjuvantation is that all processes are initiated by physical effects with no foreign chemicals administered into the body. Here, we review the recent advances in using laser technology to facilitate vaccine delivery and augment vaccine efficacy as well as the underlying mechanisms.

Trivalent MDCK cell culture-derived influenza vaccine Optaflu (Novartis Vaccines).

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Doroshenko, Alexander; Halperin, Scott A

2009-06-01

Annual influenza epidemics continue to have a considerable impact in both developed and developing countries. Vaccination remains the principal measure to prevent seasonal influenza and reduce associated morbidity and mortality. The WHO recommends using established mammalian cell culture lines as an alternative to egg-based substrates in the manufacture of influenza vaccine. In June 2007, the EMEA approved Optaflu, a Madin Darby canine kidney cell culture-derived influenza vaccine manufactured by Novartis Vaccines. This review examines the advantages and disadvantages of cell culture-based technology for influenza vaccine production, compares immunogenicity and safety data for Optaflu with that of currently marketed conventional egg-based influenza vaccines, and considers the prospects for wider use of cell culture-based influenza vaccines.

Surveillance guidelines for smallpox vaccine (vaccinia) adverse reactions.

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Casey, Christine; Vellozzi, Claudia; Mootrey, Gina T; Chapman, Louisa E; McCauley, Mary; Roper, Martha H; Damon, Inger; Swerdlow, David L

2006-02-03

CDC and the U.S. Food and Drug Administration rely on state and local health departments, health-care providers, and the public to report the occurrence of adverse events after vaccination to the Vaccine Adverse Event Reporting System. With such data, trends can be accurately monitored, unusual occurrences of adverse events can be detected, and the safety of vaccination intervention activities can be evaluated. On January 24, 2003, the U.S. Department of Health and Human Services (DHHS) implemented a preparedness program in which smallpox (vaccinia) vaccine was administered to federal, state, and local volunteers who might be first responders during a biologic terrorism event. As part of the DHHS Smallpox Preparedness and Response Program, CDC in consultation with experts, established surveillance case definitions for adverse events after smallpox vaccination. Adverse reactions after smallpox vaccination identified during the 1960s surveillance activities were classified on the basis of clinical description and included eczema vaccinatum; fetal vaccinia; generalized vaccinia; accidental autoinoculation, nonocular; ocular vaccinia; progressive vaccinia; erythema multiforme major; postvaccinial encephalitis or encephalomyelitis; and pyogenic infection of the vaccination site. This report provides uniform criteria used for the surveillance case definition and classification for these previously recognized adverse reactions used during the DHHS Smallpox Preparedness and Response Program. Inadvertent inoculation was changed to more precisely describe this event as inadvertent autoinoculation and contact transmission, nonocular and ocular vaccinia. Pyogenic infection also was renamed superinfection of the vaccination site or regional lymph nodes. Finally, case definitions were developed for a new cardiac adverse reaction (myo/pericarditis) and for a cardiac adverse event (dilated cardiomyopathy) and are included in this report. The smallpox vaccine surveillance case

Rotavirus vaccines

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Kang G

2006-01-01

Full Text Available Rotavirus, the most common cause of severe diarrhea and a leading cause of mortality in children, has been a priority target for vaccine development for the past several years. The first rotavirus vaccine licensed in the United States was withdrawn because of an association of the vaccine with intussusception. However, the need for a vaccine is greatest in the developing world, because the benefits of preventing deaths due to rotavirus disease are substantially greater than the risk of intussusception. Early vaccines were based on animal strains. More recently developed and licenced vaccines are either animal-human reassortants or are based on human strains. In India, two candidate vaccines are in the development process, but have not yet reached efficacy trials. Many challenges regarding vaccine efficacy and safety remain. In addition to completing clinical evaluations of vaccines in development in settings with the highest disease burden and virus diversity, there is also a need to consider alternative vaccine development strategies.

[Evaluation of immunogenicity and safety of 2 immunizations with allantoic intranasal live influenza vaccine Ultragrivac].

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Shishkina, L N; Mazurkova, N A; Ternovoĭ, V A; Bulychev, L E; Tumanov, Iu V; Skarnovich, M O; Kabanov, A S; Ryndiuk, N N; Kuzubov, V I; Mironov, A N; Stavskiĭ, E A; Drozdov, I G

2011-01-01

Evaluate reactogenicity, safety and immunogenicity in phase 2 clinical trials of 2 immunization schedules with Ultragrivac--an allantoic intranasal life influenza vaccine based on A/17/ duck/Potsdam/86/92 [17/H5] reassortant strain. 4 groups of volunteers participated in the study: group 1--40 individuals were vaccinated twice with a 10 day interval; group 2--40 individuals were vaccinated twice with a 21 day interval; group 3 (control)--10 individuals received placebo twice with a 10 day interval; group 4 (control)--10 individuals received placebo twice with a 21 day interval. Local (secretory IgA), cellular and humoral immune response were evaluated. Humoral immunity was evaluated by the intensity of increase of geometric mean antibody titers against 2 influenza virus strains A/17/duck/Potsdam/86/92 [17/H5] and A/chicken/Suzdalka/Nov-1 1/2005 (H5N1), and by the level of significant (4 times or more) antibody seroconversions after the vaccination. After the use of Ultragrivac the level of secretory IgA in the nasal cavity of vaccinated volunteers in the groups with revaccination intervals of 10 and 21 days increased significantly. The second immunization with 10 or 21 day intervals significantly increased postvaccinal humoral immune response. Humoral immune response induction after 2 vaccinations with 10 day interval was no less effective than with 21 day interval. Ultragrivac allantoic intranasal live influenza vaccine is areactogenic, harmless for vaccinated individuals, safe for those around, and has immunogenic properties against not only homologous virus A(H5N2), but also against influenza strain A(H5N1).

Safety and immunogenicity of Onderstepoort Biological Products’ Rift Valley fever Clone 13 vaccine in sheep and goats under field conditions in Senegal

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Modou M. Lo

2015-05-01

Full Text Available This blinded field safety study was conducted in Senegal to assess safety and immunogenicity of administration of the registered dose of Rift Valley fever virus (RVFV Clone 13 vaccine (Onderstepoort Biological Products to sheep and goats of West African breeds under natural conditions. A total of 267 small ruminants (220 sheep, 47 goats were included; half received RVFV Clone 13 vaccine at the recommended dose and half received the diluent (as placebo only. The study was performed on three commercial farms in the northern and eastern region of Senegal in accordance with veterinary good clinical practices. The animals were observed daily for 3 days after vaccination, and then weekly for 1 year. In both sheep and goats vaccinated against RVFV seroconversion rates above 70% were recorded. No seroconversion related to RVFV was observed in placebo-treated animals. No statistically significant differences were determined between placebo and vaccinated groups for mean rectal temperatures for the first 3 days after administration (p > 0.05. No abnormal clinical signs related to treatment were noted, and only one slight injection site reaction was observed in one vaccinated animal for 2 days after vaccination. Out of 176 births assessed over 1 year (93 from the vaccinated group, 83 from the placebo group, 9 were abnormal in the placebo group and 3 in the vaccinated group (p > 0.05. The frequency of adverse events was similar in the placebo and vaccinated groups. RVFV Clone 13 vaccine administered according to the manufacturer’s instructions was safe and well tolerated in West African breeds of sheep and goats, including animals of approximately 6 months of age and pregnant females, under field conditions in Senegal. Antibody levels persisted up to 1 year after vaccination.

Clinical Efficacy, Safety, and Immunogenicity of a Live Attenuated Tetravalent Dengue Vaccine (CYD-TDV in Children: A Systematic Review with Meta-analysis

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Moffat Malisheni

2017-08-01

Full Text Available BackgroundDengue hemorrhagic fever is the leading cause of hospitalization and death in children living in Asia and Latin America. There is an urgent need for an effective and safe dengue vaccine to reduce morbidity and mortality in this high-risk population given the lack of dengue specific treatment at present. This review aims to determine the efficacy, safety, and immunogenicity of CYD-TDV vaccine in children.MethodsThis is a systematic review including meta-analysis of randomized controlled clinical trial data from Embase, Medline, the Cochrane Library, Web of Science, and ClinicalTrials.gov. Studies that assessed CYD-TDV vaccine efficacy [(1 − RR*100], safety (RR, and immunogenicity (weighted mean difference in children were included in this study. Random effects model was employed to analyze patient-level data extracted from primary studies.ResultsThe overall efficacy of CYD-TDV vaccine was 54% (40–64, while serotype-specific efficacy was 77% (66–85 for DENV4, 75% (65–82 for DENV3, 50% (36–61 for DENV1, and 34% (14–49 for DENV2. 15% (−174–74 vaccine efficacy was obtained for the unknown serotype. Meta-analysis of included studies with longer follow-up time (25 months revealed that CYD-TDV vaccine significantly increased the risk of injection site reactions (RR = 1.1: 1.04–1.17; p-value = 0.001. Immunogenicity (expressed as geometric mean titers in descending order was 439.7 (331.7–547.7, 323 (247 – 398.7, 144.1 (117.9–170.2, and 105 (88.7–122.8 for DENV3, DENV2, DENV1, and DENV4, respectively.ConclusionCYD-TDV vaccine is effective and immunogenic in children overall. Reduced efficacy of CYD-TDV vaccine against DENV2 notoriously known for causing severe dengue infection and dengue outbreaks cause for serious concern. Post hoc meta-analysis of long-term follow-up data (≥25 months from children previously vaccinated with CYD-TDV vaccine is needed to make a conclusion regarding CYD-TDV vaccine

Safety and protective efficacy of porcine reproductive and respiratory syndrome recombinant virus vaccines in young pigs.

NARCIS (Netherlands)

Verheije, M.H.; Kroese, M.V.; Linden, van der I.F.A.; Boer-Luijtze, de E.A.; Rijn, van P.A.; Pol, J.M.A.; Meulenberg, J.J.M.; Steverink, P.J.G.M.

2003-01-01

Three porcine reproductive and respiratory syndrome virus (PRRSV) recombinants, generated by mutagenesis of an infectious cDNA clone of the Lelystad virus (LV) isolate, were tested for their safety and protective efficacy as potential PRRSV vaccines in pigs. Recombinant vABV688 contains two amino

The Evolution of the Meningitis Vaccine Project.

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Tiffay, Kathleen; Jodar, Luis; Kieny, Marie-Paule; Socquet, Muriel; LaForce, F Marc

2015-11-15

In 2001, the Meningitis Vaccine Project (MVP) was tasked to develop, test, license, and introduce a group A meningococcal (MenA) conjugate vaccine for sub-Saharan Africa. African public health officials emphasized that a vaccine price of less than US$0.50 per dose was necessary to ensure introduction and sustained use of this new vaccine. Initially, MVP envisioned partnering with a multinational vaccine manufacturer, but the target price and opportunity costs were problematic and formal negotiations ended in 2002. MVP chose to become a "virtual vaccine company," and over the next decade managed a network of public-private and public-public partnerships for pharmaceutical development, clinical development, and regulatory submission. MVP supported the transfer of key know-how for the production of group A polysaccharide and a new conjugation method to the Serum Institute of India, Ltd, based in Pune, India. A robust staff structure supported by technical consultants and overseen by advisory groups in Europe and Africa ensured that the MenA conjugate vaccine would meet all international standards. A robust project structure including a team of technical consultants and 3 advisory groups in Europe and Africa ensured that the MenA conjugate vaccine (PsA-TT, MenAfriVac) was licensed by the Drug Controller General of India and prequalified by the World Health Organization in June 2010. The vaccine was introduced in Burkina Faso, Mali, and Niger in December 2010. The development, through a public-private partnership, of a safe, effective, and affordable vaccine for sub-Saharan Africa, PsA-TT, offers a new paradigm for the development of vaccines specifically targeting populations in resource-poor countries. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Safety and immunogenicity of an intramuscular quadrivalent influenza vaccine in children 3 to 8 y of age: A phase III randomized controlled study.

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Pepin, Stephanie; Szymanski, Henryk; Rochín Kobashi, Ilya Angélica; Villagomez Martinez, Sandra; González Zamora, José Francisco; Brzostek, Jerzy; Huang, Li-Min; Chiu, Cheng-Hsun; Chen, Po-Yen; Ahonen, Anitta; Forstén, Aino; Seppä, Ilkka; Quiroz, René Farfán; Korhonen, Tiina; Rivas, Enrique; Monfredo, Celine; Hutagalung, Yanee; Menezes, Josemund; Vesikari, Timo

2016-12-01

A quadrivalent, inactivated, split-virion influenza vaccine containing a strain from both B lineages (IIV4) has been developed, but its safety and immunogenicity in young children has not been described. This was a phase III, randomized, double-blind, active-controlled, multi-center study to examine the immunogenicity and safety of IIV4 in children 3-8 y of age (EudraCT no. 2011-005374-33). Participants were randomized 5:1:1 to receive the 2013/2014 Northern Hemisphere formulation of IIV4, an investigational trivalent comparator (IIV3) containing the B/Victoria lineage strain, or the licensed Northern Hemisphere IIV3 containing the B/Yamagata lineage strain. Participants who had not previously received a full influenza vaccination schedule received 2 doses of vaccine 28 d apart; all others received a single dose. 1242 children were included. For all 4 strains, IIV4 induced geometric mean haemagglutination inhibition titres non-inferior to those induced by the IIV3 comparators. For both B strains, geometric mean antibody titres induced by IIV4 were superior to those induced by the IIV3 with the alternative lineage strain. Similar proportions of participants vaccinated with IIV4 and IIV3 reported solicited injection-site reactions, solicited systemic reactions, and vaccine-related adverse events. A single vaccine-related serious adverse event, thrombocytopenia, was reported 9 d after vaccination with IIV4 and resolved without sequelae. In conclusion, in children aged 3-8 y who received one dose or 2 doses 28 d apart, IIV4 had an acceptable safety profile, was as immunogenic as IIV3 for the shared strains, and had superior immunogenicity for the additional B strain.

Safety and long-term immunological effects of CryJ2-LAMP plasmid vaccine in Japanese red cedar atopic subjects: A phase I study.

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Su, Yan; Romeu-Bonilla, Eliezer; Anagnostou, Athanasia; Fitz-Patrick, David; Hearl, William; Heiland, Teri

2017-12-02

Japanese Red Cedar (JRC) pollen induced allergy affects one third of Japanese and the development of effective therapies remains an unachieved challenge. We designed a DNA vaccine encoding CryJ2 allergen from the JRC pollen and Lysosomal Associated Membrane Protein 1 (LAMP-1) to treat JRC allergy. These Phase IA and IB trials assessed safety and immunological effects of the investigational CryJ2-LAMP DNA vaccine in both non-sensitive and sensitive Japanese expatriates living in Honolulu, Hawaii. In the Phase IA trial, 6 JRC non-sensitive subjects and 9 JRC and/or Mountain Cedar (MC) sensitive subjects were given 4 vaccine doses (each 4mg/1ml) intramuscularly (IM) at 14-day intervals. Nine JRC and/or MC sensitive subjects were given 4 doses (2 mg/0.5 ml) IM at 14-day intervals. The safety and functional biomarkers were followed for 132 d. Following this, 17 of 24 subjects were recruited into the IB trial and received one booster dose (2 mg/0.5 ml) IM approximately 300 d after the first vaccination dose to which they were randomized in the first phase of the trial. All safety endpoints were met and all subjects tolerated CryJ2-LAMP vaccinations well. At the end of the IA trial, 10 out of 12 JRC sensitive and 6 out of 11 MC sensitive subjects experienced skin test negative conversion, possibly related to the CryJ2-LAMP vaccinations. Collectively, these data suggested that the CryJ2-LAMP DNA vaccine is safe and may be immunologically effective in treating JRC induced allergy.

