Active SMS-based influenza vaccine safety surveillance in Australian children.

PubMed

Pillsbury, Alexis; Quinn, Helen; Cashman, Patrick; Leeb, Alan; Macartney, Kristine

2017-12-18

Australia's novel, active surveillance system, AusVaxSafety, monitors the post-market safety of vaccines in near real time. We analysed cumulative surveillance data for children aged 6 months to 4 years who received seasonal influenza vaccine in 2015 and/or 2016 to determine: adverse event following immunisation (AEFI) rates by vaccine brand, age and concomitant vaccine administration. Parent/carer reports of AEFI occurring within 3 days of their child receiving an influenza vaccine in sentinel immunisation clinics were solicited by Short Message Service (SMS) and/or email-based survey. Retrospective data from 2 years were combined to examine specific AEFI rates, particularly fever and medical attendance as a proxy for serious adverse events (SAE), with and without concomitant vaccine administration. As trivalent influenza vaccines (TIV) were funded in Australia's National Immunisation Program (NIP) in 2015 and quadrivalent (QIV) in 2016, respectively, we compared their safety profiles. 7402 children were included. Data were reported weekly through each vaccination season; no safety signals or excess of adverse events were detected. More children who received a concomitant vaccine had fever (7.5% versus 2.8%; p < .001). Meningococcal B vaccine was associated with the highest increase in AEFI rates among children receiving a specified concomitant vaccine: 30.3% reported an AEFI compared with 7.3% who received an influenza vaccine alone (p < .001). Reported fever was strongly associated with medical attendance (OR: 42.6; 95% Confidence Interval (CI): 25.6-71.0). TIV and QIV safety profiles included low and expected AEFI rates (fever: 4.3% for TIV compared with 3.2% for QIV (p = .015); injection site reaction: 1.9% for TIV compared with 3.0% for QIV (p < .001)). There was no difference in safety profile between brands. Active participant-reported data provided timely vaccine brand-specific safety information. Our surveillance system has

Safety of human papillomavirus vaccines: a review

PubMed Central

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

2015-01-01

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

Safety of human papillomavirus vaccines: a review.

PubMed

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

2015-05-01

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

Safety assessment of adjuvanted vaccines: Methodological considerations

PubMed Central

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

2015-01-01

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

A signal detection method for temporal variation of adverse effect with vaccine adverse event reporting system data.

PubMed

Cai, Yi; Du, Jingcheng; Huang, Jing; Ellenberg, Susan S; Hennessy, Sean; Tao, Cui; Chen, Yong

2017-07-05

To identify safety signals by manual review of individual report in large surveillance databases is time consuming; such an approach is very unlikely to reveal complex relationships between medications and adverse events. Since the late 1990s, efforts have been made to develop data mining tools to systematically and automatically search for safety signals in surveillance databases. Influenza vaccines present special challenges to safety surveillance because the vaccine changes every year in response to the influenza strains predicted to be prevalent that year. Therefore, it may be expected that reporting rates of adverse events following flu vaccines (number of reports for a specific vaccine-event combination/number of reports for all vaccine-event combinations) may vary substantially across reporting years. Current surveillance methods seldom consider these variations in signal detection, and reports from different years are typically collapsed together to conduct safety analyses. However, merging reports from different years ignores the potential heterogeneity of reporting rates across years and may miss important safety signals. Reports of adverse events between years 1990 to 2013 were extracted from the Vaccine Adverse Event Reporting System (VAERS) database and formatted into a three-dimensional data array with types of vaccine, groups of adverse events and reporting time as the three dimensions. We propose a random effects model to test the heterogeneity of reporting rates for a given vaccine-event combination across reporting years. The proposed method provides a rigorous statistical procedure to detect differences of reporting rates among years. We also introduce a new visualization tool to summarize the result of the proposed method when applied to multiple vaccine-adverse event combinations. We applied the proposed method to detect safety signals of FLU3, an influenza vaccine containing three flu strains, in the VAERS database. We showed that it had high

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

PubMed

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 <2 years of age; 2588 (13%) in persons 2-18 years and 5867 (29%) 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 <1 month, were nervous system disorders (15) among 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

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

PubMed

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

2014-05-23

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

Safety of human papillomavirus vaccines: a review.

PubMed

Macartney, Kristine K; Chiu, Clayton; Georgousakis, Melina; Brotherton, Julia M L

2013-06-01

Vaccination to prevent human papillomavirus (HPV)-related infection leading to cancer, particularly cervical cancer, is a major public health breakthrough. There are currently two licensed HPV vaccines, both of which contain recombinant virus-like particles of HPV types 16 and 18 (which account for approximately 70 % of cervical cancer). One vaccine also protects against HPV types 6 and 11, which cause genital warts. The safety profile of both vaccines was assessed extensively in randomised controlled clinical trials conducted prior to licensure and has been further elucidated following licensure from surveillance and specific studies in large populations. This review aims to examine current evidence regarding the safety of HPV vaccines. In summary, both vaccines are associated with relatively high rates of injection site reactions, particularly pain, but this is usually of short duration and resolves spontaneously. Systemic reactions have generally been mild and self-limited. Post vaccination syncope has occurred, but can be avoided with appropriate care. Serious vaccine-attributable adverse events, such as anaphylaxis, are rare, and although not recommended for use in pregnancy, abnormal pregnancy outcomes following inadvertent administration do not appear to be associated with vaccination. HPV vaccines are used in a three-dose schedule predominantly in adolescent females: as such case reports linking vaccination with a range of new onset chronic conditions, including autoimmune diseases, have been made. However, well-conducted population-based studies show no association between HPV vaccine and a range of such conditions. Whilst this reassuring safety profile affirms the positive risk benefit of vaccination, as HPV vaccine use expands into more diverse populations, including males, ongoing safety assessment using well-conducted studies is appropriate.

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

PubMed

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

2011-05-01

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

Safety of the yellow Fever vaccine: a retrospective study.

PubMed

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

2013-01-01

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

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

PubMed

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.

Flu Vaccine Safety Information

MedlinePlus

... Types Seasonal Avian Swine Variant Pandemic Other Flu Vaccine Safety Information Questions & Answers Language: English (US) Español ... of flu vaccines monitored? Egg Allergy Are flu vaccines safe? Flu vaccines have good safety record. Hundreds ...

Association rule mining in the US Vaccine Adverse Event Reporting System (VAERS).

PubMed

Wei, Lai; Scott, John

2015-09-01

Spontaneous adverse event reporting systems are critical tools for monitoring the safety of licensed medical products. Commonly used signal detection algorithms identify disproportionate product-adverse event pairs and may not be sensitive to more complex potential signals. We sought to develop a computationally tractable multivariate data-mining approach to identify product-multiple adverse event associations. We describe an application of stepwise association rule mining (Step-ARM) to detect potential vaccine-symptom group associations in the US Vaccine Adverse Event Reporting System. Step-ARM identifies strong associations between one vaccine and one or more adverse events. To reduce the number of redundant association rules found by Step-ARM, we also propose a clustering method for the post-processing of association rules. In sample applications to a trivalent intradermal inactivated influenza virus vaccine and to measles, mumps, rubella, and varicella (MMRV) vaccine and in simulation studies, we find that Step-ARM can detect a variety of medically coherent potential vaccine-symptom group signals efficiently. In the MMRV example, Step-ARM appears to outperform univariate methods in detecting a known safety signal. Our approach is sensitive to potentially complex signals, which may be particularly important when monitoring novel medical countermeasure products such as pandemic influenza vaccines. The post-processing clustering algorithm improves the applicability of the approach as a screening method to identify patterns that may merit further investigation. Copyright © 2015 John Wiley & Sons, Ltd.

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

PubMed

He, Yongqun

2014-07-01

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

Severe Autoimmune Adverse Events Post Herpes Zoster Vaccine: A Case-Control Study of Adverse Events in a National Database.

PubMed

Lai, Yi Chun; Yew, Yik Weng

2015-07-01

Zoster vaccine is recommended to reduce the incidence of herpes zoster and its complication of postherpetic neuralgia in older adults. However, there have been reports of autoimmune side effects post vaccination. We therefore aim to investigate the possible relationship of severe autoimmune adverse events (arthritis, vasculitis, systemic lupus erythematosus, thrombocytopenia, alopecia, Guillain-Barre syndrome, optic neuritis and multiple sclerosis) post zoster vaccination with a matched case-control study of reported events in the Vaccine Adverse Event Reporting System (VAERS). Our study showed no significantly increased risks of severe autoimmune adverse events, except arthritis and alopecia, after vaccination. Compared to the unexposed, patients with zoster vaccination had 2.2 and 2.7 times the odds of developing arthritis and alopecia, respectively (P<0.001 and P=0.015, respectively). However, almost none of these events was life threatening. Zoster vaccine is, therefore, relatively safe and unlikely to exacerbate or induce autoimmune diseases. Given its benefits and safety but low coverage, dermatologists and primary care physicians should encourage zoster vaccine use in elderly patients, including selected patients with autoimmune diseases.

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

PubMed

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

2007-01-01

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

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

PubMed

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

2015-01-01

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

[H1N1 influenza vaccines in Tunisia: efficiency and safety].

PubMed

Chaabane, Amel; Aouam, Karim; Ben Fredj, Nadia; Toumi, Adnen; Braham, Dorra; A Boughattas, Naceur; Chakroun, Mohamed

2011-01-01

We carried out this study in order to evaluate the effectiveness and the safety of the two H1N1 vaccines available in Tunisia: Focetria(®) and Panenza(®). It's a prospective epidemiological study including 601 vaccinated subjects. The vaccine effectiveness was based on the occurrence of flu clinical symptoms after vaccination. The safety was based on the occurrence of unexpected events after vaccines administration. The vaccines imputability was established according to Begaud et al. method. The number of subjects vaccinated by Focetria(®) is more important than Panenza(®). The efficiency of vaccines would be 93.6%. Neither the medical statue nor the type of the vaccine used influence the occurrence of a flu episode after vaccination. We recorded 406 adverse effects (32.4%) with a high score of imputability (I3). Focetria(®) adverse effects were more frequent than Panenza(®) ones (p = 0.009). Almost all adverse events disappeared within few days. The two vaccines used in Tunisia remain enough efficient to face the influenza (H1N1) pandemia and are well tolerated independently of the demographic and pathological statue of the vaccinated person as well as nature of the vaccine used. © 2011 Société Française de Pharmacologie et de Thérapeutique.

Post licensure surveillance of influenza vaccines in the Vaccine Safety Datalink in the 2013-2014 and 2014-2015 seasons.

PubMed

Li, Rongxia; Stewart, Brock; McNeil, Michael M; Duffy, Jonathan; Nelson, Jennifer; Kawai, Alison Tse; Baxter, Roger; Belongia, Edward A; Weintraub, Eric

2016-08-01

The changes in each year in influenza vaccine antigenic components as well as vaccine administration patterns may pose new risks of adverse events following immunization (AEs). To evaluate the safety of influenza vaccines annually administered to people ≥ 6 months, we conducted weekly post licensure surveillance for seven pre-specified adverse events following receipt of influenza vaccines during the 2013-2014 and 2014-2015 seasons in the Vaccine Safety Datalink (VSD). We used both a historically-controlled cohort design with the Poisson-based maximized sequential probability ratio test (maxSPRT) and a self-controlled risk interval (SCRI) design with the binomial-based maxSPRT. For each adverse event outcome, we defined the risk interval on the basis of biologic plausibility and prior literature. For the historical cohort design, numbers of expected adverse events were calculated from the prior seven seasons, adjusted for age and site. For the SCRI design, a comparison window was defined either before vaccination or after vaccination, depending on each specific outcome. An elevated risk of febrile seizures 0-1 days following trivalent inactivated influenza vaccine (IIV3) was identified in children aged 6-23 months during the 2014-2015 season using the SCRI design. We found the relative risk (RR) of febrile seizures following concomitant administration of IIV3 and PCV13 was 5.3 with a 95% CI 1.87-14.75. Without concomitant PCV 13 administration, the estimated risk decreased and was no longer statistically significant (RR: 1.4; CI: 0.54 - 3.61). No increased risks, other than for febrile seizures, were identified in influenza vaccine safety surveillance during 2013-2014 and 2014-2015 seasons in the VSD. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

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

PubMed Central

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

2005-01-01

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

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

PubMed Central

He, Yongqun

2016-01-01

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

Vaxtracker: Active on-line surveillance for adverse events following inactivated influenza vaccine in children.

PubMed

Cashman, Patrick; Moberley, Sarah; Dalton, Craig; Stephenson, Jody; Elvidge, Elissa; Butler, Michelle; Durrheim, David N

2014-09-22

Vaxtracker is a web based survey for active post marketing surveillance of Adverse Events Following Immunisation. It is designed to efficiently monitor vaccine safety of new vaccines by early signal detection of serious adverse events. The Vaxtracker system automates contact with the parents or carers of immunised children by email and/or sms message to their smart phone. A hyperlink on the email and text messages links to a web based survey exploring adverse events following the immunisation. The Vaxtracker concept was developed during 2011 (n=21), and piloted during the 2012 (n=200) and 2013 (n=477) influenza seasons for children receiving inactivated influenza vaccine (IIV) in the Hunter New England Local Health District, New South Wales, Australia. Survey results were reviewed by surveillance staff to detect any safety signals and compare adverse event frequencies among the different influenza vaccines administered. In 2012, 57% (n=113) of the 200 participants responded to the online survey and 61% (290/477) in 2013. Vaxtracker appears to be an effective method for actively monitoring adverse events following influenza vaccination in children. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

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

PubMed

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

2012-01-01

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

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

PubMed

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

2014-08-01

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

Disease-specific adverse events following nonlive vaccines: a paradoxical placebo effect or a nocebo phenomenon?

PubMed

Okaïs, Claire; Gay, Constance; Seon, Fabrice; Buchaille, Lydie; Chary, Emilie; Soubeyrand, Benoît

2011-08-26

Vaccines can cause adverse reactions (AR), i.e. adverse events following immunization (AEFIs) due to the vaccine, such as local reactions or fever. In addition, live attenuated vaccines which replicate in vaccinees can cause disease-specific AR, e.g. measles-like rash following measles vaccination. However, nonlive vaccines because they are inactivated and they do not replicate in vaccinees, are not likely to cause disease-specific AR. The aim of the study was to assess whether safety signals could be generated by an undescribed bias in spontaneous reporting of disease-specific AEFIs with nonlive vaccines. All AEFIs of Sanofi Pasteur MSD vaccines spontaneously reported in France from January 2000 to June 2010, coded according to MedDRA terms and collected in the company's pharmacovigilance database were analyzed. Vaccine-event pairs of interest were selected a priori. The disproportionality reporting rate methodology was used, comparing the proportion of a given event reported following a given vaccine to its proportion reported following all other studied vaccines. The Reporting Odds Ratio (ROR) was used for signals detection for each vaccine-event pair selected. A total of 33,275 AEFIs were analyzed. The calculated ROR showed a statistically disproportionate reporting rate and generated false safety signals for almost all the pairs tested. Three nonlive vaccine pairs were striking: gynaecological symptoms and the quadrivalent human papillomavirus (qHPV) vaccine; trismus and tetanus vaccines; hepatobiliary disorders and hepatitis B vaccines. In conclusion we have identified a new vaccine AE spontaneous reporting bias: "disease-specific adverse events following nonlive vaccines", showing that vaccinees and healthcare professionals tend to report preferentially the symptoms of the disease against which the nonlive vaccine was administered. We suggest that bias is subordinate to a paradoxical placebo effect and/or a nocebo phenomenon. Copyright © 2011 Elsevier Ltd

Adverse events after anthrax vaccination reported to the Vaccine Adverse Event Reporting System (VAERS), 1990-2007.

PubMed

Niu, Manette T; Ball, Robert; Woo, Emily Jane; Burwen, Dale R; Knippen, Maureen; Braun, M Miles

2009-01-07

During the period March 1, 1998 to January 14, 2007, approximately 6 million doses of Anthrax vaccine adsorbed (AVA) vaccine were administered. As of January 16, 2007, 4753 reports of adverse events following receipt of AVA vaccination had been submitted to the Vaccine Adverse Event Reporting System (VAERS). Taken together, reports to VAERS did not definitively link any serious unexpected risk to this vaccine, and review of death and serious reports did not show a distinctive pattern indicative of a causal relationship to AVA vaccination. Continued monitoring of VAERS and analysis of potential associations between AVA vaccination and rare, serious events is warranted.

Adverse event reports following yellow fever vaccination, 2007-13.

PubMed

Lindsey, Nicole P; Rabe, Ingrid B; Miller, Elaine R; Fischer, Marc; Staples, J Erin

2016-05-01

Yellow fever (YF) vaccines have been available since the 1930s and are generally considered safe and effective. However, rare reports of serious adverse events (SAE) following vaccination have prompted the Advisory Committee for Immunization Practices to periodically expand the list of conditions considered contraindications and precautions to vaccination. We describe adverse events following YF vaccination reported to the U.S. Vaccine Adverse Event Reporting System (VAERS) from 2007 through 2013 and calculate age- and sex-specific reporting rates of all SAE, anaphylaxis, YF vaccine-associated neurologic disease (YEL-AND) and YF vaccine-associated viscerotropic disease (YEL-AVD). There were 938 adverse events following YF vaccination reported to VAERS from 2007 through 2013. Of these, 84 (9%) were classified as SAEs for a rate of 3.8 per 100 000 doses distributed. Reporting rates of SAEs increased with increasing age with a rate of 6.5 per 100 000 in persons aged 60-69 years and 10.3 for ≥70 years. The reporting rate for anaphylaxis was 1.3 per 100 000 doses distributed and was highest in persons ≤18 years (2.7 per 100 000). Reporting rates of YEL-AND and YEL-AVD were 0.8 and 0.3 per 100 000 doses distributed, respectively; both rates increased with increasing age. These findings reinforce the generally acceptable safety profile of YF vaccine, but highlight the importance of continued physician and traveller education regarding the risks and benefits of YF vaccination, particularly for older travellers. Published by Oxford University Press on behalf of the International Society of Travel Medicine, 2016. This work is written by US Government employees and is in the public domain in the United States.

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

PubMed Central

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

2004-01-01

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

Active surveillance for influenza vaccine adverse events: the integrated vaccine surveillance system.

PubMed

Newes-Adeyi, Gabriella; Greece, Jacey; Bozeman, Sam; Walker, Deborah Klein; Lewis, Faith; Gidudu, Jane

2012-02-01

We conducted a pilot study of the Integrated Vaccine Surveillance System (IVSS), a novel active surveillance system for monitoring influenza vaccine adverse events that could be used in mass vaccination settings. We recruited 605 adult vaccinees from a convenience sample of 12 influenza vaccine clinics conducted by public health departments of two U.S. metropolitan regions. Vaccinees provided daily reports on adverse reactions following immunization (AEFI) using an interactive voice response system (IVR) or the internet for 14 consecutive days following immunization. Followup with nonrespondents was conducted through computer-assisted telephone interviewing (CATI). Data on vaccinee reports were available real-time through a dedicated secure website. 90% (545) of vaccinees made at least one daily report and 49% (299) reported consecutively for the full 14-day period. 58% (315) used internet, 20% (110) IVR, 6% (31) CATI, and 16% (89) used a combination for daily reports. Of the 545 reporters, 339 (62%) reported one or more AEFI, for a total of 594 AEFIs reported. The majority (505 or 85%) of these AEFIs were mild symptoms. It is feasible to develop a system to obtain real-time data on vaccine adverse events. Vaccinees are willing to provide daily reports for a considerable time post vaccination. Offering multiple modes of reporting encourages high response rates. Study findings on AEFIs showed that the IVSS was able to exhibit the emerging safety profile of the 2008 seasonal influenza vaccine. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

PubMed Central

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 of Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis and Influenza Vaccinations in Pregnancy.

PubMed

Sukumaran, Lakshmi; McCarthy, Natalie L; Kharbanda, Elyse O; Weintraub, Eric S; Vazquez-Benitez, Gabriela; McNeil, Michael M; Li, Rongxia; Klein, Nicola P; Hambidge, Simon J; Naleway, Allison L; Lugg, Marlene M; Jackson, Michael L; King, Jennifer P; DeStefano, Frank; Omer, Saad B; Orenstein, Walter A

2015-11-01

To evaluate the safety of coadministering tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) and influenza vaccines during pregnancy by comparing adverse events after concomitant and sequential vaccination. We conducted a retrospective cohort study of pregnant women aged 14-49 years in the Vaccine Safety Datalink from January 1, 2007, to November 15, 2013. We compared medically attended acute events (fever, any acute reaction) and adverse birth outcomes (preterm delivery, low birth weight, small for gestational age) in women receiving concomitant Tdap and influenza vaccination and women receiving sequential vaccination. Among 36,844 pregnancies in which Tdap and influenza vaccines were administered, the vaccines were administered concomitantly in 8,464 (23%) pregnancies and sequentially in 28,380 (77%) pregnancies. Acute adverse events after vaccination were rare. We found no statistically significant increased risk of fever or any medically attended acute adverse event in pregnant women vaccinated concomitantly compared with sequentially. When analyzing women at 20 weeks of gestation or greater during periods of influenza vaccine administration, there were no differences in preterm delivery, low-birth-weight, or small-for-gestational-age neonates between women vaccinated concomitantly compared with sequentially in pregnancy. Concomitant administration of Tdap and influenza vaccines during pregnancy was not associated with a higher risk of medically attended adverse acute outcomes or birth outcomes compared with sequential vaccination. II.

[Immunogenicity and safety of a booster dose of inactivated polio vaccine].

PubMed

Li, Xiao-mei; Zhang, Zhu-jia-zi; Wang, Hai-hong; Liu, Fang; Zhang, Li-wen; Chu, Ping; Xu, Ying; Zhang, He-run; Li, Juan; Liu, Dong-lei; Lu, Li

2013-10-01

To evaluate the immunogenicity and safety of a boost dose of inactivated polio vaccine (IPV) among children aged 18 months who had been administered with primary doses of IPV. Form 2011 to 2012, a total of 97 children were enrolled in the present study who were vaccinated with IPV at 2, 3, 4 months of age and boosted with the same vaccine at 18 months of age. Anti-poliovirus neutralizing antibody titers in serum were measured before and after booster vaccination, geometric mean titers (GMT) and seroprotection rate were calculated. Adverse events occurring within 30 days after booster vaccination were observed, including pain, redness/swelling and induration at the injection site, fever, vomit, abnormal crying, drowsiness, loss of appetite, irritability, and all other physical discomfort and related medications were also recorded. A descriptive analysis was performed for the safety assessment. Immunogenicity was assessed in 84 subjects. The pre-booster seropositivity rates of neutralizing antibody against poliovirus type 1, 2, 3 before booster were all 100% (84/84) and the corresponding GMT (95% CI) was 1: 148.5 (116.49-189.29) , 1: 237.68 (178.39-316.67) and 1: 231.87 (181.27-296.58) , respectively. The seropositivity rates of neutralizing antibody against the three types of poliovirus after booster were all 100% (84/84) and the corresponding GMT (95% CI) was 1: 1612.14 (1470.57-1767.34) , 1: 1854.92 (1715.83-2005.29) and 1: 1625.50 (1452.12-1819.58) , respectively. The pre-booster titer of neutralizing antibody against poliovirus type 1, 2, 3 mainly ranged 1: 128-1: 512, which accounted for 65% (55/84) , 55% (46/84) , 74% (62/84) in each type. After the booster immunization, titers of neutralizing antibody against type 1, 2, 3 were increased as subjects with titer ≥ 1: 1024 accounted for 94% (78/84) , 95% (80/84) , 92% (77/84) , respectively.Safety was evaluated in 96 subjects, of which 16 subjects reported adverse events with the rate of 17%. The observed local

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

PubMed

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

2016-01-01

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

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

PubMed

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

2016-02-15

While the large majority of parents in the U.S. vaccinate their children according to the recommended immunization schedule, some parents have refused or delayed vaccinating, often citing safety concerns. In response to public concern, the U.S. Institute of Medicine (IOM) evaluated existing research regarding the safety of the recommended immunization schedule. The IOM concluded that although available evidence strongly supported the safety of the currently recommended schedule as a whole, additional observational research was warranted to compare health outcomes between fully vaccinated children and those on a delayed or alternative schedule. In addition, the IOM identified the Vaccine Safety Datalink (VSD) as an important resource for conducting this research. Guided by the IOM findings, the Centers for Disease Control and Prevention (CDC) commissioned a White Paper to assess how the VSD could be used to study the safety of the childhood immunization schedule. Guided by subject matter expert engagement, the resulting White Paper outlines a 4 stage approach for identifying exposure groups of undervaccinated children, presents a list of health outcomes of highest priority to examine in this context, and describes various study designs and statistical methods that could be used to analyze the safety of the schedule. While it appears feasible to study the safety of the recommended immunization schedule in settings such as the VSD, these studies will be inherently complex, and as with all observational studies, will need to carefully address issues of confounding and bias. In light of these considerations, decisions about conducting studies of the safety of the schedule will also need to assess epidemiological evidence of potential adverse events that could be related to the schedule, the biological plausibility of an association between an adverse event and the schedule, and public concern about the safety of the schedule. Copyright © 2015 Elsevier Ltd. All rights

Analyzing and strengthening the vaccine safety program in Manitoba.

PubMed

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.

Vaccine Safety Datalink

Cancer.gov

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

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

PubMed

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.

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

PubMed

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

2012-05-28

Vacunas.org (http://www.vacunas.org), a website founded by the Spanish Association of Vaccinology offers a personalized service called Ask the Expert, which answers any questions posed by the public or health professionals about vaccines and vaccination. The aim of this study was to analyze the factors associated with questions on vaccination safety and determine the characteristics of questioners and the type of question asked during the period 2008-2010. A total of 1341 questions were finally included in the analysis. Of those, 30% were related to vaccine safety. Questions about pregnant women had 5.01 higher odds of asking about safety (95% CI 2.82-8.93) than people not belonging to any risk group. Older questioners (>50 years) were less likely to ask about vaccine safety compared to younger questioners (OR: 0.44, 95% CI 0.25-0.76). Questions made after vaccination or related to influenza (including H1N1) or travel vaccines were also associated with a higher likelihood of asking about vaccine safety. These results identify risk groups (pregnant women), population groups (older people) and some vaccines (travel and influenza vaccines, including H1N1) where greater efforts to provide improved, more-tailored vaccine information in general and on the Internet are required. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

PubMed

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.

Effective vaccine safety systems in all countries: a challenge for more equitable access to immunization.

PubMed

Amarasinghe, Ananda; Black, Steve; Bonhoeffer, Jan; Carvalho, Sandra M Deotti; Dodoo, Alexander; Eskola, Juhani; Larson, Heidi; Shin, Sunheang; Olsson, Sten; Balakrishnan, Madhava Ram; Bellah, Ahmed; Lambach, Philipp; Maure, Christine; Wood, David; Zuber, Patrick; Akanmori, Bartholomew; Bravo, Pamela; Pombo, María; Langar, Houda; Pfeifer, Dina; Guichard, Stéphane; Diorditsa, Sergey; Hossain, Md Shafiqul; Sato, Yoshikuni

2013-04-18

Serious vaccine-associated adverse events are rare. To further minimize their occurrence and to provide adequate care to those affected, careful monitoring of immunization programs and case management is required. Unfounded vaccine safety concerns have the potential of seriously derailing effective immunization activities. To address these issues, vaccine pharmacovigilance systems have been developed in many industrialized countries. As new vaccine products become available to prevent new diseases in various parts of the world, the demand for effective pharmacovigilance systems in low- and middle-income countries (LMIC) is increasing. To help establish such systems in all countries, WHO developed the Global Vaccine Safety Blueprint in 2011. This strategic plan is based on an in-depth analysis of the vaccine safety landscape that involved many stakeholders. This analysis reviewed existing systems and international vaccine safety activities and assessed the financial resources required to operate them. The Blueprint sets three main strategic goals to optimize the safety of vaccines through effective use of pharmacovigilance principles and methods: to ensure minimal vaccine safety capacity in all countries; to provide enhanced capacity for specific circumstances; and to establish a global support network to assist national authorities with capacity building and crisis management. In early 2012, the Global Vaccine Safety Initiative (GVSI) was launched to bring together and explore synergies among on-going vaccine safety activities. The Global Vaccine Action Plan has identified the Blueprint as its vaccine safety strategy. There is an enormous opportunity to raise awareness for vaccine safety in LMIC and to garner support from a large number of stakeholders for the GVSI between now and 2020. Synergies and resource mobilization opportunities presented by the Decade of Vaccines can enhance monitoring and response to vaccine safety issues, thereby leading to more equitable

Using SMS to monitor adverse events following trivalent influenza vaccination in pregnant women.

PubMed

Regan, Annette K; Blyth, Christopher C; Mak, Donna B; Richmond, Peter C; Effler, Paul V

2014-12-01

Trivalent influenza vaccine (TIV) has been recommended for pregnant women in Australia for more than a decade and funded since 2009, yet vaccination coverage remains low. Misperceptions of the safety of TIV in pregnancy have been identified as a major contributor to low vaccination rates. Ongoing safety monitoring with dissemination of results could help improve antenatal influenza vaccine uptake. To implement a real-time safety monitoring program for TIV administered to pregnant women. Between March and July 2013, a cohort of 3,173 pregnant women who received the 2013 TIV agreed to follow-up regarding possible adverse events following immunisation (AEFI); 3,047 (96%) provided a mobile telephone number and were sent a short message service (SMS) inquiring whether they had experienced an AEFI; attempts were made to contact the remaining 126 (4%) women by voice telephone call. Responses were obtained from 2,885 (90.9%) women, 413 (14.3%) of whom reported a suspected AEFI. Local reactions were the most frequently reported AEFI (4.9%), followed by headache (3.3%), fever (2.7%), fatigue (2.5%), diarrhoea (2.5%) and malaise (1.2%); 39 women (1.4%) sought medical advice and no serious vaccine-related AEFIs were identified. Response rates were higher for SMS compared to telephone (84% vs 63%; P < 0.001). These findings support the safety of TIV in pregnant women. Mobile phone technology proved an efficient method for timely surveillance of adverse events following vaccination. The low level of AEFI observed should be reassuring to antenatal patients and their providers and help promote TIV uptake. © 2014 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Monitoring signals for vaccine safety: the assessment of individual adverse event reports by an expert advisory committee. Advisory Committee on Causality Assessment.

PubMed Central

Collet, J. P.; MacDonald, N.; Cashman, N.; Pless, R.

2000-01-01

Monitoring vaccine safety is a complex and shared responsibility. It can be carried out in many ways, one of which is the reporting of individual cases of adverse reactions thought to be due to vaccination. The task is difficult because ascribing causality to an individual case report is fraught with challenges. A standardized evaluation instrument--known as the causality assessment form--was therefore developed for use by an expert advisory committee to facilitate the process. By following the several sections in this form, the members of the committee are taken through a series of points to establish causality. These points include the basic criteria for causation such as biological plausibility, the time elapsed between the vaccine administration and the onset of the adverse event, and whether other factors (drugs, chemicals or underlying disease) could account for the adverse symptoms. The form concludes with a consensus assessment of causality, a commentary about the assessment, and advice for further study or follow-up. This method of assessing the more serious cases of adverse reaction reported to vaccination has proven useful in evaluating ongoing safety of vaccines in Canada. Through analyses such as this, new signals can be identified and investigated further. PMID:10743282

Analyzing and strengthening the vaccine safety program in Manitoba

PubMed Central

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 immunogenicity of a quadrivalent inactivated influenza vaccine in adults.

PubMed

Pépin, Stéphanie; Donazzolo, Yves; Jambrecina, Alen; Salamand, Camille; Saville, Melanie

2013-11-12

Although two antigenically distinct B strain lineages of influenza have co-circulated globally since the mid-1980s, trivalent influenza vaccines (TIVs) contain only one, resulting in frequent mismatches. This study examined the safety and immunogenicity of an inactivated quadrivalent influenza vaccine (QIV) candidate. This was a phase III, randomized, active-controlled, multicenter trial in adults during the 2011/2012 influenza season. Enrollment was stratified to include equal numbers of subjects 18-60 and >60 years of age. Subjects were randomized 5:1:1 to be vaccinated with the QIV, the licensed TIV, or an investigational TIV containing the alternate B strain lineage. Hemagglutinin inhibition antibody titers were assessed pre-vaccination and 21 days post-vaccination. 1116 subjects were vaccinated with QIV, 226 with the licensed TIV, and 223 with the investigational TIV. For all four vaccine strains, antibody responses to the QIV were non-inferior to the response to the TIV for the matched strains. For both B strains, post-vaccination antibody responses to the QIV were superior to the responses to the TIVs lacking the corresponding B strain. The QIV met all European Medicines Agency criteria for all four vaccine strains. Solicited reactions, unsolicited adverse events, and serious adverse events were similar for the QIV and pooled TIV groups. The most commonly reported solicited reactions were injection-site pain, headache, and myalgia, and most solicited reactions were mild or moderate and appeared and resolved within 3 days of vaccination. No treatment-related serious adverse events or deaths were reported. The inactivated QIV was well tolerated without any safety concerns. For all four vaccine strains, antibody responses to the QIV were superior to the responses to TIV for the unmatched strains and non-inferior for the matched strains. QIV could therefore help address an unmet need due to mismatched B strains in previous influenza vaccines. EudraCT: 2011

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

PubMed

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

2017-07-13

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

Safety of pandemic H1N1 vaccines in children and adolescents.

PubMed

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

2011-10-06

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

Conflicts of interest in vaccine safety research.

PubMed

DeLong, Gayle

2012-01-01

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

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

PubMed

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

2014-08-01

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

Countermeasures and vaccination against terrorism using smallpox: pre-event and post-event smallpox vaccination and its contraindications.

PubMed

Sato, Hajime

2011-09-01

Smallpox, when used as a biological weapon, presents a serious threat to civilian populations. Core components of the public health management of a terrorism attack using smallpox are: vaccination (ring vaccination and mass vaccination), adverse event monitoring, confirmed and suspected smallpox case management, contact management, identifying, tracing, monitoring contacts, and quarantine. Above all, pre-event and post-event vaccination is an indispensable part of the strategies. Since smallpox patients are most infectious from onset of the rash through the first 7-10 days of the rash, vaccination should be administered promptly within a limited time frame. However, vaccination can accompany complications, such as postvaccinial encephalitis, progressive vaccinia, eczema vaccinatum, and generalized vaccinia. Therefore, vaccination is not recommended for certain groups. Public health professionals, as well as physicians and government officials, should also be well equipped with all information necessary for appropriate and effective smallpox management in the face of such a bioterrorism attack.

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

PubMed

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.

Safety of herpes zoster vaccine in the shingles prevention study: a randomized trial.

PubMed

Simberkoff, Michael S; Arbeit, Robert D; Johnson, Gary R; Oxman, Michael N; Boardman, Kathy D; Williams, Heather M; Levin, Myron J; Schmader, Kenneth E; Gelb, Lawrence D; Keay, Susan; Neuzil, Kathleen; Greenberg, Richard N; Griffin, Marie R; Davis, Larry E; Morrison, Vicki A; Annunziato, Paula W

2010-05-04

The herpes zoster vaccine is effective in preventing herpes zoster and postherpetic neuralgia in immunocompetent older adults. However, its safety has not been described in depth. To describe local adverse effects and short- and long-term safety profiles of herpes zoster vaccine in immunocompetent older adults. Randomized, placebo-controlled trial with enrollment from November 1998 to September 2001 and follow-up through April 2004 (mean, 3.4 years). A Veterans Affairs Coordinating Center generated the permutated block randomization scheme, which was stratified by site and age. Participants and follow-up study personnel were blinded to treatment assignments. (ClinicalTrials.gov registration number: NCT00007501) 22 U.S. academic centers. 38 546 immunocompetent adults 60 years or older, including 6616 who participated in an adverse events substudy. Single dose of herpes zoster vaccine or placebo. Serious adverse events and rashes in all participants and inoculation-site events in substudy participants during the first 42 days after inoculation. Thereafter, vaccination-related serious adverse events and deaths were monitored in all participants, and hospitalizations were monitored in substudy participants. After inoculation, 255 (1.4%) vaccine recipients and 254 (1.4%) placebo recipients reported serious adverse events. Local inoculation-site side effects were reported by 1604 (48%) vaccine recipients and 539 (16%) placebo recipients in the substudy. A total of 977 (56.6%) of the vaccine recipients reporting local side effects were aged 60 to 69 years, and 627 (39.2%) were older than 70 years. After inoculation, herpes zoster occurred in 7 vaccine recipients versus 24 placebo recipients. Long-term follow-up (mean, 3.39 years) showed that rates of hospitalization or death did not differ between vaccine and placebo recipients. Participants in the substudy were not randomly selected. Confirmation of reported serious adverse events with medical record data was not always

Safety of a Meningococcal Group B Vaccine Used in Response to Two University Outbreaks

ERIC Educational Resources Information Center

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

2017-01-01

Objective: To assess the safety of meningococcal group B (MenB)-4C vaccine. Participants: 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. Methods: Adverse events (AEs) were identified by 15 minutes of…

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

PubMed

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

2016-12-20

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

Monitoring the safety of quadrivalent human papillomavirus vaccine: findings from the Vaccine Safety Datalink.

PubMed

Gee, Julianne; Naleway, Allison; Shui, Irene; Baggs, James; Yin, Ruihua; Li, Rong; Kulldorff, Martin; Lewis, Edwin; Fireman, Bruce; Daley, Matthew F; Klein, Nicola P; Weintraub, Eric S

2011-10-26

In 7 large managed care organizations (MCOs), we performed a post-licensure safety assessment of quadrivalent human papillomavirus vaccine (HPV4) among 9-26 year-old female vaccine recipients between August 2006 and October 2009. Sequential analyses were conducted weekly to detect associations between HPV4 exposure and pre-specified outcomes. The pre-specified outcomes identified by ICD-9 codes using computerized data at the participating MCOs included: Guillan-Barré Syndrome (GBS), stroke, venous thromboembolism (VTE), appendicitis, seizures, syncope, allergic reactions, and anaphylaxis. For rare outcomes, historical background rates were used as the comparison group. For more common outcomes, a concurrent unexposed comparison group was utilized. A standardized review of medical records was conducted for all cases of GBS, VTE, and anaphylaxis. A total of 600,558 HPV4 doses were administered during the study period. We found no statistically significant increased risk for the outcomes studied. However, a non-statistically significant relative risk (RR) for VTE ICD-9 codes following HPV4 vaccination of 1.98 was detected among females age 9-17 years. Medical record review of all 8 vaccinated potential VTE cases in this age group revealed that 5 met the standard case definition for VTE. All 5 confirmed cases had known risk factors for VTE (oral contraceptive use, coagulation disorders, smoking, obesity or prolonged hospitalization). In a study of over 600,000 HPV4 vaccine doses administered, no statistically significant increased risk for any of the pre-specified adverse events after vaccination was detected. Further study of a possible association with VTE following HPV4 vaccination is warranted. Published by Elsevier Ltd.

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

PubMed

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.

A systematic review of safety data reporting in clinical trials of vaccines against malaria, tuberculosis, and human immunodeficiency virus.

PubMed

Tamminga, Cindy; Kavanaugh, Michael; Fedders, Charlotte; Maiolatesi, Santina; Abraham, Neethu; Bonhoeffer, Jan; Heininger, Ulrich; Vasquez, Carlos S; Moorthy, Vasee S; Epstein, Judith E; Richie, Thomas L

2013-08-02

Malaria, tuberculosis (TB) and human immunodeficiency virus (HIV) are diseases with devastating effects on global public health, especially in the developing world. Clinical trials of candidate vaccines for these diseases are being conducted at an accelerating rate, and require accurate and consistent methods for safety data collection and reporting. We performed a systematic review of publications describing the safety results from clinical trials of malaria, TB and HIV vaccines, to ascertain the nature and consistency of safety data collection and reporting. The target for the review was pre-licensure trials for malaria, TB and HIV vaccines published in English from 2000 to 2009. Search strategies were customized for each of the databases utilized (MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews and the Database of Reviews and Effects). Data extracted included age of trial participants, vaccine platform, route and method of vaccine administration, duration of participant follow-up, reporting of laboratory abnormalities, and the type, case definitions, severity, reporting methods and internal reporting consistency of adverse events. Of 2278 publications screened, 124 were eligible for inclusion (malaria: 66, TB: 9, HIV: 49). Safety data reporting was found to be highly variable among publications and often incomplete: overall, 269 overlapping terms were used to describe specific adverse events. 17% of publications did not mention fever. Descriptions of severity or degree of relatedness to immunization of adverse events were frequently omitted. 26% (32/124) of publications failed to report data on serious adverse events. The review demonstrated lack of standardized safety data reporting in trials for vaccines against malaria, TB and HIV. Standardization of safety data collection and reporting should be encouraged to improve data quality and comparability. The search strategy missed studies published in languages other than English and excluded studies

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

PubMed

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

2016-06-17

In 1999, the Global Advisory Committee on Vaccine Safety (GACVS) was established by the World Health Organization (WHO) to provide independent scientific advice on issues relating to the safety of vaccines and immunization. Fifteen years onward, we conducted a multi-faceted review to evaluate the impact, reach and challenges facing GACVS, including the role GACVS plays in informing global, regional and WHO member state vaccine policy. The methods included measures of organizational structure, citation impact, themes approached, and a discussion by previous and current members to evaluate past, present and future challenges. Given the increasing range of data sources and the deployment of many new vaccines, the Committee is facing the complex task of identifying the best available evidence for recommendations on vaccine safety. To help meet the increased demand for public transparency in decision making, GACVS-structured methodology for evidence-based decisions is evolving. GACVS also promotes best practices and capacity building for timely and accurate risk assessment; risk communications; outreach to help countries maintain and, if needed, rebuild public trust in vaccines; and advocacy for bridging the major gaps in vaccine safety capacity globally. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Ontology of Vaccine Adverse Events (OVAE) and its usage in representing and analyzing adverse events associated with US-licensed human vaccines.

PubMed

Marcos, Erica; Zhao, Bin; He, Yongqun

2013-11-26

Licensed human vaccines can induce various adverse events (AE) in vaccinated patients. Due to the involvement of the whole immune system and complex immunological reactions after vaccination, it is difficult to identify the relations among vaccines, adverse events, and human populations in different age groups. Many known vaccine adverse events (VAEs) have been recorded in the package inserts of US-licensed commercial vaccine products. To better represent and analyze VAEs, we developed the Ontology of Vaccine Adverse Events (OVAE) as an extension of the Ontology of Adverse Events (OAE) and the Vaccine Ontology (VO). Like OAE and VO, OVAE is aligned with the Basic Formal Ontology (BFO). The commercial vaccines and adverse events in OVAE are imported from VO and OAE, respectively. A new population term 'human vaccinee population' is generated and used to define VAE occurrence. An OVAE design pattern is developed to link vaccine, adverse event, vaccinee population, age range, and VAE occurrence. OVAE has been used to represent and classify the adverse events recorded in package insert documents of commercial vaccines licensed by the USA Food and Drug Administration (FDA). OVAE currently includes over 1,300 terms, including 87 distinct types of VAEs associated with 63 human vaccines licensed in the USA. For each vaccine, occurrence rates for every VAE in different age groups have been logically represented in OVAE. SPARQL scripts were developed to query and analyze the OVAE knowledge base data. To demonstrate the usage of OVAE, the top 10 vaccines accompanying with the highest numbers of VAEs and the top 10 VAEs most frequently observed among vaccines were identified and analyzed. Asserted and inferred ontology hierarchies classify VAEs in different levels of AE groups. Different VAE occurrences in different age groups were also analyzed. The ontology-based data representation and integration using the FDA-approved information from the vaccine package insert documents

Ontology-Based Vaccine Adverse Event Representation and Analysis.

PubMed

Xie, Jiangan; He, Yongqun

2017-01-01

), have been developed with a specific aim to standardize AE categorization. However, these controlled terminologies have many drawbacks, such as lack of textual definitions, poorly defined hierarchies, and lack of semantic axioms that provide logical relations among terms. A biomedical ontology is a set of consensus-based and computer and human interpretable terms and relations that represent entities in a specific biomedical domain and how they relate each other. To represent and analyze vaccine adverse events (VAEs), our research group has initiated and led the development of a community-based ontology: the Ontology of Adverse Events (OAE) (He et al., J Biomed Semant 5:29, 2014). The OAE has been found to have advantages to overcome the drawbacks of those controlled terminologies (He et al., Curr Pharmacol Rep :1-16. doi:10.1007/s40495-016-0055-0, 2014). By expanding the OAE and the community-based Vaccine Ontology (VO) (He et al., VO: vaccine ontology. In The 1st International Conference on Biomedical Ontology (ICBO-2009). Nature Precedings, Buffalo. http://precedings.nature.com/documents/3552/version/1 ; J Biomed Semant 2(Suppl 2):S8; J Biomed Semant 3(1):17, 2009; Ozgur et al., J Biomed Semant 2(2):S8, 2011; Lin Y, He Y, J Biomed Semant 3(1):17, 2012), we have also developed the Ontology of Vaccine Adverse Events (OVAE) to represent known VAEs associated with licensed vaccines (Marcos E, Zhao B, He Y, J Biomed Semant 4:40, 2013).In this book chapter, we will first introduce the basic information of VAEs, VAE safety surveillance systems, and how to specifically query and analyze VAEs using the US VAE database VAERS (Chen et al., Vaccine 12(10):960-960, 1994). In the second half of the chapter, we will introduce the development and applications of the OAE and OVAE. Throughout this chapter, we will use the influenza vaccine Flublok as the vaccine example to launch the corresponding elaboration (Huber VC, McCullers JA, Curr Opin Mol Ther 10(1):75-85, 2008). Flublok is a

Adverse events after tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccine administered to adults 65 years of age and older reported to the Vaccine Adverse Event Reporting System (VAERS), 2005-2010.

PubMed

Moro, Pedro L; Yue, Xin; Lewis, Paige; Haber, Penina; Broder, Karen

2011-11-21

Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine was not licensed for use in adults aged ≥65 years due to lack of sufficient efficacy and safety data. To characterize reports to the Vaccine Adverse Event Reporting System (VAERS) among adults aged ≥65 years who received Tdap vaccine 'off-label' to assess for potential vaccine safety concerns. We searched VAERS for US reports of adverse events (AEs) in subjects aged ≥65 years who received Tdap vaccine from 9/1/2005 to 9/08/2010. Medical records were requested for all reports coded as serious (death, hospitalization, prolonged hospitalization, permanent disability, life-threatening-illness). Proportional reporting ratio (PRR) was used to assess for higher proportionate reporting for AEs after Tdap compared with Td reports in subjects aged ≥65 years. VAERS received 243 reports following Tdap administered to persons aged ≥65 years. Eleven (4.5%) reports were serious, including two deaths. Most common AEs were local reactions in 100 (41.2%) reports. Seventy-eight (32.1%) reports contained coding terms that denoted inappropriate administration of vaccine. 'Cough' was the only term associated with disproportionately higher reporting after Tdap compared with Td. Six of seven Tdap reports containing the term 'Cough' were non-serious. Clinical review of serious reports identified no unusual patterns of AEs. Our VAERS review of the 'off-label' use of Tdap vaccine in adults ≥65 years did not find any safety concerns that warrant further study. These data will provide useful baseline information to assist CDC and FDA with monitoring efforts as permissive recommendations for Tdap in older persons are adopted. Published by Elsevier Ltd.

Safety of Zoster Vaccine in Elderly Adults Following Documented Herpes Zoster

PubMed Central

Morrison, Vicki A.; Oxman, Michael N.; Levin, Myron J.; Schmader, Kenneth E.; Guatelli, John C.; Betts, Robert F.; Gelb, Larry D.; Pachucki, Constance T.; Keay, Susan K.; Menzies, Barbara; Griffin, Marie R.; Kauffman, Carol A.; Marques, Adriana R.; Toney, John F.; Simberkoff, Michael S.; Serrao, Richard; Arbeit, Robert D.; Gnann, John W.; Greenberg, Richard N.; Holodniy, Mark; Keitel, Wendy A.; Yeh, Shingshing S.; Davis, Larry E.; Crawford, George E.; Neuzil, Kathy M.; Johnson, Gary R.; Zhang, Jane H.; Harbecke, Rith; Chan, Ivan S. F.; Keller, Paul M.; Williams, Heather M.; Boardman, Kathy D.; Silber, Jeffrey L.; Annunziato, Paula W.

2013-01-01

Background. After completion of the Shingles Prevention Study (SPS; Department of Veterans Affairs Cooperative Studies Program Number 403), SPS participants who had initially received placebo were offered investigational zoster vaccine without charge. This provided an opportunity to determine the relative safety of zoster vaccine in older adults following documented herpes zoster (HZ). Methods. A total of 13 681 SPS placebo recipients who elected to receive zoster vaccine were followed for serious adverse events (SAE) for 28 days after vaccination. In contrast to the SPS, a prior episode of HZ was not a contraindication to receiving zoster vaccine. The SPS placebo recipients who received zoster vaccine included 420 who had developed documented HZ during the SPS. Results. The mean interval between the onset of HZ and the receipt of zoster vaccine in the 420 recipients with prior HZ was 3.61 years (median interval, 3.77 years [range, 3–85 months]); the interval was <5 years for approximately 80% of recipients. The proportion of vaccinated SPS placebo recipients with prior HZ who developed ≥1 SAE (0.95%) was not significantly different from that of vaccinated SPS placebo recipients with no prior history of HZ (0.66%), and the distribution of SAEs in the 2 groups was comparable. Conclusions. These results demonstrate that the general safety of zoster vaccine in older persons is not altered by a recent history of documented HZ, supporting the safety aspect of the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices recommendation to administer zoster vaccine to all persons ≥60 years of age with no contraindications, regardless of a prior history of HZ. PMID:23633406

Safety of zoster vaccine in elderly adults following documented herpes zoster.

PubMed

Morrison, Vicki A; Oxman, Michael N; Levin, Myron J; Schmader, Kenneth E; Guatelli, John C; Betts, Robert F; Gelb, Larry D; Pachucki, Constance T; Keay, Susan K; Menzies, Barbara; Griffin, Marie R; Kauffman, Carol A; Marques, Adriana R; Toney, John F; Simberkoff, Michael S; Serrao, Richard; Arbeit, Robert D; Gnann, John W; Greenberg, Richard N; Holodniy, Mark; Keitel, Wendy A; Yeh, Shingshing S; Davis, Larry E; Crawford, George E; Neuzil, Kathy M; Johnson, Gary R; Zhang, Jane H; Harbecke, Rith; Chan, Ivan S F; Keller, Paul M; Williams, Heather M; Boardman, Kathy D; Silber, Jeffrey L; Annunziato, Paula W

2013-08-15

After completion of the Shingles Prevention Study (SPS; Department of Veterans Affairs Cooperative Studies Program Number 403), SPS participants who had initially received placebo were offered investigational zoster vaccine without charge. This provided an opportunity to determine the relative safety of zoster vaccine in older adults following documented herpes zoster (HZ). A total of 13 681 SPS placebo recipients who elected to receive zoster vaccine were followed for serious adverse events (SAE) for 28 days after vaccination. In contrast to the SPS, a prior episode of HZ was not a contraindication to receiving zoster vaccine. The SPS placebo recipients who received zoster vaccine included 420 who had developed documented HZ during the SPS. The mean interval between the onset of HZ and the receipt of zoster vaccine in the 420 recipients with prior HZ was 3.61 years (median interval, 3.77 years [range, 3-85 months]); the interval was <5 years for approximately 80% of recipients. The proportion of vaccinated SPS placebo recipients with prior HZ who developed ≥ 1 SAE (0.95%) was not significantly different from that of vaccinated SPS placebo recipients with no prior history of HZ (0.66%), and the distribution of SAEs in the 2 groups was comparable. These results demonstrate that the general safety of zoster vaccine in older persons is not altered by a recent history of documented HZ, supporting the safety aspect of the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices recommendation to administer zoster vaccine to all persons ≥ 60 years of age with no contraindications, regardless of a prior history of HZ.

Vaccine Safety Resources for Nurses

PubMed Central

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

2015-01-01

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

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

PubMed

Grein, K; Papadopoulos, O; Tollis, M

2007-08-01

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

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

PubMed

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

2015-12-01

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

Incidence of adverse events in ferrets vaccinated with distemper or rabies vaccine: 143 cases (1995-2001).

PubMed

Greenacre, Cheryl B

2003-09-01

To determine the incidence of adverse events in ferrets vaccinated with a modified-live avian cell culture canine distemper virus vaccine licensed for use in ferrets, an inactivated rabies vaccine licensed for use in ferrets, or both. Retrospective study. 143 ferrets. Medical records were reviewed to identify ferrets that had an adverse event after vaccination. Adverse events developed within 25 minutes after vaccination in 13 ferrets. One ferret developed an adverse event after receiving a distemper and a rabies vaccine simultaneously and developed a second adverse event the following year after receiving the rabies vaccine alone. Therefore, a total of 14 adverse events were identified. All adverse events were an anaphylactic reaction characterized by generalized hyperemia, hypersalivation, and vomiting. Ten of the 14 anaphylactic reactions occurred after ferrets received both vaccines, 3 occurred after ferrets received the distemper vaccine alone, and 1 occurred after a ferret received the rabies vaccine alone. Incidences of adverse events after administration of both vaccines, the distemper vaccine alone, and the rabies vaccine alone were 5.6, 5.9, and 5.6%, respectively. Ferrets that had an anaphylactic reaction were significantly older at the time of vaccination than were ferrets that did not. Results suggest that there may be a high incidence of anaphylactic reactions after vaccination of domestic ferrets. Ferrets should be observed for at least 25 minutes after vaccination, and veterinarians who vaccinate ferrets should be prepared to treat anaphylactic reactions.

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

PubMed

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.

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

PubMed Central

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

2014-01-01

Purpose 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). Methods 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). Results 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. Conclusion 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. PMID:24644078

Safety comparison of four types of rabies vaccines in patients with WHO category II animal exposure

PubMed Central

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

2016-01-01

Abstract 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. PMID:27893654

Safety of vaccines that have been kept outside of recommended temperatures: Reports to the Vaccine Adverse Event Reporting System (VAERS), 2008-2012.

PubMed

Hibbs, Beth F; Miller, Elaine; Shi, Jing; Smith, Kamesha; Lewis, Paige; Shimabukuro, Tom T

2018-01-25

Vaccines should be stored and handled according to manufacturer specifications. Inadequate cold chain management can affect potency; but, limited data exist on adverse events (AE) following administration of vaccines kept outside of recommended temperatures. To describe reports to the Vaccine Adverse Event Reporting System (VAERS) involving vaccines inappropriately stored outside of recommended temperatures and/or exposed to temperatures outside of manufacturer specifications for inappropriate amounts of time. We searched the VAERS database (analytic period 2008-2012) for reports describing vaccines kept outside of recommended temperatures. We analyzed reports by vaccine type, length outside of recommended temperature and type of temperature excursion, AE following receipt of potentially compromised vaccine, and reasons for cold chain breakdown. We identified 476 reports of vaccines kept outside of recommended temperatures; 77% described cluster incidents involving multiple patients. The most commonly reported vaccines were quadrivalent human papillomavirus (n = 146, 30%), 23-valent pneumococcal polysaccharide (n = 51, 11%), and measles, mumps, and rubella (n = 45, 9%). Length of time vaccines were kept outside of recommended temperatures ranged from 15 mins to 6 months (median 51 h). Most (n = 458, 96%) reports involved patients who were administered potentially compromised vaccines; AE were reported in 32 (7%), with local reactions (n = 21) most frequent. Two reports described multiple patients contracting diseases they were vaccinated against, indicating possible influenza vaccine failure. Lack of vigilance, inadequate training, and equipment failure were reasons cited for cold chain management breakdowns. Our review does not indicate any substantial direct health risk from administration of vaccines kept outside of recommended temperatures. However, there are potential costs and risks, including vaccine wastage, possible decreased

Bias correction of risk estimates in vaccine safety studies with rare adverse events using a self-controlled case series design.

PubMed

Zeng, Chan; Newcomer, Sophia R; Glanz, Jason M; Shoup, Jo Ann; Daley, Matthew F; Hambidge, Simon J; Xu, Stanley

2013-12-15

The self-controlled case series (SCCS) method is often used to examine the temporal association between vaccination and adverse events using only data from patients who experienced such events. Conditional Poisson regression models are used to estimate incidence rate ratios, and these models perform well with large or medium-sized case samples. However, in some vaccine safety studies, the adverse events studied are rare and the maximum likelihood estimates may be biased. Several bias correction methods have been examined in case-control studies using conditional logistic regression, but none of these methods have been evaluated in studies using the SCCS design. In this study, we used simulations to evaluate 2 bias correction approaches-the Firth penalized maximum likelihood method and Cordeiro and McCullagh's bias reduction after maximum likelihood estimation-with small sample sizes in studies using the SCCS design. The simulations showed that the bias under the SCCS design with a small number of cases can be large and is also sensitive to a short risk period. The Firth correction method provides finite and less biased estimates than the maximum likelihood method and Cordeiro and McCullagh's method. However, limitations still exist when the risk period in the SCCS design is short relative to the entire observation period.

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

PubMed Central

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

2018-01-01

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

Safety and Efficacy of Neonatal Vaccination

PubMed Central

Demirjian, Alicia; Levy, Ofer

2009-01-01

Newborns have an immature immune system that renders them at high risk for infection while simultaneously reducing responses to most vaccines, thereby posing challenges in protecting this vulnerable population. Nevertheless, certain vaccines, such as Bacillus Calmette Guérin (BCG) and Hepatitis B vaccine (HBV), do demonstrate safety and some efficacy at birth, providing proof of principal that certain antigen-adjuvant combinations are able to elicit protective neonatal responses. Moreover, birth is a major point of healthcare contact globally meaning that effective neonatal vaccines achieve high population penetration. Given the potentially significant benefit of vaccinating at birth, availability of a broader range of more effective neonatal vaccines is an unmet medical need and a public health priority. This review focuses on safety and efficacy of neonatal vaccination in humans as well as recent research employing novel approaches to enhance the efficacy of neonatal vaccination. PMID:19089811

Communicating vaccine safety during the development and introduction of vaccines.

PubMed

Kochhar, Sonali

2015-01-01

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

Current controversies in the USA regarding vaccine safety.

PubMed

Chatterjee, Archana; O'Keefe, Catherine

2010-05-01

As a result of the vaccines discovered in the 20th Century, parents and many healthcare providers of the 21st Century have limited or no experience with the devastating effects of diseases such as polio, smallpox or measles. Fear of disease has shifted to concerns regarding vaccine safety. Scientific evidence has refuted many of the misconceptions regarding vaccine safety; however, parental refusal of vaccines is increasing. Here we review six of the most prevalent controversies surrounding vaccine safety: the proposed causal relationship between receipt of the measles-mumps-rubella vaccine and autism; thimerosal as a potential trigger for autism; religious objection based on some vaccine viruses being grown in cell lines from aborted fetal tissues; parental worries that use of the human papillomavirus vaccine may lead to youth promiscuity; fears regarding the purported association between pertussis vaccination and adverse neurological outcomes; and concerns regarding too many vaccines overloading or weakening the infant immune system. Healthcare providers are ideally positioned to correct these misconceptions, but they must recognize and acknowledge parents' concerns, educate themselves on the latest scientific research that addresses these, and dedicate sufficient time to discuss vaccine safety with worried parents.