Comparison of safety and immunogenicity of purified chick embryo cell vaccine using Zagreb and Essen regimens in patients with category II exposure in China.

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Hu, Quan; Liu, Man-Qing; Zhu, Zheng-Gang; Zhu, Ze-Rong; Lu, Sha

2014-01-01

The aim was to compare the safety and immunogenicity of purified chick embryo cell vaccine (PCECV) with Zagreb 2-1-1 and Essen 1-1-1-1-1 regimens in patients with WHO category II exposure in China. Side effects including systemic and local symptoms were recorded for all patients during vaccination with purified chick embryo cell vaccine (PCECV) under Zagreb 2-1-1 or Essen 1-1-1-1-1 regimens, and the rabies neutralization antibody titers in patients' serum at days 0, 7, 14, 45, 365 post-immunization were measured to determine the immunogenicity. Fever and pain were the most common events for systemic and local symptoms respectively, and most side effects (86.78%, 105/121) occurred after the first dose of vaccination. Safety analysis showed differences in side effects inZagreb and Essen regimens, especially after the first dose of vaccination (P = 0.043). Immunogenicity analysis indicated that Zagreb can achieve higher neutralization antibody titers and a greater seroconversion rate in a shorter time but had less persistence than Essen. When compared with the Essen regimen, the Zagreb regimen had a different immunogenicity in all study subjects, and different safety profile in young children, and a further study with a larger population and longer surveillance is warranted.

Pragmatic trial of an intervention to increase human papillomavirus vaccination in safety-net clinics

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Maureen Sanderson

2017-02-01

Full Text Available Abstract Background Human papillomavirus (HPV infection has been causally linked to six cancers, and many disproportionately affect minorties. This study reports on the development and effectiveness of an intervention aimed at increasing HPV vaccine uptake among African American and Hispanic pediatric patients in safety-net clinics. Methods Formative research, community engagement, and theory guided development of the intervention. A clustered, non-randomized controlled pragmatic trial was conducted in four clinics providing healthcare for the underserved in Tennessee, U.S., with two intervention sites and two usual care sites. Patients aged 9-18 years (N = 408 and their mothers (N = 305 enrolled, with children clustered within families. The intervention consisted of two provider/staff training sessions and provision of patient education materials, consisting of a video/flyer promoting HPV vaccine. Medical records were reviewed before/after the initial visit and after 12 months. Results At the initial visit, provision of patient education materials and provider recommendation were higher at intervention sites versus usual care sites, and receipt of HPV vaccine was higher at intervention sites (45.4% versus 32.9% but not significantly after adjusting for patient’s age and mother’s education. Provider recommendation, but not education materials, increased the likelihood of vaccine receipt at the initial visit, although over one-third of intervention mothers cited the flyer/video as motivating vaccination. Completion of the 3-dose series at follow-up was lower in the intervention arm. Conclusions Future interventions should combine patient education, intensive provider/staff education, and patient reminders. Research should compare patient education focusing on HPV vaccine only versus all adolescent vaccines. Trial registration Retrospectively registered with ClinicalTrials.gov NCT02808832 , 9/12/16

Human papillomavirus 16/18 AS04-adjuvanted cervical cancer vaccine: immunogenicity and safety in 15-25 years old healthy Korean women.

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Kim, Seung Cheol; Song, Yong Sang; Kim, Young-Tae; Kim, Young Tak; Ryu, Ki-Sung; Gunapalaiah, Bhavyashree; Bi, Dan; Bock, Hans L; Park, Jong-Sup

2011-06-30

The study assessed the immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted cervical cancer vaccine in healthy Korean women aged 15-25 years. Phase IIIB, double-blind, randomised (2:1), multi-centre trial was conducted in Korea from June 2007 to March 2008. The study enrolled 225 women in the HPV (N=149) and placebo (N=76) groups who received three doses of HPV-16/18 AS04-adjuvanted vaccine or placebo (aluminium hydroxide) administered intramuscularly at 0, 1, and 6 months and were followed until one month post-dose 3. Serum samples were collected pre-vaccination and one month post-dose 3. Safety and reactogenicity data were collected throughout. In this trial, 208 women completed the study (141 in HPV group; 67 in placebo group). At month 7, all initially seronegative women had seroconverted for HPV-16 and HPV-18 antibodies with anti-HPV-16 and anti-HPV-18 geometric mean titres of 9,351.4 El.U/mL (95% CI, 8,145.5 to 10,735.8) and 4204.1 El.U/mL (95% CI, 3,626.5 to 4,873.6), respectively. Initially seropositive women showed similar increase in geometric mean titre levels. Compliance to the three dose vaccination course was 95.3% in HPV and 89.5% in placebo group. Solicited local (pain) and general (fatigue, myalgia or headache) symptoms were commonly reported in both groups. Three serious adverse events were reported (two in HPV group; one in placebo group), all unrelated to vaccination by the investigator; all recovered. The HPV-16/18 AS04-adjuvanted vaccine was highly immunogenic with a clinically acceptable safety profile in Korean women. This study was in line with previous global studies in Europe, North America, and Brazil. (ClinicalTrials.gov number, NCT 00485732.).

Vaccines Stop Illness

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... the disease no longer exists. If we keep vaccinating now, parents in the future may be able to trust that diseases like polio and meningitis won't infect, cripple, or kill children. Vaccine Safety In light of recent questions about ...

Safety of herpes zoster vaccination among inflammatory bowel disease patients being treated with anti-TNF medications.

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Khan, N; Shah, Y; Trivedi, C; Lewis, J D

2017-10-01

The risk of herpes zoster (HZ) is elevated in inflammatory bowel disease (IBD) patients treated with anti-TNF medications. While it is optimal to give herpes zoster vaccine prior to initiation of therapy clinical circumstances may not always allow this. To determine the safety of giving herpes zoster vaccine while patients are on anti-TNF therapy. We conducted a retrospective cohort study involving IBD patients who were followed in the Veterans Affairs (VA) healthcare system between 2001 and 2016. Patients who received herpes zoster vaccine while on anti-TNF medication were identified through vaccination codes and confirmed through individual chart review. Our outcome of interest was development of HZ between 0 and 42 days after herpes zoster vaccine administration. Fifty-six thousand four hundred and seventeen patients with IBD were followed in the VA healthcare system. A total of 59 individuals were on anti-TNF medication when they were given herpes zoster vaccine, and amongst them, 12 (20%) were also taking a thiopurine. Median age at the time of herpes zoster vaccine was 64.9 years and 95% of patients had a Charlson Comorbidity Index of ≥2. Median number of encounters within 42 days after receiving herpes zoster vaccine was two. No case of HZ was found within 0-42 days of HZV administration. Our data suggest that co-administering the herpes zoster vaccine to patients who are taking anti-TNF medications is relatively safe. This study significantly expands the evidence supporting the use of herpes zoster vaccine in this population, having included an elderly group of patients with a high Charlson Comorbidity Index who are likely at a much higher risk of developing HZ. © 2017 John Wiley & Sons Ltd.

Immunogenicity, reactogenicity, and safety of a P1.7b,4 strain-specific serogroup B meningococcal vaccine given to preteens.

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Hosking, Jamie; Rasanathan, Kumanan; Mow, Florina Chan; Jackson, Catherine; Martin, Diana; O'Hallahan, Jane; Oster, Philipp; Ypma, Ellen; Reid, Stewart; Aaberge, Ingeborg; Crengle, Sue; Stewart, Joanna; Lennon, Diana

2007-11-01

New Zealand (NZ) has experienced a Neisseria meningitidis serogroup B epidemic since 1991. MeNZB, a strain-specific outer membrane vesicle vaccine made using an NZ epidemic strain isolate, NZ98/254 (B:4:P1.7b,4), from two manufacturing sites, the Norwegian Institute of Public Health (NIPH) and Chiron Vaccines (CV; now Novartis), was evaluated for safety, immunogenicity, and reactogenicity in this observer-blind trial with 8- to 12-year-old children. In year 1, cohort A (n = 302) was randomized 4:1 for receipt of NIPH-MeNZB or MenBvac (Norwegian parent vaccine strain 44/76; B:15:P1.7,16). In year 2, cohort B (n = 313) was randomized 4:1 for receipt of CV-MeNZB or NIPH-MeNZB. Participants all received three vaccinations 6 weeks apart. Local and systemic reactions were monitored for 7 days. Seroresponse was defined as a fourfold or greater rise in the serum bactericidal antibody titer from the baseline titer as measured by a serum bactericidal assay. Those with baseline titers of /=1:8 to serorespond. Intention-to-treat (ITT) and per protocol (PP) analyses are presented. In cohort A, 74% (ITT) and 73% (PP) of NIPH-MeNZB recipients demonstrated seroresponses against NZ98/254 after three doses, versus 32% (ITT and PP) of MenBvac recipients. In cohort B, seroresponses against NZ98/254 after three doses occurred in 79% (ITT and PP) of CV-MeNZB versus 75% (ITT) and 76% (PP) of NIPH-MeNZB recipients. Vaccines were tolerable, with no vaccine-related serious adverse events. In conclusion, the NZ strain meningococcal B vaccine (MeNZB) from either manufacturing site was immunogenic against New Zealand epidemic vaccine strain meningococci with no safety concerns when given in three doses to these 8- to 12-year-old children.

Immunogenicity and safety of human papillomavirus (HPV) vaccination in Asian populations from six countries : a meta-analysis

NARCIS (Netherlands)

Setiawan, Didik; Luttjeboer, Jos; Pouwels, Koen B.; Wilschut, Jan C.; Postma, Maarten J.

Cervical cancer is a serious public-health problem in Asian countries. Since human papillomavirus (HPV) infection is the main risk factor for cervical cancer, HPV vaccination is considered a promising strategy to prevent cervical cancer. However, comprehensive immunogenicity and safety information

HPV vaccines: a controversial issue?

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Nicol, A F; Andrade, C V; Russomano, F B; Rodrigues, L L S; Oliveira, N S; Provance, D W

2016-01-01

Controversy still exists over whether the benefits of the available HPV vaccines outweigh the risks and this has suppressed uptake of the HPV vaccines in comparison to other vaccines. Concerns about HPV vaccine safety have led some physicians, healthcare officials and parents to withhold the recommended vaccination from the target population. The most common reason for not administering the prophylactic HPV vaccines are concerns over adverse effects. The aim of this review is the assessment of peer-reviewed scientific data related to measurable outcomes from the use of HPV vaccines throughout the world with focused attention on the potential adverse effects. We found that the majority of studies continue to suggest a positive risk-benefit from vaccination against HPV, with minimal documented adverse effects, which is consistent with other vaccines. However, much of the published scientific data regarding the safety of HPV vaccines appears to originate from within the financially competitive HPV vaccine market. We advocate a more independent monitoring system for vaccine immunogenicity and adverse effects to address potential conflicts of interest with regular systematic literature reviews by qualified individuals to vigilantly assess and communicate adverse effects associated with HPV vaccination. Finally, our evaluation suggests that an expanded use of HPV vaccine into more diverse populations, particularly those living in low-resource settings, would provide numerous health and social benefits.

HPV vaccines: a controversial issue?

Directory of Open Access Journals (Sweden)

A.F. Nicol

2016-01-01

Full Text Available Controversy still exists over whether the benefits of the available HPV vaccines outweigh the risks and this has suppressed uptake of the HPV vaccines in comparison to other vaccines. Concerns about HPV vaccine safety have led some physicians, healthcare officials and parents to withhold the recommended vaccination from the target population. The most common reason for not administering the prophylactic HPV vaccines are concerns over adverse effects. The aim of this review is the assessment of peer-reviewed scientific data related to measurable outcomes from the use of HPV vaccines throughout the world with focused attention on the potential adverse effects. We found that the majority of studies continue to suggest a positive risk-benefit from vaccination against HPV, with minimal documented adverse effects, which is consistent with other vaccines. However, much of the published scientific data regarding the safety of HPV vaccines appears to originate from within the financially competitive HPV vaccine market. We advocate a more independent monitoring system for vaccine immunogenicity and adverse effects to address potential conflicts of interest with regular systematic literature reviews by qualified individuals to vigilantly assess and communicate adverse effects associated with HPV vaccination. Finally, our evaluation suggests that an expanded use of HPV vaccine into more diverse populations, particularly those living in low-resource settings, would provide numerous health and social benefits.

Vaccines, inspiring innovation in health.

Science.gov (United States)

Pagliusi, Sonia; Dennehy, Maureen; Kim, Hun

2018-05-19

This report covers the topics of pandemics, epidemics and partnerships, including regulatory convergence initiatives, new technologies and novel vaccines, discussed by leading public and private sector stakeholders at the 18th Annual General Meeting (AGM) of the Developing Countries Vaccine Manufacturers' Network (DCVMN). Contributions of Gavi and the vaccine industry from emerging countries to the growing global vaccine market, by improving the supply base from manufacturers in developing countries and contributing to 58% of doses, were highlighted. The Coalition for Epidemic Preparedness Innovations (CEPI), the International Vaccine Institute (IVI) and others reported on new strategies to ensure speedy progress in preclinical and clinical development of innovative vaccines for future MERS, Zika or other outbreak response. Priorities for vaccine stockpiling, to assure readiness during emergencies and to prevent outbreaks due to re-emerging diseases such as yellow fever, cholera and poliomyelitis, were outlined. The role of partnerships in improving global vaccine access, procurement and immunization coverage, and shared concerns were reviewed. The World Health Organization (WHO) and other international collaborating partners provided updates on the Product, Price and Procurement database, the prequalification of vaccines, the control of neglected tropical diseases, particularly the new rabies elimination initiative, and regulatory convergence proposals to accelerate vaccine registration in developing countries. Updates on supply chain innovations and novel vaccine platforms were presented. The discussions enabled members and partners to reflect on efficiency of research & development, supply chain tools and trends in packaging technologies improving delivery of existing vaccines, and allowing a deeper understanding of the current public-health objectives, industry financing, and global policies, required to ensure optimal investments, alignment and stability of

Preclinical and clinical safety studies on DNA vaccines.

NARCIS (Netherlands)

Schalk, Johanna A C; Mooi, Frits R; Berbers, Guy A M; Aerts, Leon A G J M van; Ovelgönne, Hans; Kimman, Tjeerd G

2007-01-01

DNA vaccines are based on the transfer of genetic material, encoding an antigen, to the cells of the vaccine recipient. Despite high expectations of DNA vaccines as a result of promising preclinical data their clinical utility remains unproven. However, much data is gathered in preclinical and

Safety and immunogenicity of adjuvanted inactivated split-virion and whole-virion influenza A (H5N1) vaccines in children: a phase I-II randomized trial.