Differential misclassification between self-reported status and official HPV vaccination records in Japan: Implications for evaluating vaccine safety and effectiveness.

PubMed

Yamaguchi, Manako; Sekine, Masayuki; Kudo, Risa; Adachi, Sosuke; Ueda, Yutaka; Miyagi, Etsuko; Hara, Megumi; Hanley, Sharon J B; Enomoto, Takayuki

2018-05-25

Japan has no national vaccine registry and approximately 1700 municipalities manage the immunization records independently. In June 2013, proactive recommendations for the human papillomavirus (HPV) vaccine were suspended after unconfirmed reports of adverse events following immunization in the media, despite no vaccine safety signal having been raised. Furthermore, studies assessing HPV vaccine safety and effectiveness published post suspension are predominantly based on self-reported information. Our aim was to examine the accuracy of self-reported vaccination status compared with official municipal records. Participants were women aged 20-22 yrs, who were attending for cervical screening in Niigata city. Among the 1230 eligible registrants, vaccine uptake, defined as any dose, was 75.0% and 77.2% according to a self-reported questionnaire and municipal records, respectively. The accuracy rate of self-reported information was as follows: positive predictive value (PPV) was 87.7%; negative predictive value (NPV) was 54.5%; sensitivity was 85.2%; and specificity was 59.8%. The validity of self-reported information was only moderate (Kappa statistic = 0.44, 95% confidence interval 0.37-0.50). This combined with the low NPV may lead to reduced estimation of effectiveness and safety. A more reliable method, such as a national HPV vaccine registry, needs to be established for assessing HPV immunization status in Japan. Copyright © 2018. Published by Elsevier B.V.

Causality Assessment of Serious Neurologic Adverse Events Following 2009 H1N1 Vaccination

PubMed Central

Williams, S Elizabeth; Pahud, Barbara A; Vellozzi, Claudia; Donofrio, Peter D; Dekker, Cornelia L; Halsey, Neal; Klein, Nicola P; Baxter, Roger P; Marchant, Colin D; LaRussa, Philip S; Barnett, Elizabeth D; Tokars, Jerome I; McGeeney, Brian E; Sparks, Robert C; Aukes, Laurie L.; Jakob, Kathleen; Coronel, Silvia; Sejvar, James J; Slade, Barbara A; Edwards, Kathryn M

2016-01-01

Background Adverse events occurring after vaccination are routinely reported to the Vaccine Adverse Event Reporting System (VAERS). We studied serious adverse events (SAEs) of a neurologic nature reported after receipt of influenza A (H1N1) 2009 monovalent vaccine during the 2009–10 influenza season. Investigators in the Clinical Immunization Safety Assessment (CISA) Network sought to characterize these SAEs and to assess their possible causal relationship to vaccination. Methods Centers for Disease Control and Prevention (CDC) and Food and Drug Administration (FDA) physicians reviewed all SAE reports (as defined by the Code of Federal Regulations, 21CFR§314.80) after receipt of H1N1 vaccine reported to VAERS between October 1st 2009 and March 31st 2010. Non-fatal SAE reports with neurologic presentation were referred to CISA investigators, who requested and reviewed additional medical records and clinical information as available. CISA investigators assessed the causal relationship between vaccination and the event using modified WHO criteria as defined. Results 212 VAERS reports of non-fatal serious neurological events were referred for CISA review. Case reports were equally distributed by gender (50.9% female) with an age range of 6 months to 83 years (median 38 years). The most frequent diagnoses reviewed were: Guillain-Barré Syndrome (37.3%), seizures (10.8%), cranial neuropathy (5.7%), and acute disseminated encephalomyelitis (3.8%). Causality assessment resulted in classification of 72 events as “possibly” related (33%), 108 as “unlikely” related (51%), and 20 as “unrelated” (9%) to H1N1 vaccination; none were classified as “probable” or “definite” and 12 were unclassifiable (6%). Conclusion The absence of a specific test to indicate whether a vaccine component contributes to the pathogenesis of an event occurring within a biologically plausible time period makes assessing causality difficult. The development of standardized protocols

Adverse events following school-based vaccination of girls with quadrivalent human papillomavirus vaccine in Slovenia, 2009 to 2013.

PubMed

Šubelj, Maja; Učakar, Veronika; Kraigher, Alenka; Klavs, Irena

2016-01-01

Adverse events following immunisation (AEFIs) with qHPV reported to the Slovenian AEFI Registry for the first four school years of the vaccination programme were analysed. We calculated annual reporting rates for 11-14 year-old vaccinees with AEFIs, using the number of qHPV doses distributed within the school-based vaccination programme as the denominator. Between September 2009 and August 2013, 211 AEFIs that occurred in 89 vaccinees were reported, a rate of 149.5 vaccinees with AEFI per 100,000 qHPV doses distributed. For five vaccinees, serious AEFIs (8.4 per 100,000 doses distributed) were reported. The highest reporting rates were for fatigue, headache, and fever (≥ 38.0⁰) (53.8, 40.3, and 35.3 per 100,000 qHPV doses distributed, respectively). As no AEFI resulted in permanent sequelae and they all were categorised as serious only due to the criterion of a minimum of one day of hospitalisation, this provides reassurance for the safety of our school-based HPV vaccination programme. Further AEFI surveillance is warranted to provide data for HPV vaccination programme monitoring and evaluation of its safety.

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

PubMed

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

2013-10-25

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

Serious adverse events after HPV vaccination: a critical review of randomized trials and post-marketing case series.

PubMed

Martínez-Lavín, Manuel; Amezcua-Guerra, Luis

2017-10-01

This article critically reviews HPV vaccine serious adverse events described in pre-licensure randomized trials and in post-marketing case series. HPV vaccine randomized trials were identified in PubMed. Safety data were extracted. Post-marketing case series describing HPV immunization adverse events were reviewed. Most HPV vaccine randomized trials did not use inert placebo in the control group. Two of the largest randomized trials found significantly more severe adverse events in the tested HPV vaccine arm of the study. Compared to 2871 women receiving aluminum placebo, the group of 2881 women injected with the bivalent HPV vaccine had more deaths on follow-up (14 vs. 3, p = 0.012). Compared to 7078 girls injected with the 4-valent HPV vaccine, 7071 girls receiving the 9-valent dose had more serious systemic adverse events (3.3 vs. 2.6%, p = 0.01). For the 9-valent dose, our calculated number needed to seriously harm is 140 (95% CI, 79–653) [DOSAGE ERROR CORRECTED] . The number needed to vaccinate is 1757 (95% CI, 131 to infinity). Practically, none of the serious adverse events occurring in any arm of both studies were judged to be vaccine-related. Pre-clinical trials, post-marketing case series, and the global drug adverse reaction database (VigiBase) describe similar post-HPV immunization symptom clusters. Two of the largest randomized HPV vaccine trials unveiled more severe adverse events in the tested HPV vaccine arm of the study. Nine-valent HPV vaccine has a worrisome number needed to vaccinate/number needed to harm quotient. Pre-clinical trials and post-marketing case series describe similar post-HPV immunization symptoms.

Safety and Immunogenicity of a Candidate Parvovirus B19 Vaccine

PubMed Central

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 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. PMID:21807052

Safety and immunogenicity of a candidate parvovirus B19 vaccine.

PubMed

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.

Canadian Adverse Events Following Immunization Surveillance System (CAEFISS): Annual report for vaccines administered in 2012

PubMed Central

Law, BJ; Laflèche, J; Ahmadipour, N; Anyoti, H

2014-01-01

Background To describe the adverse event following immunization (AEFI) reporting profile for vaccines administered in Canada during 2012 and surveillance trends relative to reports for vaccines administered from 2005 through 2011. Methods Analysis of data based on AEFI reports received by the Public Health Agency of Canada by April 30, 2013, for vaccines marketed in Canada and administered from January 1, 2005, through December 31, 2012. Results The AEFI reporting rate was 10.1 per 100,000 population in Canada for vaccines administered in 2012 and was inversely proportional to age. There was a trend of declining rates from 2005 (14.8) to 2012 overall and by age group. The vast majority of reports (94%−95%) were non-serious involving reactions at or near the vaccination site, rash and febrile events. Conclusion Canada has a strong pharmacovigilance system for vaccines with one of the highest AEFI reporting rates in developed countries. Vaccines marketed in Canada have a very good safety profile. This report enables comparisons across jurisdictions in Canada and globally. PMID:29769908

Reference set for performance testing of pediatric vaccine safety signal detection methods and systems.

PubMed

Brauchli Pernus, Yolanda; Nan, Cassandra; Verstraeten, Thomas; Pedenko, Mariia; Osokogu, Osemeke U; Weibel, Daniel; Sturkenboom, Miriam; Bonhoeffer, Jan

2016-12-12

Safety signal detection in spontaneous reporting system databases and electronic healthcare records is key to detection of previously unknown adverse events following immunization. Various statistical methods for signal detection in these different datasources have been developed, however none are geared to the pediatric population and none specifically to vaccines. A reference set comprising pediatric vaccine-adverse event pairs is required for reliable performance testing of statistical methods within and across data sources. The study was conducted within the context of the Global Research in Paediatrics (GRiP) project, as part of the seventh framework programme (FP7) of the European Commission. Criteria for the selection of vaccines considered in the reference set were routine and global use in the pediatric population. Adverse events were primarily selected based on importance. Outcome based systematic literature searches were performed for all identified vaccine-adverse event pairs and complemented by expert committee reports, evidence based decision support systems (e.g. Micromedex), and summaries of product characteristics. Classification into positive (PC) and negative control (NC) pairs was performed by two independent reviewers according to a pre-defined algorithm and discussed for consensus in case of disagreement. We selected 13 vaccines and 14 adverse events to be included in the reference set. From a total of 182 vaccine-adverse event pairs, we classified 18 as PC, 113 as NC and 51 as unclassifiable. Most classifications (91) were based on literature review, 45 were based on expert committee reports, and for 46 vaccine-adverse event pairs, an underlying pathomechanism was not plausible classifying the association as NC. A reference set of vaccine-adverse event pairs was developed. We propose its use for comparing signal detection methods and systems in the pediatric population. Published by Elsevier Ltd.

Safety of quadrivalent live attenuated influenza vaccine in subjects aged 2-49years.

PubMed

Baxter, Roger; Eaton, Abigail; Hansen, John; Aukes, Laurie; Caspard, Herve; Ambrose, Christopher S

2017-03-01

Quadrivalent live attenuated influenza vaccine (Q/LAIV) was licensed in 2012 and replaced trivalent live attenuated influenza vaccine in the United States during the 2013-2014 influenza season. This study assessed the safety of Q/LAIV in children and adults aged 2-49years. This was a prospective observational cohort study using data collected from Kaiser Permanente Northern California. Post-vaccination events of interest were any hospitalization, hospitalization for lower respiratory tract infection, and the following medically attended events: hypersensitivity, seizures/convulsions, lower respiratory tract infection, wheezing, Guillain-Barré syndrome, Bell's palsy, encephalitis, neuritis, vasculitis, and narcolepsy/cataplexy. The rates of these events during the risk interval post-vaccination were compared with rates observed during reference periods later in the follow-up (within-cohort analysis) and with rates observed in frequency-matched unvaccinated controls and inactivated influenza vaccine (IIV) recipients. A total of 62,040 eligible Q/LAIV recipients were identified during the 2013-2014 influenza season. Within-cohort comparisons of all Q/LAIV recipients as well as comparisons between Q/LAIV recipients and unvaccinated controls or IIV recipients did not show any significantly higher risk of hospitalizations or medically attended events following administration of Q/LAIV. Additional analyses by setting (clinic visits, emergency department visits, and hospital admissions) and age group (2-4, 5-8, 9-17, and 18-49years) also did not reveal clinically consistent findings that suggested any increased risk after administration of Q/LAIV. In this large population study of individuals aged 2-49years, no safety signals associated with the administration of Q/LAIV were observed. A much larger study population would be needed to confidently reject any association between Q/LAIV and very rare events, specifically those with an incidence of <1 event/10,000 person

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

PubMed

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

2015-01-01

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

Neurological adverse events associated with vaccination.

PubMed

Piyasirisilp, Sucheep; Hemachudha, Thiravat

2002-06-01

Public tolerance to adverse reactions is minimal. Several reporting systems have been established to monitor adverse events following immunization. The present review summarizes data on neurologic complications following vaccination, and provides evidence that indicates whether they were directly associated with the vaccines. These complications include autism (measles vaccine), multiple sclerosis (hepatitis B vaccine), meningoencephalitis (Japanese encephalitis vaccine), Guillain-Barré syndrome and giant cell arteritis (influenza vaccine), and reactions after exposure to animal rabies vaccine. Seizures and hypotonic/hyporesponsive episodes following pertussis vaccination and potential risks associated with varicella vaccination, as well as vaccine-associated paralytic poliomyelitis following oral poliovirus vaccination, are also described. In addition, claims that complications are caused by adjuvants, preservatives and contaminants [i.e. macrophagic myofasciitis (aluminium), neurotoxicity (thimerosal), and new variant Creutzfeldt-Jakob disease (bovine-derived materials)] are discussed.

Post-marketing surveillance of live-attenuated Japanese encephalitis vaccine safety in China.

PubMed

Wang, Yali; Dong, Duo; Cheng, Gang; Zuo, Shuyan; Liu, Dawei; Du, Xiaoxi

2014-10-07

Japanese encephalitis (JE) is the most severe form of viral encephalitis in Asia and no specific treatment is available. Vaccination provides an effective intervention to prevent JE. In this paper, surveillance data for adverse events following immunization (AEFI) related to SA-14-14-2 live-attenuated Japanese encephalitis vaccine (Chengdu Institute of Biological Products) was presented. This information has been routinely generated by the Chinese national surveillance system for the period 2009-2012. There were 6024 AEFI cases (estimated reported rate 96.55 per million doses). Most common symptoms of adverse events were fever, redness, induration and skin rash. There were 70 serious AEFI cases (1.12 per million doses), including 9 cases of meningoencephalitis and 4 cases of death. The post-marketing surveillance data add the evidence that the Chengdu institute live attenutated vaccine has a reasonable safety profile. The relationship between encephalitis and SA-14-14-2 vaccination should be further studied. Copyright © 2014 Elsevier Ltd. All rights reserved.

Adverse Events following 12 and 18 Month Vaccinations: a Population-Based, Self-Controlled Case Series Analysis

PubMed Central

Wilson, Kumanan; Hawken, Steven; Kwong, Jeffrey C.; Deeks, Shelley; Crowcroft, Natasha S.; Van Walraven, Carl; Potter, Beth K.; Chakraborty, Pranesh; Keelan, Jennifer; Pluscauskas, Michael; Manuel, Doug

2011-01-01

Background Live vaccines have distinct safety profiles, potentially causing systemic reactions one to 2 weeks after administration. In the province of Ontario, Canada, live MMR vaccine is currently recommended at age 12 months and 18 months. Methods Using the self-controlled case series design we examined 271,495 12 month vaccinations and 184,312 18 month vaccinations to examine the relative incidence of the composite endpoint of emergency room visits or hospital admissions in consecutive one day intervals following vaccination. These were compared to a control period 20 to 28 days later. In a post-hoc analysis we examined the reasons for emergency room visits and the average acuity score at presentation for children during the at-risk period following the 12 month vaccine. Results Four to 12 days post 12 month vaccination, children had a 1.33 (1.29–1.38) increased relative incidence of the combined endpoint compared to the control period, or at least one event during the risk interval for every 168 children vaccinated. Ten to 12 days post 18 month vaccination, the relative incidence was 1.25 (95%, 1.17–1.33) which represented at least one excess event for every 730 children vaccinated. The primary reason for increased events was statistically significant elevations in emergency room visits following all vaccinations. There were non-significant increases in hospital admissions. There were an additional 20 febrile seizures for every 100,000 vaccinated at 12 months. Conclusions There are significantly elevated risks of primarily emergency room visits approximately one to two weeks following 12 and 18 month vaccination. Future studies should examine whether these events could be predicted or prevented. PMID:22174753

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

PubMed

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

2015-09-15

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

Adverse events following immunisation with bacille Calmette-Guérin vaccination: baseline data to inform monitoring in Australia following introduction of new unregistered BCG vaccine.

PubMed

Hendry, Alexandra J; Dey, Aditi; Beard, Frank H; Khandaker, Gulam; Hill, Richard; Macartney, Kristine K

2016-12-24

In recent years there has been a global shortage of bacille Calmette-Guérin (BCG) vaccine and, from September 2012, unregistered vaccines have needed to be used in Australia (a Danish product initially until the end of 2015, and a Polish product used in some jurisdictions from early 2016). We examined rates and types of adverse events following immunisation (AEFI) with BCG vaccine reported to the Therapeutic Goods Administration between 2009 and 2014 in children aged less than 7 years. Reporting rates of AEFI with BCG vaccine increased from 87 per 100,000 doses (registered Sanofi Pasteur product) in 2009 to 201 per 100,000 doses (unregistered Danish Statens Serum Institute product) in 2014, with Victoria having the highest rate each year. Substantial variation between jurisdictions exists, suggesting differential reporting of BCG vaccine doses administered and/or BCG vaccine-related AEFI. The most commonly reported reactions were abscess (31%), injection site reaction (27%) and lymphadenopathy/lymphadenitis (17%). This study provides baseline data on BCG vaccine safety to inform surveillance. Given the current use of unregistered vaccines in the context of vaccine supply issues, improved recording of both administered BCG vaccine doses and the reporting of BCG vaccine-related AEFI are required to facilitate close monitoring of vaccine safety.

A scan statistic for identifying optimal risk windows in vaccine safety studies using self-controlled case series design.

PubMed

Xu, Stanley; Hambidge, Simon J; McClure, David L; Daley, Matthew F; Glanz, Jason M

2013-08-30

In the examination of the association between vaccines and rare adverse events after vaccination in postlicensure observational studies, it is challenging to define appropriate risk windows because prelicensure RCTs provide little insight on the timing of specific adverse events. Past vaccine safety studies have often used prespecified risk windows based on prior publications, biological understanding of the vaccine, and expert opinion. Recently, a data-driven approach was developed to identify appropriate risk windows for vaccine safety studies that use the self-controlled case series design. This approach employs both the maximum incidence rate ratio and the linear relation between the estimated incidence rate ratio and the inverse of average person time at risk, given a specified risk window. In this paper, we present a scan statistic that can identify appropriate risk windows in vaccine safety studies using the self-controlled case series design while taking into account the dependence of time intervals within an individual and while adjusting for time-varying covariates such as age and seasonality. This approach uses the maximum likelihood ratio test based on fixed-effects models, which has been used for analyzing data from self-controlled case series design in addition to conditional Poisson models. Copyright © 2013 John Wiley & Sons, Ltd.

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

PubMed

Piedra, Pedro A

2002-04-01

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

Oral Cholera Vaccine Coverage, Barriers to Vaccination, and Adverse Events following Vaccination, Haiti, 2013.

PubMed

Tohme, Rania A; François, Jeannot; Wannemuehler, Kathleen; Iyengar, Preetha; Dismer, Amber; Adrien, Paul; Hyde, Terri B; Marston, Barbara J; Date, Kashmira; Mintz, Eric; Katz, Mark A

2015-06-01

In 2013, the first government-led oral cholera vaccination (OCV) campaign in Haiti was implemented in Petite Anse and Cerca Carvajal. To evaluate vaccination coverage, barriers to vaccination, and adverse events following vaccination, we conducted a cluster survey. We enrolled 1,121 persons from Petite Anse and 809 persons from Cerca Carvajal, categorized by 3 age groups (1-4, 5-14, >15 years). Two-dose OCV coverage was 62.5% in Petite Anse and 76.8% in Cerca Carvajal. Two-dose coverage was lowest among persons >15 years of age. In Cerca Carvajal, coverage was significantly lower for male than female respondents (69% vs. 85%; p<0.001). No major adverse events were reported. The main reason for nonvaccination was absence during the campaign. Vaccination coverage after this campaign was acceptable and comparable to that resulting from campaigns implemented by nongovernmental organizations. Future campaigns should be tailored to reach adults who are not available during daytime hours.

Immunogenicity and safety of pandemic influenza A (H1N1) 2009 vaccine: systematic review and meta-analysis.

PubMed

Yin, J Kevin; Khandaker, Gulam; Rashid, Harunor; Heron, Leon; Ridda, Iman; Booy, Robert

2011-09-01

The emergence of the 2009 H1N1 pandemic has highlighted the need to have immunogenicity and safety data on the new pandemic vaccines. There is already considerable heterogeneity in the types of vaccine available and of study performed around the world. A systematic review and meta-analysis is needed to assess the immunogenicity and safety of pandemic influenza A (H1N1) 2009 vaccines. We searched Medline, EMBASE, the Cochrane Library and other online databases up to 1st October 2010 for studies in any language comparing different pandemic H1N1 vaccines, with or without placebo, in healthy populations aged at least 6 months. The primary outcome was seroprotection according to haemagglutination inhibition (HI). Safety outcomes were adverse events. Meta-analysis was performed for the primary outcome. We identified 18 articles, 1 only on safety and 17 on immunogenicity, although 1 was a duplicate. We included 16 articles in the meta-analysis, covering 17,921 subjects. Adequate seroprotection (≥70%) was almost invariably achieved in all age groups, and even after one dose and at low antigen content (except in children under 3 years receiving one dose of non-adjuvanted vaccine). Non-adjuvanted vaccine from international companies and adjuvanted vaccines containing oil in water emulsion (e.g. AS03, MF59), rather than aluminium, performed better. Two serious vaccination-associated adverse events were reported, both of which resolved fully. No death or case of Guillain-Barré syndrome was reported. The pandemic influenza (H1N1) 2009 vaccine, with or without adjuvant, appears generally to be seroprotective after just one dose and safe among healthy populations aged ≥36 months; very young children (6-35 months) may need to receive two doses of non-adjuvanted vaccine or one dose of AS03(A/B)-adjuvanted product to achieve seroprotection. © 2011 Blackwell Publishing Ltd.

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

PubMed

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

2015-07-01

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

Biological safety concepts of genetically modified live bacterial vaccines.

PubMed

Frey, Joachim

2007-07-26

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

Safety and immunogenicity of pneumococcal protein vaccine candidates: monovalent choline-binding protein A (PcpA) vaccine and bivalent PcpA-pneumococcal histidine triad protein D vaccine.

PubMed

Bologa, Monica; Kamtchoua, Thierry; Hopfer, Robert; Sheng, Xiaohua; Hicks, Bryony; Bixler, Garvin; Hou, Victor; Pehlic, Vildana; Yuan, Tao; Gurunathan, Sanjay

2012-12-14

Pneumococcal vaccines based on protein antigens may provide expanded protection against Streptococcus pneumoniae. To evaluate safety and immunogenicity in adults of pneumococcal vaccine candidates comprising S. pneumoniae pneumococcal histidine triad protein D (PhtD) and pneumococcal choline-binding protein A (PcpA) in monovalent and bivalent formulations. This was a phase I, randomized, observer-blinded, placebo-controlled, step-wise dose-escalation study. Following a pilot safety study in which participants received one intramuscular injection of either aluminum hydroxide (AH)-adjuvanted PcpA (25 μg) or PhtD-PcpA (10 μg each), participants in the main study received AH-adjuvanted PcpA (25 μg), AH-adjuvanted PhtD-PcpA (10, 25, or 50 μg each), unadjuvanted PhtD-PcpA (25 μg each), or placebo as 2 injections 30 days apart. Assignment of successive dose cohorts was made after blinded safety reviews after each dose level. Safety endpoints included rates of solicited injection site and systemic reactions, unsolicited adverse events (AEs), serious AEs (SAEs), and safety laboratory tests. Immunogenicity endpoints included levels of anti-PhtD and anti-PcpA antibodies (ELISA). Six adults 18-50 years of age were included in the pilot study and 125 in the main study. No obvious increases in solicited reactions or unsolicited AEs were reported with escalating doses (adjuvanted vaccine) after either injection, or with repeated administration. Adjuvanted vaccine candidates were associated with a higher incidence of solicited reactions (particularly injection site reactions) than unadjuvanted vaccine candidates. However, no SAE or discontinuation due to an AE occurred. Geometric mean concentrations of anti-PhtD IgG and anti-PcpA IgG increased significantly after injection 2 compared with injection 1 at each dose level. No enhancement of immune responses was shown with adjuvanted vaccine candidates compared with the unadjuvanted vaccine candidate. In the dose

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

PubMed

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

2017-09-01

Pneumococcal, tetanus and influenza vaccinations are recommended for patients with cryopyrin-associated periodic syndromes (CAPS) when treated with immunosuppressive medication. The aim of this publication is to report the safety of pneumococcal and other vaccinations in CAPS patients. All CAPS patients followed in the β-CONFIDENT (Clinical Outcomes and Safety Registry study of Ilaris patients) registry were analysed if they had received a vaccination. The β-CONFIDENT registry is a global, long-term, prospective, observational registry, capturing and monitoring patients treated with canakinumab. Sixty-eight CAPS patients had received a total of 159 vaccine injections, 107 injections against influenza, 19 pneumococcal vaccinations, 12 against tetanus/diphtheria antigens and 21 other vaccinations. Fourteen per cent of injections had elicited at least one vaccine reaction. All five vaccine-related serious adverse events were associated with pneumococcal vaccination. Vaccine reactions were observed in 70% of pneumococcal vaccinations, compared with 7% in influenza and 17% in tetanus/diphtheria vaccinations. The odds ratios to react to the pneumococcal vaccines compared with influenza and tetanus/diphtheria vaccines were 31.0 (95% CI: 8, 119) and 10.8 (95% CI: 2, 74). Vaccine reactions after pneumococcal vaccinations were more severe and lasted significantly longer (up to 3 weeks) compared with other vaccinations. In two patients, pneumococcal vaccination also elicited symptoms consistent with systemic inflammation due to CAPS reactivation. Pneumococcal vaccines, unlike other vaccines, frequently trigger severe local and systemic inflammation in CAPS patients. Clinicians must balance potential benefits of pneumococcal immunization against safety concerns. The 13-valent pneumococcal conjugate vaccine might be favourable over the polysaccharide vaccine in CAPS patients. © The Author 2017. Published by Oxford University Press on behalf of the British Society for

Safety and immunogenicity of a live attenuated mumps vaccine

PubMed Central

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

2014-01-01

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

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

PubMed

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

2017-10-09

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

Adversomics: a new paradigm for vaccine safety and design

PubMed Central

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

2015-01-01

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

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

Code of Federal Regulations, 2013 CFR

2013-04-01

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

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

Code of Federal Regulations, 2011 CFR

2011-04-01

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

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

Code of Federal Regulations, 2012 CFR

2012-04-01

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

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

Code of Federal Regulations, 2014 CFR

2014-04-01

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

[Human papillomavirus vaccine. Efficacy and safety].

PubMed

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

2015-05-01

Human papillomavirus (HPV) related disease remains a major cause of morbidity and mortality worldwide. Prophylactic vaccines have been recognized as the most effective intervention to control for HPV-related diseases. This article reviews the major phaseii/iii trials of the bivalent (HPVs16/18), quadrivalent (HPVs6/11/16/18), and the recently approved 9-valent vaccine (HPVs6/11/16/18/31/33/45/52/58). Large trials have been conducted showing the safety, immunogenicity and high efficacy of the bivalent and quadrivalent vaccines in the prevention of pre-invasive lesions and infection, especially when administered at young ages before exposure to HPV. Trials of the 9-valent vaccine have also demonstrated the safety, immunogenicity and efficacy of the vaccine in the prevention of infection and disease associated with the vaccine types, and its potential to substantially increase the overall prevention of HPV-related diseases. Post-licensure country reports have shown the recent and early impact of these vaccines at population level after the implementation of established HPV vaccination programs, including decreases in the prevalence of vaccine HPV types, the incidence of genital warts, and the incidence of high-grade cervical abnormalities. If widely implemented, current HPV vaccines may drastically reduce the incidence of cervical cancer and other HPV-related cancers and diseases. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

Current safety issues with quadrivalent meningococcal conjugate vaccines.

PubMed

Myers, Tanya R; McNeil, Michael M

2018-05-04

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

Safety and immunogenicity of a quadrivalent intradermal influenza vaccine in adults.