Science.gov (United States)

Wu, Jiang; Liu, Shu-Zhen; Dong, Shan-Shan; Dong, Xiao-Ping; Zhang, Wu-Li; Lu, Min; Li, Chang-Gui; Zhou, Ji-Chen; Fang, Han-Hua; Liu, Yan; Liu, Li-Ying; Qiu, Yuan-Zheng; Gao, Qiang; Zhang, Xiao-Mei; Chen, Jiang-Ting; Zhong, Xiang; Yin, Wei-Dong; Feng, Zi-Jian

2010-08-31

Highly pathogenic avian influenza A virus H5N1 has the potential to cause a pandemic. Many prototype pandemic influenza A (H5N1) vaccines had been developed and well evaluated in adults in recent years. However, data in children are limited. Herein we evaluate the safety and immunogenicity of adjuvanted split-virion and whole-virion H5N1 vaccines in children. An open-labelled phase I trial was conducted in children aged 3-11 years to receive aluminum-adjuvated, split-virion H5N1 vaccine (5-30 microg) and in children aged 12-17 years to receive aluminum-adjuvated, whole-virion H5N1 vaccine (5-15 microg). Safety of the two formulations was assessed. Then a randomized phase II trial was conducted, in which 141 children aged 3-11 years received the split-virion vaccine (10 or 15 microg) and 280 children aged 12-17 years received the split-virion vaccine (10-30 microg) or the whole-virion vaccine (5 microg). Serum samples were collected for hemagglutination-inhibition (HI) assays. 5-15 microg adjuvated split-virion vaccines were well tolerated in children aged 3-11 years and 5-30 microg adjuvated split-virion vaccines and 5 microg adjuvated whole-virion vaccine were well tolerated in children aged 12-17 years. Most local and systemic reactions were mild or moderate. Before vaccination, all participants were immunologically naïve to H5N1 virus. Immune responses were induced after the first dose and significantly boosted after the second dose. In 3-11 years children, the 10 and 15 microg split-virion vaccine induced similar responses with 55% seroconversion and seroprotection (HI titer >or=1:40) rates. In 12-17 years children, the 30 microg split-virion vaccine induced the highest immune response with 71% seroconversion and seroprotection rates. The 5 microg whole-virion vaccine induced higher response than the 10 microg split-virion vaccine did. The aluminum-adjuvanted, split-virion prototype pandemic influenza A (H5N1) vaccine showed good safety and immunogenicity in

EFFICACY AND SAFETY OF 23-VALENT PNEUMOCOCCAL POLYSACCHARIDE VACCINE IN PATIENTS WITH RHEUMATOID ARTHRITIS

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M. S. Naumtseva

2015-01-01

Full Text Available Objective: to study the clinical efficacy, immunogenicity, and safety of a 23-valent pneumococcal vaccine in patients with rheumatoid arthritis (RA. Subjects and methods. The investigation enrolled 70 patients (55 women and 15 men aged 23–70 years, including 40 patients with RA and 30 people without systemic inflammatory rheumatic diseases (a control group who had a recent history of 2 and more cases of lower respiratory tract infections (bronchitis, pneumonia. When included, all the patients received anti-inflammatory therapy with methotrexate (MT (n = 24, leflunomide (LEF (n = 6, or MT + tumor necrosis factor-α (TNF-α inhibitors (n = 10. A single 0.5-ml dose of the 23-valent pneumococcal vaccine Pneumo-23 (Sanofi Pasteur was administered subcutaneously or intramuscularly during continuous MT or LEF therapy for the underlying disease or 3–4 weeks before the use of a TNF-α inhibitor. During control visits (1 and 3 months and 1 year after administration of the vaccine, the patients underwent physical examination and routine clinical and laboratory studies. Results. No clinical and radiological symptoms of pneumonia were recorded in any case during a 12-month follow-up. The RA and control groups showed a more than 2-fold increase in anti-pneumococcal antibody levels 1 year after vaccination. The vaccine was well tolerated by 50 patients. Sixteen patients were observed to have pain, cutaneous swelling and hyperemia and 4 had subfebrility. There were neither episodes of RA exacerbation nor new autoimmune disorders during the follow-up. Conclusion. The findings suggest that 23-valent pneumococcal vaccine shows a good clinical efficacy, adequate immunogenicity, and good tolerability in the patients with RA. 

Efficacy, Immunogenicity and Safety of a Human Rotavirus Vaccine RIX4414 in Singaporean Infants.

Science.gov (United States)

Phua, Kong Boo; Lim, Fong Seng; Quak, Seng Hock; Lee, Bee Wah; Teoh, Yee Leong; Suryakiran, Pemmaraju V; Han, Htay Htay; Bock, Hans L

2016-02-01

This was the first study conducted to evaluate the efficacy of 2 oral doses of the human rotavirus vaccine, RIX4414 in Singaporean infants during the first 3 years of life. Healthy infants, 11 to 17 weeks of age were enrolled in this randomised (1:1), double-blinded, placebo-controlled study to receive 2 oral doses of RIX4414 vaccine/placebo following a 0-, 1-month schedule. Vaccine efficacy against severe rotavirus (RV) gastroenteritis (Vesikari score ≥11) caused by wild-type RV strains from a period starting from 2 weeks post-Dose 2 until 2 and 3 years of age was calculated with 95% confidence interval (CI). Immunogenicity and safety of the vaccine were also assessed. Of 6542 infants enrolled, 6466 were included in the efficacy analysis and a subset of 100 infants was included in the immunogenicity analysis. Fewer severe RV gastroenteritis episodes were reported in the RIX4414 group when compared to placebo at both 2 and 3 year follow-up periods. Vaccine efficacy against severe RV gastroenteritis at the respective time points were 93.8% (95% CI, 59.9 to 99.9) and 95.2% (95% CI, 70.5 to 99.9). One to 2 months post-Dose 2 of RIX4414, 97.5% (95% CI, 86.8 to 99.9) of infants seroconverted for anti-RV IgA antibodies. The number of serious adverse events recorded from Dose 1 until 3 years of age was similar in both groups. Two oral doses of RIX4414 vaccine was immunogenic and provided high level of protection against severe RV gastroenteritis in Singaporean children, during the first 3 years of life when the disease burden is highest.

Serologic evaluation, efficacy, and safety of a commerical modified-live canine distemper vaccine in domestic ferrets.

Science.gov (United States)

Wimsatt, J; Jay, M T; Innes, K E; Jessen, M; Collins, J K

2001-05-01

To determine efficacy and safety of a commercial modified-live canine distemper virus (CDV) vaccine used for prophylaxis in domestic ferrets. Sixteen 16-week-old neutered male ferrets. Equal groups of ferrets were inoculated subcutaneously at 16 and 20 weeks of age with saline (0.9% NaCl) solution or a vaccine derived from the Onderstepoort CDV strain and attenuated in a primate cell line. Live virulent CDV was administered to all ferrets intranasally and orally 3 weeks after the second inoculation. Clinical signs and body weights were monitored regularly during the study. Blood samples for serologic examination were drawn prior to each inoculation, before challenge exposure, and 10, 15, and 21 days after exposure. Blood samples for reverse transcriptase polymerase chain reaction (RT-PCR) were obtained 5 days after the first vaccination, and 5, 10, 15, and 21 days after challenge exposure. After challenge exposure, control ferrets had significantly more clinical signs and weight loss, compared with vaccinates. All vaccinated ferrets survived, whereas all control ferrets died. The RT-PCR assay was successful in detecting CDV in blood and fresh or formalin-fixed tissues from infected ferrets. Findings suggest that the vaccine when given SC to domestic ferrets as directed is safe and protective against challenge exposure with virulent CDV. The RT-PCR assay may simplify detection of CDV in fresh and fixed tissues.

Co-administration of a meningococcal glycoconjugate ACWY vaccine with travel vaccines: a randomized, open-label, multi-center study.

Science.gov (United States)

Alberer, Martin; Burchard, Gerd; Jelinek, Tomas; Reisinger, Emil; Beran, Jiri; Meyer, Seetha; Forleo-Neto, Eduardo; Gniel, Dieter; Dagnew, Alemnew F; Arora, Ashwani Kumar

2014-01-01

Potential interactions between vaccines may compromise the immunogenicity and/or safety of individual vaccines so must be assessed before concomitant administration is recommended. In this study, the immunogenicity and safety of travel vaccines against Japanese encephalitis (JEV) and rabies (PCECV) administered together with or without a quadrivalent meningococcal glycoconjugate ACWY-CRM vaccine were evaluated (NCT01466387). Healthy adults aged 18 to ≤60 years were randomized to one of four vaccine regimens: JEV + PCECV + MenACWY-CRM, JEV + PCECV, PCECV or MenACWY-CRM. Immunogenicity at baseline and 28 days post-complete vaccination was assessed by serum bactericidal assay using human complement or neutralization tests. Adverse events (AEs) were collected throughout the study period. JEV + PCECV + MenACWY-CRM was non-inferior to JEV + PCECV. Post-vaccination seroprotective neutralizing titers or concentrations were achieved in 98-99% (JE) and 100% (rabies) of subjects across the vaccine groups. Antibody responses to vaccine meningococcal serogroups were in the same range for MenACWY-CRM and JEV + PCECV + MenACWY-CRM. Rates of reporting of AEs were similar for JEV + PCECV and JEV + PCECV + MenACWY-CRM. MenACWY-CRM was administered with an inactivated adjuvanted JE and a purified chick embryo cell-culture rabies vaccine without compromising immunogenicity or safety of the individual vaccines. These data provide evidence that MenACWY-CRM could be effectively incorporated into travel vaccination programs. NCT01466387. Copyright © 2014 Elsevier Ltd. All rights reserved.

Are HPV vaccination services accessible to high-risk communities? A spatial analysis of HPV-associated cancer and Chlamydia rates and safety-net clinics.

Science.gov (United States)

Tsui, Jennifer; Rodriguez, Hector P; Gee, Gilbert C; Escobedo, Loraine A; Kominski, Gerald F; Bastani, Roshan

2013-12-01

While HPV vaccines can greatly benefit adolescents and young women from high-risk areas, little is known about whether safety-net immunization services are geographically accessible to communities at greatest risk for HPV-associated diseases. We explore the spatial relationship between areas with high HPV risk and proximity to safety-net clinics from an ecologic perspective. We used cancer registry data and Chlamydia surveillance data to identify neighborhoods within Los Angeles County with high risk for HPV-associated cancers. We examined proximity to safety-net clinics among neighborhoods with the highest risk. Proximity was measured as the shortest distance between each neighborhood center and the nearest clinic and having a clinic within 3 miles of each neighborhood center. The average 5-year non-age-adjusted rates were 1,940 cases per 100,000 for Chlamydia and 60 per 100,000 for HPV-associated cancers. A large majority, 349 of 386 neighborhoods with high HPV-associated cancer rates and 532 of 537 neighborhoods with high Chlamydia rates, had a clinic within 3 miles of the neighborhood center. Clinics were more likely to be located within close proximity to high-risk neighborhoods in the inner city. High-risk neighborhoods outside of this urban core area were less likely to be near accessible clinics. The majority of high-risk neighborhoods were geographically near safety-net clinics with HPV vaccination services. Due to low rates of vaccination, these findings suggest that while services are geographically accessible, additional efforts are needed to improve uptake. Programs aimed to increase awareness about the vaccine and to link underserved groups to vaccination services are warranted.

Adversomics: a new paradigm for vaccine safety and design.

Science.gov (United States)

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.

CLINICAL STUDIES OF REACTOGENICITY, SAFETY AND IMMUNOGENICITY OF LIVE MONOVALENT INFLUENZA VACCINE (STRAIN А/17/CALIFORNIA/2009/38 — H1N1 IN CHILDREN

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D.S. Bushmenkov

2010-01-01

Full Text Available Results of performed pre-clinical and clinical studies with volunteers 18-60 years old allowed registration of vaccine «INFLUVIR» (live monovalent vaccine for the prophylaxis of influenza A/H1N1, strain A/17/California/2009/38 (H1N1, developed by NPO «Microgen» in Russian Federation so timely vaccination campaign was performed. As a result, the level of morbidity with influenza A/H1N1 in Russia was decreased, and development of complication was prevented. Clinical studies in different groups of children were performed for the purpose of widening indications for vaccine «INFLUVIR» administration. According to the results of studies vaccine «INFLUVIR» has good tolerability and safety, low reactogenicity, and significant immunogenicity. This fact will allow changing of present normative documentation and administration of «INFLUVIR» in children of different age for prophylaxis of influenza A/H1N1.Key words: children, influenza, virus A/H1N1, live influenza vaccine, tolerability, safety, immunogenicity.(Voprosy sovremennoi pediatrii — Current Pediatrics. – 2010;9(4:101-105

Study on the efficacy and safety of different antigens and oil formulations of infectious coryza vaccines containing an NAD-independent strain of Avibacterium paragallinarum

Directory of Open Access Journals (Sweden)

B. Dungu

2009-09-01

Full Text Available The present study was designed to assess and compare three different formulations of the new Onderstepoort infectious coryza (IC quadrivalent vaccine, which contain an NAD-independent strain of Avibacterium paragallinarum (previously known as Haemophilus paragallinarum, and a commercial IC vaccine, not containing an NAD-independent strain, for their safety and ability to protect chickens of varying ages against virulent challenges with four different serovars of A. paragallinarum, including the NAD-independent strain of the C-3 serovar. Four groups of 140 chickens each were vaccinated at the age of 17 weeks and revaccinated at the age of 19 weeks with each of the four vaccine formulations. A similar sized group of non-vaccinated chickens was used as control. Two rounds of challenge were conducted: a group of chicken in each vaccination group was challenged between 31 and 35 weeks of age, while another group was challenged between 51 and 55 weeks of age. The ''in-contact'' challenge model was used in this experiment. For each vaccination group, the four challenge strains representing four local serovars were used in each challenge round. The efficacy of the vaccines was compared based on overall protection levels obtained and the duration of protection. The safety of the different vaccines was determined by the severity of post-vaccination reactions. The need for the incorporation of the NAD-independent strain in the vaccine was evidenced by the low protection level against NAD-independent challenge recorded in the group of birds vaccinated with the commercial vaccine. The results obtained confirmed not only the variation in virulence of different South African serovars, with serovar C-3 being the most virulent and serovar B having almost no virulence but also the age related increase in susceptibility. The importance of a suitable formulation of the vaccine is discussed.

Evaluation of immunogenicity and safety of Genevac B: A new recombinant hepatitis b vaccine in comparison with Engerix B and Shanvac B in healthy adults

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Vijayakumar V

2004-01-01

Full Text Available PURPOSE: Genevac B, a new indigenous recombinant hepatitis B vaccine was evaluated for its immunogenicity and safety in comparison with Engerix B (Smithkline Beecham Biologicals, Belgium and Shanvac B (Shantha Biotechnics, India in healthy adult volunteers. METHODS: While 240 study subjects were included in the Genevac B group, 80 each were the subjects for Engerix B and Shanvac B. A three dose regimen of 0,1,2 months was adopted with 20 gm dosage uniformly in all the three groups. Vaccinees were assessed during prevaccination, followup and post vaccination periods for clinical, haematological, biochemical and immunological parameters for safety and immunogenicity. RESULTS: Successful follow-up in all parameters for four months could be achieved in 92.5% (222/240 for Genevac B study subjects and the same was 85% (68/80 and 80% (64/80 for Engerix B and Shanvac B respectively. While 100% seroconversion was observed in all the three groups, the rate of seroprotectivity was 99.5% by Genevac B, 98.5% by Engerix B and 98.4% for Shanvac B. However the difference was not statistically significant (p>0.05. The GMT values of anti HBs after one month of completion of the vaccination were 735.50, 718.23 and 662.20 mIU/mL respectively. No systemic reaction was either seen or reported by the volunteers during the vaccination process of Genevac B and other two vaccines. Clinical, haematological and biochemical safety parameters remained within normal limits throughout the study period. CONCLUSION: The study confirms that Genevac B, the new recombinant Hepatitis B vaccine has the acceptable international standards of safety and immunogenicity.