PubMed

Gorse, Geoffrey J; Falsey, Ann R; Ozol-Godfrey, Ayca; Landolfi, Victoria; Tsang, Peter H

2015-02-25

An intradermal (ID) trivalent split-virion influenza vaccine (IIV3-ID) (Fluzone(®) Intradermal, Sanofi Pasteur, Swiftwater, PA) has been available in the US since the 2011/2012 influenza season for adults aged 18-64 years. This study examined whether adding a second B-lineage strain affects immunogenicity and safety. This randomized, double-blind, multicentre trial evaluated the immunogenicity and safety of an intradermal quadrivalent split-virion influenza vaccine (IIV4-ID) in adults 18-64 years of age in the US during the 2012-2013 influenza season. Participants were randomized 2:1:1 to receive a single injection of IIV4-ID, licensed IIV3-ID, or an investigational IIV3-ID containing the alternate B-lineage strain. Haemagglutination inhibition antibody titres were assessed in two-thirds of participants before vaccination and 28 days after vaccination. 1672 participants were vaccinated with IIV4-ID, 837 with licensed IIV3-ID, and 846 with an investigational IIV3-ID. For all four vaccine strains, antibody responses to IIV4-ID were statistically non-inferior to the response to the IIV3-ID vaccines containing the matched strains. For both B strains, post-vaccination antibody responses to IIV4-ID were statistically superior to the responses to IIV3-ID lacking the corresponding B strain. Adverse events were similar for IIV4-ID and IIV3-ID. The most commonly reported solicited reactions were pain, pruritus, myalgia, headache, and malaise; and most were grade 1 or 2 and appeared and resolved within 3 days of vaccination. IIV4-ID was statistically non-inferior to the two pooled IIV3-ID vaccines for the proportions of participants with at least one grade 2 or 3 systemic reaction. Antibody responses to the IIV4-ID were non-inferior to IIV3-ID for the A and matched B strains and superior for the unmatched B strains. IIV4-ID was well tolerated without any safety concerns. IIV4-ID may help address an unmet need due to mismatched B strains in previous influenza vaccines

Subunit influenza vaccines produced from cell culture or in embryonated chicken eggs: comparison of safety, reactogenicity, and immunogenicity.

PubMed

Reisinger, Keith S; Block, Stanley L; Izu, Allen; Groth, Nicola; Holmes, Sandra J

2009-09-15

This study assessed the safety, reactogenicity, and immunogenicity of an injectable cell culture-derived influenza vaccine (CCIV), compared with those of an injectable egg-based trivalent inactivated influenza vaccine (TIV). Adult subjects (n = 613; 18 to <50 years of age) were randomized (1:1) to receive either CCIV or TIV. The safety and reactogenicity of the 2 vaccines were assessed on the basis of solicited indicators and other adverse events (AEs) within 7 days of vaccination. All serious AEs and those AEs resulting in withdrawal were recorded throughout the study. Antibody titers were determined by the hemagglutination inhibition assay, using egg- and cell-derived antigens. Immunogenicity was assessed on the basis of the ratio of postvaccination (day 22) geometric mean titers (GMTs) between the 2 vaccines, seroprotection rates, and seroconversion rates. There was no clinically relevant difference between the safety and reactogenicity profiles of the 2 vaccines. The immunogenicity of CCIV was demonstrated to be noninferior to that of TIV on the basis of the ratio of postvaccination GMTs between the 2 vaccines. GMTs, seroprotection rates, and seroconversion rates were comparable between the 2 vaccines. The safety, reactogenicity, and immunogenicity of the CCIV and the egg-based TIV are comparable.

Vaccine adverse events in the new millennium: is there reason for concern?

PubMed Central

Ward, B. J.

2000-01-01

As more and more infectious agents become targets for immunization programmes, the spectrum of adverse events linked to vaccines has been widening. Although some of these links are tenuous, relatively little is known about the immunopathogenesis of even the best characterized vaccine-associated adverse events (VAAEs). The range of possible use of active immunization is rapidly expanding to include vaccines against infectious diseases that require cellular responses to provide protection (e.g. tuberculosis, herpes viral infections), therapeutic vaccines for chronic infections (e.g. human immunodeficiency virus (HIV) infection, viral hepatitis B and C), and vaccines against non-infectious conditions (e.g. cancer, autoimmune diseases). Less virulent pathogens (e.g. varicella, rotavirus in the developed world) are also beginning to be targeted, and vaccine use is being justified in terms of societal and parental "costs" rather than in straightforward morbidity and mortality costs. In the developed world the paediatric immunization schedule is becoming crowded, with pressure to administer increasing numbers of antigens simultaneously in ever simpler forms (e.g. subcomponent, peptide, and DNA vaccines). This trend, while attractive in many ways, brings hypothetical risks (e.g. genetic restriction, narrowed shield of protection, and loss of randomness), which will need to be evaluated and monitored. The available epidemiological and laboratory tools to address the issues outlined above are somewhat limited. As immunological and genetic tools improve in the years ahead, it is likely that we shall be able to explain the immunopathogenesis of many VAAEs and perhaps even anticipate and avoid some of them. However, this will only happen if the human and financial resources needed for monitoring and studying vaccine safety stay in step with the accelerating pace of vaccine development. Failure to make such a commitment would put all immunization programmes at risk. PMID

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

PubMed

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.

Evaluating the Safety of New Vaccines: Summary of a Workshop

PubMed Central

Ellenberg, Susan S.; Foulkes, Mary A.; Midthun, Karen; Goldenthal, Karen L.

2005-01-01

Public concerns about the safety of vaccines arise on a regular basis. In November 2000, a workshop titled “Evaluation of New Vaccines: How Much Safety Data?” was convened by US Public Health Service agencies, including the Food and Drug Administration, the National Institutes of Health, the Centers for Disease Control and Prevention, and the Health Resources and Services Administration, to discuss appropriate methods for evaluating the safety of new vaccines. Workshop presentations addressed the current standards and approaches for new vaccine evaluation and postlicensure surveillance, as well as public views about vaccine safety and alternative approaches that could be considered. The advantages and disadvantages of conducting large controlled trials before licensure or widespread use of a new vaccine were discussed. We summarize these presentations and discussions. PMID:15855455

Safety and immunogenicity of revaccination with reduced dose intradermal and standard dose intramuscular influenza vaccines in adults 18-64 years of age.

PubMed

Gorse, Geoffrey J; Falsey, Ann R; Johnson, Carol M; Morrison, Dennis; Fried, David L; Ervin, John E; Greenberg, David P; Ozol-Godfrey, Ayca; Landolfi, Victoria; Tsang, Peter H

2013-12-05

This clinical trial examined the safety and immunogenicity of annual revaccination with Fluzone(®) Intradermal (Sanofi Pasteur, Swiftwater, PA) vaccine compared to a standard intramuscular (IM) split-virion trivalent influenza vaccine (Fluzone(®), Sanofi Pasteur). This phase II, active-controlled, multi-centre, open-label trial was conducted in 2009 and 2010, and enrolled 1250 adults 18-64 years of age who were randomly selected from participants in a phase III influenza vaccine trial the previous year (NCT00772109). Subjects who had previously received the ID vaccine were randomized 2:1 to be revaccinated with the ID or IM vaccine and those who previously received the IM vaccine were randomized 1:1. Solicited reactions were recorded on the day of vaccination and continuing for the next 7 days, non-serious adverse events for 28 days, and serious adverse events for 6 months after vaccination. Hemagglutination inhibition antibody titres were assessed pre-vaccination and at day 28. Reactions were well-tolerated and resolved in the first 7 days, but erythema, induration, swelling, pruritus and ecchymosis were reported by more subjects receiving the ID vaccine than the IM vaccine. Compared to receipt of IM vaccine in the previous year, ID vaccine in the previous year led to statistically higher rates of erythema, swelling and induration after IM vaccine in the second year. Injection-site pain and systemic reactions did not differ between ID and IM vaccines. No treatment-related serious adverse events were reported. Geometric mean antibody titres, seroprotection rates, and seroconversion rates were non-inferior for the ID and IM vaccines for all three viral strains. The ID vaccine was as immunogenic as the IM vaccine, and raised no safety concerns. It can be used interchangeably with the IM vaccine for annual revaccination in adults 18-64 years of age in consecutive years without safety concerns. Copyright © 2013 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.

PubMed

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.

Post-marketing surveillance of adverse events following immunization with inactivated quadrivalent and trivalent influenza vaccine in health care providers in Western Australia.

PubMed

Regan, Annette K; Tracey, Lauren; Gibbs, Robyn

2015-11-17

In 2015, inactivated quadrivalent influenza vaccine (QIV) was first introduced into the Australian market. A routine vaccine safety surveillance system in Western Australia was used to conduct post-licensure surveillance of adverse events following immunization with inactivated QIV and trivalent influenza vaccines (TIV) in a sample of 1685 healthcare providers (HCPs). A similar percentage of HCPs who received QIV reported having any reaction seven days post-vaccination as HCPs who received TIV (13.6 vs. 12.8%, respectively; p=0.66). However, a slightly higher percentage of HCPs who received QIV reported pain or swelling at the injection site as compared to HCPs who received TIV (6.9% vs. 4.2%, respectively; p=0.02). No serious vaccine-associated adverse events were detected during follow-up of either vaccine. Acknowledging the study limitations, the results of this post-marketing surveillance support the safety of QIV, suggesting there is little difference in the reactogenicity of QIV as compared to TIV. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

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.

PubMed

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 <1 year. Quadrivalent meningococcal conjugate vaccination has the potential to prevent IMD caused by serogroups A, C, W and Y. This phase 3b, multinational, open-label, randomized, parallel-group, multicenter study evaluated the safety of a 4-dose series of MenACWY-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 <6%). A total of 7744 subjects were randomized with 1898 in the detailed safety arm. The percentage of subjects with severe systemic reactions was 16% after MenACWY-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

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

PubMed

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 <5 years old worldwide. To increase serotype coverage globally, a 13-valent pneumococcal conjugate 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 <12 months) received two PCV13 doses with a booster at 12-16 months of age; Group 2 (aged 12 to <24 months) received two vaccine doses only; and Group 3 (aged 24 to <72 months) received a single dose of PCV13. Statistical analyses were descriptive. The proportion of immunological "responders" achieving serotype-specific antipneumococcal polysaccharide concentrations ≥0.35μg/mL, 1-month after the last dose of 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.

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

PubMed

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

2010-05-14

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

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

PubMed

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

2016-02-03

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

The safety profile of Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y tetanus toxoid conjugate vaccine (HibMenCY).

PubMed

Rinderknecht, Stephen; Bryant, Kristina; Nolan, Terry; Pavia-Ruz, Noris; Doniz, Carlos Aranza; Weber, Miguel Angel Rodriguez; Cohen, Christopher; Aris, Emmanuel; Mesaros, Narcisa; Miller, Jacqueline M

2012-03-01

The safety profile of HibMenCY was compared with licensed Hib conjugate vaccines in a pooled analysis that included more than 8,500 subjects who were administered a four-dose series of HibMenCY or commercially available Hib vaccines at 2, 4, 6 and 12-15 mo of age in two primary vaccination and two fourth dose phase 3 studies. In all studies, HibMenCY or Hib vaccine was co-administered with age-appropriate, routinely recommended vaccines. In one primary and one fourth dose study (n = 4180), local and general symptoms were solicited using diary cards for 4 d after each dose. Serious adverse events (SAEs) and the occurrence of adverse events (AEs) indicating new onset of chronic disease (NOCD), rash, and conditions prompting Emergency Room (ER) visits were reported from dose 1 until 6 mo after dose 4. The incidences of solicited local and general symptoms were similar following HibMenCY and commercially available Hib vaccines. For some solicited symptoms (pain at the injection site and irritability), rates were lower in the HibMenCY group compared with the Hib control group (p value < 0.05). There were no statistically significant differences between groups in the incidences of SAEs, NOCDs, rash, or AEs leading to ER visits, with the exceptions of anemia and viral gastroenteritis, which occurred significantly less frequently in those receiving HibMenCY than those receiving commercially available Hib vaccines. In this pooled safety analysis, the safety profile of HibMenCY was similar to the safety profile of licensed monovalent Hib vaccines, despite the addition of meningococcal antigens. These studies are registered at www.clinicaltrials.gov NCT00345579 (primary vaccination study), NCT00345683 (fourth dose vaccination study) and NCT00289783 (primary and fourth dose vaccination studies).

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

PubMed

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

2011-01-01

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

Serious adverse events associated with yellow fever vaccine.

PubMed

de Menezes Martins, Reinaldo; Fernandes Leal, Maria da Luz; Homma, Akira

2015-01-01

Yellow fever vaccine was considered one of the safest vaccines, but in recent years it was found that it could rarely cause invasive and disseminated disease in some otherwise healthy individuals, with high lethality. After extensive studies, although some risk factors have been identified, the real cause of causes of this serious adverse event are largely unknown, but findings point to individual host factors. Meningoencephalitis, once considered to happen only in children less than 6 months of age, has also been identified in older children and adults, but with good prognosis. Efforts are being made to develop a safer yellow fever vaccine, and an inactivated vaccine or a vaccine prepared with the vaccine virus envelope produced in plants are being tested. Even with serious and rare adverse events, yellow fever vaccine is the best way to avoid yellow fever, a disease of high lethality and should be used routinely in endemic areas, and on people from non-endemic areas that could be exposed, according to a careful risk-benefit analysis.

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

PubMed

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 < .001. When combined into a block variable for analysis, two survey items measuring confidence in the value of vaccines accounted for 40% of the variance in 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.

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

PubMed

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

Responding to Vaccine Safety Signals during Pandemic Influenza: A Modeling Study

PubMed Central

Maro, Judith C.; Fryback, Dennis G.; Lieu, Tracy A.; Lee, Grace M.; Martin, David B.

2014-01-01

Background 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. Methods 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. Results 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. Conclusions 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. PMID:25536228

RotaTeq vaccine adverse events and policy considerations.

PubMed

Geier, David A; King, Paul G; Sykes, Lisa K; Geier, Mark R

2008-03-01

Rotavirus is the leading cause of severe gastroenteritis in children <5 years-old worldwide. On February 3, 2006, the US Food and Drug Administration licensed RotaTeq (Merck and Co.), a bioengineered combination of five human-bovine hybridized reassortment rotaviruses. In August of 2006, the Advisory Committee on Immunization Practices recommended RotaTeq for routine vaccination of US infants administered orally at the ages 2, 4, and 6 months. An evaluation of data reported to VAERS following the first five quarters of post-marketing surveillance of RotaTeq was undertaken. Trends in adverse events reported following RotaTeq and cost-effectiveness calculations of RotaTeq in the context of the disease burden of rotavirus in the US were examined. From February 3, 2006 through July 31, 2007, a total of 160 (of the 165 reported) intussusception and 11 (of the 16 reported) Kawasaki disease adverse event reports were identified when RotaTeq was administered or co-administered with other vaccines. Time-trend analyses showed that there were significant increases in the total number of intussusception and Kawasaki disease adverse events entered into VAERS in comparison to previous years. These observations, coupled with limited rotavirus disease burden, cost-effectiveness, and potential contact viral transmission concerns, raise serious questions regarding the use of RotaTeq in the US. Healthcare providers should diligently report adverse events following RotaTeq vaccination to VAERS, and those who have experienced a vaccine-associated adverse event should be made aware that they may be eligible for compensation from the no-fault National Vaccine Injury Compensation Program (NVICP).

Assuring the quality, safety, and efficacy of DNA vaccines.

PubMed

Robertson, J S; Griffiths, E

2001-02-01

Scientists in academia whose research is aimed at the development of a novel vaccine or approach to vaccination may not always be fully aware of the regulatory process by which a candidate vaccine becomes a licensed product. It is useful for such scientists to be aware of these processes as the development of a novel vaccine could be problematic owing to the starting material often being developed in a research laboratory under ill-defined conditions. This paper examines the regulatory process with respect to the development of a DNA vaccine. DNA vaccines present unusual safety considerations that must be addressed during preclinical safety studies, including adverse immunopathology, genotoxicity through integration into a vaccinees chromosomes, and the potential for the formation of anti-DNA antibodies.

Assuring the quality, safety, and efficacy of DNA vaccines.

PubMed

Robertson, James S; Griffiths, Elwyn

2006-01-01

Scientists in academia whose research is aimed at the development of a novel vaccine or approach to vaccination may not always be fully aware of the regulatory process by which a candidate vaccine becomes a licensed product. It is useful for such scientists to be aware of these processes, as the development of a novel vaccine could be problematic as a result of the starting material often being developed in a research laboratory under ill-defined conditions. This chapter examines the regulatory process with respect to the development of a DNA vaccine. DNA vaccines present unusual safety considerations which must be addressed during nonclinical safety studies, including adverse immunopathology, genotoxicity through integration into a vaccinee's chromosomes and the potential for the formation of anti-DNA antibodies.

Safety and immunogenicity of a quadrivalent inactivated influenza vaccine compared to licensed trivalent inactivated influenza vaccines in adults.

PubMed

Greenberg, David P; Robertson, Corwin A; Noss, Michael J; Blatter, Mark M; Biedenbender, Rex; Decker, Michael D

2013-01-21

To evaluate the safety and immunogenicity of a prototype quadrivalent inactivated influenza vaccine (QIV) containing two influenza B strains, one of each lineage, compared with licensed trivalent inactivated influenza vaccines (TIVs) containing either a Victoria B-lineage strain (2009-2010 TIV) or a Yamagata B-lineage strain (2008-2009 TIV). Healthy adults ≥18 years of age were eligible to participate in this phase II, open-label, randomized, controlled, multicenter study conducted in the US. Participants received a single dose of 2009-2010 TIV, 2008-2009 TIV, or QIV. Sera were collected before and 21 days after vaccine administration to test for hemagglutination inhibition (HAI) antibodies to each of the four influenza strains. Immunogenicity endpoints included geometric mean HAI antibody titers (GMTs) and rates of seroprotection (titer ≥1:40) and seroconversion (4-fold rise pre- to post-vaccination). Safety endpoints included frequency of solicited injection-site and systemic reactions occurring within 3 days of vaccination, and unsolicited non-serious adverse events (AEs) and serious AEs (SAEs) within 21 days of vaccination. One hundred and ninety participants were enrolled to each vaccine group. QIV induced GMTs to each A and B strain that were noninferior to those induced by the 2009-2010 and 2008-2009 TIVs (i.e., lower limit of the two-sided 95% confidence interval of the ratio of GMT(QIV)/GMT(TIV)>0.66 for each strain). Rates of seroprotection and seroconversion were similar in all groups. Incidence and severity of solicited injection-site and systemic reactions, AEs, and SAEs were similar among groups. QIV, containing two B strains (one from each B lineage), was as safe and immunogenic as licensed TIV. QIV has the potential to be a useful alternative to TIV and offer protection against both B lineages. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

PubMed Central

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 novel quadrivalent meningococcal CRM-conjugate vaccine given concomitantly with routine vaccinations in infants.

PubMed

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

2012-01-01

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

Key terms for the assessment of the safety of vaccines in pregnancy: Results of a global consultative process to initiate harmonization of adverse event definitions.

PubMed

Munoz, Flor M; Eckert, Linda O; Katz, Mark A; Lambach, Philipp; Ortiz, Justin R; Bauwens, Jorgen; Bonhoeffer, Jan

2015-11-25

The variability of terms and definitions of Adverse Events Following Immunization (AEFI) represents a missed opportunity for optimal monitoring of safety of immunization in pregnancy. In 2014, the Brighton Collaboration Foundation and the World Health Organization (WHO) collaborated to address this gap. Two Brighton Collaboration interdisciplinary taskforces were formed. A landscape analysis included: (1) a systematic literature review of adverse event definitions used in vaccine studies during pregnancy; (2) a worldwide stakeholder survey of available terms and definitions; (3) and a series of taskforce meetings. Based on available evidence, taskforces proposed key terms and concept definitions to be refined, prioritized, and endorsed by a global expert consultation convened by WHO in Geneva, Switzerland in July 2014. Using pre-specified criteria, 45 maternal and 62 fetal/neonatal events were prioritized, and key terms and concept definitions were endorsed. In addition recommendations to further improve safety monitoring of immunization in pregnancy programs were specified. This includes elaboration of disease concepts into standardized case definitions with sufficient applicability and positive predictive value to be of use for monitoring the safety of immunization in pregnancy globally, as well as the development of guidance, tools, and datasets in support of a globally concerted approach. There is a need to improve the safety monitoring of immunization in pregnancy programs. A consensus list of terms and concept definitions of key events for monitoring immunization in pregnancy is available. Immediate actions to further strengthen monitoring of immunization in pregnancy programs are identified and recommended. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Assessing the safety and immunogenicity of recombinant vesicular stomatitis virus Ebola vaccine in healthy adults: a randomized clinical trial

PubMed Central

ElSherif, May S.; Brown, Catherine; MacKinnon-Cameron, Donna; Li, Li; Racine, Trina; Alimonti, Judie; Rudge, Thomas L.; Sabourin, Carol; Silvera, Peter; Hooper, Jay W.; Kwilas, Steven A.; Kilgore, Nicole; Badorrek, Christopher; Ramsey, W. Jay; Heppner, D. Gray; Kemp, Tracy; Monath, Thomas P.; Nowak, Teresa; McNeil, Shelly A.; Langley, Joanne M.; Halperin, Scott A.

2017-01-01

BACKGROUND: The 2013–2016 Ebola virus outbreak in West Africa was the most widespread in history. In response, alive attenuated recombinant vesicular stomatitis virus (rVSV) vaccine expressing Zaire Ebolavirus glycoprotein (rVSVΔG-ZEBOV-GP) was evaluated in humans. METHODS: In a phase 1, randomized, dose-ranging, observer-blind, placebo-controlled trial, healthy adults aged 18–65 years were randomized into 4 groups of 10 to receive one of 3 vaccine doses or placebo. Follow-up visits spanned 180 days postvaccination for safety monitoring, immunogenicity testing and any rVSV virus shedding. RESULTS: Forty participants were injected with rVSVΔG-ZEBOV-GP vaccine (n = 30) or saline placebo (n = 10). No serious adverse events related to the vaccine or participant withdrawals were reported. Solicited adverse events during the 14-day follow-up period were mild to moderate and self-limited, with the exception of injection-site pain and headache. Viremia following vaccination was transient and no longer detectable after study day 3, with no virus shedding in saliva or urine. All vaccinated participants developed serum immunoglobulin G (IgG), as measured by Ebola virus envelope glycoprotein-based enzyme-linked immunosorbent assay (ELISA). Immunogenicity was comparable across all dose groups, and sustained IgG titers were detectable through to the last visit, at study day 180. INTERPRETATION: In this phase 1 study, there were no safety concerns after a single dose of rVSVΔG-ZEBOV-GP vaccine. IgG ELISA showed persistent high titers at 180 days postimmunization. There was a period of reactogenicity, but in general, the vaccine was well tolerated. This study provides evidence of the safety and immunogenicity of rVSVΔG-ZEBOV-GP vaccine and importance of its further investigation. Trial registration: Clinical-Trials.gov no., NCT02374385 PMID:28630358

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

PubMed Central

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

2016-01-01

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

Vaccine Adverse Events Reported during the First Ten Years (1998–2008) after Introduction in the State of Rondonia, Brazil

PubMed Central

Cunha, Mônica P. L.; Dórea, José G.; Marques, Rejane C.; Leão, Renata S.

2013-01-01

Despite good safety records, vaccines given to young children can cause adverse events. We investigated the reported adverse events following immunization (AEFI) of vaccines given to children of less than seven years of age during the first ten years (1998 to 2008) in the state of Rondonia, Brazil. We worked with the events related to BCG (Bacillus Calmett-Guérin), HB (hepatitis B), DTwP/Hib (diphtheria-tetanus-pertussis+Hemophillus influenza b), DTP (diphtheria-tetanus-pertussis), MMR (mumps, measles, rubella), and YF (yellow fever) vaccines because they were part of the recommended scheme. The number of doses of vaccines given was 3,231,567 with an average of AEFI of 57.2/year during the studied period. DTwP/Hib was responsible for 298 (57.8%), DTP 114 (22.9%), HB 31 (6%), MMR 28 (5.4%), BCG 24 (4.7%), and YF 20 (3.9%) of the reported AEFI. The combination of the AEFI for DTwP/Hib vaccines showed the highest number of systemic (61.4%) and local events (33.8%). Young children (≤1-year old) were more susceptible to AEFI occurring in the 6 hours (54.2%) following vaccine uptake. This study suggests significant differences in reactogenicity of vaccines and that despite limitations of the AEFI Brazilian registry system we cannot ignore underreporting and should use the system to expand our understanding of adverse events and effects. PMID:23509790

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

PubMed

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.

Preventable mix-ups of tuberculin and vaccines: reports to the US Vaccine and Drug Safety Reporting Systems.

PubMed

Chang, Soju; Pool, Vitali; O'Connell, Kathryn; Polder, Jacquelyn A; Iskander, John; Sweeney, Colleen; Ball, Robert; Braun, M Miles

2008-01-01

Errors involving the mix-up of tuberculin purified protein derivative (PPD) and vaccines leading to adverse reactions and unnecessary medical management have been reported previously. To determine the frequency of PPD-vaccine mix-ups reported to the US Vaccine Adverse Event Reporting System (VAERS) and the Adverse Event Reporting System (AERS), characterize adverse events and clusters involving mix-ups and describe reported contributory factors. We reviewed AERS reports from 1969 to 2005 and VAERS reports from 1990 to 2005. We defined a mix-up error event as an incident in which a single patient or a cluster of patients inadvertently received vaccine instead of a PPD product or received a PPD product instead of vaccine. We defined a cluster as inadvertent administration of PPD or vaccine products to more than one patient in the same facility within 1 month. Of 115 mix-up events identified, 101 involved inadvertent administration of vaccines instead of PPD. Product confusion involved PPD and multiple vaccines. The annual number of reported mix-ups increased from an average of one event per year in the early 1990s to an average of ten events per year in the early part of this decade. More than 240 adults and children were affected and the majority reported local injection site reactions. Four individuals were hospitalized (all recovered) after receiving the wrong products. Several patients were inappropriately started on tuberculosis prophylaxis as a result of a vaccine local reaction being interpreted as a positive tuberculin skin test. Reported potential contributory factors involved both system factors (e.g. similar packaging) and human errors (e.g. failure to read label before product administration). To prevent PPD-vaccine mix-ups, proper storage, handling and administration of vaccine and PPD products is necessary.

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

PubMed Central

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

Safety and immunogenicity of an AS01-adjuvanted varicella-zoster virus subunit candidate vaccine against herpes zoster in adults >=50 years of age.

PubMed

Chlibek, Roman; Bayas, José M; Collins, Harry; de la Pinta, Maria Luisa Rodriguez; Ledent, Edouard; Mols, Johann F; Heineman, Thomas C

2013-12-15

An adjuvanted varicella-zoster virus glycoprotein E (gE) subunit vaccine candidate for herpes zoster is in development. In this trial we compared the safety, reactogenicity, and immunogenicity of the vaccine antigen combined with different adjuvant doses. This was a phase II, observer-blind, randomized, multinational study. Adults ≥50 years old were randomized 4:4:2:1 to be vaccinated at months 0 and 2 with gE combined with a higher (AS01B) or lower (AS01E) dose adjuvant, unadjuvanted gE, or saline. Following each dose, solicited events were recorded for 7 days and unsolicited adverse events for 30 days. Serious adverse events were collected for 1 year. Cell-mediated and humoral immune responses were assessed at baseline and following each dose. No vaccine-related severe adverse events were reported. Solicited adverse events were generally mild to moderate and transient. For all gE-based vaccines, pain was the most common local symptom and fatigue the most common general symptom. Immune responses were significantly enhanced by AS01B and AS01E compared to unadjuvanted gE and were significantly stronger for gE/AS01B than for gE/AS01E. AS01 improved the immunogenicity of gE while retaining acceptable safety and reactogenicity profiles. The enhancement of gE-specific cellular and humoral responses was adjuvant dose dependent. NCT00802464.

Safety of the pentavalent rotavirus vaccine (PRV), RotaTeq(®), in Kenya, including among HIV-infected and HIV-exposed infants.

PubMed

Laserson, Kayla F; Nyakundi, Daveline; Feikin, Daniel R; Nyambane, Geoffrey; Cook, Earnest; Oyieko, Janet; Ojwando, Joel; Rivers, Stephen B; Ciarlet, Max; Neuzil, Kathleen M; Breiman, Robert F

2012-04-27

Two multicenter Phase III trials were conducted in five countries from March 2007 to March 2009 to evaluate the safety and efficacy of the pentavalent rotavirus vaccine (PRV), RotaTeq(®), in Africa and Asia. In this report, we evaluate the safety of this vaccine, including among HIV-infected and HIV-exposed infants, in Kenya. 1308 Infants were randomized 1:1 to receive 3 doses of PRV/placebo at approximately 6, 10, and 14 weeks of age. HIV counseling and testing were offered to all participants. A positive PCR result indicated HIV infection; the presence of HIV antibody in PCR-negative children indicated HIV exposure without HIV infection. All serious adverse events (SAE) within 14 days of any dose, and vaccine-related SAEs, intussusception, and deaths occurring at any time during the study, were reported ("SAE surveillance"). In addition, 297 participants were followed for 42 days after any dose for any adverse event (AE), regardless of severity ("intensive safety surveillance"). The safety evaluation was stratified by HIV status. SAEs were reported in 20/649 vaccine recipients (3.1%) and 21/643 placebo recipients (3.3%) within 14 days following vaccination (p = 0.9). The most common SAE in the vaccinated group was pneumonia (1.7%). No individual SAE was significantly more common among vaccine vs. placebo recipients. Seventy-two deaths were reported, 38 (5.9%) and 34 (5.3%) among vaccine and placebo recipients, respectively (p = 0.66). No cases of intussusception were reported. During intensive safety surveillance, 137/147 (93.2%) vaccine recipients and 147/150 (98.0%) placebo recipients experienced one or more AEs (risk ratio = 0.95; 95% CI: 0.91-1.0; p = 0.05). 88.5% of the infants were tested for HIV infection; 21/581 (3.6%) children in the vaccine group and 17/577 (2.9%) in the placebo group were HIV-infected. Among the 37 HIV-infected infants with full safety follow-up, 5/21 (23.8%) vaccine recipients and 2/16 (12.5%) placebo recipients reported an SAE (p

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

PubMed

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.

Safety and immunogenicity of a seasonal trivalent inactivated split influenza vaccine: a phase I randomized clinical trial in healthy Serbian adults

PubMed Central

Stevanovic, Goran; Lavadinovic, Lidija; Filipovic Vignjevic, Svetlana; Holt, Renée; Ilic, Katarina; Berlanda Scorza, Francesco; Sparrow, Erin; Stoiljkovic, Vera; Torelli, Guido; Madenwald, Tamra; Socquet, Muriel; Barac, Aleksandra; Ilieva-Borisova, Yordanka; Pelemis, Mijomir; Flores, Jorge

2018-01-01

ABSTRACT This study was a phase I double-blind, randomized, placebo-controlled trial to evaluate the safety and immunogenicity of a Serbian-produced seasonal trivalent split, inactivated influenza vaccine in healthy adults. The vaccine was manufactured in eggs by the Torlak Institute of Virology, Vaccines and Sera, Belgrade, Serbia and contained A/H1N1, A/H3N2 and B viruses. The clinical trial took place at the Clinical Center of Serbia in Belgrade. Sixty healthy volunteers, aged 18–45 years, were enrolled in the trial. On the day of immunization, volunteers were randomly assigned to receive either a single dose of the trivalent seasonal influenza vaccine (15 μg of hemagglutinin per strain) or placebo (phosphate-buffered saline). Subjects were monitored for adverse events through a clinical history and physical examination, and blood was taken for testing at screening and on day 8 to assess vaccine safety. Serum samples obtained before and 21 days after immunization were tested for influenza antibody titers using hemagglutination-inhibition (HAI) and microneutralization (MN) tests. No serious adverse events were reported. Pain and tenderness at the injection site were the most commonly reported symptoms in both vaccine and placebo groups. Overall, serum HAI responses of fourfold or greater magnitude were observed to H1, H3, and B antigen in 80%, 75%, and 70% of subjects, respectively. Seroprotection rates as measured by HAI were also high (100%, 100% and 86.67%, respectively, for H1, H3 and B). Thus, Torlak's seasonal trivalent influenza vaccine was not associated with adverse events, was well-tolerated and immunogenic. It should be further evaluated in clinical trials to provide sufficient safety and immunogenicity data for licensing in Serbia. PMID:29239682

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

PubMed

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

2015-01-01

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

Individual, Cultural and Structural Predictors of Vaccine Safety Confidence and Influenza Vaccination Among Hispanic Female Subgroups.

PubMed

Moran, Meghan Bridgid; Chatterjee, Joyee S; Frank, Lauren B; Murphy, Sheila T; Zhao, Nan; Chen, Nancy; Ball-Rokeach, Sandra

2017-08-01

Rates of influenza vaccination among US Hispanics are lower than for non-Hispanic whites, yet little is known about factors affecting vaccination in this population. Additionally, although Hispanics are a diverse population with culturally distinct subgroups, they are often treated as a homogenous population. This study (1) examines how confidence in vaccine safety and influenza vaccine use vary by Hispanic subgroup and (2) identifies individual, cultural and structural correlates of these outcomes. This study analyzed survey data from 1565 Hispanic women who were recruited at clinic- and community-based sites in Los Angeles. Education, healthcare coverage, acculturation, fatalism, and religiosity were predictors of influenza vaccination behavior and predictors varied by subgroup. These findings provide guidance for how influenza vaccine promotion efforts can be developed for Hispanic subgroups. Confidence in the safety of a vaccine is a major predictor of flu vaccination and an important modifiable target for intervention.

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

PubMed Central

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.

2016-01-01

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. PMID:27022153

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

PubMed

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.

Adverse events of vaccines and the consequences of non-vaccination: a critical review

PubMed Central

Aps, Luana Raposo de Melo Moraes; Piantola, Marco Aurélio Floriano; Pereira, Sara Araujo; de Castro, Julia Tavares; Santos, Fernanda Ayane de Oliveira; Ferreira, Luís Carlos de Souza

2018-01-01

ABSTRACT OBJECTIVE: To analyze the risks related to vaccines and the impacts of non-vaccination on the world population. METHODS: This is a narrative review that has considered information present in the bibliographic databases NCBI-PubMed, Medline, Lilacs, and Scientific Electronic Library Online (SciELO), between November 2015 and November 2016. For the analysis of outbreaks caused by non-vaccination, we considered the work published between 2010 and 2016. RESULTS: We have described the main components of the vaccines offered by the Brazilian public health system and the adverse events associated with these elements. Except for local inflammatory reactions and rare events, such as exacerbation of autoimmune diseases and allergies, no causal relationship has been demonstrated between the administration of vaccines and autism, Alzheimer's disease, or narcolepsy. On the other hand, the lack of information and the dissemination of non-scientific information have contributed to the reemergence of infectious diseases in several countries in the world and they jeopardize global plans for the eradication of these diseases. CONCLUSIONS: The population should be well informed about the benefits of vaccination and health professionals should assume the role of disseminating truthful information with scientific support on the subject, as an ethical and professional commitment to society. PMID:29668817

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

PubMed

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

Adverse events following immunisation with a meningococcal serogroup B vaccine: report from post-marketing surveillance, Germany, 2013 to 2016.

PubMed

Mentzer, Dirk; Oberle, Doris; Keller-Stanislawski, Brigitte

2018-04-01

Background and aimIn January 2013, a novel vaccine against Neisseria meningitidis serogroup B, the multicomponent meningococcal serogroup B vaccine (4CMenB), was approved by the European Medicines Agency. We aimed to evaluate the safety profile of this vaccine. Methods: All adverse events following immunisation (AEFI) reported from Germany since the vaccine's launch in Germany in November 2013 through December 2016 were reviewed and analysed. Results: Through December 2016, a total of 664 individual case safety reports (ICSR) notifying 1,960 AEFI were received. A majority of vaccinees for whom AEFI were reported were children 2 to 11 years of age (n = 280; 42.2%) followed by infants and toddlers aged 28 days to 23 months (n = 170; 25.6%). General disorders and administration site conditions was the System Organ Class (SOC) with the majority of AEFI (n = 977; 49.8%), followed by nervous system disorders (n = 249; 12.7%), and skin and subcutaneous tissue disorders (n = 191; 9.7%). Screening of patient records for immune-mediated and neurological diseases did not raise any safety signal in terms of an increased proportional reporting ratio (PRR). Conclusions: The safety profile described in the Summary of Product Characteristics, in general, is confirmed by data from spontaneous reporting. No safety concerns were identified.

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

PubMed Central

2014-01-01

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

Neurological adverse events temporally associated to mass vaccination against yellow fever in Juiz de Fora, Brazil, 1999-2005.

PubMed

Fernandes, Guilherme Côrtes; Camacho, Luiz Antonio Bastos; Sá Carvalho, Marilia; Batista, Maristela; de Almeida, Sonia Maria Rodrigues

2007-04-20

The identification of adverse events following immunization (AEFI) and their prompt investigation are important to allow a timely and scientifically based response to the users of immunization services. This article presents an analysis of notified AEFI cases between 1999 and 2005 and their temporal association with 2001 yellow fever vaccination campaign, AEFI notification attributed to yellow fever vaccination rose from 0.06 to 1.32 per 100,000 vaccinees in Brazil, between 1998 and 2000. During the 2001 yellow fever mass vaccination campaign held in Juiz de Fora, Brazil, 12 cases of aseptic meningitis were temporally associated to yellow fever vaccination, but clinical and laboratory data were not available to confirm nor deny causality. Epidemiological studies associated to enhanced surveillance and standardized protocols should take advantage of public health interventions like mass vaccination campaigns and implementation of new vaccination strategies in order to assess and investigate vaccine safety.

Ring vaccination with rVSV-ZEBOV under expanded access in response to an outbreak of Ebola virus disease in Guinea, 2016: an operational and vaccine safety report.

PubMed

Gsell, Pierre-Stéphane; Camacho, Anton; Kucharski, Adam J; Watson, Conall H; Bagayoko, Aminata; Nadlaou, Séverine Danmadji; Dean, Natalie E; Diallo, Abdourahamane; Diallo, Abdourahmane; Honora, Djidonou A; Doumbia, Moussa; Enwere, Godwin; Higgs, Elizabeth S; Mauget, Thomas; Mory, Diakite; Riveros, Ximena; Oumar, Fofana Thierno; Fallah, Mosoka; Toure, Alhassane; Vicari, Andrea S; Longini, Ira M; Edmunds, W J; Henao-Restrepo, Ana Maria; Kieny, Marie Paule; Kéïta, Sakoba

2017-12-01

In March, 2016, a flare-up of Ebola virus disease was reported in Guinea, and in response ring vaccination with the unlicensed rVSV-ZEBOV vaccine was introduced under expanded access, the first time that an Ebola vaccine has been used in an outbreak setting outside a clinical trial. Here we describe the safety of rVSV-ZEBOV candidate vaccine and operational feasibility of ring vaccination as a reactive strategy in a resource-limited rural setting. Approval for expanded access and compassionate use was rapidly sought and obtained from relevant authorities. Vaccination teams and frozen vaccine were flown to the outbreak settings. Rings of contacts and contacts of contacts were defined and eligible individuals, who had given informed consent, were vaccinated and followed up for 21 days under good clinical practice conditions. Between March 17 and April 21, 2016, 1510 individuals were vaccinated in four rings in Guinea, including 303 individuals aged between 6 years and 17 years and 307 front-line workers. It took 10 days to vaccinate the first participant following the confirmation of the first case of Ebola virus disease. No secondary cases of Ebola virus disease occurred among the vaccinees. Adverse events following vaccination were reported in 47 (17%) 6-17 year olds (all mild) and 412 (36%) adults (individuals older than 18 years; 98% were mild). Children reported fewer arthralgia events than adults (one [<1%] of 303 children vs 81 [7%] of 1207 adults). No severe vaccine-related adverse events were reported. The results show that a ring vaccination strategy can be rapidly and safely implemented at scale in response to Ebola virus disease outbreaks in rural settings. WHO, Gavi, and the World Food Programme. Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

Safety of engineered allergen-specific immunotherapy vaccines

PubMed Central

Focke-Tejkl, Margarete; Valenta, Rudolf

2015-01-01

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

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

PubMed Central

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

2000-01-01

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

Establishment of a New Quality Control and Vaccine Safety Test for Influenza Vaccines and Adjuvants Using Gene Expression Profiling

PubMed Central

Momose, Haruka; Mizukami, Takuo; Kuramitsu, Madoka; Takizawa, Kazuya; Masumi, Atsuko; Araki, Kumiko; Furuhata, Keiko; Yamaguchi, Kazunari; Hamaguchi, Isao

2015-01-01

We have previously identified 17 biomarker genes which were upregulated by whole virion influenza vaccines, and reported that gene expression profiles of these biomarker genes had a good correlation with conventional animal safety tests checking body weight and leukocyte counts. In this study, we have shown that conventional animal tests showed varied and no dose-dependent results in serially diluted bulk materials of influenza HA vaccines. In contrast, dose dependency was clearly shown in the expression profiles of biomarker genes, demonstrating higher sensitivity of gene expression analysis than the current animal safety tests of influenza vaccines. The introduction of branched DNA based-concurrent expression analysis could simplify the complexity of multiple gene expression approach, and could shorten the test period from 7 days to 3 days. Furthermore, upregulation of 10 genes, Zbp1, Mx2, Irf7, Lgals9, Ifi47, Tapbp, Timp1, Trafd1, Psmb9, and Tap2, was seen upon virosomal-adjuvanted vaccine treatment, indicating that these biomarkers could be useful for the safety control of virosomal-adjuvanted vaccines. In summary, profiling biomarker gene expression could be a useful, rapid, and highly sensitive method of animal safety testing compared with conventional methods, and could be used to evaluate the safety of various types of influenza vaccines, including adjuvanted vaccine. PMID:25909814

Occurrence of early adverse events after vaccination against influenza at a Brazilian reference center.

PubMed

Lopes, Marta Heloísa; Mascheretti, Melissa; Franco, Marilia Miranda; Vasconcelos, Ricardo; Gutierrez, Eliana Battaggia

2008-02-01

Since 1999, the Ministry of Health in Brazil has conducted campaigns of vaccination against influenza targeted towards the elderly, chronically-diseased people and health care workers. The vaccine against influenza is associated with adverse events of minor importance. To investigate the early adverse events related to the vaccine against influenza. CASUISTICS AND METHODS: One hundred and ninety seven elderly individuals and health care workers vaccinated against influenza were included. An inquiry regarding adverse events related to the vaccine was applied seven days after the vaccination. Local adverse events were reported by 32.5% and systemic effects by 26.4% of the vaccinated subjects. Pain in the region of the injection, headache, myalgia, malaise, and coryza were more frequent in the workers than in the elderly (p<0.05). There was no statistically significant difference in the occurrence of fever. The belief of part of the population that credits frequent and uncomfortable adverse events to the vaccine was not confirmed. The subjective adverse events were more frequent in the health care workers, which can influence, in a negative way, the disclosure of the benefits of this vaccine due to their role as opinion makers.

Assessment of Quadrivalent Human Papillomavirus Vaccine Safety Using the Self-Controlled Tree-Temporal Scan Statistic Signal-Detection Method in the Sentinel System.

PubMed

Yih, W Katherine; Maro, Judith C; Nguyen, Michael; Baker, Meghan A; Balsbaugh, Carolyn; Cole, David V; Dashevsky, Inna; Mba-Jonas, Adamma; Kulldorff, Martin

2018-06-01

The self-controlled tree-temporal scan statistic-a new signal-detection method-can evaluate whether any of a wide variety of health outcomes are temporally associated with receipt of a specific vaccine, while adjusting for multiple testing. Neither health outcomes nor postvaccination potential periods of increased risk need be prespecified. Using US medical claims data in the Food and Drug Administration's Sentinel system, we employed the method to evaluate adverse events occurring after receipt of quadrivalent human papillomavirus vaccine (4vHPV). Incident outcomes recorded in emergency department or inpatient settings within 56 days after first doses of 4vHPV received by 9- through 26.9-year-olds in 2006-2014 were identified using International Classification of Diseases, Ninth Revision, diagnosis codes and analyzed by pairing the new method with a standard hierarchical classification of diagnoses. On scanning diagnoses of 1.9 million 4vHPV recipients, 2 statistically significant categories of adverse events were found: cellulitis on days 2-3 after vaccination and "other complications of surgical and medical procedures" on days 1-3 after vaccination. Cellulitis is a known adverse event. Clinically informed investigation of electronic claims records of the patients with "other complications" did not suggest any previously unknown vaccine safety problem. Considering that thousands of potential short-term adverse events and hundreds of potential risk intervals were evaluated, these findings add significantly to the growing safety record of 4vHPV.

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

PubMed

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.

An early (3-6 weeks) active surveillance study to assess the safety of pandemic influenza vaccine Focetria in a province of Emilia-Romagna region, Italy - part one.

PubMed

Candela, Silvia; Pergolizzi, Sara; Ragni, Pietro; Cavuto, Silvio; Nobilio, Lucia; Di Mario, Simona; Dragosevic, Valentina; Groth, Nicola; Magrini, Nicola

2013-02-27

An observational, non-comparative, prospective, surveillance study of individuals vaccinated with the MF59-adjuvanted A/H1N1 influenza vaccine, Focetria, (Novartis Vaccines & Diagnostics, Siena, Italy), was performed in Italy during the 2009 A/H1N1 influenza pandemic. This study assessed the short-term (six-week) safety profile of the investigational vaccine in real time. After vaccination (N=7943), adverse events (AE) were assessed using both active (telephone) and passive (healthcare database) follow-up in enrolled vaccinated subjects, including infants (6-23 months), pregnant women, and the immunosuppressed. The treating physicians of all subjects experiencing AEs post-vaccination were consulted for clinical information on the conditions reported. All AEs were coded according to ICD-10. A total of 1583 AEs occurred during the study, 67 (4.2%) of which were serious adverse events (SAEs). One SAE was considered to be possibly related to vaccination (transitory and ill-defined neurologic disorder experienced by a 16-year-old asthmatic male). Three adverse events of special interest (AESI) were identified (convulsions experienced by two epileptic subjects), none of which were considered to be vaccine-related. Six individuals died during the study period, in each case the cause of death was not related to vaccination (four cases of severe underlying co-morbidity, one case of psychoactive drug misuse, and one case of acute myocardial infarction). No cases of clinically relevant AEs, SAEs, or AESI were observed within a six-week period of vaccine administration. In accordance with existing clinical and post-marketing safety data, the results of this active surveillance study demonstrate a good safety profile for the MF59-adjuvanted A/H1N1 vaccine, Focetria, within the general population. Copyright © 2012 Elsevier Ltd. All rights reserved.

Post-licensure surveillance of quadrivalent inactivated influenza (IIV4) vaccine in the United States, Vaccine Adverse Event Reporting System (VAERS), July 1, 2013-May 31, 2015.

PubMed

Haber, Penina; Moro, Pedro L; Lewis, Paige; Woo, Emily Jane; Jankosky, Christopher; Cano, Maria

2016-05-11

Quadrivalent inactivated influenza vaccines (IIV4) were first available for use during 2013-14 influenza season for individuals aged ≥6 months. IIV4 is designed to protect against four different flu viruses; two influenza A viruses and two influenza B viruses. We searched the Vaccine Adverse Event Reporting System (VAERS) for US reports after IIV4 and trivalent inactivated influenza vaccine (IIV3) from 7/1/2013-5/31/2015. Medical records were requested for non-manufacturer reports classified as serious (i.e. death, hospitalization, prolonged hospitalization, life-threatening illness, permanent disability). The review included automated data analysis, clinical review of all serious reports, reports of special interest, and empirical Bayesian data mining. VAERS received 1,838 IIV4 reports; 512 (28%) in persons aged 6 months-17 years of which 42 (8.2%) were serious reports; 1,265 (69%) in persons aged >18 years of which 84 (6.6%) were serious reports; two in children <6 months and 59 in persons of unknown age. Injection site erythema (24%), fever (14%) and injection site swelling (17%) were the most frequent adverse events among persons aged 6 months-17 years, while injection site pain (16%), pain (15%) and pain in extremity (13%) were the most frequent among persons aged 18-64 years given the vaccine alone. Among non-death serious reports, injection site reactions, constitutional symptoms, Guillain-Barré syndrome, seizures, and anaphylaxis were the most frequently reported adverse events. Data mining detected disproportional reporting for incorrect vaccine administration with no associated adverse events. Adverse events following IIV4 reported to VAERS were similar to those following IIV3. In our review of VAERS reports, IIV4 had a similar safety profile to IIV3. Most of the reported AEs were non-serious. Our findings are consistent with data from pre-licensure studies of IIV4. Published by Elsevier Ltd.

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

PubMed

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

2017-04-01

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

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

PubMed

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.

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.

PubMed

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

[STUDY OF SAFETY OF PAROTITIS VACCINE].

PubMed

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

2015-01-01

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

Post-licensure safety surveillance study of routine use of tetanus toxoid, reduced diphtheria toxoid and 5-component acellular pertussis vaccine.

PubMed

Baxter, Roger; Hansen, John; Timbol, Julius; Pool, Vitali; Greenberg, David P; Johnson, David R; Decker, Michael D

2016-11-01

An observational post-licensure (Phase IV) retrospective large-database safety study was conducted at Kaiser Permanente, a US integrated medical care organization, to assess the safety of Tetanus Toxoid, Reduced Diphtheria Toxoid and 5-Component Acellular Pertussis Vaccine (Tdap5) administered as part of routine healthcare among adolescents and adults. We evaluated incidence rates of various clinical events resulting in outpatient clinic, emergency department (ED), and hospital visits during various time intervals (windows) following Tdap5 vaccination using 2 pharmacoepidemiological methods (risk interval and historic cohort) and several screening thresholds. Plausible outcomes of interest with elevated incidence rate ratios (IRRs) were further evaluated by reviewing individual patient records to confirm the diagnosis, timing (temporal relationship), alternative etiology, and other health record details to discern possible relatedness of the health events to vaccination. Overall, 124,139 people received Tdap5 vaccine from September 2005 through mid-October 2006, and 203,154 in the comparison cohort received a tetanus and diphtheria toxoid adsorbed vaccine (and no live virus vaccine) during the year prior to initiation of this study. In the outpatient, ED and hospital databases, respectively, we identified 11/26, 179/700 and 187/700 unique health outcomes with IRRs significantly >1.0. Among the same unique health outcomes in the outpatient, ED, and hospital databases, 9, 146, and 385, respectively, had IRRs significantly <1.0. Further scrutiny of the outcomes with elevated IRRs did not reveal unexpected signals of adverse outcomes related to vaccination. In conclusion, Tdap5 vaccine was found to be safe among this large population of adolescents and adults.

Yellow fever vaccine-associated adverse events following extensive immunization in Argentina.

PubMed

Biscayart, Cristián; Carrega, María Eugenia Pérez; Sagradini, Sandra; Gentile, Angela; Stecher, Daniel; Orduna, Tomás; Bentancourt, Silvia; Jiménez, Salvador García; Flynn, Luis Pedro; Arce, Gabriel Pirán; Uboldi, María Andrea; Bugna, Laura; Morales, María Alejandra; Digilio, Clara; Fabbri, Cintia; Enría, Delia; Diosque, Máximo; Vizzotti, Carla

2014-03-05

As a consequence of YF outbreaks that hit Brazil, Argentina, and Paraguay in 2008-2009, a significant demand for YF vaccination was subsequently observed in Argentina, a country where the usual vaccine recommendations are restricted to provinces that border Brazil, Paraguay, and Bolivia. The goal of this paper is to describe the adverse events following immunization (AEFI) against YF in Argentina during the outbreak in the northeastern province of Misiones, which occurred from January 2008 to January 2009. During this time, a total of nine cases were reported, almost two million doses of vaccine were administered, and a total of 165 AEFI were reported from different provinces. Case study analyses were performed using two AEFI classifications. Forty-nine events were classified as related to the YF vaccine (24 serious and 1 fatal case), and 12 events were classified as inconclusive. As the use of the YF 17D vaccine can be a challenge to health systems of countries with different endemicity patterns, a careful clinical and epidemiological evaluation should be performed before its prescription to minimize serious adverse events. Copyright © 2014 Elsevier Ltd. All rights reserved.

The Immunogenicity and Safety of a Combined DTaP-IPV//Hib Vaccine Compared with Individual DTaP-IPV and Hib (PRP~T) Vaccines: a Randomized Clinical Trial in South Korean Infants.

PubMed

Kang, Jin Han; Lee, Hoan Jong; Kim, Kyung Hyo; Oh, Sung Hee; Cha, Sung Ho; Lee, Jin; Kim, Nam Hee; Eun, Byung Wook; Kim, Chang Hwi; Hong, Young Jin; Kim, Hyun Hee; Lee, Kyung Yil; Kim, Yae Jean; Cho, Eun Young; Kim, Hee Soo; Guitton, Fabrice; Ortiz, Esteban

2016-09-01

Recommended infant vaccination in Korea includes DTaP-IPV and Hib vaccines administered as separate injections. In this randomized, open, controlled study we assessed the non-inferiority of immunogenicity of DTaP-IPV//Hib pentavalent combination vaccine (Pentaxim™) compared with licensed DTaP-IPV and Hib (PRP~T) vaccines. We enrolled 418 healthy Korean infants to receive either separate DTaP-IPV and Hib vaccines (n = 206) or the pentavalent DTaP-IPV//Hib (n = 208) vaccine at 2, 4, 6 months of age. Antibodies to all components were measured before the first vaccination and one month after the third, and safety was assessed after each vaccination including recording of reactions by parents. We confirmed the non-inferiority of DTaP-IPV//Hib compared with DTaP-IPV and Hib vaccines; 100% of both groups achieved seroprotection against D, T, IPV and PRP~T, and 97.5%-99.0% demonstrated seroresponses to pertussis antigens. Antibody levels were similar in both groups, except for those to the Hib component, PRP~T. In separate and combined groups geometric mean concentrations of anti-PRP~T antibodies were 23.9 and 11.0 μg/mL, respectively, but 98.3% and 97.4% had titers ≥ 1 μg/mL, indicative of long-term protection. All vaccines were well tolerated, with no vaccine-related serious adverse event. Both groups had similar safety profiles, but the combined vaccine group had fewer injection site reactions. The immunological non-inferiority and similar safety profile of DTaP-IPV//Hib vaccine to separate DTaP-IPV and Hib vaccines, with the advantage of fewer injections and injection site reactions, supports the licensure and incorporation of DTaP-IPV//Hib into the Korean national vaccination schedule (Clinical trial registry, NCT01214889).

Evaluating efficiency and statistical power of self-controlled case series and self-controlled risk interval designs in vaccine safety.

PubMed

Li, Rongxia; Stewart, Brock; Weintraub, Eric

2016-01-01

The self-controlled case series (SCCS) and self-controlled risk interval (SCRI) designs have recently become widely used in the field of post-licensure vaccine safety monitoring to detect potential elevated risks of adverse events following vaccinations. The SCRI design can be viewed as a subset of the SCCS method in that a reduced comparison time window is used for the analysis. Compared to the SCCS method, the SCRI design has less statistical power due to fewer events occurring in the shorter control interval. In this study, we derived the asymptotic relative efficiency (ARE) between these two methods to quantify this loss in power in the SCRI design. The equation is formulated as [Formula: see text] (a: control window-length ratio between SCRI and SCCS designs; b: ratio of risk window length and control window length in the SCCS design; and [Formula: see text]: relative risk of exposed window to control window). According to this equation, the relative efficiency declines as the ratio of control-period length between SCRI and SCCS methods decreases, or with an increase in the relative risk [Formula: see text]. We provide an example utilizing data from the Vaccine Safety Datalink (VSD) to study the potential elevated risk of febrile seizure following seasonal influenza vaccine in the 2010-2011 season.

Neurologic adverse events associated with smallpox vaccination in the United States – response and comment on reporting of headaches as adverse events after smallpox vaccination among military and civilian personnel

PubMed Central

Schumm, Walter R

2006-01-01

Background Accurate reporting of adverse events occurring after vaccination is an important component of determining risk-benefit ratios for vaccinations. Controversy has developed over alleged underreporting of adverse events within U.S. military samples. This report examines the accuracy of adverse event rates recently published for headaches, and examines the issue of underreporting of headaches as a function of civilian or military sources and as a function of passive versus active surveillance. Methods A report by Sejvar et al was examined closely for accuracy with respect to the reporting of neurologic adverse events associated with smallpox vaccination in the United States. Rates for headaches were reported by several scholarly sources, in addition to Sejvar et al, permitting a comparison of reporting rates as a function of source and type of surveillance. Results Several major errors or omissions were identified in Sejvar et al. The count of civilian subjects vaccinated and the totals of both civilians and military personnel vaccinated were reported incorrectly by Sejvar et al. Counts of headaches reported in VAERS were lower (n = 95) for Sejvar et al than for Casey et al (n = 111) even though the former allegedly used 665,000 subjects while the latter used fewer than 40,000 subjects, with both using approximately the same civilian sources. Consequently, rates of nearly 20 neurologic adverse events reported by Sejvar et al were also incorrectly calculated. Underreporting of headaches after smallpox vaccination appears to increase for military samples and for passive adverse event reporting systems. Conclusion Until revised or corrected, the rates of neurologic adverse events after smallpox vaccinated reported by Sejvar et al must be deemed invalid. The concept of determining overall rates of adverse events by combining small civilian samples with large military samples appears to be invalid. Reports of headaches as adverse events after smallpox vaccination

Immunogenicity and safety of Southern Hemisphere inactivated quadrivalent influenza vaccine: a Phase III, open-label study of adults in Brazil.

PubMed

Zerbini, Cristiano A F; Ribeiro Dos Santos, Rodrigo; Jose Nunes, Maria; Soni, Jyoti; Li, Ping; Jain, Varsha K; Ofori-Anyinam, Opokua

The World Health Organization influenza forecast now includes an influenza B strain from each of the influenza B lineages (B/Yamagata and B/Victoria) for inclusion in seasonal influenza vaccines. Traditional trivalent influenza vaccines include an influenza B strain from one lineage, but because two influenza B lineages frequently co-circulate, the effectiveness of trivalent vaccines may be reduced in seasons of influenza B vaccine-mismatch. Thus, quadrivalent vaccines may potentially reduce the burden of influenza compared with trivalent vaccines. In this Phase III, open-label study, we assessed the immunogenicity and safety of Southern Hemisphere inactivated quadrivalent influenza vaccine (Fluarix™ Tetra) in Brazilian adults (NCT02369341). The primary objective was to assess hemagglutination-inhibition antibody responses against each vaccine strain 21 days after vaccination in adults (aged ≥18-60 years) and older adults (aged >60 years). Solicited adverse events for four days post-vaccination, and unsolicited adverse events and serious adverse events for 21 days post-vaccination were also assessed. A total of 63 adults and 57 older adults received one dose of inactivated quadrivalent influenza vaccine at the beginning of the 2015 Southern Hemisphere influenza season. After vaccination, in adults and older adults, the hemagglutination-inhibition titers fulfilled the European licensure criteria for immunogenicity. In adults, the seroprotection rates with HI titer ≥1:40 were 100% (A/H1N1), 98.4% (A/H3N2), 100% (B/Yamagata), and 100% (B/Victoria); in older adults were 94.7% (A/H1N1), 96.5% (A/H3N2), 100% (B/Yamagata), and 100% (B/Victoria). Pain was the most common solicited local adverse events in adults (27/62) and in older adults (13/57), and the most common solicited general adverse events in adults was myalgia (9/62), and in older adults were myalgia and arthralgia (both 2/57). Unsolicited adverse events were reported by 11/63 adults and 10/57 older adults

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

PubMed

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

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

PubMed

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

2014-01-01

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

Ten-year immune persistence and safety of the HPV-16/18 AS04-adjuvanted vaccine in females vaccinated at 15-55 years of age.