ESSENCE OF THE PROBLEM OF ENSURING FOOD SECURITY

OpenAIRE

Lalayan G. G.

2013-01-01

In this article we have revealed the essence of the problem of ensuring food security in detail. The components of economic safety at macroeconomic level are described, defining conditions of ensuring national food security are shown

Health Information Sources, Perceived Vaccination Benefits, and Maintenance of Childhood Vaccination Schedules.

Science.gov (United States)

Hwang, Juwon; Shah, Dhavan V

2018-06-05

Parental concerns over the safety or necessity of childhood vaccination have increased over the past decades. At the same time, there has been a proliferation of vaccine-related information available through a range of health information sources. This study investigates the associations between evaluations of health information sources, parental perceptions of childhood vaccination benefits, and the maintenance of vaccination schedules for their children. Specifically, this study aims to (a) incorporate social media into the battery of health information sources and (b) differentiate households with a childhood autism diagnosis and those without, given unsubstantiated but persistent concerns about vaccine safety and autism. Analyzing a sample of U.S. households, a total of 4,174 parents who have at least one child under the age of 18 were analyzed, including 138 of parents of households with a childhood autism diagnosis. Results show that the more the parents value interpersonal communication and magazines as sources of health information, the more they perceive vaccination benefits, and the more the value they put on television, the better they keep vaccination schedules up-to-date for their children. On the other hand, social media are negatively associated with their perceptions of vaccination benefits. Although parents of children diagnosed with autism are less likely to perceive vaccination benefits, no interaction effects with evaluations of health information sources are found on parental perceptions of vaccination benefits or maintenance of schedules.

Long-Term Safety and Immunogenicity of a Tetravalent Live-Attenuated Dengue Vaccine and Evaluation of a Booster Dose Administered to Healthy Thai Children.

Science.gov (United States)

Watanaveeradej, Veerachai; Simasathien, Sriluck; Mammen, Mammen P; Nisalak, Ananda; Tournay, Elodie; Kerdpanich, Phirangkul; Samakoses, Rudiwilai; Putnak, Robert J; Gibbons, Robert V; Yoon, In-Kyu; Jarman, Richard G; De La Barrera, Rafael; Moris, Philippe; Eckels, Kenneth H; Thomas, Stephen J; Innis, Bruce L

2016-06-01

We evaluated the safety and immunogenicity of two doses of a live-attenuated, tetravalent dengue virus vaccine (F17/Pre formulation) and a booster dose in a dengue endemic setting in two studies. Seven children (7- to 8-year-olds) were followed for 1 year after dose 2 and then given a booster dose (F17/Pre formulation), and followed for four more years (Child study). In the Infant study, 49 2-year-olds, vaccinated as infants, were followed for approximately 3.5 years after dose 2 and then given a booster dose (F17) and followed for one additional year. Two clinically notable events were observed, both in dengue vaccine recipients in the Infant study: 1 case of dengue approximately 2.7 years after dose 2 and 1 case of suspected dengue after booster vaccinations. The booster vaccinations had a favorable safety profile in terms of reactogenicity and adverse events reported during the 1-month follow-up periods. No vaccine-related serious adverse events were reported during the studies. Neutralizing antibodies against dengue viruses 1-4 waned during the 1-3 years before boosting, which elicited a short-lived booster response but did not provide a long-lived, multivalent antibody response in most subjects. Overall, this candidate vaccine did not elicit a durable humoral immune response. © The American Society of Tropical Medicine and Hygiene.

Safety and immunogenicity of inactivated poliovirus vaccine when given with measles-rubella combined vaccine and yellow fever vaccine and when given via different administration routes: a phase 4, randomised, non-inferiority trial in The Gambia.

Science.gov (United States)

Clarke, Ed; Saidu, Yauba; Adetifa, Jane U; Adigweme, Ikechukwu; Hydara, Mariama Badjie; Bashorun, Adedapo O; Moneke-Anyanwoke, Ngozi; Umesi, Ama; Roberts, Elishia; Cham, Pa Modou; Okoye, Michael E; Brown, Kevin E; Niedrig, Matthias; Chowdhury, Panchali Roy; Clemens, Ralf; Bandyopadhyay, Ananda S; Mueller, Jenny; Jeffries, David J; Kampmann, Beate

2016-08-01

The introduction of the inactivated poliovirus vaccine (IPV) represents a crucial step in the polio eradication endgame. This trial examined the safety and immunogenicity of IPV given alongside the measles-rubella and yellow fever vaccines at 9 months and when given as a full or fractional dose using needle and syringe or disposable-syringe jet injector. We did a phase 4, randomised, non-inferiority trial at three periurban government clinics in west Gambia. Infants aged 9-10 months who had already received oral poliovirus vaccine were randomly assigned to receive the IPV, measles-rubella, and yellow fever vaccines, singularly or in combination. Separately, IPV was given as a full intramuscular or fractional intradermal dose by needle and syringe or disposable-syringe jet injector at a second visit. The primary outcomes were seroprevalence rates for poliovirus 4-6 weeks post-vaccination and the rate of seroconversion between baseline and post-vaccination serum samples for measles, rubella, and yellow fever; and the post-vaccination antibody titres generated against each component of the vaccines. We did a per-protocol analysis with a non-inferiority margin of 10% for poliovirus seroprevalence and measles, rubella, and yellow fever seroconversion, and (1/3) log2 for log2-transformed antibody titres. This trial is registered with ClinicalTrials.gov, number NCT01847872. Between July 10, 2013, and May 8, 2014, we assessed 1662 infants for eligibility, of whom 1504 were enrolled into one of seven groups for vaccine interference and one of four groups for fractional dosing and alternative route of administration. The rubella and yellow fever antibody titres were reduced by co-administration but the seroconversion rates achieved non-inferiority in both cases (rubella, -4·5% [95% CI -9·5 to -0·1]; yellow fever, 1·2% [-2·9 to 5·5]). Measles and poliovirus responses were unaffected (measles, 6·8% [95% CI -1·4 to 14·9]; poliovirus serotype 1, 1·6% [-6·7 to 4·7

Technical Note: FIELD STUDY OF SAFETY AND ANTIBODY PRODUCTION FURTHER TO A COMBINED MYXOMATOSIS AND VIRAL HAEMORRHAGIC DISEASE (VHD) VACCINATION IN DWARF RABBITS BY INTRADERMAL ROUTE.

OpenAIRE

Lemière, S.; Alaphilippe, A.; Boucher, S.; Bertagnoli, S.

2003-01-01

A study of safety of combined vaccination against myxomatosis and VHD was performed using a duly reconstituted vaccine made of a live homologous myxomatosis component SG33 strain and of an inactivated VHD component in adjuvant AG88 strain. The vaccine was administered intradermally to a representative sample of pet rabbits. A local reaction at the vaccine administration area was frequently observed from 2 to 3 days after vaccination in young animals. These local reactions were less frequently...

Skepticism Regarding Vaccine and Gluten-Free Food Safety Among Patients with Celiac Disease and Non-celiac Gluten Sensitivity.

Science.gov (United States)

Rabinowitz, Loren G; Zylberberg, Haley M; Levinovitz, Alan; Stockwell, Melissa S; Green, Peter H R; Lebwohl, Benjamin

2018-05-01

There has been a marked increase in the adoption of the gluten-free (GF) diet. To query individuals with celiac disease (CD) and non-celiac gluten sensitivity (NCGS) on their beliefs toward the health effects of gluten, and safety of vaccines and GF food products. We distributed a Web-based survey to individuals with CD and NCGS on a CD center e-mail list. We used univariate and multivariate analysis to compare responses of respondents with CD and NCGS. The overall response rate was 27% (NCGS n = 217, CD n = 1291). Subjects with NCGS were more likely than those with CD to disagree with the statement that "vaccines are safe for people with celiac disease" (NCGS 41.3% vs. CD 26.4% (p diet improves energy and concentration (aOR 2.52; 95% CI 1.86-3.43). Subjects with NCGS were more likely than those with CD to have doubts about vaccine safety and believe in the value of non-GMO and organic foods. Our findings suggest that the lack of reliable information on gluten and its content in food and medications may reinforce beliefs that result in a detriment to public health.

Safety, immunogenicity, and lot-to-lot consistency of a quadrivalent inactivated influenza vaccine in children, adolescents, and adults: A randomized, controlled, phase III trial.

Science.gov (United States)

Cadorna-Carlos, Josefina B; Nolan, Terry; Borja-Tabora, Charissa Fay; Santos, Jaime; Montalban, M Cecilia; de Looze, Ferdinandus J; Eizenberg, Peter; Hall, Stephen; Dupuy, Martin; Hutagalung, Yanee; Pépin, Stéphanie; Saville, Melanie

2015-05-15

Inactivated quadrivalent influenza vaccine (IIV4) containing two influenza A strains and one strain from each B lineage (Yamagata and Victoria) may offer broader protection against seasonal influenza than inactivated trivalent influenza vaccine (IIV3), containing a single B strain. This study examined the safety, immunogenicity, and lot consistency of an IIV4 candidate. This phase III, randomized, controlled, multicenter trial in children/adolescents (9 through 17 years) and adults (18 through 60 years) was conducted in Australia and in the Philippines in 2012. The study was double-blind for IIV4 lots and open-label for IIV4 vs IIV3. Children/adolescents were randomized 2:2:2:1 and adults 10:10:10:1 to receive one of three lots of IIV4 or licensed IIV3. Safety data were collected for up to 6 months post-vaccination. Hemagglutination inhibition and seroneutralization antibody titers were assessed pre-vaccination and 21 days post-vaccination. 1648 adults and 329 children/adolescents received IIV4, and 56 adults and 55 children/adolescents received IIV3. Solicited reactions, unsolicited adverse events, and serious adverse events were similar for IIV3 and IIV4 recipients in both age groups. Injection-site pain, headache, malaise, and myalgia were the most frequently reported solicited reactions, most of which were mild and resolved within 3 days. No vaccine-related serious adverse events or deaths were reported. Post-vaccination antibody responses, seroconversion rates, and seroprotection rates for the 3 strains common to both vaccines were comparable for IIV3 and IIV4 in both age groups. Antibody responses to IIV4 were equivalent among vaccine lots and comparable between age groups for each of the 4 strains. IIV4 met all European Medicines Agency immunogenicity criteria for adults for all 4 strains. In both age groups, IIV4 was well tolerated and caused no safety concerns, induced robust antibody responses to all 4 influenza strains, and met all EMA immunogenicity

Apparent field safety of a raccoon poxvirus-vectored plague vaccine in free-ranging prairie dogs (Cynomys spp.), Colorado, USA.

Science.gov (United States)

Tripp, Daniel W; Rocke, Tonie E; Streich, Sean P; Abbott, Rachel C; Osorio, Jorge E; Miller, Michael W

2015-04-01

Prairie dogs (Cynomys spp.) suffer high rates of mortality from plague. An oral sylvatic plague vaccine using the raccoon poxvirus vector (designated RCN-F1/V307) has been developed for prairie dogs. This vaccine is incorporated into palatable bait along with rhodamine B as a biomarker. We conducted trials in August and September 2012 to demonstrate uptake and apparent safety of the RCN-F1/V307 vaccine in two prairie dog species under field conditions. Free-ranging prairie dogs and other associated small rodents readily consumed vaccine-laden baits during field trials with no apparent adverse effects; most sampled prairie dogs (90%) and associated small rodents (78%) had consumed baits. Visual counts of prairie dogs and their burrows revealed no evidence of prairie dog decline after vaccine exposure. No vaccine-related morbidity, mortality, or gross or microscopic lesions were observed. Poxviruses were not isolated from any animal sampled prior to bait distribution or on sites that received placebo baits. We isolated RCN-F1/V307 from 17 prairie dogs and two deer mice (Peromyscus maniculatus) captured on sites where vaccine-laden baits were distributed. Based on these findings, studies examining the utility and effectiveness of oral vaccination to prevent plague-induced mortality in prairie dogs and associated species are underway.

Apparent field safety of a raccoon poxvirus-vectored plague vaccine in free-ranging prairie dogs (Cynomys spp.), Colorado, USA

Science.gov (United States)

Tripp, Daniel W.; Rocke, Tonie E.; Streich, Sean P.; Abbott, Rachel C.; Osorio, Jorge E.; Miller, Michael W.

2015-01-01

Prairie dogs (Cynomys spp.) suffer high rates of mortality from plague. An oral sylvatic plague vaccine using the raccoon poxvirus vector (designated RCN-F1/V307) has been developed for prairie dogs. This vaccine is incorporated into palatable bait along with rhodamine B as a biomarker. We conducted trials in August and September 2012 to demonstrate uptake and apparent safety of the RCN-F1/V307 vaccine in two prairie dog species under field conditions. Free-ranging prairie dogs and other associated small rodents readily consumed vaccine-laden baits during field trials with no apparent adverse effects; most sampled prairie dogs (90%) and associated small rodents (78%) had consumed baits. Visual counts of prairie dogs and their burrows revealed no evidence of prairie dog decline after vaccine exposure. No vaccine-related morbidity, mortality, or gross or microscopic lesions were observed. Poxviruses were not isolated from any animal sampled prior to bait distribution or on sites that received placebo baits. We isolated RCN-F1/V307 from 17 prairie dogs and two deer mice (Peromyscus maniculatus) captured on sites where vaccine-laden baits were distributed. Based on these findings, studies examining the utility and effectiveness of oral vaccination to prevent plague-induced mortality in prairie dogs and associated species are underway.

Ensuring the quality of occupational safety risk assessment.

Science.gov (United States)

Pinto, Abel; Ribeiro, Rita A; Nunes, Isabel L

2013-03-01

In work environments, the main aim of occupational safety risk assessment (OSRA) is to improve the safety level of an installation or site by either preventing accidents and injuries or minimizing their consequences. To this end, it is of paramount importance to identify all sources of hazards and assess their potential to cause problems in the respective context. If the OSRA process is inadequate and/or not applied effectively, it results in an ineffective safety prevention program and inefficient use of resources. An appropriate OSRA is an essential component of the occupational safety risk management process in industries. In this article, we performed a survey to elicit the relative importance for identified OSRA tasks to enable an in-depth evaluation of the quality of risk assessments related to occupational safety aspects on industrial sites. The survey involved defining a questionnaire with the most important elements (tasks) for OSRA quality assessment, which was then presented to safety experts in the mining, electrical power production, transportation, and petrochemical industries. With this work, we expect to contribute to the main question of OSRA in industries: "What constitutes a good occupational safety risk assessment?" The results obtained from the questionnaire showed that experts agree with the proposed OSRA process decomposition in steps and tasks (taxonomy) and also with the importance of assigning weights to obtain knowledge about OSRA task relevance. The knowledge gained will enable us, in the near future, to build a framework to evaluate OSRA quality for industrial sites. © 2012 Society for Risk Analysis.

Safety and immunogenicity of a combined hepatitis B virus-Haemophilus influenzae type B vaccine comprising a synthetic antigen in healthy adults.

Science.gov (United States)

Aguilar-Betancourt, Arístides; González-Delgado, Carlos Alberto; Cinza-Estévez, Z; Martínez-Cabrera, Jesus; Véliz-Ríos, Gloria; Alemán-Zaldívar, Regis; Alonso-Martínez, M I; Lago-Baños, M; Puble-Alvarez, N; Delahanty-Fernandez, A; Juvier-Madrazo, A I; Ortega-León, D; Olivera-Ruano, L; Correa-Fernández, A; Abreu-Reyes, D; Soto-Mestre, E; Pérez-Pérez, M V; Figueroa-Baile, N; Pérez, L Hernandez; Rodríguez-Silva, A; Martínez-Díaz, E; Guillén-Nieto, G E; Muzio-González, Verena L

2008-01-01

The combined HB-Hib vaccine candidate Hebervac HB-Hib (CIGB, La Habana), comprising recombinant HBsAg and tetanus toxoid conjugate synthetic PRP antigens has shown to be highly immunogenic in animal models. A phase I open, controlled, randomized clinical trial was carried out to assess the safety and immunogenicity profile of this bivalent vaccine in 25 healthy adults who were positive for antibody to HBsAg (anti-HBs). The trial was performed according to Good Clinical Practices and Guidelines. Volunteers were randomly allocated to receive the combined vaccine or simultaneous administration of HB vaccine Heberbiovac-HB and Hib vaccine QuimiHib (CIGB, La Habana). All individuals were intramuscularly immunized with a unique dose of 10 microg HBsAg plus 10 microg conjugated synthetic PRP. Adverse events were actively recorded after vaccine administration. Total anti-HBs and IgG anti-PRP antibody titers were evaluated using commercial ELISA kits at baseline and 30 days post-vaccination. The combined vaccine candidate was safe and well tolerated. The most common adverse reactions were local pain, febricula, fever and local erythema. These reactions were all mild in intensity and resolved without medical treatment. Adverse events were mostly reported during the first 6-72 hours post-vaccination. There were no serious adverse events during the study. No severe or unexpected events were either recorded during the trial. The combined vaccine elicited an anti-HBs and anti-PRP booster response in 100% of subjects at day 30 of the immunization schedule. Anti-HBs and anti-PRP antibody levels had at least a two-fold increase compared to baseline sera. Even more, anti-HBs antibody titer showed a four-fold increase in 100% of volunteers in the study group. The results indicate that the combined HB-Hib vaccine produces increased antibody levels in healthy adults who have previously been exposed to these two antigens. To our knowledge, this is the first demonstration of safety and

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

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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...

Immunogenicity and safety of a fully liquid aluminum phosphate adjuvanted Haemophilus influenzae type b PRP-CRM197-conjugate vaccine in healthy Japanese children: A phase III, randomized, observer-blind, multicenter, parallel-group study.

Science.gov (United States)

Togashi, Takehiro; Mitsuya, Nodoka; Kogawara, Osamu; Sumino, Shuji; Takanami, Yohei; Sugizaki, Kayoko

2016-08-31

Broad use of monovalent Haemophilus influenzae type b (Hib) conjugate vaccines based on the capsular polysaccharide polyribosyl-ribitol phosphate (PRP), has significantly reduced invasive Hib disease burden in children worldwide, particularly in children aged vaccine has been widely used since the initiation of public funding programs followed by a routine vaccination designation in 2013. We compared the immunogenicity and safety of PRP conjugated to a non-toxic diphtheria toxin mutant (PRP-CRM197) vaccine with the PRP-T vaccine when administered subcutaneously to healthy Japanese children in a phase III study. Additionally, we evaluated the immunogenicity and safety profiles of a diphtheria-tetanus acellular pertussis (DTaP) combination vaccine when concomitantly administered with either PRP-CRM197 or PRP-T vaccines. The primary endpoint was the "long-term seroprotection rate", defined as the group proportion with anti-PRP antibody titers ⩾1.0μg/mL, after the primary series. Long-term seroprotection rates were 99.3% in the PRP-CRM197 group and 95.6% in the PRP-T group. The intergroup difference (PRP-CRM197 group - PRP-T group) was 3.7% (95% confidence interval: 0.099-7.336), demonstrating that PRP-CRM197 vaccine was non-inferior to PRP-T vaccine (pvaccination was higher in the PRP-CRM197 group than in PRP-T. Concomitant administration of PRP-CRM197 vaccine with DTaP vaccine showed no differences in terms of immunogenicity compared with concomitant vaccination with PRP-T vaccine and DTaP vaccine. Although CRM197 vaccine had higher local reactogenicity, overall, both Hib vaccines had acceptable safety and tolerability profiles. The immunogenicity of PRP-CRM197 vaccine administered subcutaneously as a three-dose primary series in children followed by a booster vaccination 1year after the primary series induced protective levels of Hib antibodies with no safety or tolerability concerns. Registered on ClinicalTrials.gov: NCT01379846. Copyright © 2016 The Authors

Multicenter study on the immunogenicity and safety of two recombinant vaccines against hepatitis B

Directory of Open Access Journals (Sweden)

Reinaldo Menezes Martins

2004-12-01

Full Text Available The immunogenicity and safety of a new recombinant hepatitis B vaccine from the Instituto Butantan (Butang® were evaluated in a multicenter, double-blind, prospective equivalence study in three centers in Brazil. Engerix B® was the standard vaccine. A total of 3937 subjects were recruited and 2754 (70% met all protocol criteria at the end of the study. All the subjects were considered healthy and denied having received hepatitis B vaccine before the study. Study subjects who adhered to the protocol were newborn infants (566, children 1 to 10 years old (484, adolescents from 11 to 19 years (740, adults from 20 to 30 years (568, and adults from 31 to 40 years (396. Vaccine was administered in three doses on the schedule 0, 1, and 6 months (newborn infants, adolescents, and adults or 0, 1, and 7 months (children. Vaccine dose was intramuscular 10 µg (infants, children, and adolescents or 20 µg (adults. Percent seroprotection (assumed when anti-HBs titers were > 10mIU/ml and geometric mean titer (mIU/ml were: newborn infants, 93.7% and 351.1 (Butang® and 97.5% and 1530.6 (Engerix B®; children, 100% and 3600.0 (Butang® and 97.7% and 2753.1 (Engerix B®; adolescents, 95.1% and 746.3 (Butang® and 96% and 1284.3 (Engerix B®; adults 20-30 years old, 91.8% and 453.5 (Butang® and 95.5% and 1369.0 (Engerix B®; and adults 31-40 years old, 79.8% and 122.7 (Butang® and 92.4% and 686.2 (Engerix B®. There were no severe adverse events following either vaccine. The study concluded that Butang® was equivalent to Engerix B® in children, and less immunogenic but acceptable for use in newborn infants, adolescents, and young adults.

Immunogenicity and Safety of a Booster Injection of DTap-IPV//Hib (Pentaxim) Administered Concomitantly With Tetravalent Dengue Vaccine in Healthy Toddlers 15-18 Months of Age in Mexico: A Randomized Trial.

Science.gov (United States)

Melo, Flor Irene Rodriguez; Morales, José Juan Renteria; De Los Santos, Abiel Homero Mascareñas; Rivas, Enrique; Vigne, Claire; Noriega, Fernando

2017-06-01

The live, attenuated, tetravalent dengue vaccine (CYD-TDV) is licensed in a number of dengue endemic countries for individuals ≥9 years of age. Before the integration of any vaccine into childhood vaccination schedules, a lack of immune interference and acceptable safety when coadministered with other recommended vaccines should be demonstrated. This randomized, multi-center phase III trial was conducted in Mexico. Healthy toddlers (n = 732) received a booster dose of a licensed pentavalent combination vaccine [diphtheria, tetanus, acellular pertussis, inactivated polio vaccine and Haemophilus influenzae type b (DTaP-IPV//Hib)] either concomitantly or sequentially, with the second dose of CYD-TDV administered as a 3-dose schedule. Antibody titers against diphtheria toxoid, tetanus toxoid and pertussis antigens were measured by enzyme-linked immunosorbent assay. Antibodies against poliovirus and dengue serotypes were measured using a plaque reduction neutralization test. Noninferiority was demonstrated for each of the DTaP-IPV//Hib antigens if the lower limit of the 2-sided 95% confidence interval of the difference in seroconversion rates between the 2 groups (CYD-TDV and placebo) was ≥10%. Safety of both vaccines was assessed. Noninferiority in immune response was demonstrated for all DTaP-IPV//Hib antigens. After 3 doses of CYD-TDV, no difference was observed in the immune response for CYD-TDV between groups. There were no safety concerns during the study. Coadministration of the DTaP-IPV//Hib booster vaccine with CYD-TDV has no observed impact on the immunogenicity or safety profile of the DTaP-IPV//Hib booster vaccine. No difference was observed on the CYD-TDV profile when administered concomitantly or sequentially with the DTaP-IPV//Hib booster vaccine.

Methods for ensuring compliance with regulatory requirements: regulators and operators

International Nuclear Information System (INIS)

Fleischmann, A.W.

1989-01-01

Some of the methods of ensuring compliance with regulatory requirements contained in various radiation protection documents such as Regulations, ICRP Recommendations etc. are considered. These include radiation safety officers and radiation safety committees, personnel monitoring services, dissemination of information, inspection services and legislative power of enforcement. Difficulties in ensuring compliance include outmoded legislation, financial and personnel constraints

Safety and immunogenicity of inactivated poliovirus vaccine made from Sabin strains: a phase II, randomized, positive-controlled trial.

Science.gov (United States)

Liao, Guoyang; Li, Rongcheng; Li, Changgui; Sun, Mingbo; Li, Yanping; Chu, Jiayou; Jiang, Shude; Li, Qihan

2012-01-15

The production of Sabin inactivated poliovirus vaccine (IPV) can reduce biosafety requirements in the posteradication/post-oral poliovirus vaccine (OPV) era. We conducted a phase II, randomized, positive-controlled trial to assess the safety and immunogenicity of Sabin IPV. The test groups (A, B, and C) received 3 doses of high, middle, and low D antigen (D Ag) of Sabin IPV at ages 2, 3, and 4 months, respectively. Infants in 2 control groups, group D and group E, received 3 doses of trivalent OPV and conventional IPV (cIPV), respectively, on the same schedule as that of groups A, B, and C. Serum samples were collected before and 30 days after the administration of the third dose. In total, 500 infants were randomly assigned to 5 groups, and 449 infants completed the vaccine series. No serious adverse events were associated with vaccinations. After 3 doses, the seroconversion rates in groups A, B, C, D, and E were 100%, 97.8%, 96.6%, 100%, and 90.1%, respectively, for type 1 poliovirus; 97.7%, 95.7%, 78.7%, 100%, and 90.1%, respectively, for type 2; and 98.8%, 98.9%, 93.3%, 100%, and 97.8%, respectively, for type 3. Sabin IPV has good safety characteristics. The seroconversion rates for type 1 poliovirus (most appropriate concentration, 15 D Ag units [DU]), type 2 (32 DU), and type 3 (45 DU) Sabin IPV were similar to those of the OPV and cIPV control groups. NCT01056705.

Vero cell technology for rapid development of inactivated whole virus vaccines for emerging viral diseases.

Science.gov (United States)

Barrett, P Noel; Terpening, Sara J; Snow, Doris; Cobb, Ronald R; Kistner, Otfried

2017-09-01

Rapid development and production of vaccines against emerging diseases requires well established, validated, robust technologies to allow industrial scale production and accelerated licensure of products. Areas covered: A versatile Vero cell platform has been developed and utilized to deliver a wide range of candidate and licensed vaccines against emerging viral diseases. This platform builds on the 35 years' experience and safety record with inactivated whole virus vaccines such as polio vaccine. The current platform has been optimized to include a novel double inactivation procedure in order to ensure a highly robust inactivation procedure for novel emerging viruses. The utility of this platform in rapidly developing inactivated whole virus vaccines against pandemic (-like) influenza viruses and other emerging viruses such as West Nile, Chikungunya, Ross River and SARS is reviewed. The potential of the platform for development of vaccines against other emerging viruses such as Zika virus is described. Expert commentary: Use of this platform can substantially accelerate process development and facilitate licensure because of the substantial existing data set available for the cell matrix. However, programs to provide vaccines against emerging diseases must allow alternative clinical development paths to licensure, without the requirement to carry out large scale field efficacy studies.

[Evaluation of safety of haemophilus influenza type b(Hib) conjugate vaccine in postmarketing based on the immunization information management system].

Science.gov (United States)

Wang, Zhiguo; Ma, Fubao; Zhang, Jinlin; Yu, Jing; Kang, Guodong; Gao, Jun

2015-06-01

To analyze the occurrence feature of adverse events following immunization (AEFI) of Hib conjugate vaccine (HibCV) and to evaluate the safety of HibCV in postmarketing. 2008-2013 HibCV AEFI data were collected through national AEFI information management system, which were downloaded in March 18, 2014.The demographic information and inoculation quantity of HibCV were from Immunization information management system in Jiangsu province. The incidence rate and 95% CI value of AEFI, common vaccine reaction and rare vaccine reaction following immunization of HibCV were calculated. The differences in the incidence rate of common vaccine reaction and rare vaccine reaction among sex, months of age, and number of injections were compared by means of (χ² tests. A total of 6.16 million doses of vaccine were administered in Jiangsu province during 2008-2013, and 4 718 vaccinees reported having adverse event, for a rate of 76.60/100 000 (95% CI: 74.42/100 000-78.79/100 000). The incidence rate of common vaccine reaction and rare vaccine reaction was 71.10/100 000 (95% CI: 68.99/100 000-73.20/100 000) and 5.16/100 000 (95% CI: 4.60/100 000-5.73/100 000), respectively. The main symptoms of common vaccine reactions were fever, swelling, indurations and gastrointestinal reactions. The incidence rates of them were 40.54/100 000, 35.09/100 000, 12.94/100 000 and 0.36/100 000 in turn. The main symptoms of rare vaccine reactions were anaphylactic rashes and angioedema, the incidence rates of which were 4.77/100 000 and 0.15/100 000 respectively. 91.39% (4 002/4 379) of common vaccine reactions and 88.36% (281/318) of rare vaccine reactions happened within 1 d after vaccination. Anaphylactic shock (3 cases) and laryngeal edema (1 case) all happened within 1 d after vaccination. The incidence rate of common vaccine reactions among boys (79.72/100 000, 2 641/3 313 071) was higher than that of girls (61.07/100 000, 1 738/2 846 001) (χ² = 74.92, P < 0.001). The incidence rate of common

Ensuring ecology safety, furthering the development of nuclear energy

International Nuclear Information System (INIS)

Shang Zhaorong; Chen Xiaoqiu; Tang Senming

2008-01-01

Ecology safety is as important as political safety, national defense safety, economy safety, food safety, etc. The nuclear power development is an important step for the national energy structure optimization, ecology caring, and implementing sustainable development. The aquatic ecology is important on disposal of low-level liquid waste and cooling water from NPPs and nuclear fuel cycle facilities, and people pay more attention to ecology impact and human threat from the nuclear energy. The author describes relevant ecology problems correlated with nuclear energy such as impact of thermal discharge, ecology sensitive zone, ecology restoration, etc. in order to emphasis that development of nuclear energy should guarantee ecology safety for the sustainable development of nuclear energy. (authors)

Vaccination of School Children With Live Mumps Virus Vaccine

Science.gov (United States)

Furesz, J.; Nagler, F. P.

1970-01-01

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

Better vaccines for healthier life. Part II. Conference report of the DCVMN International 14th Annual General Meeting Hanoi, Vietnam.