PubMed

Schwarz, Tino F; Galaj, Andrzej; Spaczynski, Marek; Wysocki, Jacek; Kaufmann, Andreas M; Poncelet, Sylviane; Suryakiran, Pemmaraju V; Folschweiller, Nicolas; Thomas, Florence; Lin, Lan; Struyf, Frank

2017-11-01

Women remain at risk of human papillomavirus (HPV) infection for most of their lives. The duration of protection against HPV-16/18 from prophylactic vaccination remains unknown. We investigated the 10-year immune response and long-term safety profile of the HPV-16/18 AS04-adjuvanted vaccine (AS04-HPV-16/18 vaccine) in females aged between 15 and 55 years at first vaccination. Females who received primary vaccination with three doses of AS04-HPV-16/18 vaccine in the primary phase-III study (NCT00196937) were invited to attend annual evaluations for long-term immunogenicity and safety. Anti-HPV-16/18 antibodies in serum and cervico-vaginal secretions (CVS) were measured using enzyme-linked immunosorbent assay (ELISA). Serious adverse events (SAEs) were recorded throughout the follow-up period. Seropositivity rates for anti-HPV-16 remained high (≥96.3%) in all age groups 10 years after first vaccination. It was found that 99.2% of 15-25-year olds remained seropositive for anti-HPV-18 compared to 93.7% and 83.8% of 26-45-year olds and 45-55-year olds, respectively. Geometric mean titers (GMT) remained above natural infection levels in all age groups. Anti-HPV-16 and anti-HPV-18 titers were at least 5.3-fold and 3.1-fold higher than titers observed after natural infection, respectively, and were predicted to persist above natural infection levels for ≥30 years in all age groups. At Year 10, anti-HPV-16/18 antibody titers in subjects aged 15-25 years remained above plateau levels observed in previous studies. Correlation coefficients for antibody titers in serum and CVS were 0.64 (anti-HPV-16) and 0.38 (anti-HPV-18). This study concluded that vaccinated females aged 15-55 years elicited sustained immunogenicity with an acceptable safety profile up to 10 years after primary vaccination, suggesting long-term protection against HPV. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

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

PubMed

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® (P< 0.05). The anti-PRN IgG, anti-tetanus and anti-diphtheria 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

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

PubMed

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

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

PubMed

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

2015-01-03

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

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

PubMed

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

2017-10-04

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

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

PubMed

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

2013-01-01

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

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

PubMed

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.

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

PubMed

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

2008-12-09

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

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

PubMed

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 <15 years in the Russian Federation. The aim of this phase III, multicenter, open-label study was to assess the immunogenicity and 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.

Quadrivalent human papillomavirus vaccine and autoimmune adverse events: a case-control assessment of the vaccine adverse event reporting system (VAERS) database.

PubMed

Geier, David A; Geier, Mark R

2017-02-01

Gardasil is a quadrivalent human papillomavirus (HPV4) vaccine that was approved for use by the US Food and Drug Administration in June 2006. HPV4 vaccine is routinely recommended for administration to women in the USA who are 11-12 years old by the Advisory Committee on Immunization Practices. Previous studies suggest HPV4 vaccine administration was associated with autoimmune diseases. As a consequence, an epidemiological assessment of the vaccine adverse event reporting system database was undertaken for adverse event reports associated with vaccines administered from 2006 to 2014 to 6-39 year-old recipients with a listed US residence and a specified female gender. Cases with the serious autoimmune adverse event (SAAE) outcomes of gastroenteritis (odds ratio (OR) 4.627, 95 % confidence interval (CI) 1.892-12.389), rheumatoid arthritis (OR 5.629, 95 % CI 2.809-12.039), thrombocytopenia (OR 2.178, 95 % CI 1.222-3.885), systemic lupus erythematosus (OR 7.626, 95 % CI 3.385-19.366), vasculitis (OR 3.420, 95 % CI 1.211-10.408), alopecia (OR 8.894, 95 % CI 6.255-12.914), CNS demyelinating conditions (OR 1.585, 95 % CI 1.129-2.213), ovarian damage (OR 14.961, 95 % CI 6.728-39.199), or irritable bowel syndrome (OR 10.021, 95 % CI 3.725-33.749) were significantly more likely than controls to have received HPV4 vaccine (median onset of initial symptoms ranged from 3 to 37 days post-HPV4 vaccination). Cases with the outcome of Guillain-Barre syndrome (OR 0.839, 95 % CI 0.601-1.145) were no more likely than controls to have received HPV4 vaccine. In addition, cases with the known HPV4-related outcome of syncope were significantly more likely than controls to have received HPV4 vaccine (OR 5.342, 95 % CI 4.942-5.777). Cases with the general health outcomes of infection (OR 0.765, 95 % CI 0.428-1.312), conjunctivitis (OR 1.010, 95 % CI 0.480-2.016), diarrhea (OR 0.927, 95 % CI 0.809-1.059), or pneumonia (OR 0.785, 95 % CI 0.481-1.246) were no more likely

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

PubMed

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

2014-01-01

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

Post-licensure safety surveillance study of routine use of tetanus toxoid, reduced diphtheria toxoid and 5-component acellular pertussis vaccine

PubMed Central

Baxter, Roger; Hansen, John; Timbol, Julius; Pool, Vitali; Greenberg, David P.; Johnson, David R.; Decker, Michael D.

2016-01-01

ABSTRACT An observational post-licensure (Phase IV) retrospective large-database safety study was conducted at Kaiser Permanente, a US integrated medical care organization, to assess the safety of Tetanus Toxoid, Reduced Diphtheria Toxoid and 5-Component Acellular Pertussis Vaccine (Tdap5) administered as part of routine healthcare among adolescents and adults. We evaluated incidence rates of various clinical events resulting in outpatient clinic, emergency department (ED), and hospital visits during various time intervals (windows) following Tdap5 vaccination using 2 pharmacoepidemiological methods (risk interval and historic cohort) and several screening thresholds. Plausible outcomes of interest with elevated incidence rate ratios (IRRs) were further evaluated by reviewing individual patient records to confirm the diagnosis, timing (temporal relationship), alternative etiology, and other health record details to discern possible relatedness of the health events to vaccination. Overall, 124,139 people received Tdap5 vaccine from September 2005 through mid-October 2006, and 203,154 in the comparison cohort received a tetanus and diphtheria toxoid adsorbed vaccine (and no live virus vaccine) during the year prior to initiation of this study. In the outpatient, ED and hospital databases, respectively, we identified 11/26, 179/700 and 187/700 unique health outcomes with IRRs significantly >1.0. Among the same unique health outcomes in the outpatient, ED, and hospital databases, 9, 146, and 385, respectively, had IRRs significantly <1.0. Further scrutiny of the outcomes with elevated IRRs did not reveal unexpected signals of adverse outcomes related to vaccination. In conclusion, Tdap5 vaccine was found to be safe among this large population of adolescents and adults. PMID:27388557

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

PubMed Central

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

2017-01-01

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

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

PubMed

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.

Safety and immunogenicity of a killed Leishmania (L.) amazonensis vaccine against cutaneous leishmaniasis in Colombia: a randomized controlled trial.

PubMed

Vélez, I D; del Pilar Agudelo, S; Arbelaez, M P; Gilchrist, K; Robledo, S M; Puerta, J A; Zicker, F; Berman, J; Modabber, F

2000-01-01

The safety and immunogenicity of an intramuscular (i.m.) and intradermal (ID) formulation of autoclaved Leishmania (Leishmania) amazonensis vaccine was evaluated in 296 volunteers in a randomized, placebo-controlled, double-blind trial in Colombia. There were 4 vaccination groups: i.m. vaccine, i.m. placebo, ID vaccine, and ID placebo. The ID formulations were mixed with BCG as adjuvant at the time of injection. For each group, 3 vaccinations were given with a 20-day interval between injections, and adverse events were monitored at 20 min, and at 2, 7 and 21 days after each injection. BCG-induced adverse reactions resulted in cancellation of the third vaccine administration in the ID groups. Antibody titres did not differ significantly between the groups. Montenegro skin-test conversion was achieved by 86.4% and 90% of the i.m. vaccine group and by 25% and 5% of the i.m. placebo group 80 days and 1 year after vaccination, respectively. A significant increase in mean Leishmania-antigen lymphocyte proliferation indexes was observed after i.m. vaccine immunization, but not after i.m. placebo immunization, 80 days and 1 year after vaccination. Significant levels of IFN gamma but not IL-10 were observed 1 year after vaccination in the i.m. vaccine group compared to the i.m. placebo group. The good safety profile and evidence of Th1 immune reactions due to i.m. vaccination in this phase-I/II study suggest that a population-based phase-III efficacy trial of the i.m. vaccine should be initiated.

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

PubMed

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

2017-08-24

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

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

PubMed Central

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

2017-01-01

ABSTRACT Background: 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. Methods: 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. Results: 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. Conclusions: The vaccination schedules with bOPV followed by one or 2 doses of IPV were

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

PubMed Central

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

2016-01-01

ABSTRACT Purpose: 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). Methods: 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. Results: 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. Conclusions: 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. PMID:27494163

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

PubMed

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 Immunogenicity Testing of a Pilot Polysaccharide Vaccine Preparation to Pseudomonas aeruginosa.

DTIC Science & Technology

1981-09-01

8217-NAL." BUR-._,AL)- ’..O,.-,.S.AN--DA. .-D-S.... . . . .A AD___________ Safety and Immunogenicity Testing of a Pilot Polysaccharide Vaccine Preparation...COVERED Safety and Immunogenicity Testing of a Pilot Annual Report Polysaccharide Vaccine Preparation to (16 Aug. 80 - 1 Aug. 81) Pseudomonas...immunogenic or biologically active component of the vaccine. The vaccine is a high molecu- lar weight polysaccharide (PS) material isolated from the outer

Burden of vaccine preventable diseases at large events.

PubMed

Alqahtani, Amani S; Alfelali, Mohammad; Arbon, Paul; Booy, Robert; Rashid, Harunor

2015-11-27

Large events or mass gatherings (MGs) are known to amplify the risk of infectious diseases, many of which can be prevented by vaccination. In this review we have evaluated the burden of vaccine preventable diseases (VPDs) in MGs. Major databases like PubMed and Embase, Google Scholar and pertinent websites were searched by using MeSH terms and text words; this was supplemented by hand searching. Following data abstraction, the pooled estimate of the burden of VPDs was calculated when possible; otherwise a narrative synthesis was conducted. In the past, at religious MGs like Hajj and Kumbh Mela, cholera caused explosive outbreaks; but currently respiratory infections, notably influenza, are the commonest diseases not only at Hajj but also at World Youth Day and Winter Olympiad. The recent cumulative attack rate of influenza at Hajj is 8.7% (range 0.7-15.8%), and the cumulative prevalence is 3.6% (range: 0.3-38%). Small outbreaks of measles (13-42 cases per event) have been reported at sport, entertainment and religious events. A sizeable outbreak (>200 cases) was reported following a special Easter Festival in Austria. An outbreak of hepatitis A occurred following the 'Jam bands' music festival. Other VPDs including pneumococcal disease, pertussis and tuberculosis have been reported in relation to MG attendance. VPDs not only affect the participants of MGs but also their contacts; vaccine uptake is variable and vaccine implementation is likely to have beneficial effects. Research to address the knowledge gaps surrounding VPDs at MGs is needed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Patterns of emergency room visits, admissions and death following recommended pediatric vaccinations - a population based study of 969,519 vaccination events.

PubMed

Wilson, Kumanan; Hawken, Steven; Potter, Beth K; Chakraborty, Pranesh; Kwong, Jeff; Crowcroft, Natasha; Rothwell, Deanna; Manuel, Doug

2011-05-12

The risk of immediate adverse events due to the inflammation created by a vaccine is a potential concern for pediatric vaccine programs. We analyzed data on children born between March 2006 and March 2009 in the province of Ontario. Using the self-controlled case series design, we examined the risk of the combined endpoint of emergency room visit and hospital admission in the immediate 3 days post vaccination to a control period 9-18 days after vaccination. We examined the end points of emergency room visits, hospital admissions and death separately as secondary outcomes. We examined 969,519 separate vaccination events. The relative incidence of our combined end point was 0.85 (0.80-0.90) for vaccination at age 2 months, 0.74 (0.69-0.79) at age 4 months and 0.68 (0.63-0.72) at age 6 months. The relative incidence was reduced for the individual endpoints of emergency room visits, admissions and death. There were 5 or fewer deaths in the risk interval of all 969,519 vaccination events. In a post hoc analysis we observed a large reduction in events in the immediate 3 days prior to vaccination suggesting a large healthy vaccinee effect. There was no increased incidence of the combined end point of emergency room visits and hospitalizations in the 3-day period immediately following vaccination, nor for individual endpoints or death. The health vaccinee effect could create the perception of worsening health following vaccines in the absence of any vaccine adverse effect and could also mask an effect in the immediate post-vaccination period. Copyright © 2011 Elsevier Ltd. All rights reserved.

Pre-event smallpox vaccination for healthcare workers revisited--the need for a carefully screened multidisciplinary cadre.

PubMed

Malone, John D

2007-03-01

As healthcare institutions are a focus of smallpox transmission early in an epidemic, several mathematical models support pre-event smallpox vaccination of healthcare workers (HCWs). The deciding factor for HCW voluntary vaccination is the risk of disease exposure versus the risk of vaccine adverse events. In a United States military population, with careful screening to exclude atopic dermatitis/eczema and immunosuppression, over 1 million vaccinia (smallpox) vaccinations were delivered with one fatality attributed to vaccination. Among 37901 United States civilian volunteer HCWs vaccinated, 100 serious adverse events were reported including 10 ischemic cardiac episodes and six myocardial infarctions - two were fatal. This older population had a higher rate of adverse events due to age-related coronary artery disease. T-cell mediated inflammatory processes induced by live vaccinia vaccination may have a role in the observed acute coronary artery events. With exclusion of individuals at risk for coronary artery disease, atopic dermatitis/eczema, and immunosuppression, HCWs can be smallpox vaccinated with minimal risk. A carefully screened multidisciplinary cadre (physician, nurse, infection control practitioner, technician), pre-event vaccinated for smallpox, will supply the necessary leadership to alleviate fear and uncertainty while limiting spread and initial mortality of smallpox.

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.

PubMed

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.

Ontology-Based Combinatorial Comparative Analysis of Adverse Events Associated with Killed and Live Influenza Vaccines

PubMed Central

Sarntivijai, Sirarat; Xiang, Zuoshuang; Shedden, Kerby A.; Markel, Howard; Omenn, Gilbert S.; Athey, Brian D.; He, Yongqun

2012-01-01

Vaccine adverse events (VAEs) are adverse bodily changes occurring after vaccination. Understanding the adverse event (AE) profiles is a crucial step to identify serious AEs. Two different types of seasonal influenza vaccines have been used on the market: trivalent (killed) inactivated influenza vaccine (TIV) and trivalent live attenuated influenza vaccine (LAIV). Different adverse event profiles induced by these two groups of seasonal influenza vaccines were studied based on the data drawn from the CDC Vaccine Adverse Event Report System (VAERS). Extracted from VAERS were 37,621 AE reports for four TIVs (Afluria, Fluarix, Fluvirin, and Fluzone) and 3,707 AE reports for the only LAIV (FluMist). The AE report data were analyzed by a novel combinatorial, ontology-based detection of AE method (CODAE). CODAE detects AEs using Proportional Reporting Ratio (PRR), Chi-square significance test, and base level filtration, and groups identified AEs by ontology-based hierarchical classification. In total, 48 TIV-enriched and 68 LAIV-enriched AEs were identified (PRR>2, Chi-square score >4, and the number of cases >0.2% of total reports). These AE terms were classified using the Ontology of Adverse Events (OAE), MedDRA, and SNOMED-CT. The OAE method provided better classification results than the two other methods. Thirteen out of 48 TIV-enriched AEs were related to neurological and muscular processing such as paralysis, movement disorders, and muscular weakness. In contrast, 15 out of 68 LAIV-enriched AEs were associated with inflammatory response and respiratory system disorders. There were evidences of two severe adverse events (Guillain-Barre Syndrome and paralysis) present in TIV. Although these severe adverse events were at low incidence rate, they were found to be more significantly enriched in TIV-vaccinated patients than LAIV-vaccinated patients. Therefore, our novel combinatorial bioinformatics analysis discovered that LAIV had lower chance of inducing these two

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

PubMed Central

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

2014-01-01

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

Events supposedly attributable to vaccination or immunization during pandemic influenza A (H1N1) vaccination campaigns in Latin America and the Caribbean.

PubMed

Ropero-Álvarez, A M; Whittembury, A; Bravo-Alcántara, P; Kurtis, H J; Danovaro-Holliday, M C; Velandia-González, M

2015-01-01

As part of the vaccination activities against influenza A[H1N1]pdm vaccine in 2009-2010, countries in Latin American and the Caribbean (LAC) implemented surveillance of events supposedly attributable to vaccines and immunization (ESAVI). We describe the serious ESAVI reported in LAC in order to further document the safety profile of this vaccine and highlight lessons learned. We reviewed data from serious H1N1 ESAVI cases from LAC countries reported to the Pan American Health Organization/World Health Organization. We estimated serious ESAVI rates by age and target group, as well as by clinical diagnosis, and completed descriptive analyses of final outcomes and classifications given in country. A total of 1000 serious ESAVI were reported by 18 of the 29 LAC countries that vaccinated against A[H1N1]pdm. The overall reporting rate in LAC was 6.91 serious ESAVI per million doses, with country reporting rates ranging from 0.77 to 64.68 per million doses. Rates were higher among pregnant women (16.25 per million doses) when compared to health care workers (13.54 per million doses) and individuals with chronic disease (4.03 per million doses). The top three most frequent diagnoses were febrile seizures (12.0%), Guillain-Barré Syndrome (10.5%) and acute pneumonia (8.0%). Almost half (49.1%) of the serious ESAVI were reported among children aged <18 years of age; within this group, the highest proportion of cases was reported among those aged <2 years (53.1%). Of all serious ESAVI reported, 37.8% were classified as coincidental, 35.3% as related to vaccine components, 26.4% as non-conclusive and 0.5% as a programmatic error. This regional overview of A[H1N1]pdm vaccine safety data in LAC estimated the rate of serious ESAVI at lower levels than other studies. However, the ESAVI diagnosis distribution is comparable to the published literature. Lessons learned can be applied in the response to future pandemics. Copyright © 2014. Published by Elsevier Ltd.

Vaccine and adjuvant design for emerging viruses

PubMed Central

McAuley, Alexander J

2011-01-01

Vaccination is currently the most effective strategy to medically control viral diseases. However, developing vaccines is a long and expensive process and traditional methods, such as attenuating wild-type viruses by serial passage, may not be suitable for all viruses and may lead to vaccine safety considerations, particularly in the case of the vaccination of particular patient groups, such as the immunocompromised and the elderly. In particular, developing vaccines against emerging viral pathogens adds a further level of complexity, as they may only be administered to small groups of people or only in response to a specific event or threat, limiting our ability to study and evaluate responses. In this commentary, we discuss how novel techniques may be used to engineer a new generation of vaccine candidates as we move toward a more targeted vaccine design strategy, driven by our understanding of the mechanisms of viral pathogenesis, attenuation and the signaling events which are required to develop a lasting, protective immunity. We will also briefly discuss the potential future role of vaccine adjuvants, which could be used to bridge the gap between vaccine safety and lasting immunity from a single vaccination. PMID:21637006

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

PubMed Central

2016-01-01

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

Immunogenicity and safety of a respiratory syncytial virus fusion protein (RSV F) nanoparticle vaccine in older adults.

PubMed

Fries, Louis; Shinde, Vivek; Stoddard, Jeffrey J; Thomas, D Nigel; Kpamegan, Eloi; Lu, Hanxin; Smith, Gale; Hickman, Somia P; Piedra, Pedro; Glenn, Gregory M

2017-01-01

A preventative strategy for Respiratory Syncytial Virus (RSV) infection constitutes an under-recognized unmet medical need among older adults. Four formulations of a novel recombinant RSV F nanoparticle vaccine (60 or 90 μg RSV F protein, with or without aluminum phosphate adjuvant) administered concurrently with a licensed inactivated trivalent influenza vaccine (TIV) in older adult subjects were evaluated for safety and immunogenicity in this randomized, observer-blinded study. A total of 220 healthy males and females ≥ 60 years of age, without symptomatic cardiopulmonary disease, were vaccinated concurrently with TIV and RSV F vaccine or placebo. All vaccine formulations produced an acceptable safety profile, with no vaccine-related serious adverse events or evidence of systemic toxicity. Vaccine-induced immune responses were rapid, rising as early as 7 days post-vaccination; and were comparable in all formulations in terms of magnitude, with maximal levels attained within 28 (unadjuvanted) or 56 (adjuvanted) days post-vaccination. Peak anti-F protein IgG antibody levels rose 3.6- to 5.6-fold, with an adjuvant effect observed at the 60 μg dose, and a dose-effect observed between the unadjuvanted 60 and 90 μg regimens. The anti-F response persisted through 12 months post-vaccination. Palivizumab-competitive antibodies were below quantifiable levels (<33 μg/mL) at day 0. The rise of antibodies with specificity for Site II peptide, and the palivizumab-competitive binding activity, denoting antibodies binding at, or in proximity to, antigenic Site II on the F protein, closely paralleled the anti-F response. However, a larger proportion of antibodies in adjuvanted vaccine recipients bound to the Site II peptide at high avidity. Day 0 neutralizing antibodies were high in all subjects and rose 1.3- to 1.7-fold in response to vaccination. Importantly, the RSV F vaccine co-administered with TIV did not impact the serum hemagglutination inhibition

Real-World Effectiveness and Safety of a Live-Attenuated Herpes Zoster Vaccine: A Comprehensive Review.

PubMed

Ansaldi, Filippo; Trucchi, Cecilia; Alicino, Cristiano; Paganino, Chiara; Orsi, Andrea; Icardi, Giancarlo

2016-07-01

Herpes zoster (HZ) is a common, painful and debilitating disease caused by the reactivation of latent varicella-zoster virus in ganglia. This clinical event occurs more frequently in the elderly and those who are immunocompromised. The most common complication of HZ is post-herpetic neuralgia (PHN) which is responsible for the highest HZ-related burden of illness and is challenging to treat. Due to the important clinical and economic impact of HZ and PHN, and the suboptimal treatments that are currently available, HZ vaccination is an important approach to reduce the burden of illness. Currently, one-dose, live-attenuated vaccine is licensed in the United States and Europe to prevent HZ and it is included in some national immunization programs. The clinical efficacy, safety and tolerability of the vaccine has been demonstrated in two large phase III clinical trials, involving more than 38,000 and 22,000 individuals aged ≥60 and 50-59 years, respectively. This comprehensive review summarizes the extensive "real-world" effectiveness and safety data from both immunocompetent and immunocompromised individuals. These data confirm those from the clinical trials, supporting the use of HZ vaccine in clinical practice and provide evidence that the current recommendations for immunocompromised individuals should be revised. Funding for the editorial assistance, article processing charges, and open access fee for this publication was provided by Sanofi Pasteur MSD.

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

PubMed

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

2012-09-01

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

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

PubMed Central

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

Immunogenicity and Safety of a Booster Dose of a Live Attenuated Japanese Encephalitis Chimeric Vaccine Given 1 Year After Primary Immunization in Healthy Children in the Republic of Korea.

PubMed

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

2016-02-01

This study evaluated the effect of a booster vaccination of a new, live attenuated, Japanese encephalitis chimeric vaccine (JE-CV). Previously this vaccine has been used as a booster 12 months after priming with an inactivated vaccine and at >24 months after priming with the same JE-CV. This study evaluates the immunogenicity and safety of the JE-CV given at 12-24 months after JE-CV priming. Phase III, open-label study in the Republic of Korea in which 119 children previously vaccinated with JE-CV at 12-24 months of age received a JE-CV booster at 12-24 months after primary vaccination. JE neutralizing antibody titers were measured using >50% plaque reduction neutralization test prebooster and 1 month postbooster vaccination. Seroprotection (SP) was defined as ≥10 (1/dil). Safety was assessed for 28 days postvaccination by parental reports. Serious adverse events were monitored for 6 months postvaccination. Antibody persistence was high prebooster (SP rate 93.5%). There was a strong anamnestic response postbooster vaccination, with an SP rate of 100% and a >50-fold increase in geometric mean titer from the prebooster level. Both antibody persistence and the booster response were independent of whether the booster was given at 12-17 or 18-24 months. The safety profile was good and comparable with the primary vaccination; there were no vaccine-related serious adverse events and no deaths. This study confirms the suitability of a JE-CV booster vaccination at 12-24 months after a primary dose of the same vaccine given at 12-24 months of age in children in the Republic of Korea.

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

PubMed

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

2017-10-27

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.

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

PubMed

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

2016-01-02

Obesity may be a risk factor for increased hospitalization and deaths from infections due to respiratory pathogens. Additionally, obese patients appear to have impaired immunity after some vaccinations. To evaluate the immunogenicity, safety and tolerability of an inactivated trivalent influenza vaccine (TIV) in overweight and obese children, 28 overweight/obese pediatric patients and 23 healthy normal weight controls aged 3-14 years received a dose of TIV. Four weeks after vaccine administration, significantly higher seroprotection rates against the A/H1N1 strain were observed among overweight/obese children compared with normal weight controls (p<0.05). Four months after vaccination, similar or slightly higher seroconversion and seroprotection rates against the A/H1N1 and A/H3N2 strains were detected in overweight/obese than in normal weight children, whereas significantly higher rates of seroconversion and seroprotection against the B strain were found in overweight/obese patients than in normal weight controls (p<0.05 for seroconversion and seroprotection). Geometric mean titers (GMTs) and fold increase against B strains were significantly higher in overweight/obese patients than in normal weight controls 4 months after vaccine administration (p<0.01 for GMT values and p<0.05 for fold increase). The frequency of local and systemic reactions was similar between the groups, and there were no serious adverse events. The results of this study indicate that in overweight and obese children, antibody response to TIV administration is similar or slightly higher than that evidenced in normal weight subjects of similar age and this situation persists for at least 4 months after vaccine administration in the presence of a favorable safety profile. Copyright © 2015 Elsevier Ltd. All rights reserved.

Developing a national system for dealing with adverse events following immunization.

PubMed Central

Mehta, U.; Milstien, J. B.; Duclos, P.; Folb, P. I.

2000-01-01

Although vaccines are among the safest of pharmaceuticals, the occasional severe adverse event or cluster of adverse events associated with their use may rapidly become a serious threat to public health. It is essential that national monitoring and reporting systems for vaccine safety are efficient and adequately coordinated with those that conventionally deal with non-vaccine pharmaceuticals. Equally important is the need for an enlightened and informed national system to be in place to deal with public concerns and rapid evaluation of the risk to public safety when adverse events occur. Described in this article is the outcome of efforts by the WHO Global Training Network to describe a simple national system for dealing with vaccine safety and with emergencies as they arise. The goals of a training programme designed to help develop such a system are also outlined. PMID:10743281

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

PubMed

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 <5years in Thailand as a primary (Group 1) or booster (Group 2) 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 (<0.1%) in Group 2. There were no cases of Japanese encephalitis reported. No Grade 3 immediate systemic AEs were reported after any JE-CV 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.

First Outbreak Response Using an Oral Cholera Vaccine in Africa: Vaccine Coverage, Acceptability and Surveillance of Adverse Events, Guinea, 2012

PubMed Central

Luquero, Francisco J.; Grout, Lise; Ciglenecki, Iza; Sakoba, Keita; Traore, Bala; Heile, Melat; Dialo, Alpha Amadou; Itama, Christian; Serafini, Micaela; Legros, Dominique; Grais, Rebecca F.