Science.gov (United States)

Pagliusi, Sonia; Tippoo, Patrick; Sivaramakrishnan, Venkatraman; Nguyen, Thuvan

2014-11-12

New vaccines are required to meet the public health challenges of the next generation and many unmet global health needs can be addressed by developing countries vaccine manufacturers such as lower-cost vaccines based on single-dose, thermostable formulations, efficacious in children with compromised gastrointestinal tracts. GMP compliance is also a challenge, as sometimes innovation and clinical development focus is not accompanied by command of scale-up and quality assurance for large volume manufacturing and supply. Identifying and addressing such challenges, beyond cost and cold-chain space, including safety considerations and health worker behavior, regulatory alliances and harmonization to foster access to vaccines, will help countries to ensure sustainable immunization. There needs to be continuous and close management of the global vaccine supply both at national and international levels, requiring careful risk management, coordination and cooperation with manufacturers. Successful partnership models based on sharing a common goal, mutual respect and good communication were discussed among stakeholders. Copyright © 2014. Published by Elsevier Ltd.. All rights reserved.

ZIKA-001: Safety and Immunogenicity of an Engineered DNA Vaccine Against ZIKA virus infection

Science.gov (United States)

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

2017-01-01

Abstract Background While Zika virus (ZIKV) infection is typically self-limited, congenital birth defects and Guillain-Barré syndrome are well-described. There are no therapies or vaccines against ZIKV infection. Methods ZIKA-001 is a phase I, open label, clinical trial designed to evaluate the safety, side effect profile, and immunogenicity of a synthetic, DNA vaccine (GLS-5700) targeting the pre-membrane+envelope proteins (prME) of the virus. Two groups of 20 participants received GLS-5700 at one of two dose levels: 1 mg or 2 mg DNA/dose at 0, 4, and 12 weeks. Vaccine was administered as 0.1 or 0.2 ml (1 or 2 mg) intradermal (ID) injection followed by electroporation (EP) with the CELLECTRA®-3P device Results The median age of the 40 participants was 38 (IQR 30–54) years; 60% were female 30% Latino and 78% white. No SAEs have been reported to date. Local minor AEs were injection site pain, redness, swelling and itching that occurred in half of the participants. Systemic adverse events were rare and included headache, myalgias, upper respiratory infections, fatigue/malaise and nausea. Four weeks after the first dose 25% vs. 60% of the participants in the 1 mg and 2 mg dose seroconverted. By week 6, 2 weeks after the second dose, the response was 65 and 84% respectively and 2 weeks after the third dose all participants in both dosing groups developed antibodies. At the end of the vaccination period over 60% of vaccinated person neutralized Zika virus in a vero cell assay and greater than 80% on neuronal cell targets. The protective efficacy of the antibodies generated by the vaccine was evaluated in the lethal IFNAR−/− mouse model. After the intraperitoneal administration of 0.1 ml of either baseline, week 14 serum or PBS the animals were challenged with 106 PFUs of ZIKV PR209 isolate. Whereas animals administered PBS (control) or baseline serum succumbed after a median of 5 days, those pretreated with week 14 serum from study participants survived

Vaccines Stop Illness | NIH MedlinePlus the Magazine

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... please turn JavaScript on. Feature: Diseases and Vaccinations Vaccines Stop Illness Past Issues / Spring 2015 Table of ... like polio and meningitis will affect their children. Vaccine Safety In light of recent questions about vaccine ...

Vaccines for Older Adults.

Science.gov (United States)

Worz, Chad; Martin, Caren McHenry; Travis, Catherine

2017-09-01

Several vaccine-preventable diseases-influenza, pneumonia, herpes zoster, and pertussis-threaten the health of older adults in the United States. Both the costs associated with treating these diseases and the potential to increase morbidity and mortality are high for this patient population. Pharmacists and other health care professionals play a significant role in ensuring the elderly patient receives the recommended vaccines at the recommended intervals.

Legal basis for risk analysis methodology while ensuring food safety in the Eurasian Economic union and the Republic of Belarus

Directory of Open Access Journals (Sweden)

E.V. Fedorenko

2015-09-01

Full Text Available Health risk analysis methodology is an internationally recognized tool for ensuring food safety. Three main elements of risk analysis are risk assessment, risk management and risk communication to inform the interested parties on the risk, are legislated and implemented in the Eurasian Economic Union and the Republic of Belarus. There is a corresponding organizational and functional framework for the application of risk analysis methodology as in the justification of production safety indicators and the implementation of public health surveillance. Common methodological approaches and criteria for evaluating public health risk are determined, which are used in the development and application of food safety requirements. Risk assessment can be used in justifying the indicators of safety (contaminants, food additives, and evaluating the effectiveness of programs on enrichment of food with micronutrients.

The Long-Term Safety, Public Health Impact, and Cost-Effectiveness of Routine Vaccination with a Recombinant, Live-Attenuated Dengue Vaccine (Dengvaxia): A Model Comparison Study.

Science.gov (United States)

Flasche, Stefan; Jit, Mark; Rodríguez-Barraquer, Isabel; Coudeville, Laurent; Recker, Mario; Koelle, Katia; Milne, George; Hladish, Thomas J; Perkins, T Alex; Cummings, Derek A T; Dorigatti, Ilaria; Laydon, Daniel J; España, Guido; Kelso, Joel; Longini, Ira; Lourenco, Jose; Pearson, Carl A B; Reiner, Robert C; Mier-Y-Terán-Romero, Luis; Vannice, Kirsten; Ferguson, Neil

2016-11-01

Large Phase III trials across Asia and Latin America have recently demonstrated the efficacy of a recombinant, live-attenuated dengue vaccine (Dengvaxia) over the first 25 mo following vaccination. Subsequent data collected in the longer-term follow-up phase, however, have raised concerns about a potential increase in hospitalization risk of subsequent dengue infections, in particular among young, dengue-naïve vaccinees. We here report predictions from eight independent modelling groups on the long-term safety, public health impact, and cost-effectiveness of routine vaccination with Dengvaxia in a range of transmission settings, as characterised by seroprevalence levels among 9-y-olds (SP9). These predictions were conducted for the World Health Organization to inform their recommendations on optimal use of this vaccine. The models adopted, with small variations, a parsimonious vaccine mode of action that was able to reproduce quantitative features of the observed trial data. The adopted mode of action assumed that vaccination, similarly to natural infection, induces transient, heterologous protection and, further, establishes a long-lasting immunogenic memory, which determines disease severity of subsequent infections. The default vaccination policy considered was routine vaccination of 9-y-old children in a three-dose schedule at 80% coverage. The outcomes examined were the impact of vaccination on infections, symptomatic dengue, hospitalised dengue, deaths, and cost-effectiveness over a 30-y postvaccination period. Case definitions were chosen in accordance with the Phase III trials. All models predicted that in settings with moderate to high dengue endemicity (SP9 ≥ 50%), the default vaccination policy would reduce the burden of dengue disease for the population by 6%-25% (all simulations: -3%-34%) and in high-transmission settings (SP9 ≥ 70%) by 13%-25% (all simulations: 10%- 34%). These endemicity levels are representative of the participating sites in

The Long-Term Safety, Public Health Impact, and Cost-Effectiveness of Routine Vaccination with a Recombinant, Live-Attenuated Dengue Vaccine (Dengvaxia: A Model Comparison Study.

Directory of Open Access Journals (Sweden)

Stefan Flasche

2016-11-01

Full Text Available Large Phase III trials across Asia and Latin America have recently demonstrated the efficacy of a recombinant, live-attenuated dengue vaccine (Dengvaxia over the first 25 mo following vaccination. Subsequent data collected in the longer-term follow-up phase, however, have raised concerns about a potential increase in hospitalization risk of subsequent dengue infections, in particular among young, dengue-naïve vaccinees. We here report predictions from eight independent modelling groups on the long-term safety, public health impact, and cost-effectiveness of routine vaccination with Dengvaxia in a range of transmission settings, as characterised by seroprevalence levels among 9-y-olds (SP9. These predictions were conducted for the World Health Organization to inform their recommendations on optimal use of this vaccine.The models adopted, with small variations, a parsimonious vaccine mode of action that was able to reproduce quantitative features of the observed trial data. The adopted mode of action assumed that vaccination, similarly to natural infection, induces transient, heterologous protection and, further, establishes a long-lasting immunogenic memory, which determines disease severity of subsequent infections. The default vaccination policy considered was routine vaccination of 9-y-old children in a three-dose schedule at 80% coverage. The outcomes examined were the impact of vaccination on infections, symptomatic dengue, hospitalised dengue, deaths, and cost-effectiveness over a 30-y postvaccination period. Case definitions were chosen in accordance with the Phase III trials. All models predicted that in settings with moderate to high dengue endemicity (SP9 ≥ 50%, the default vaccination policy would reduce the burden of dengue disease for the population by 6%-25% (all simulations: -3%-34% and in high-transmission settings (SP9 ≥ 70% by 13%-25% (all simulations: 10%- 34%. These endemicity levels are representative of the

Technology transfer of oil-in-water emulsion adjuvant manufacturing for pandemic influenza vaccine production in Romania: Preclinical evaluation of split virion inactivated H5N1 vaccine with adjuvant.

Science.gov (United States)

Stavaru, Crina; Onu, Adrian; Lupulescu, Emilia; Tucureanu, Catalin; Rasid, Orhan; Vlase, Ene; Coman, Cristin; Caras, Iuliana; Ghiorghisor, Alina; Berbecila, Laurentiu; Tofan, Vlad; Bowen, Richard A; Marlenee, Nicole; Hartwig, Airn; Bielefeldt-Ohmann, Helle; Baldwin, Susan L; Van Hoeven, Neal; Vedvick, Thomas S; Huynh, Chuong; O'Hara, Michael K; Noah, Diana L; Fox, Christopher B

2016-04-02

Millions of seasonal and pandemic influenza vaccine doses containing oil-in-water emulsion adjuvant have been administered in order to enhance and broaden immune responses and to facilitate antigen sparing. Despite the enactment of a Global Action Plan for Influenza Vaccines and a multi-fold increase in production capabilities over the past 10 years, worldwide capacity for pandemic influenza vaccine production is still limited. In developing countries, where routine influenza vaccination is not fully established, additional measures are needed to ensure adequate supply of pandemic influenza vaccines without dependence on the shipment of aid from other, potentially impacted first-world countries. Adaptation of influenza vaccine and adjuvant technologies by developing country influenza vaccine manufacturers may enable antigen sparing and corresponding increases in global influenza vaccine coverage capacity. Following on previously described work involving the technology transfer of oil-in-water emulsion adjuvant manufacturing to a Romanian vaccine manufacturing institute, we herein describe the preclinical evaluation of inactivated split virion H5N1 influenza vaccine with emulsion adjuvant, including immunogenicity, protection from virus challenge, antigen sparing capacity, and safety. In parallel with the evaluation of the bioactivity of the tech-transferred adjuvant, we also describe the impact of concurrent antigen manufacturing optimization activities. Depending on the vaccine antigen source and manufacturing process, inclusion of adjuvant was shown to enhance and broaden functional antibody titers in mouse and rabbit models, promote protection from homologous virus challenge in ferrets, and facilitate antigen sparing. Besides scientific findings, the operational lessons learned are delineated in order to facilitate adaptation of adjuvant technologies by other developing country institutes to enhance global pandemic influenza preparedness.

Safety and immunogenicity of an investigational meningococcal ACWY conjugate vaccine (MenACWY-CRM) in healthy Indian subjects aged 2 to 75 years.

Science.gov (United States)

Lalwani, Sanjay; Agarkhedkar, Sharad; Gogtay, Nithya; Palkar, Sonali; Agarkhedkar, Shalaka; Thatte, Urmila; Vakil, Hoshang; Jonnalagedda, Rekha; Pedotti, Paola; Hoyle, Margaret; Bhusal, Chiranjiwi; Arora, Ashwani

2015-09-01

This phase 3, multi-center, open-label study evaluated the immunogenicity and safety of a quadrivalent meningococcal conjugate vaccine (MenACWY-CRM, Menveo(®); Novartis Vaccines and Diagnostics S.r.l., Siena, Italy) in healthy Indian subjects aged 2-75 years, to provide data for licensure in India. A total of 180 subjects were enrolled (60 subjects 2-10 years, 60 subjects 11-18 years, and 60 subjects 19-75 years) and received one dose of MenACWY-CRM. Serum bactericidal activity with human complement (hSBA) was measured before and 1 month after vaccination. Adverse events were collected throughout the 29-day study period. Percentages of subjects with post-vaccination hSBA ≥8 were 72%, 95%, 94%, and 90% for serogroups A, C, W, and Y, respectively. Geometric mean titers rose 7-fold to 42-fold against the four serogroups. Similar immune responses were observed for the age subgroups 2-10 years, 11-18 years, and 19-75 years. Seroresponse rates at 1 month following vaccination were 72%, 88%, 55%, and 71% for serogroups A, C, W, and Y, respectively. The vaccine was well tolerated with no safety concerns. A single dose of MenACWY-CRM induced a robust immune response against all four meningococcal serogroups and was well tolerated in an Indian population 2-75 years of age. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

9 CFR 113.328 - Fowl Laryngotracheitis Vaccine.

Science.gov (United States)

2010-01-01

... REQUIREMENTS Live Virus Vaccines § 113.328 Fowl Laryngotracheitis Vaccine. Fowl Laryngotracheitis Vaccine shall be prepared from virus-bearing cell culture fluids or embryonated chicken eggs. Only Master Seed... each serial of modified live virus vaccine shall be tested for safety as provided in this paragraph...

Ways of ensuring short/long term safety

International Nuclear Information System (INIS)

Boeck, B. de; Baltes, B.; Besnus, F.

2006-01-01

Various strategies have been adopted among countries to manage radioactive waste. The present publication gives to this respect a broad overview of the policies and strategies adopted by Germany, Belgium and France. It appears that these may show remarkable differences, but motivated mainly by political and societal considerations. With regard to safety, practices for waste management are consistent and reflect the broad international consensus that has been progressively established. As an illustration, safety practices and possible specificities for the storage and geological disposal of spent fuel and high level radioactive waste from reprocessing are shortly described. (authors)

A Multicenter, Open-Label, Controlled Phase II Study to Evaluate Safety and Immunogenicity of MVA Smallpox Vaccine (IMVAMUNE in 18-40 Year Old Subjects with Diagnosed Atopic Dermatitis.

Directory of Open Access Journals (Sweden)

Richard N Greenberg

Full Text Available Replicating smallpox vaccines can cause severe complications in individuals with atopic dermatitis (AD. Prior studies evaluating Modified Vaccinia Ankara virus (MVA, a non-replicating vaccine in humans, showed a favorable safety and immunogenicity profile in healthy volunteers.This Phase II study compared the safety and immunogenicity of MVA enrolling groups of 350 subjects with AD (SCORAD ≤ 30 and 282 healthy subjects.Subjects were vaccinated twice with MVA, each dose given subcutaneously 4 weeks apart. Adverse events, cardiac parameters, and the development of vaccinia virus humoral immune responses were monitored.The overall safety of the vaccine was similar in both groups. Adverse events affecting skin were experienced significantly more often in subjects with AD, but the majority of these events were mild to moderate in intensity. Seroconversion rates and geometric mean titers for total and neutralizing vaccinia-specific antibodies in the AD group were non-inferior compared to the healthy subjects.The size of the study population limited the detection of serious adverse events occurring at a frequency less than 1%.MVA has a favorable safety profile and the ability to elicit vaccinia-specific immune responses in subjects with AD.ClinicalTrials.gov NCT00316602.