2013-01-01

Background Despite World Health Organization (WHO) prequalification of two safe and effective oral cholera vaccines (OCV), concerns about the acceptability, potential diversion of resources, cost and feasibility of implementing timely campaigns has discouraged their use. In 2012, the Ministry of Health of Guinea, with the support of Médecins Sans Frontières organized the first mass vaccination campaign using a two-dose OCV (Shanchol) as an additional control measure to respond to the on-going nationwide epidemic. Overall, 316,250 vaccines were delivered. Here, we present the results of vaccination coverage, acceptability and surveillance of adverse events. Methodology/Principal Findings We performed a cross-sectional cluster survey and implemented adverse event surveillance. The study population included individuals older than 12 months, eligible for vaccination, and residing in the areas targeted for vaccination (Forécariah and Boffa, Guinea). Data sources were household interviews with verification by vaccination card and notifications of adverse events from surveillance at vaccination posts and health centres. In total 5,248 people were included in the survey, 3,993 in Boffa and 1,255 in Forécariah. Overall, 89.4% [95%CI:86.4–91.8%] and 87.7% [95%CI:84.2–90.6%] were vaccinated during the first round and 79.8% [95%CI:75.6–83.4%] and 82.9% [95%CI:76.6–87.7%] during the second round in Boffa and Forécariah respectively. The two dose vaccine coverage (including card and oral reporting) was 75.8% [95%CI: 71.2–75.9%] in Boffa and 75.9% [95%CI: 69.8–80.9%] in Forécariah respectively. Vaccination coverage was higher in children. The main reason for non-vaccination was absence. No severe adverse events were notified. Conclusions/Significance The well-accepted mass vaccination campaign reached high coverage in a remote area with a mobile population. Although OCV should not be foreseen as the long-term solution for global cholera control, they should be

Randomized, Double-blind, Active-controlled Study Evaluating the Safety and Immunogenicity of Three Vaccination Schedules and Two Dose Levels of AV7909 Vaccine for Anthrax Post-exposure Prophylaxis in Healthy Adults

PubMed Central

Hopkins, Robert J.; Kalsi, Gurdyal; Montalvo-Lugo, Victor M.; Sharma, Mona; Wu, Yukun; Muse, Derek D.; Sheldon, Eric.A.; Hampel, Frank C.; Lemiale, Laurence

2016-01-01

AV7909 vaccine being developed for post-exposure prophylaxis of anthrax disease may require fewer vaccinations and reduced amount of antigen to achieve an accelerated immune response over BioThrax® (Anthrax Vaccine Adsorbed). A phase 2, randomized, double-blind, BioThrax vacccine-controlled study was conducted to evaluate the safety and immunogenicity of three intramuscular vaccination schedules and two dose levels of AV7909 in 168 healthy adults. Subjects were randomized at a 4:3:2:4:2 ratio to 5 groups: 1) AV7909 on Days 0/14; 2) AV7909 on Days 0/28; 3) AV7909 on Days 0/14/28; 4) half dose AV7909 on Days 0/14/28; and 5) BioThrax vaccine on Days 0/14/28. Vaccinations in all groups were well tolerated. The incidences of adverse events (AEs) were 79% for AV7909 subjects and 65% for BioThrax subjects; 92% of AV7909 subjects and 87% of BioThrax subjects having AEs reported Grade 1-2 AEs. No serious AEs were assessed as potentially vaccine-related, and no AEs of potential autoimmune etiology were reported. There was no discernible pattern indicative of a safety concern across groups in the incidence or severity of reactogenicity events. Groups 2, 3, and 4 achieved success for the primary endpoint, demonstrated by a lower 95% confidence limit of the percentage of subjects with protective toxin neutralizing antibody NF50 values (≥ 0.56) to be ≥ 40% at Day 63. Group 1 marginally missed the criterion (lower bound 95% confidence limit of 39.5%). Immune responses were above this threshold for Groups 1, 3 and 4 at Day 28 and all groups at Day 42. Further study of an AV7909 two-dose schedule given 2 weeks apart is warranted in light of the favorable tolerability profile and immunogenicity response relative to three doses of BioThrax vaccine, as well as preliminary data from nonclinical studies indicating similar immune responses correlate with higher survival for AV7909 than BioThrax vaccine. PMID:26979136

Immunogenicity, safety and antibody persistence of a purified vero cell cultured rabies vaccine (Speeda) administered by the Zagreb regimen or Essen regimen in post-exposure subjects.

PubMed

Shi, Nianmin; Zhang, Yibin; Zheng, Huizhen; Zhu, Zhenggang; Wang, Dingming; Li, Sihai; Li, Yuhua; Yang, Liqing; Zhang, Junnan; Bai, Yunhua; Lu, Qiang; Zhang, Zheng; Luo, Fengji; Yu, Chun; Li, Li

2017-06-03

To compare the safety, immunogenicity and long-term effect of a purified vero cell cultured rabies vaccine in post-exposure subjects following 2 intramuscular regimens, Zagreb or Essen regimen. Serum samples were collected before vaccination and on days 7, 14, 42, 180 and 365 post vaccination. Solicited adverse events were recorded for 7 d following each vaccine dose, and unsolicited adverse events throughout the entire study period. This study was registered with ClinicalTrials.gov (NCT01821911 and NCT01827917). No serious adverse events were reported. Although Zagreb regimen had a higher incidence of adverse reactions than Essen regimen at the first and second injection, the incidence was similar at the third and fourth injection between these 2 groups as well. At day 42, 100% subjects developed adequate rabies virus neutralizing antibody concentrations (≥ 0.5IU/ml) for both regimens. At days 180 and 365, the antibody level decreased dramatically, however, the percentage of subjects with adequate antibody concentrations still remained high (above 75% and 50% respectively). None of confirmed rabies virus exposured subjects had rabies one year later, and percentage of subjects with adequate antibody concentrations reached 100% at days 14 and 42. Rabies post-exposure prophylaxis vaccination with PVRV following a Zagreb regimen had a similar safety, immunogenicity and long-term effect to the Essen regimen in China.

Immunogenicity, safety and antibody persistence of a purified vero cell cultured rabies vaccine (Speeda) administered by the Zagreb regimen or Essen regimen in post-exposure subjects

PubMed Central

Shi, Nianmin; Zhang, Yibin; Zheng, Huizhen; Zhu, Zhenggang; Wang, Dingming; Li, Sihai; Li, Yuhua; Yang, Liqing; Zhang, Junnan; Bai, Yunhua; Lu, Qiang; Zhang, Zheng; Luo, Fengji; Yu, Chun; Li, Li

2017-01-01

ABSTRACT Aim: To compare the safety, immunogenicity and long-term effect of a purified vero cell cultured rabies vaccine in post-exposure subjects following 2 intramuscular regimens, Zagreb or Essen regimen. Methods: Serum samples were collected before vaccination and on days 7, 14, 42, 180 and 365 post vaccination. Solicited adverse events were recorded for 7 d following each vaccine dose, and unsolicited adverse events throughout the entire study period. This study was registered with ClinicalTrials.gov (NCT01821911 and NCT01827917). Results: No serious adverse events were reported. Although Zagreb regimen had a higher incidence of adverse reactions than Essen regimen at the first and second injection, the incidence was similar at the third and fourth injection between these 2 groups as well. At day 42, 100% subjects developed adequate rabies virus neutralizing antibody concentrations (≥ 0.5IU/ml) for both regimens. At days 180 and 365, the antibody level decreased dramatically, however, the percentage of subjects with adequate antibody concentrations still remained high (above 75% and 50% respectively). None of confirmed rabies virus exposured subjects had rabies one year later, and percentage of subjects with adequate antibody concentrations reached 100% at days 14 and 42. Conclusions: Rabies post-exposure prophylaxis vaccination with PVRV following a Zagreb regimen had a similar safety, immunogenicity and long-term effect to the Essen regimen in China. PMID:28121231

Immunization safety in US print media, 1995-2005.

PubMed

Hussain, Hamidah; Omer, Saad B; Manganello, Jennifer A; Kromm, Elizabeth Edsall; Carter, Terrell C; Kan, Lilly; Stokley, Shannon; Halsey, Neal A; Salmon, Daniel A

2011-05-01

To identify and describe vaccine safety in US newspaper articles. Articles (1147) from 44 states and Washington, DC, between January 1, 1995, and July 15, 2005, were identified by using the search terms "immunize or vaccine" and "adverse events or safety or exemption or danger or risk or damage or injury or side effect" and were coded by using a standardized data-collection instrument. The mean number of vaccine-safety articles per state was 26. Six (not mutually exclusive) topics were identified: vaccine-safety concerns (46%); vaccine policy (44%); vaccines are safe (20%); immunizations are required (10%); immunizations are not required (8%); and state/school exemption (8%). Three spikes in the number of newspaper articles about vaccine-safety issues were observed: in 1999 regarding rotavirus vaccine and in 2002 and 2003 regarding smallpox vaccine. Excluding articles that referred to rotavirus and smallpox vaccines, 37% of the articles had a negative take-home message. Ongoing monitoring of news on vaccine safety may help the content and framing of vaccine-safety messages.

Safety of an Escherichia coli-expressed bivalent human papillomavirus (types 16 and 18) L1 virus-like particle vaccine: an open-label phase I clinical trial.

PubMed

Hu, Yue-Mei; Huang, Shou-Jie; Chu, Kai; Wu, Ting; Wang, Zhong-Ze; Yang, Chang-Lin; Cai, Jia-Ping; Jiang, Han-Min; Wang, Yi-Jun; Guo, Meng; Liu, Xiao-Hui; Huang, Hong-Jiang; Zhu, Feng-Cai; Zhang, Jun; Xia, Ning-Shao

2014-01-01

An Escherichia coli-expressed recombinant bivalent human papillomavirus (types 16 and 18) vaccine candidate has been shown to be safe and immunogenic in preclinical trials. The safety of this vaccine was analyzed in an open-label phase I clinical trial in Jiangsu province, China. Thirty-eight healthy women from 18 to 55 y of age were enrolled and vaccinated at 0, 1, and 6 mo. Adverse events that occurred within 30 d after each injection and serious adverse events that occurred throughout the study were recorded. In addition, blood parameters were tested before and after each injection. All but one woman received all 3 doses. Thirty-two (84.2%) of the participants reported adverse events, all adverse events of which were mild, of short duration and resolved spontaneously. No serious adverse events occurred during the study. Changes in blood parameters after each injection were random, mild, and not clinically significant. These preliminary results show that a new Escherichia coli-expressed recombinant HPV 16/18 bivalent vaccine is well tolerated in healthy women and support further immunogenicity and efficacy studies for this HPV vaccine candidate.

Safety of the HPV Bivalent and Quadrivalent Vaccines During Pregnancy.

PubMed

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

2011-02-01

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

Safety and immunogenicity of the M72/AS01E candidate tuberculosis vaccine in adults with tuberculosis: A phase II randomised study.

PubMed

Gillard, Paul; Yang, Pan-Chyr; Danilovits, Manfred; Su, Wei-Juin; Cheng, Shih-Lung; Pehme, Lea; Bollaerts, Anne; Jongert, Erik; Moris, Philippe; Ofori-Anyinam, Opokua; Demoitié, Marie-Ange; Castro, Marcela

2016-09-01

Previous studies have shown that the M72/AS01E candidate tuberculosis vaccine is immunogenic with a clinically acceptable safety profile in healthy and Mycobacterium tuberculosis-infected adults. This phase II, observer-blind, randomised study compared the safety, reactogenicity, and immunogenicity of M72/AS01E in 3 cohorts: tuberculosis-naïve adults (n = 80), adults previously treated for tuberculosis (n = 49), and adults who have completed the intensive phase of tuberculosis treatment (n = 13). In each cohort, 18-59-year-old adults were randomised (1:1) to receive two doses of M72/AS01E (n = 71) or placebo (n = 71) and followed-up until six months post-dose 2. Safety and reactogenicity were assessed as primary objective. Recruitment in the study ended prematurely because of a high incidence of large injection site redness/swelling reactions in M72/AS01E-vaccinated adults undergoing tuberculosis treatment. No additional clinically relevant adverse events were observed, except one possibly vaccine-related serious adverse event (hypersensitivity in a tuberculosis-treated-M72/AS01E participant). Robust and persistent M72-specific humoral and polyfunctional CD4(+) T-cell-mediated immune responses were observed post-M72/AS01E vaccination in each cohort. In conclusion, the M72/AS01E vaccine was immunogenic in adults previously or currently treated for tuberculosis, but further analyses are needed to explain the high local reactogenicity in adults undergoing tuberculosis treatment. ClinicalTrials.gov: NCT01424501. Copyright © 2016 GlaxoSmithKline Biologicals SA. Published by Elsevier Ltd.. All rights reserved.

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.

PubMed

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.

Surveillance of adverse events following vaccination in the French armed forces, 2011-2012.

PubMed

Mayet, A; Duron, S; Meynard, J-B; Koeck, J-L; Deparis, X; Migliani, R

2015-06-01

French military personnel are subject to a compulsory vaccination schedule. The aim of this study was to present the results of surveillance of vaccine adverse events (VAEs) reported from 2011 to 2012 in the French armed forces. VAEs were surveyed among all French armed forces from 2011 to 2012 by the epidemiological departments of the military health service. For each case, a notification form providing patient and clinical information was provided. Case definitions were derived from the French drug safety guidelines. Three types of VAE were considered: non-serious, serious and unexpected. Incidence rates were calculated by relating VAEs to the number of vaccine doses delivered. In total, 161 VAE cases were reported. The overall VAE reporting rate was 24.6 VAEs per 100,000 doses, and the serious VAE rate was 1.3 per 100,000 doses (nine cases). The serious VAEs included two cases of Guillain-Barré syndrome, one case of optic neuritis, one case of a meningeal-like syndrome, one case of rheumatoid purpura, one case of acute asthma and three cases of fainting. The highest rates of VAE were observed with the Bacille Calmette-Guérin vaccine (BCG) (482.3 per 100,000 doses), inactivated diphtheria-tetanus-poliovirus with acellular pertussis vaccine (dTap-IPV) (106.1 per 100,000 doses) and meningococcal quadrivalent glycoconjugate vaccine (MenACWY-CRM) (39.3 per 100,000 doses). The global rates of VAE observed in 2011 and 2012 confirm the increase that has been observed since 2009 in the French armed forces, which could reflect improved practitioner awareness about VAEs and the use of certain vaccines added to the vaccination schedule recently (dTap-IPV in 2008 and MenACWY-CRM in 2010). VAEs appear to be relatively rare, particularly serious VAEs, which indicates acceptable tolerance of vaccines. Copyright © 2015 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

A mass vaccination campaign targeting adults and children to prevent typhoid fever in Hechi; Expanding the use of Vi polysaccharide vaccine in Southeast China: A cluster-randomized trial

PubMed Central

Yang, Jin; Acosta, Camilo J; Si, Guo-ai; Zeng, Jun; Li, Cui-yun; Liang, Da-bin; Ochiai, R Leon; Page, Anne-Laure; Danovaro-Holliday, M Carolina; Zhang, Jie; Zhou, Bao-de; Liao, He-zhuang; Wang, Ming-liu; Tan, Dong-mei; Tang, Zhen-zhu; Gong, Jian; Park, Jin-Kyung; Ali, Mohammad; Ivanoff, Bernard; Liang, Gui-chen; Yang, Hong-hui; Pang, Tikki; Xu, Zhi-yi; Donner, Allan; Galindo, Claudia M; Dong, Bai-qing; Clemens, John D

2005-01-01

Background One of the goals of this study was to learn the coverage, safety and logistics of a mass vaccination campaign against typhoid fever in children and adults using locally produced typhoid Vi polysaccharide (PS) and group A meningococcal PS vaccines in southern China. Methods The vaccination campaign targeted 118,588 persons in Hechi, Guangxi Province, aged between 5 to 60 years, in 2003. The study area was divided into 107 geographic clusters, which were randomly allocated to receive one of the single-dose parenteral vaccines. All aspects regarding vaccination logistics, feasibility and safety were documented and systematically recorded. Results of the logistics, feasibility and safety are reported. Results The campaign lasted 5 weeks and the overall vaccination coverage was 78%. On average, the 30 vaccine teams gave immunizations on 23 days. Vaccine rates were higher in those aged ≤ 15 years (90%) than in adolescents and young adults (70%). Planned mop-up activities increased the coverage by 17%. The overall vaccine wastage was 11%. The cold chain was maintained and documented. 66 individuals reported of adverse events out of all vaccinees, where fever (21%), malaise (19%) and local redness (19%) were the major symptoms; no life-threatening event occurred. Three needle-sharp events were reported. Conclusion The mass immunization proved feasible and safe, and vaccine coverage was high. Emphasis should be placed on: injection safety measures, community involvement and incorporation of mop-up strategies into any vaccination campaign. School-based and all-age Vi mass immunizations programs are potentially important public health strategies for prevention of typhoid fever in high-risk populations in southern China. PMID:15904514

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

PubMed

Amanna, Ian J; Slifka, Mark K

2016-12-01

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

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

PubMed Central

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.

PubMed

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

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

PubMed

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

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

PubMed

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 < .0001), and the 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 < .0001). Geometric mean titers of neutralizing antibody in participants remained high during the 2-year follow-up period, and no 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.

New challenges in assuring vaccine quality.

PubMed Central

Dellepiane, N.; Griffiths, E.; Milstien, J. B.

2000-01-01

In the past, quality control of vaccines depended on use of a variety of testing methods to ensure that the products were safe and potent. These methods were developed for vaccines whose safety and efficacy were based on several years worth of data. However, as vaccine production technologies have developed, so have the testing technologies. Tests are now able to detect potential hazards with a sensitivity not possible a few years ago, and an increasing array of physicochemical methods allows a much better characterization of the product. In addition to sophisticated tests, vaccine regulation entails a number of other procedures to ensure safety. These include characterization of starting materials by supplier audits, cell banking, seed lot systems, compliance with the principles of good manufacturing practices, independent release of vaccines on a lot-by-lot basis by national regulatory authorities, and enhanced pre- and post-marketing surveillance for possible adverse events following immunization. These procedures help assure vaccine efficacy and safety, and some examples are given in this article. However, some contaminants of vaccines that can be detected by newer assays raise theoretical safety concerns but their presence may be less hazardous than not giving the vaccines. Thus risk-benefit decisions must be well informed and based on scientific evidence. PMID:10743279

Adverse events following yellow fever preventive vaccination campaigns in eight African countries from 2007 to 2010.

PubMed

Breugelmans, J G; Lewis, R F; Agbenu, E; Veit, O; Jackson, D; Domingo, C; Böthe, M; Perea, W; Niedrig, M; Gessner, B D; Yactayo, S

2013-04-03

Serious, but rare adverse events following immunization (AEFI) have been reported with yellow fever (YF) 17D vaccine, including severe allergic reactions, YF vaccine-associated neurologic disease (YEL-AND) and YF vaccine-associated viscerotropic disease (YEL-AVD). The frequency with which YEL-AND and YEL-AVD occur in YF endemic countries is mostly unknown. From 2007 to 2010, eight African countries - Benin, Cameroon, Guinea, Liberia, Mali, Senegal, Sierra Leone, and Togo- implemented large-scale YF preventive vaccination campaigns. Each country established vaccine pharmacovigilance systems that included standard case definitions, procedures to collect and transport biological specimens, and National Expert Committees to review data and classify cases. Staff in all countries received training and laboratory capacity expanded. In total, just over 38 million people were vaccinated against YF and 3116 AEFIs were reported of which 164 (5%) were classified as serious. Of these, 22 (13%) were classified as YF vaccine reactions, including 11 (50%) hypersensitivity reactions, six (27%) suspected YEL-AND, and five (23%) suspected YEL-AVD. The incidence per 100,000 vaccine doses administered was 8.2 for all reported AEFIs, 0.43 for any serious AEFI, 0.058 for YF vaccine related AEFIs, 0.029 for hypersensitivity reactions, 0.016 for YEL-AND, and 0.013 for YEL-AVD. Our findings were limited by operational challenges, including difficulties in obtaining recommended biological specimens leading to incomplete laboratory evaluation, unknown case ascertainment, and variable levels of staff training and experience. Despite limitations, active case-finding in the eight different countries did not find an incidence of YF vaccine associated AEFIs that was higher than previous reports. These data reinforce the safety profile of YF vaccine and support the continued use of attenuated YF vaccine during preventive mass vaccination campaigns in YF endemic areas. Copyright © 2013 Elsevier Ltd

Influenza vaccination of cancer patients during PD-1 blockade induces serological protection but may raise the risk for immune-related adverse events.

PubMed

Läubli, Heinz; Balmelli, Catharina; Kaufmann, Lukas; Stanczak, Michal; Syedbasha, Mohammedyaseen; Vogt, Dominik; Hertig, Astrid; Müller, Beat; Gautschi, Oliver; Stenner, Frank; Zippelius, Alfred; Egli, Adrian; Rothschild, Sacha I

2018-05-22

Immune checkpoint inhibiting antibodies were introduced into routine clinical practice for cancer patients. Checkpoint blockade has led to durable remissions in some patients, but may also induce immune-related adverse events (irAEs). Lung cancer patients show an increased risk for complications, when infected with influenza viruses. Therefore, vaccination is recommended. However, the efficacy and safety of influenza vaccination during checkpoint blockade and its influence on irAEs is unclear. Similarly, the influence of vaccinations on T cell-mediated immune reactions in patients during PD-1 blockade remains poorly defined. We vaccinated 23 lung cancer patients and 11 age-matched healthy controls using a trivalent inactivated influenza vaccine to investigate vaccine-induced immunity and safety during checkpoint blockade. We did not observe significant differences between patients and healthy controls in vaccine-induced antibody titers against all three viral antigens. Influenza vaccination resulted in protective titers in more than 60% of patients/participants. In cancer patients, the post-vaccine frequency of irAEs was 52.2% with a median time to occurrence of 3.2 months after vaccination. Six of 23 patients (26.1%) showed severe grade 3/4 irAEs. This frequency of irAEs might be higher than the rate previously published in the literature and the rate observed in a non-study population at our institution (all grades 25.5%, grade 3/4 9.8%). Although this is a non-randomized trial with a limited number of patients, the increased rate of immunological toxicity is concerning. This finding should be studied in a larger patient population.

Reversibility and safety of KISS1 metastasis suppressor gene vaccine in immunocastration of ram lambs

PubMed Central

2018-01-01

Objective The aim of this study was to investigate the reversibility and safety of KISS1 metastasis suppressor (KISS1) gene vaccine in immunocastration. Methods Six eight-week old ram lambs were randomly divided into vaccinated and control groups. The vaccine (1 mg/ram lamb) was injected at weeks 0, 3, and 6 of the study. Blood samples were collected from the jugular vein before primary immunization and at weeks 2, 4, 6, 10, 14, 22, and 30 after primary immunization. All ram lambs were slaughtered at 38 weeks of age, and samples were collected. Results The specific anti-KISS1 antibody titers in vaccinated animals were significantly higher and the serum testosterone level was significantly lower than those in the control groups from week 4 to 14 after primary immunization (p<0.05). No significant difference was observed at weeks 22 and 30 after the primary immunization. Similar results were also found for scrotal circumference, testicular weight, length, breadth, and spermatogenesis in seminiferous tubules in week 30 after primary immunization. KS (KISS1-hepatitis B surface antigen S) fusion fragment of KISS1 gene vaccine was not detected in host cell genomic DNA of 9 tissues of the vaccinated ram lambs by polymerase chain reaction. Conclusion The effects of KISS1 gene vaccine in immunocastration were reversible and no integration events were recorded. PMID:29268573

Reversibility and safety of KISS1 metastasis suppressor gene vaccine in immunocastration of ram lambs.

PubMed

Han, Yan-Guo; Liu, Gui-Qiong; Jiang, Xun-Ping; Xiang, Xing-Long; Huang, Yong-Fu; Nie, Bin; Zhao, Jia-Yu; Nabeel, Ijaz; Tesema, Birhanu

2018-06-01

The aim of this study was to investigate the reversibility and safety of KISS1 metastasis suppressor ( KISS1 ) gene vaccine in immunocastration. Six eight-week old ram lambs were randomly divided into vaccinated and control groups. The vaccine (1 mg/ram lamb) was injected at weeks 0, 3, and 6 of the study. Blood samples were collected from the jugular vein before primary immunization and at weeks 2, 4, 6, 10, 14, 22, and 30 after primary immunization. All ram lambs were slaughtered at 38 weeks of age, and samples were collected. The specific anti- KISS1 antibody titers in vaccinated animals were significantly higher and the serum testosterone level was significantly lower than those in the control groups from week 4 to 14 after primary immunization (p<0.05). No significant difference was observed at weeks 22 and 30 after the primary immunization. Similar results were also found for scrotal circumference, testicular weight, length, breadth, and spermatogenesis in seminiferous tubules in week 30 after primary immunization. KS ( KISS1 -hepatitis B surface antigen S ) fusion fragment of KISS1 gene vaccine was not detected in host cell genomic DNA of 9 tissues of the vaccinated ram lambs by polymerase chain reaction. The effects of KISS1 gene vaccine in immunocastration were reversible and no integration events were recorded.

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

PubMed

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

2016-12-01

Much has been written about the patient-physician relationship over the years. This relationship is essential in maintaining trust in the complex arena of modern diagnostic techniques, treatment and prevention, including vaccines and vaccine safety. However, a great deal of this material was written from the viewpoint of clinicians and academics. The patient voice may be positive or negative, fragmented or complex. Information sources are weighed and treated differently, according to the value system and risk perceptions of the individual. In post-trust societies, when people have less confidence in health authorities, communication needs to be more than a paternalistic top-down process. Notions of empowerment and individual patient choice are becoming crucial in medical care. The 'voice of the patient', which includes healthy individuals receiving vaccines, needs to be heard, considered and addressed. With respect to childhood immunizations, this will be the voice of the parent or caregiver. The key to addressing any concerns could be to listen more and to develop a communication style that is trust-based and science-informed. Regulatory agencies are encouraging clinical and patient-reported outcomes research under the umbrella of personalized medicine, and this is an important step forward. This paper attempts to reflect the paradigm shift towards increasing attention to the patient voice in vaccination and vaccine safety. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Confidence in the safety of standard childhood vaccinations among New Zealand health professionals.

PubMed

Lee, Carol; Duck, Isabelle; Sibley, Chris G

2018-05-04

To investigate the level of confidence in the safety of standard childhood vaccinations among health professionals in New Zealand. Data from the 2013/14 New Zealand Attitudes and Values Study (NZAVS) was used to investigate the level of agreement that "it is safe to vaccinate children following the standard New Zealand immunisation schedule" among different classes of health professionals (N=1,032). Most health professionals showed higher levels of vaccine confidence, with 96.7% of those describing their occupation as GP or simply 'doctor' (GPs/doctor) and 90.7% of pharmacists expressing strong vaccine confidence. However, there were important disparities between some other classes of health professionals, with only 65.1% of midwives and 13.6% of practitioners of alternative medicine expressing high vaccine confidence. As health professionals are a highly trusted source of vaccine information, communicating the consensus of belief among GPs/doctors that vaccines are safe may help provide reassurance for parents who ask about vaccine safety. However, the lower level of vaccine confidence among midwives is a matter of concern that may have negative influence on parental perceptions of vaccinations.

Can Natural Language Processing Improve the Efficiency of Vaccine Adverse Event Report Review?

PubMed

Baer, B; Nguyen, M; Woo, E J; Winiecki, S; Scott, J; Martin, D; Botsis, T; Ball, R

2016-01-01

Individual case review of spontaneous adverse event (AE) reports remains a cornerstone of medical product safety surveillance for industry and regulators. Previously we developed the Vaccine Adverse Event Text Miner (VaeTM) to offer automated information extraction and potentially accelerate the evaluation of large volumes of unstructured data and facilitate signal detection. To assess how the information extraction performed by VaeTM impacts the accuracy of a medical expert's review of the vaccine adverse event report. The "outcome of interest" (diagnosis, cause of death, second level diagnosis), "onset time," and "alternative explanations" (drug, medical and family history) for the adverse event were extracted from 1000 reports from the Vaccine Adverse Event Reporting System (VAERS) using the VaeTM system. We compared the human interpretation, by medical experts, of the VaeTM extracted data with their interpretation of the traditional full text reports for these three variables. Two experienced clinicians alternately reviewed text miner output and full text. A third clinician scored the match rate using a predefined algorithm; the proportion of matches and 95% confidence intervals (CI) were calculated. Review time per report was analyzed. Proportion of matches between the interpretation of the VaeTM extracted data, compared to the interpretation of the full text: 93% for outcome of interest (95% CI: 91-94%) and 78% for alternative explanation (95% CI: 75-81%). Extracted data on the time to onset was used in 14% of cases and was a match in 54% (95% CI: 46-63%) of those cases. When supported by structured time data from reports, the match for time to onset was 79% (95% CI: 76-81%). The extracted text averaged 136 (74%) fewer words, resulting in a mean reduction in review time of 50 (58%) seconds per report. Despite a 74% reduction in words, the clinical conclusion from VaeTM extracted data agreed with the full text in 93% and 78% of reports for the outcome of

Reactogenicity, safety and immunogenicity of a protein-based pneumococcal vaccine in Gambian children aged 2-4 years: A phase II randomized study.

PubMed

Odutola, A; Ota, M O; Ogundare, E O; Antonio, M; Owiafe, P; Worwui, A; Greenwood, B; Alderson, M; Traskine, M; Verlant, V; Dobbelaere, K; Borys, D

2016-01-01

Pneumococcal conjugate vaccines (PCVs) have been successful in preventing invasive pneumococcal disease but effectiveness has been challenged by replacement of vaccine serotypes with non-vaccine serotypes. Vaccines targeting common pneumococcal protein(s) found in most/all pneumococci may overcome this limitation. This phase II study assessed safety and immunogenicity of a new protein-based pneumococcal vaccine containing polysaccharide conjugates of 10 pneumococcal serotypes combined with pneumolysin toxoid(dPly) and pneumococcal histidine triad protein D(PhtD) (PHiD-CV/dPly/PhtD-30) in African children. 120 Gambian children (2-4 years, not previously vaccinated against Streptococcus pneumoniae) randomized (1:1) received a single dose of PHiD-CV/dPly/PhtD-30 or PCV13. Adverse events occurring over 4 d post-vaccination were reported, and blood samples obtained pre- and 1-month post-vaccination. Serious adverse events were reported for 6 months post-vaccination. Solicited local and systemic adverse events were reported at similar frequency in each group. One child (PHiD-CV/dPly/PhtD-30 group) reported a grade 3 local reaction to vaccination. Haematological and biochemical parameters seemed similar pre- and 1-month post-vaccination in each group. High pre-vaccination Ply and PhtD antibody concentrations were observed in each group, but only increased in PHiD-CV/dPly/PhtD-30 vaccinees one month post-vaccination. One month post-vaccination, for each vaccine serotype ≥96.2% of PHiD-CV/dPly/PhtD-30 vaccinees had serotype-specific polysaccharide antibody concentrations ≥0.20µg/mL except serotypes 6B (80.8%) and 23F (65.4%), and ≥94.1% had OPA titres of ≥8 except serotypes 1 (51.9%), 5 (38.5%) and 6B (78.0%), within ranges seen in PCV13-vaccinated children. A single dose of PHiD-CV/dPly/PhtD-30 vaccine, administered to Gambian children aged 2-4 y not previously vaccinated with a pneumococcal vaccine, was well-tolerated and immunogenic.