Vaxjo: A Web-Based Vaccine Adjuvant Database and Its Application for Analysis of Vaccine Adjuvants and Their Uses in Vaccine Development

Directory of Open Access Journals (Sweden)

Samantha Sayers

2012-01-01

Full Text Available Vaccine adjuvants are compounds that enhance host immune responses to co-administered antigens in vaccines. Vaxjo is a web-based central database and analysis system that curates, stores, and analyzes vaccine adjuvants and their usages in vaccine development. Basic information of a vaccine adjuvant stored in Vaxjo includes adjuvant name, components, structure, appearance, storage, preparation, function, safety, and vaccines that use this adjuvant. Reliable references are curated and cited. Bioinformatics scripts are developed and used to link vaccine adjuvants to different adjuvanted vaccines stored in the general VIOLIN vaccine database. Presently, 103 vaccine adjuvants have been curated in Vaxjo. Among these adjuvants, 98 have been used in 384 vaccines stored in VIOLIN against over 81 pathogens, cancers, or allergies. All these vaccine adjuvants are categorized and analyzed based on adjuvant types, pathogens used, and vaccine types. As a use case study of vaccine adjuvants in infectious disease vaccines, the adjuvants used in Brucella vaccines are specifically analyzed. A user-friendly web query and visualization interface is developed for interactive vaccine adjuvant search. To support data exchange, the information of vaccine adjuvants is stored in the Vaccine Ontology (VO in the Web Ontology Language (OWL format.

Vaxjo: a web-based vaccine adjuvant database and its application for analysis of vaccine adjuvants and their uses in vaccine development.

Science.gov (United States)

Sayers, Samantha; Ulysse, Guerlain; Xiang, Zuoshuang; He, Yongqun

2012-01-01

Vaccine adjuvants are compounds that enhance host immune responses to co-administered antigens in vaccines. Vaxjo is a web-based central database and analysis system that curates, stores, and analyzes vaccine adjuvants and their usages in vaccine development. Basic information of a vaccine adjuvant stored in Vaxjo includes adjuvant name, components, structure, appearance, storage, preparation, function, safety, and vaccines that use this adjuvant. Reliable references are curated and cited. Bioinformatics scripts are developed and used to link vaccine adjuvants to different adjuvanted vaccines stored in the general VIOLIN vaccine database. Presently, 103 vaccine adjuvants have been curated in Vaxjo. Among these adjuvants, 98 have been used in 384 vaccines stored in VIOLIN against over 81 pathogens, cancers, or allergies. All these vaccine adjuvants are categorized and analyzed based on adjuvant types, pathogens used, and vaccine types. As a use case study of vaccine adjuvants in infectious disease vaccines, the adjuvants used in Brucella vaccines are specifically analyzed. A user-friendly web query and visualization interface is developed for interactive vaccine adjuvant search. To support data exchange, the information of vaccine adjuvants is stored in the Vaccine Ontology (VO) in the Web Ontology Language (OWL) format.

Randomized trial on the safety, tolerability, and immunogenicity of MenACWY-CRM, an investigational quadrivalent meningococcal glycoconjugate vaccine, administered concomitantly with a combined tetanus, reduced diphtheria, and acellular pertussis vaccine in adolescents and young adults.

Science.gov (United States)

Gasparini, Roberto; Conversano, Michele; Bona, Gianni; Gabutti, Giovanni; Anemona, Alessandra; Dull, Peter M; Ceddia, Francesca

2010-04-01

This study evaluated the safety, tolerability, and immunogenicity of an investigational quadrivalent meningococcal conjugate vaccine, MenACWY-CRM, when administered concomitantly with a combined tetanus, reduced diphtheria, and acellular pertussis (Tdap) vaccine, in subjects aged 11 to 25 years. Subjects received either MenACWY-CRM and Tdap, MenACWY-CRM and saline placebo, or Tdap and saline placebo. No significant increase in reactogenicity and no clinically significant vaccine-related adverse events (AEs) occurred when MenACWY-CRM and Tdap were administered concomitantly. Similar immunogenic responses to diphtheria, tetanus, and meningococcal (serogroups A, C, W-135, and Y) antigens were observed, regardless of concomitant vaccine administration. Antipertussis antibody responses were comparable between vaccine groups for filamentous hemagglutinin and were slightly lower, although not clinically significantly, for pertussis toxoid and pertactin when the two vaccines were administered concomitantly. These results indicate that the investigational MenACWY-CRM vaccine is well tolerated and immunogenic and that it can be coadministered with Tdap to adolescents and young adults.

Vaccines for Prevention of Cervical Cancer

International Nuclear Information System (INIS)

Mahomed, M.F.

2017-01-01

The characteristics of two prophylactic Human Papilloma Virus HPV vaccines and ethical issues related to HPV vaccination are reviewed in this paper. These vaccines have the potential of substantially reducing HPV-related morbidity and mortality, and in particular cervical cancer. The vaccines cannot treat women with current HPV infection or HPV related disease. They should be administered before the commencement of sexual activity. The ideal age group is adolescent girls between the ages 9-13. Both vaccines are highly efficacious and immunogenic and induce high levels of serum antibodies after three doses for all vaccine-related HPV types. School-based vaccination is considered as a costeffective method for its delivery. Adequate education of both clinicians and patients is an essential to ensure effective implementation when considering a national vaccination program. (author)

Vigilância de eventos adversos pós-vacinação e segurança de programas de imunização Vigilancia de eventos adversos post vacunación y seguridad de programas de inmunización Surveillance of adverse effects following vaccination and safety of immunization programs

Directory of Open Access Journals (Sweden)

Eliseu Alves Waldman

2011-02-01

confiabilidad de los programas de vacunación.The aim of the review was to analyze conceptual and operational aspects of systems for surveillance of adverse events following immunization. Articles available in electronic format were included, published between 1985 and 2009, selected from the PubMed/Medline databases using the key words "adverse events following vaccine surveillance", "post-marketing surveillance", "safety vaccine" and "Phase IV clinical trials". Articles focusing on specific adverse events were excluded. The major aspects underlying the Public Health importance of adverse events following vaccination, the instruments aimed at ensuring vaccine safety, and the purpose, attributes, types, data interpretation issues, limitations, and further challenges in adverse events following immunization were describe, as well as strategies to improve sensitivity. The review was concluded by discussing the challenges to be faced in coming years with respect to ensuring the safety and reliability of vaccination programs.

Live virus vaccines based on a yellow fever vaccine backbone: standardized template with key considerations for a risk/benefit assessment.

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Monath, Thomas P; Seligman, Stephen J; Robertson, James S; Guy, Bruno; Hayes, Edward B; Condit, Richard C; Excler, Jean Louis; Mac, Lisa Marie; Carbery, Baevin; Chen, Robert T

2015-01-01

The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety of live, recombinant viral vaccines incorporating genes from heterologous viruses inserted into the backbone of another virus (so-called "chimeric virus vaccines"). Many viral vector vaccines are in advanced clinical trials. The first such vaccine to be approved for marketing (to date in Australia, Thailand, Malaysia, and the Philippines) is a vaccine against the flavivirus, Japanese encephalitis (JE), which employs a licensed vaccine (yellow fever 17D) as a vector. In this vaccine, two envelope proteins (prM-E) of YF 17D virus were exchanged for the corresponding genes of JE virus, with additional attenuating mutations incorporated into the JE gene inserts. Similar vaccines have been constructed by inserting prM-E genes of dengue and West Nile into YF 17D virus and are in late stage clinical studies. The dengue vaccine is, however, more complex in that it requires a mixture of four live vectors each expressing one of the four dengue serotypes. This vaccine has been evaluated in multiple clinical trials. No significant safety concerns have been found. The Phase 3 trials met their endpoints in terms of overall reduction of confirmed dengue fever, and, most importantly a significant reduction in severe dengue and hospitalization due to dengue. However, based on results that have been published so far, efficacy in preventing serotype 2 infection is less than that for the other three serotypes. In the development of these chimeric vaccines, an important series of comparative studies of safety and efficacy were made using the parental YF 17D vaccine virus as a benchmark. In this paper, we use a standardized template describing the key characteristics of the novel flavivirus vaccine vectors, in comparison to the parental YF 17D vaccine. The template facilitates scientific discourse among key stakeholders by increasing the transparency and comparability of

The Australian model of immunization advice and vaccine funding.

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Nolan, Terry M

2010-04-19

The Australian Government has implemented new arrangements for public funding of vaccines over the past 5 years. By utilising the standard Pharmaceutical Benefits Advisory Committee (PBAC) application process, whether for funding under the National Immunisation Program Schedule (NIP) or under the Pharmaceutical Benefits Scheme (PBS), a predictable and transparent process for vaccine funding recommendations has been established. This process uses the high-level technical resources available through the Australian Technical Advisory Group on Immunisation (ATAGI) to ensure that both vaccine manufacturers and the PBAC are optimally informed about all relevant aspects of population benefits and delivery of vaccines. ATAGI has a long-standing and mutually beneficial dialogue with State and Territory Governments, providers, and vaccine manufacturers to ensure that pipeline awareness, supply issues, and all relevant scientific and clinical details are well understood. Copyright © 2010 Elsevier Ltd. All rights reserved.

Barriers and facilitators to influenza vaccination and vaccine coverage in a cohort of health care personnel.

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Naleway, Allison L; Henkle, Emily M; Ball, Sarah; Bozeman, Sam; Gaglani, Manjusha J; Kennedy, Erin D; Thompson, Mark G

2014-04-01

Annual influenza vaccination is recommended for health care personnel (HCP). We describe influenza vaccination coverage among HCP during the 2010-2011 season and present reported facilitators of and barriers to vaccination. We enrolled HCP 18 to 65 years of age, working full time, with direct patient contact. Participants completed an Internet-based survey at enrollment and the end of influenza season. In addition to self-reported data, we collected information about the 2010-2011 influenza vaccine from electronic employee health and medical records. Vaccination coverage was 77% (1,307/1,701). Factors associated with higher vaccination coverage include older age, being married or partnered, working as a physician or dentist, prior history of influenza vaccination, more years in patient care, and higher job satisfaction. Personal protection was reported as the most important reason for vaccination followed closely by convenience, protection of patients, and protection of family and friends. Concerns about perceived vaccine safety and effectiveness and low perceived susceptibility to influenza were the most commonly reported barriers to vaccination. About half of the unvaccinated HCP said they would have been vaccinated if required by their employer. Influenza vaccination in this cohort was relatively high but still fell short of the recommended target of 90% coverage for HCP. Addressing concerns about vaccine safety and effectiveness are possible areas for future education or intervention to improve coverage among HCP. Copyright © 2014 Association for Professionals in Infection Control and Epidemiology, Inc. All rights reserved.

Vaccines and Kawasaki disease.

Science.gov (United States)

Esposito, Susanna; Bianchini, Sonia; Dellepiane, Rosa Maria; Principi, Nicola

2016-01-01

The distinctive immune system characteristics of children with Kawasaki disease (KD) could suggest that they respond in a particular way to all antigenic stimulations, including those due to vaccines. Moreover, treatment of KD is mainly based on immunomodulatory therapy. These factors suggest that vaccines and KD may interact in several ways. These interactions could be of clinical relevance because KD is a disease of younger children who receive most of the vaccines recommended for infectious disease prevention. This paper shows that available evidence does not support an association between KD development and vaccine administration. Moreover, it highlights that administration of routine vaccines is mandatory even in children with KD and all efforts must be made to ensure the highest degree of protection against vaccine-preventable diseases for these patients. However, studies are needed to clarify currently unsolved issues, especially issues related to immunologic interference induced by intravenous immunoglobulin and biological drugs.

Safety and tolerability of a live oral Salmonella typhimurium vaccine candidate in SIV-infected nonhuman primates.

Science.gov (United States)

Ault, Alida; Tennant, Sharon M; Gorres, J Patrick; Eckhaus, Michael; Sandler, Netanya G; Roque, Annelys; Livio, Sofie; Bao, Saran; Foulds, Kathryn E; Kao, Shing-Fen; Roederer, Mario; Schmidlein, Patrick; Boyd, Mary Adetinuke; Pasetti, Marcela F; Douek, Daniel C; Estes, Jacob D; Nabel, Gary J; Levine, Myron M; Rao, Srinivas S

2013-12-02

Nontyphoidal Salmonella (NTS) serovars are a common cause of acute food-borne gastroenteritis worldwide and can cause invasive systemic disease in young infants, the elderly, and immunocompromised hosts, accompanied by high case fatality. Vaccination against invasive NTS disease is warranted where the disease incidence and mortality are high and multidrug resistance is prevalent, as in sub-Saharan Africa. Live-attenuated vaccines that mimic natural infection constitute one strategy to elicit protection. However, they must particularly be shown to be adequately attenuated for consideration of immunocompromised subjects. Accordingly, we examined the safety and tolerability of an oral live attenuated Salmonella typhimurium vaccine candidate, CVD 1921, in an established chronic simian immunodeficiency virus (SIV)-infected rhesus macaque model. We evaluated clinical parameters, histopathology, and measured differences in mucosal permeability to wild-type and vaccine strains. Compared to the wild-type S. typhimurium strain I77 in both SIV-infected and SIV-uninfected nonhuman primate hosts, this live-attenuated vaccine shows reduced shedding and systemic spread, exhibits limited pathological disease manifestations in the digestive tract, and induces low levels of cellular infiltration in tissues. Furthermore, wild-type S. typhimurium induces increased intestinal epithelial damage and permeability, with infiltration of neutrophils and macrophages in both SIV-infected and SIV-uninfected nonhuman primates compared to the vaccine strain. Based on shedding, systemic spread, and histopathology, the live-attenuated S. typhimurium strain CVD 1921 appears to be safe and well-tolerated in the nonhuman primate model, including chronically SIV-infected rhesus macaques. Copyright © 2013. Published by Elsevier Ltd.

A T cell-inducing influenza vaccine for the elderly: safety and immunogenicity of MVA-NP+M1 in adults aged over 50 years.

Directory of Open Access Journals (Sweden)

Richard D Antrobus

Full Text Available Current influenza vaccines have reduced immunogenicity and are of uncertain efficacy in older adults. We assessed the safety and immunogenicity of MVA-NP+M1, a viral-vectored influenza vaccine designed to boost memory T cell responses, in a group of older adults.Thirty volunteers (aged 50-85 received a single intramuscular injection of MVA-NP+M1 at a dose of 1·5×10(8 plaque forming units (pfu. Safety and immunogenicity were assessed over a period of one year. The frequency of T cells specific for nucleoprotein (NP and matrix protein 1 (M1 was determined by interferon-gamma (IFN-γ ELISpot, and their phenotypic and functional properties were characterized by polychromatic flow cytometry. In a subset of M1-specific CD8(+ T cells, T cell receptor (TCR gene expression was evaluated using an unbiased molecular approach.Vaccination with MVA-NP+M1 was well tolerated. ELISpot responses were boosted significantly above baseline following vaccination. Increases were detected in both CD4(+ and CD8(+ T cell subsets. Clonality studies indicated that MVA-NP+M1 expanded pre-existing memory CD8(+ T cells, which displayed a predominant CD27(+CD45RO(+CD57(-CCR7(- phenotype both before and after vaccination.MVA-NP+M1 is safe and immunogenic in older adults. Unlike seasonal influenza vaccination, the immune responses generated by MVA-NP+M1 are similar between younger and older individuals. A T cell-inducing vaccine such as MVA-NP+M1 may therefore provide a way to circumvent the immunosenescence that impairs routine influenza vaccination.ClinicalTrials.gov NCT00942071.

Vanishing vaccinations: why are so many Americans opting out of vaccinating their children?

Science.gov (United States)

Calandrillo, Steve P

2004-01-01

Vaccinations against life-threatening diseases are one of the greatest public health achievements in history. Literally millions of premature deaths have been prevented, and countless more children have been saved from disfiguring illness. While vaccinations carry unavoidable risks, the medical, social and economic benefits they confer have led all fifty states to enact compulsory childhood vaccination laws to stop the spread of preventable diseases. Today, however, vaccines are becoming a victim of their success--many individuals have never witnessed the debilitating diseases that vaccines protect against, allowing complacency toward immunization requirements to build. Antivaccination sentiment is growing fast in the United States, in large part due to the controversial and hotly disputed link between immunizations and autism. The internet worsens fears regarding vaccination safety, as at least a dozen websites publish alarming information about the risks of vaccines. Increasing numbers of parents are refusing immunizations for their children and seeking legally sanctioned exemptions instead, apparently fearing vaccines more than the underlying diseases that they protect against. A variety of factors are at play: religious and philosophical beliefs, freedom and individualism, misinformation about risk, and overperception of risk. State legislatures and health departments now face a difficult challenge: respecting individual rights and freedoms while also safeguarding the public welfare. Nearly all states allow vaccination exemptions for religious reasons and a growing number provide "philosophical" opt-outs as well. However, in all but a handful of jurisdictions, neither objection is seriously documented or verified. Often, the law requires a parent to do no more than simply check a box indicating she does not wish her child to receive immunizations. The problem is exacerbated by financial incentives schools have to encourage students to opt out of vaccinations

Steps to Ensure a Successful Implementation of Occupational Health and Safety Interventions at an Organizational Level

Science.gov (United States)

Herrera-Sánchez, Isabel M.; León-Pérez, José M.; León-Rubio, José M.

2017-01-01

There is increasing meta-analytic evidence that addresses the positive impact of evidence-based occupational health and safety interventions on employee health and well-being. However, such evidence is less clear when interventions are approached at an organizational level and are aimed at changing organizational policies and processes. Given that occupational health and safety interventions are usually tailored to specific organizational contexts, generalizing and transferring such interventions to other organizations is a complex endeavor. In response, several authors have argued that an evaluation of the implementation process is crucial for assessing the intervention’s effectiveness and for understanding how and why the intervention has been (un)successful. Thus, this paper focuses on the implementation process and attempts to move this field forward by identifying the main factors that contribute toward ensuring a greater success of occupational health and safety interventions conducted at the organizational level. In doing so, we propose some steps that can guide a successful implementation. These implementation steps are illustrated using examples of evidence-based best practices reported in the literature that have described and systematically evaluated the implementation process behind their interventions during the last decade. PMID:29375413

Steps to Ensure a Successful Implementation of Occupational Health and Safety Interventions at an Organizational Level

Directory of Open Access Journals (Sweden)

Isabel M. Herrera-Sánchez

2017-12-01

Full Text Available There is increasing meta-analytic evidence that addresses the positive impact of evidence-based occupational health and safety interventions on employee health and well-being. However, such evidence is less clear when interventions are approached at an organizational level and are aimed at changing organizational policies and processes. Given that occupational health and safety interventions are usually tailored to specific organizational contexts, generalizing and transferring such interventions to other organizations is a complex endeavor. In response, several authors have argued that an evaluation of the implementation process is crucial for assessing the intervention’s effectiveness and for understanding how and why the intervention has been (unsuccessful. Thus, this paper focuses on the implementation process and attempts to move this field forward by identifying the main factors that contribute toward ensuring a greater success of occupational health and safety interventions conducted at the organizational level. In doing so, we propose some steps that can guide a successful implementation. These implementation steps are illustrated using examples of evidence-based best practices reported in the literature that have described and systematically evaluated the implementation process behind their interventions during the last decade.

Safety and immunogenicity of a trivalent, inactivated, mammalian cell culture-derived influenza vaccine in healthy adults, seniors, and children.

Science.gov (United States)

Halperin, Scott A; Smith, Bruce; Mabrouk, Taoufik; Germain, Marc; Trépanier, Pierre; Hassell, Thomas; Treanor, John; Gauthier, Richard; Mills, Elaine L

2002-01-15

We performed randomized, double-blind, controlled trials to assess the safety and immunogenicity of an inactivated, Madin Darby Canine Kidney (MDCK)-derived cell line produced influenza vaccine in healthy adults (19-50 years), children (3-12 years) and the elderly (> or =65 years). We studied three lots of cell culture-derived vaccine and one lot of licensed egg-derived vaccine in healthy adults (n=462), two lots of cell culture-derived vaccine and one lot of egg-derived vaccine in seniors (n=269), and one lot of each vaccine in children (n=209). Adverse events were collected during the first 3 days post-immunization; serum was collected before and 1 month after immunization. Rates of local and systemic adverse reactions were similar with both vaccines. An injection site adverse event rated at least moderate severity was reported by 21.9% of children who received the egg-derived vaccine and 25.0% of those who received the cell culture-derived vaccine. In healthy adults the proportions were 12.1 and 15.3%, respectively and 6.7 and 6.3%, respectively in seniors. Systemic events of at least moderate severity were 12.4 and 12.5% in children, 19.8 and 13.6% in healthy adults, and 14.1 and 9.7% in seniors; none of these differences were statistically significant. The antibody response against all three viruses was similar between the two vaccines. From 83 to 100% of children, healthy adults and seniors achieved hemagglutination inhibition titers in excess of 40 post-immunization. We conclude that the cell culture-derived vaccine was safe and immunogenic in children, healthy adults and seniors.

Fractional dosing of yellow fever vaccine to extend supply: a modelling study.

Science.gov (United States)

Wu, Joseph T; Peak, Corey M; Leung, Gabriel M; Lipsitch, Marc

2016-12-10

The ongoing yellow fever epidemic in Angola strains the global vaccine supply, prompting WHO to adopt dose sparing for its vaccination campaign in Kinshasa, Democratic Republic of the Congo, in July-August, 2016. Although a 5-fold fractional-dose vaccine is similar to standard-dose vaccine in safety and immunogenicity, efficacy is untested. There is an urgent need to ensure the robustness of fractional-dose vaccination by elucidation of the conditions under which dose fractionation would reduce transmission. We estimate the effective reproductive number for yellow fever in Angola using disease natural history and case report data. With simple mathematical models of yellow fever transmission, we calculate the infection attack rate (the proportion of population infected over the course of an epidemic) with various levels of transmissibility and 5-fold fractional-dose vaccine efficacy for two vaccination scenarios, ie, random vaccination in a hypothetical population that is completely susceptible, and the Kinshasa vaccination campaign in July-August, 2016, with different age cutoff for fractional-dose vaccines. We estimate the effective reproductive number early in the Angola outbreak was between 5·2 and 7·1. If vaccine action is all-or-nothing (ie, a proportion of vaccine recipients receive complete protection [VE] and the remainder receive no protection), n-fold fractionation can greatly reduce infection attack rate as long as VE exceeds 1/n. This benefit threshold becomes more stringent if vaccine action is leaky (ie, the susceptibility of each vaccine recipient is reduced by a factor that is equal to the vaccine efficacy). The age cutoff for fractional-dose vaccines chosen by WHO for the Kinshasa vaccination campaign (2 years) provides the largest reduction in infection attack rate if the efficacy of 5-fold fractional-dose vaccines exceeds 20%. Dose fractionation is an effective strategy for reduction of the infection attack rate that would be robust with a

A randomised trial to evaluate the immunogenicity, reactogenicity, and safety of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) co-administered with routine childhood vaccines in Singapore and Malaysia.

Science.gov (United States)

Lim, Fong Seng; Koh, Mia Tuang; Tan, Kah Kee; Chan, Poh Chong; Chong, Chia Yin; Shung Yehudi, Yeo Wee; Teoh, Yee Leong; Shafi, Fakrudeen; Hezareh, Marjan; Swinnen, Kristien; Borys, Dorota

2014-10-02

The immunogenicity, reactogenicity, and safety of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) co-administered with routine childhood vaccines were evaluated among infants from Singapore and Malaysia, where PHiD-CV has been licensed. In the primary vaccination phase, 298 infants from Singapore and 168 infants from Malaysia were randomised to receive the Phase III Clinical (Clin) or the Commercial (Com) lot of PHiD-CV at 2, 3, and 5 months of age. In the booster vaccination phase, 238 toddlers from Singapore received one dose of the PHiD-CV Commercial lot at 18-21 months of age. Immune responses to pneumococcal polysaccharides were measured using 22F-inhibition enzyme-linked immunosorbent assay (ELISA) and functional opsonophagocytic activity (OPA) assay and to protein D, using ELISA. Immune responses induced by primary vaccination with the PHiD-CV Commercial lot were non-inferior to the Phase III Clinical lot in terms of adjusted antibody geometric mean concentration (GMC) ratios for each vaccine pneumococcal serotype and protein D. For each vaccine pneumococcal serotype, ≥93.6% and ≥88.5% of infants from Malaysia and Singapore had post-primary vaccination antibody concentrations ≥0.2 μg/mL and OPA titres ≥8, in the Clin and Com groups, respectively. For each vaccine pneumococcal serotype, ≥60.8% and ≥98.2% of toddlers from Singapore had pre- and post-booster antibody concentrations ≥0.2 μg/mL, in the Clin and Com groups, respectively. All children, except one, had measurable anti-protein D antibodies and the primary and booster doses of the co-administered vaccines were immunogenic. The incidence of each grade 3 solicited symptom was ≤11.1% in both study phases. No serious adverse events considered causally related to vaccination were reported throughout the study. PHiD-CV given as three-dose primary vaccination to infants in Singapore and Malaysia and booster vaccination to toddlers in

Live Virus Vaccines Based on a Yellow Fever Vaccine Backbone: Standardized Template with Key Considerations for a Risk/Benefit Assessment*

Science.gov (United States)

Monath, Thomas P.; Seligman, Stephen J.; Robertson, James S.; Guy, Bruno; Hayes, Edward B.; Condit, Richard C.; Excler, Jean Louis; Mac, Lisa Marie; Carbery, Baevin; Chen, Robert T

2015-01-01

The Brighton Collaboration Viral Vector Vaccines Safety Working Group (V3SWG) was formed to evaluate the safety of live, recombinant viral vaccines incorporating genes from heterologous viruses inserted into the backbone of another virus (so-called “chimeric virus vaccines”). Many viral vector vaccines are in advanced clinical trials. The first such vaccine to be approved for marketing (to date in Australia, Thailand, Malaysia, and the Philippines) is a vaccine against the flavivirus Japanese encephalitis (JE), which employs a licensed vaccine (yellow fever 17D) as a vector. In this vaccine, two envelope proteins (prM-E) of YF 17D virus were replaced by the corresponding genes of JE virus, with additional attenuating mutations incorporated into the JE gene inserts. Similar vaccines have been constructed by inserting prM-E genes of dengue and West Nile into YF 17D virus and are in late stage clinical studies. The dengue vaccine is, however, more complex in that it requires a mixture of four live vectors each expressing one of the four dengue serotypes. This vaccine has been evaluated in multiple clinical trials. No significant safety concerns have been found. The Phase 3 trials met their endpoints in terms of overall reduction of confirmed dengue fever, and, most importantly a significant reduction in severe dengue and hospitalization due to dengue. However, based on results that have been published so far, efficacy in preventing serotype 2 infection is less than that for the other three serotypes. In the development of these chimeric vaccines, an important series of comparative studies of safety and efficacy were made using the parental YF 17D vaccine virus as a benchmark. In this paper, we use a standardized template describing the key characteristics of the novel flavivirus vaccine vectors, in comparison to the parental YF 17D vaccine. The template facilitates scientific discourse among key stakeholders by increasing the transparency and comparability of

Active surveillance for intussusception in a phase III efficacy trial of an oral monovalent rotavirus vaccine in India.

Science.gov (United States)

John, Jacob; Kawade, Anand; Rongsen-Chandola, Temsunaro; Bavdekar, Ashish; Bhandari, Nita; Taneja, Sunita; Antony, Kalpana; Bhatnagar, Veereshwar; Gupta, Arun; Kabra, Madhulika; Kang, Gagandeep

2014-08-11

Post licensure studies have identified an increased risk of intussusception following vaccination with currently licensed rotavirus vaccines, raising safety concerns generic to all rotavirus vaccines. We describe the surveillance for intussusception in a phase III clinical trial with an oral monovalent rotavirus vaccine developed from the neonatal 116E strain. Using broad screening criteria and active surveillance, the incidence of intussusception between 6 weeks and 2 years of age was measured in 4532 children who received three doses of vaccine and 2267 children who received a placebo in the clinical trial. Possible intussusceptions were evaluated with a screening ultrasonogram. An independent intussusception case adjudication committee reviewed all intussusceptions and graded them on Brighton Collaboration criteria for diagnostic certainty. We identified twenty-three intussusceptions on ultrasound from 1361 evaluated sentinel events. Eleven were of level 1 diagnostic certainty as determined by the independent intussusception case adjudication committee. None required surgical intervention, and the earliest identified intussusception was at 36 days following the third dose in a placebo recipient. Among vaccine recipients the first event of intussusception occurred 112 days after the third dose. The incidence of ultrasound-diagnosed intussusception was 200/100,000 child-years (95% CI, 120, 320) among those receiving the vaccine and 141/100,000 child-years (95% CI, 50, 310) among those receiving the placebo. The incidence rate of confirmed intussusception among vaccine recipients was 94/100,000 child-years (95% CI, 41, 185) and 71/100,000 child-years (95% CI, 15, 206) among those receiving the placebo. In this licensure study, 23 cases of intussusception were identified through an active surveillance system, but there was no temporal association with rotavirus vaccination. The use of active surveillance with broad criteria intended for ensuring safety of children

INFLUENZA AND PNEUMOCOCCAL VACCINATION IN HEMATOLOGICAL MALIGNANCIES: A SYSTEMATIC REVIEW OF EFFICACY, EFFECTIVENESS AND SAFETY

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Giuseppe La Torre

2016-09-01

Full Text Available Background The risk of getting influenza and pneumococcal disease is higher in cancer patients and serum antibody levels tend to be lower in patients with hematological malignancy. Objective To asses flu and pneumococcal vaccinations efficacy, effectiveness and safety in onco-hematological patients. Methods Two systematic reviews and possible meta-analysis were conducted to summarize the results of all primary study in scientific literature about flu and pneumococcal vaccine in onco-hematological patients. Literature searches were performed using Pub-Med and Scopus databases. StatsDirect 2.8.0 was used for the analysis. Results 23 and 26 studies were collected respectively for flu and pneumococcal vaccinations. Protection rate of booster dose was 30% (95% CI = 6.2- 61% for H1N1. Pooled prevalence protection rate of H3N2 and B was available for meta-analysis only for first dose, 42.6% (95% CI = 23.2 – 63.3 % and 39.6 % (95% CI = 26%- 54.1% for H3N2 and B, respectively. Response rate of booster dose resulted 35% (95% CI = 19.7-51.2% for H1N1, 23% (95% CI = 16.6-31.5% for H3N2, 29% (95% CI = 21.3- 37% for B. Conclusion Despite low rate of response, flu and pneumococcal vaccines are worthwhile for patients with hematological malignancies. Patients undergoing chemotherapy in particular rituximab, splenectomy, transplant recipient had lower and impaired response. No serious adverse events were reported for both vaccines.