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

PubMed

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

2016-01-01

should be answered to properly assess the safety profile of the product and the target populations of potential benefit. In this regard we consider it would be informative to complete the 6-year follow-up after starting vaccination, according to the company's own study protocol recommended by the World Health Organization. As with any new vaccine, the potential licensing and implementation of the CYD-TDV as part of Mexico's vaccination program, requires a clear definition of the balance between the expected benefits and risks. Particularly with a vaccine with variable efficacy and some signs of risk, in the probable case of licensing, the post-licensed period must involve the development of detailed protocols to immediately identify risks or any health event associated with vaccination.

Priming effect of dengue and yellow fever vaccination on the immunogenicity, infectivity, and safety of a tetravalent dengue vaccine in humans.

PubMed

Qiao, Ming; Shaw, David; Forrat, Remi; Wartel-Tram, Anh; Lang, Jean

2011-10-01

A dengue vaccine effective against all four serotypes is urgently needed. However, safety and immunogenicity could be affected by prior exposure to flaviviruses. This open, controlled, phase IIa study was conducted in 35 healthy adults who had received monovalent, live attenuated Vero cell-derived dengue vaccine against dengue virus 1 (VDV1) or 2 (VDV2) or yellow fever (YF) vaccine 1 year before or who were flavivirus-naïve. All participants received one subcutaneous injection of tetravalent dengue vaccine (TDV) and were followed for 180 days. Previous vaccination did not increase reactogenicity, laboratory abnormalities, or incidence of vaccine viremia, but it did increase the neutralizing antibody response to dengue virus that persisted at day 180. There was no increase in YF antibodies in participants previously immunized with YF vaccine. Prior exposure to YF or monovalent dengue vaccines had no adverse effects on the safety or incidence of viremia associated with this TDV, but it increased immunogenicity.

Epidemiological designs for vaccine safety assessment: methods and pitfalls.

PubMed

Andrews, Nick

2012-09-01

Three commonly used designs for vaccine safety assessment post licensure are cohort, case-control and self-controlled case series. These methods are often used with routine health databases and immunisation registries. This paper considers the issues that may arise when designing an epidemiological study, such as understanding the vaccine safety question, case definition and finding, limitations of data sources, uncontrolled confounding, and pitfalls that apply to the individual designs. The example of MMR and autism, where all three designs have been used, is presented to help consider these issues. Copyright © 2011 The International Alliance for Biological Standardization. Published by Elsevier Ltd. All rights reserved.

Safety and immunogenicity of candidate vaccine M72/AS01E in adolescents in a TB endemic setting.

PubMed

Penn-Nicholson, Adam; Geldenhuys, Hennie; Burny, Wivine; van der Most, Robbert; Day, Cheryl L; Jongert, Erik; Moris, Philippe; Hatherill, Mark; Ofori-Anyinam, Opokua; Hanekom, Willem; Bollaerts, Anne; Demoitie, Marie-Ange; Kany Luabeya, Angelique Kany; De Ruymaeker, Evi; Tameris, Michele; Lapierre, Didier; Scriba, Thomas J

2015-07-31

Vaccination that prevents tuberculosis (TB) disease, particularly in adolescents, would have the greatest impact on the global TB epidemic. Safety, reactogenicity and immunogenicity of the vaccine candidate M72/AS01E was evaluated in healthy, HIV-negative adolescents in a TB endemic region, regardless of Mycobacterium tuberculosis (M.tb) infection status. In a phase II, double-blind randomized, controlled study (NCT00950612), two doses of M72/AS01E or placebo were administered intramuscularly, one month apart. Participants were followed-up post-vaccination, for 6 months. M72-specific immunogenicity was evaluated by intracellular cytokine staining analysis of T cells and NK cells by flow cytometry. No serious adverse events were recorded. M72/AS01E induced robust T cell and antibody responses, including antigen-dependent NK cell IFN-γ production. CD4 and CD8 T cell responses were sustained at 6 months post vaccination. Irrespective of M.tb infection status, vaccination induced a high frequency of M72-specific CD4 T cells expressing multiple combinations of Th1 cytokines, and low level IL-17. We observed rapid boosting of immune responses in M.tb-infected participants, suggesting natural infection acts as a prime to vaccination. The clinically acceptable safety and immunogenicity profile of M72/AS01E in adolescents living in an area with high TB burden support the move to efficacy trials. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Safety and immunogenicity of candidate vaccine M72/AS01E in adolescents in a TB endemic setting

PubMed Central

Penn-Nicholson, Adam; Geldenhuys, Hennie; Burny, Wivine; van der Most, Robbert; Day, Cheryl L.; Jongert, Erik; Moris, Philippe; Hatherill, Mark; Ofori-Anyinam, Opokua; Hanekom, Willem

2018-01-01

Background Vaccination that prevents tuberculosis (TB) disease, particularly in adolescents, would have the greatest impact on the global TB epidemic. Safety, reactogenicity and immunogenicity of the vaccine candidate M72/AS01E was evaluated in healthy, HIV-negative adolescents in a TB endemic region, regardless of Mycobacterium tuberculosis (M.tb) infection status. Methods In a phase II, double-blind randomized, controlled study (NCT00950612), two doses of M72/AS01E or placebo were administered intramuscularly, one month apart. Participants were followed-up post-vaccination, for 6 months. M72-specific immunogenicity was evaluated by intracellular cytokine staining analysis of T cells and NK cells by flow cytometry. Results No serious adverse events were recorded. M72/AS01E induced robust T cell and antibody responses, including antigen-dependent NK cell IFN-γ production. CD4 and CD8 T cell responses were sustained at 6 months post vaccination. Irrespective of M.tb infection status, vaccination induced a high frequency of M72-specific CD4 T cells expressing multiple combinations of Th1 cytokines, and low level IL-17. We observed rapid boosting of immune responses in M.tb-infected participants, suggesting natural infection acts as a prime to vaccination. Conclusions The clinically acceptable safety and immunogenicity profile of M72/AS01E in adolescents living in an area with high TB burden support the move to efficacy trials. PMID:26072017

Safety of the recombinant cholera toxin B subunit, killed whole-cell (rBS-WC) oral cholera vaccine in pregnancy.

PubMed

Hashim, Ramadhan; Khatib, Ahmed M; Enwere, Godwin; Park, Jin Kyung; Reyburn, Rita; Ali, Mohammad; Chang, Na Yoon; Kim, Deok Ryun; Ley, Benedikt; Thriemer, Kamala; Lopez, Anna Lena; Clemens, John D; Deen, Jacqueline L; Shin, Sunheang; Schaetti, Christian; Hutubessy, Raymond; Aguado, Maria Teresa; Kieny, Marie Paule; Sack, David; Obaro, Stephen; Shaame, Attiye J; Ali, Said M; Saleh, Abdul A; von Seidlein, Lorenz; Jiddawi, Mohamed S

2012-01-01

Mass vaccinations are a main strategy in the deployment of oral cholera vaccines. Campaigns avoid giving vaccine to pregnant women because of the absence of safety data of the killed whole-cell oral cholera (rBS-WC) vaccine. Balancing this concern is the known higher risk of cholera and of complications of pregnancy should cholera occur in these women, as well as the lack of expected adverse events from a killed oral bacterial vaccine. From January to February 2009, a mass rBS-WC vaccination campaign of persons over two years of age was conducted in an urban and a rural area (population 51,151) in Zanzibar. Pregnant women were advised not to participate in the campaign. More than nine months after the last dose of the vaccine was administered, we visited all women between 15 and 50 years of age living in the study area. The outcome of pregnancies that were inadvertently exposed to at least one oral cholera vaccine dose and those that were not exposed was evaluated. 13,736 (94%) of the target women in the study site were interviewed. 1,151 (79%) of the 1,453 deliveries in 2009 occurred during the period when foetal exposure to the vaccine could have occurred. 955 (83%) out of these 1,151 mothers had not been vaccinated; the remaining 196 (17%) mothers had received at least one dose of the oral cholera vaccine. There were no statistically significant differences in the odds ratios for birth outcomes among the exposed and unexposed pregnancies. We found no statistically significant evidence of a harmful effect of gestational exposure to the rBS-WC vaccine. These findings, along with the absence of a rational basis for expecting a risk from this killed oral bacterial vaccine, are reassuring but the study had insufficient power to detect infrequent events. ClinicalTrials.gov NCT00709410.

The relationship between organizational leadership for safety and learning from patient safety events.

PubMed

Ginsburg, Liane R; Chuang, You-Ta; Berta, Whitney Blair; Norton, Peter G; Ng, Peggy; Tregunno, Deborah; Richardson, Julia

2010-06-01

To examine the relationship between organizational leadership for patient safety and five types of learning from patient safety events (PSEs). Forty-nine general acute care hospitals in Ontario, Canada. A nonexperimental design using cross-sectional surveys of hospital patient safety officers (PSOs) and patient care managers (PCMs). PSOs provided data on organization-level learning from (a) minor events, (b) moderate events, (c) major near misses, (d) major event analysis, and (e) major event dissemination/communication. PCMs provided data on organizational leadership (formal and informal) for patient safety. Hospitals were the unit of analysis. Seemingly unrelated regression was used to examine the influence of formal and informal leadership for safety on the five types of learning from PSEs. The interaction between leadership and hospital size was also examined. Formal organizational leadership for patient safety is an important predictor of learning from minor, moderate, and major near-miss events, and major event dissemination. This relationship is significantly stronger for small hospitals (<100 beds). We find support for the relationship between patient safety leadership and patient safety behaviors such as learning from safety events. Formal leadership support for safety is of particular importance in small organizations where the economic burden of safety programs is disproportionately large and formal leadership is closer to the front lines.

Acute Demyelinating Events Following Vaccines: A Case-Centered Analysis.

PubMed

Baxter, Roger; Lewis, Edwin; Goddard, Kristin; Fireman, Bruce; Bakshi, Nandini; DeStefano, Frank; Gee, Julianne; Tseng, Hung Fu; Naleway, Allison L; Klein, Nicola P

2016-12-01

 Case reports have suggested that vaccines may trigger transverse myelitis (TM) or acute disseminated encephalomyelitis (ADEM), but the evidence for a causal association is inconclusive. We analyzed the association of immunization and subsequent development of TM or ADEM.  We identified all cases of TM and ADEM in the Vaccine Safety Datalink population. Using a case-centered method, we compared vaccination of each case to vaccination of all matched persons in the study population, who received the same type of vaccine, with respect to whether or not their vaccination occurred during a predetermined exposure interval. We calculated a risk difference (excess risk) of TM and ADEM for each vaccine.  Following nearly 64 million vaccine doses, only 7 cases of TM and 8 cases of ADEM were vaccinated during the primary exposure window 5-28 days prior to onset. For TM, there was no statistically significant increased risk of immunization. For ADEM, there was no statistically significant increased risk following any vaccine except for Tdap (adolescent and adult tetanus, reduced diphtheria, acellular pertussis) vaccine. Based on 2 exposed cases, the odds ratio for Tdap exposure 5-28 days prior to ADEM onset was 15.8 (95% confidence interval [CI], 1.2-471.6; P = .04), and the estimated excess risk was 0.385 (95% CI, -.04 to 1.16) cases per million doses.  We found no association between TM and prior immunization. There was a possible association of ADEM with Tdap vaccine, but the excess risk is not likely to be more than 1.16 cases of ADEM per million vaccines administered. © 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.

Post-licensure surveillance of trivalent live attenuated influenza vaccine in adults, United States, Vaccine Adverse Event Reporting System (VAERS), July 2005-June 2013.

PubMed

Haber, Penina; Moro, Pedro L; McNeil, Michael M; Lewis, Paige; Woo, Emily Jane; Hughes, Hayley; Shimabukuro, Tom T

2014-11-12

Trivalent live attenuated influenza vaccine (LAIV3) was licensed and recommended for use in 2003 in children and adults 2-49 years of age. Post-licensure safety data have been limited, particularly in adults. We searched Vaccine Adverse Event Reporting System (VAERS) for US reports after LAIV3 from July 1, 2005-June 30, 2013 (eight influenza seasons) in adults aged ≥ 18 years old. We conducted descriptive analyses and clinically reviewed serious reports (i.e., death, life-threatening illness, hospitalization, prolonged hospitalization, or permanent disability) and reports of selected conditions of interest. We used empirical Bayesian data mining to identify adverse events (AEs) that were reported more frequently than expected. We calculated crude AE reporting rates to VAERS by influenza season. During the study period, VAERS received 1207 LAIV3 reports in adults aged 18-49 years old; 107 (8.9%) were serious, including four death reports. The most commonly reported events were expired drug administered (n=207, 17%), headache (n=192, 16%), and fever (n=133, 11%). The most common diagnostic categories for non-fatal serious reports were neurological (n=40, 39%), cardiovascular (n=14, 14%), and other non-infectious conditions (n=20, 19%). We noted a higher proportion of Guillain-Barré syndrome (GBS) and cardiovascular reports in the Department of Defense (DoD) population compared to the civilian population. Data mining detected disproportional reporting of ataxia (n=15); clinical review revealed that ataxia was a component of diverse clinical entities including GBS. Review of VAERS reports are reassuring, the only unexpected safety concern for LAIV3 identified was a higher than expected number of GBS reports in the DoD population, which is being investigated. Reports of administration of expired LAIV3 represent administration errors and indicate the need for education, training and screening regarding the approved indications. Published by Elsevier Ltd.

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

PubMed

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

PubMed

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.

Immunogenicity and safety of Intanza(®)/IDflu(®) intradermal influenza vaccine in South Korean adults: a multicenter, randomized trial.

PubMed

Hoon Han, Sang; Hee Woo, Jun; Weber, Francoise; Joo Kim, Woo; Ran Peck, Kyong; Il Kim, Sang; Hwa Choi, Young; Myung Kim, June

2013-09-01

Intanza(®)/IDflu(®) (Sanofi Pasteur, Lyon, France) is an intradermal inactivated trivalent influenza vaccine developed as an alternative to intramuscular influenza vaccine. The objective of this study was to confirm the immunogenicity and safety of Intanza/IDflu in South Korean adults. In a phase IV multicenter trial, South Korean adults 18-59 y old (n = 120) and ≥ 60 y old (n = 120) were randomized 1:1 to receive a single dose of Intanza/IDflu (9 µg for 18-59 y, 15 µg for ≥ 60 y) or trivalent intramuscular vaccine (Vaxigrip(®) 15 µg, Sanofi Pasteur, Lyon, France). Blood was collected on pre-vaccination (day 0) and on day 21. Hemagglutination inhibition titers, seroprotection rates and seroconversion rates were determined on day 21. Geometric mean titers, seroprotection and seroconversion rates were similar between the intradermal and intramuscular vaccines in both age groups for all three vaccine strains (A/H1N1, A/H3N2 and B). Both vaccines met Committee for Medicinal Products for Human Use criteria for all three strains. Solicited systemic reactions of the intradermal groups were generally mild, transient, and similar to those of the intramuscular groups. Solicited injection site reactions were more frequent in the intradermal groups but were mostly mild, transient, and consisted mainly of pain, erythema, and pruritus. No treatment-related serious adverse events or other safety concerns were reported. These results confirm that Intanza/IDflu is an effective and well-tolerated alternative to IM influenza vaccination. (Clinicaltrials.gov NCT ID: NCT01215669).

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

PubMed

Braczkowska, Bogumiła; Kowalska, Małgorzata; Barański, Kamil; Gajda, Maksymilian; Kurowski, Tomasz; Zejda, Jan E

2018-04-15

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.

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

PubMed

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.

Lot-to-lot Consistency, Safety, Tolerability and Immunogenicity of an Investigational Hexavalent Vaccine in US Infants.

PubMed

Block, Stanley L; Klein, Nicola P; Sarpong, Kwabena; Russell, Stephen; Fling, John; Petrecz, Maria; Flores, Sheryl; Xu, Jin; Liu, Guanghan; Stek, Jon E; Foglia, Ginamarie; Lee, Andrew W

2017-02-01

This multicenter phase III study (NCT01340937) evaluated the consistency of immune responses to 3 separate lots of diphtheria-tetanus toxoids-acellular pertussis 5, inactivated poliovirus vaccine, Haemophilus influenzae type b, and hepatitis B (DTaP5-IPV-Hib-HepB), an investigational hexavalent vaccine (HV). Healthy infants were randomized (2:2:2:1) to receive HV or Pentacel (Control). Groups 1, 2 and 3 received HV at 2, 4 and 6 months, and Control at 15 months. Group 4 received Control at 2, 4, 6 and 15 months, plus Recombivax HB (HepB) at 2 and 6 months. Concomitant Prevnar 13 was given to all groups at 2, 4, 6 and 15 months; pentavalent rotavirus vaccine (RV5) was given to all groups at 2, 4 and 6 months. Blood specimens (3-5 mL) were collected immediately before administration of dose 1, postdose 3, immediately before toddler dose, and after toddler dose. Adverse events were recorded after each vaccination. The 3 manufacturing lots of HV induced consistent antibody responses to all antigens. Immunogenicity of HV was noninferior to Control for all antibodies, except for pertussis filamentous hemagglutinin geometric mean concentration postdose 3, and pertussis pertactin (PRN) geometric mean concentration after toddler dose. Postdose 3 immunogenicity of concomitantly administered Prevnar 13 was generally similar (except for serotype 6B) when given with HV or Control. Adverse events of HV were similar to Control, except for a higher rate of fever ≥38.0°C [49.2% vs. 35.4%, estimated difference 13.7% (8.4, 18.8)]. HV demonstrated lot-to-lot manufacturing consistency; safety and immunogenicity were comparable with the licensed vaccines. HV provides a new combination vaccine option within the US 2-month, 4-month and 6-month vaccine series.

Highlights of Historical Events Leading to National Surveillance of Vaccination Coverage in the United States

PubMed Central

Smith, Philip J.; Wood, David; Darden, Paul M.

2011-01-01

The articles published in this special supplement of Public Health Reports provide examples of only some of the current efforts in the United States for evaluating vaccination coverage. So, how did we get here? The history of vaccination and assessment of vaccination coverage in the U.S. has its roots in the pre-Revolutionary War era. In many cases, development of vaccines, and attention devoted to the assessment of vaccination coverage, has grown from the impact of infectious disease on major world events such as wars. The purpose of this commentary is to provide a brief overview of the key historical events in the U.S. that influenced the development of vaccines and the efforts to track vaccination coverage, which laid the foundation for contemporary vaccination assessment efforts. PMID:21815302

Comparison of the immunogenicity and safety of the conventional subunit, MF59-adjuvanted, and intradermal influenza vaccines in the elderly.

PubMed

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

2014-07-01

The influenza vaccination is known as the most effective method for preventing influenza infection and its complications in the elderly. Conventional subunit (Agrippal S1; Novartis), MF59-adjuvanted (Fluad; Novartis), and intradermal (IDflu15; Sanofi Pasteur) influenza vaccines are widely used throughout South Korea. However, few comparative studies evaluating the safety and immunogenicity of these vaccines are available. Prior to the beginning of the 2011-2012 influenza season, 335 healthy elderly volunteers randomly received one of three seasonal trivalent influenza vaccines, the conventional subunit, MF59-adjuvanted, or intradermal influenza vaccine. Serum hemagglutination-inhibiting antibody levels were measured at the time of vaccination and at 1 and 6 months after vaccination. Adverse events were recorded prospectively. A total of 113 conventional subunit, 111 MF59-adjuvanted, and 111 intradermal influenza vaccine volunteers were followed up during a 6-month postvaccination period. One month after vaccination, all three vaccines satisfied Committee for Medical Products for Human Use (CHMP) immunogenicity criteria for the A/H1N1 and A/H3N2 strains but not for the B strain. Compared with the subunit vaccine, the intradermal vaccine exhibited noninferiority, while the MF59-adjuvanted vaccine exhibited superiority. Furthermore, the MF59-adjuvanted vaccine was more immunogenic against the A/H3N2 strain than was the subunit vaccine up to 6 months postvaccination. The most common local and systemic reactions to the conventional subunit, MF59-adjuvanted, and intradermal influenza vaccines were pain at the injection site (7.1%, 10.8%, and 6.3%, respectively) and generalized myalgia (0.9%, 8.1%, and 5.4%, respectively). Local and systemic reactions were similar among the three vaccine groups. MF59-adjuvanted vaccine exhibited superior immunogenicity compared with a conventional subunit vaccine and had a comparable safety profile. For older adults, the MF59-adjuvanted

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

PubMed

Black, Steven

2015-06-08

The squalene oil-in-water emulsion MF-59 adjuvant was developed initially to enhance the immunogenicity of influenza vaccines in populations such as children and adults with known suboptimal response. Developed in the 1990s, it was initially licensed in Europe for use in seasonal influenza vaccine in the elderly. Since that time, both Avian and p2009H1N1 vaccines have also been developed. Overall, more than 30,000 individuals have participated in clinical trials of MF-59 adjuvanted vaccine and more than 160 million doses of licensed vaccine have been administered. Safety and effectiveness data from clinical trials and observation studies attest to the safety of MF-59 and to its ability to enhance the effectiveness of influenza vaccines in children and the elderly. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

PubMed

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.

Historical aspects of immunization and vaccine safety communication.

PubMed

Helfert, Stephanie M

2015-01-01

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

Parent and caregiver perceptions about the safety and effectiveness of foreign and domestic vaccines in Shanghai, China.

PubMed

Huang, Zhuoying; Sun, Xiaodong; Wagner, Abram L; Ren, Jia; Boulton, Matthew L; Prosser, Lisa A; Zikmund-Fisher, Brian J

2018-01-01

Chinese parents have access to domestic and foreign vaccines for their children. Their vaccine preferences are unclear, especially given recent pharmaceutical quality scandals and widely held beliefs deriving from Traditional Chinese Medicine (TCM). This study characterized parental beliefs about the safety and effectiveness of Chinese and foreign vaccines. In May 2014, caregivers of young children at public immunization clinics in Shanghai, China, responded to a survey on vaccine perceptions. The two outcomes (differential belief in the effectiveness and safety of foreign vs domestic vaccines) were separately regressed onto demographic predictors in multinomial logistic regression models. Among 618 caregivers, 56% thought the effectiveness of domestic and foreign vaccines were comparable; 33% thought domestic were more effective and 11% foreign. Two-thirds thought foreign and domestic vaccines had similar safety; 11% thought domestic were safer and 21% thought foreign were safer. Compared to college graduates, those with a high school education or less had greater odds of believing domestic vaccines were more effective, and also had greater odds of believing imported vaccines were safer. Greater trust in TCM was not associated with differential beliefs in the effectiveness or safety of domestic vs foreign vaccines. Although there is no evidence that foreign and domestic vaccines differ in either effectiveness or safety, less educated caregivers in China (but not those with greater trust in TCM) appear to believe such differences exist. Further exploration of the causes of these beliefs may be necessary in order to optimize vaccine communications in China.

Vaccine adverse events reported in post-marketing study of the Kitasato Institute from 1994 to 2004.

PubMed

Nakayama, Tetsuo; Onoda, Kazumasa

2007-01-05

General physicians, pediatricians and parents realize that serious adverse events occur with an extremely rare incidence, but have no information on the incidences of vaccine-associated adverse events. A proper understanding of vaccine adverse events would be helpful in promoting an immunization strategy. Causal association can rarely be determined in adverse events through laboratory examinations. We examined the cases reported in the post-marketing surveillance of the Kitasato Institute, categorizing them into two groups: allergic reactions and severe systemic illnesses. Anaphylactic patients with gelatin allergy after immunization with live measles, rubella and mumps monovalent vaccines have been reported since 1993, but the number of reported cases with anaphylaxis dramatically decreased after 1999 when gelatin was removed from all brands of DPT. The incidence of anaphylactic reaction was estimated to be 0.63 per million for Japanese encephalitis virus (JEV) vaccine, 0.95 for DPT and 0.68 for Influenza vaccine, but the causative component has not yet been specified. Among 67.2 million immunization practices, 6 cases with encephalitis or encephalopathy, 7 with acute disseminated encephalomyelitis (ADEM), 10 with Guillain-Barré syndrome and 12 with idiopathic thrombocytopenic purpura (ITP) were reported. The wild-type measles virus genome was detected in a patient with encephalitis and in two of four bone marrow aspirates obtained from ITP after measles vaccination. Enterovirus infection was identified in two patients after mumps vaccination (one each with encephalitis and ADEM), one patient with encephalitis after immunization with JEV vaccine, and one with aseptic meningitis after immunization with influenza vaccine. The total estimated incidence of serious neurological illness after vaccination was 0.1-0.2 per million immunization practices. We found that enterovirus or wild-type measles virus infection was coincidentally associated with vaccination in

Safety and immunogenicity of two inactivated poliovirus vaccines in combination with an acellular pertussis vaccine and diphtheria and tetanus toxoids in seventeen- to nineteen-month-old infants.

PubMed

Halperin, S A; Davies, H D; Barreto, L; Guasparini, R; Meekison, W; Humphreys, G; Eastwood, B J

1997-04-01

To compare the safety and immunity of an acellular pertussis vaccine containing pertussis toxoid, filamentous hemagglutinin, 69 kd protein, fimbriae 2 and 3 combined with diphtheria and tetanus toxoids given as single or separate injection with inactivated poliovirus vaccine (MRC-5-or Vero cell-derived) or live attenuated polio vaccine. A total of 425 healthy children between 17 and 19 months of age who were receiving the fourth dose of their routine immunization series were randomly allocated to receive either the acellular pertussis vaccine and oral poliovirus vaccine or one of two inactivated poliovirus vaccines as a combined injection or separate injections. Although minor adverse events were commonly reported, differences between the groups were few. Fever and decreased feeding were less common in recipients of live attenuated poliovirus vaccine than the combination vaccine containing MRC-5 cell-derived inactivated poliovirus vaccine. A significant antibody response was demonstrated in all groups against all the antigens contained in the vaccines. Antibodies against poliovirus were higher in the groups immunized with the inactivated poliovirus vaccine than the live attenuated vaccine. Anti-69 kd protein antibodies were higher in the group given the MRC-5 cell-derived inactivated poliovirus vaccine as a combined injection than in the group given the separate injection or the group immunized with the live attenuated poliovirus vaccine. The five-component acellular pertussis vaccine combined with diphtherid and tetanus toxoids is safe and immunogenic when combined with either MRC-5- or Vero cell-derived inactivated poliovirus vaccine. This will facilitate the implementation of acellular pertussis vaccine and the movement to inactivated poliovirus vaccine programs.

Yellow fever vaccination status and safety in hemodialysis patients.

PubMed

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

2016-07-01

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

Is it time for a new yellow fever vaccine?

PubMed

Hayes, Edward B

2010-11-29

An inexpensive live attenuated vaccine (the 17D vaccine) against yellow fever has been effectively used to prevent yellow fever for more than 70 years. Interest in developing new inactivated vaccines has been spurred by recognition of rare but serious, sometimes fatal adverse events following live virus vaccination. A safer inactivated yellow fever vaccine could be useful for vaccinating people at higher risk of adverse events from the live vaccine, but could also have broader global health utility by lowering the risk-benefit threshold for assuring high levels of yellow fever vaccine coverage. If ongoing trials demonstrate favorable immunogenicity and safety compared to the current vaccine, the practical global health utility of an inactivated vaccine is likely to be determined mostly by cost. Copyright © 2010 Elsevier Ltd. All rights reserved.

An escalating dose study to assess the safety, tolerability and immunogenicity of a Herpes Simplex Virus DNA vaccine, COR-1.

PubMed

Dutton, Julie L; Woo, Wai-Ping; Chandra, Janin; Xu, Yan; Li, Bo; Finlayson, Neil; Griffin, Paul; Frazer, Ian H

2016-12-01

This paper describes a single site, open-label Phase I clinical trial evaluating the safety, tolerability and immunogenicity in healthy volunteers of a herpes simplex polynucleotide vaccine that has previously been shown to enhance immunogenicity and protect against lethal herpes simplex virus type 2 (HSV-2) challenge in mice. Five escalating doses of the vaccine, COR-1, were given by intradermal injection to HSV-1 and 2 seronegative healthy individuals. COR-1 was found to be safe and well-tolerated; the only vaccine-related adverse events were mild. While vaccine-induced antibody responses were not detectable, cell-mediated immune responses to HSV-specific peptide groups were identified in 19 of the 20 subjects who completed the study, and local inflammation at the immunisation site was observed. This study indicates COR-1 has potential to be used as a therapeutic vaccine for HSV-2 infection.

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

PubMed

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.

Randomized, double-blind, active-controlled study evaluating the safety and immunogenicity of three vaccination schedules and two dose levels of AV7909 vaccine for anthrax post-exposure prophylaxis in healthy adults.

PubMed

Hopkins, Robert J; Kalsi, Gurdyal; Montalvo-Lugo, Victor M; Sharma, Mona; Wu, Yukun; Muse, Derek D; Sheldon, Eric A; Hampel, Frank C; Lemiale, Laurence

2016-04-19

AV7909 vaccine being developed for post-exposure prophylaxis of anthrax disease may require fewer vaccinations and reduced amount of antigen to achieve an accelerated immune response over BioThrax(®) (Anthrax Vaccine Adsorbed). A phase 2, randomized, double-blind, BioThrax vacccine-controlled study was conducted to evaluate the safety and immunogenicity of three intramuscular vaccination schedules and two dose levels of AV7909 in 168 healthy adults. Subjects were randomized at a 4:3:2:4:2 ratio to 5 groups: (1) AV7909 on Days 0/14; (2) AV7909 on Days 0/28; (3) AV7909 on Days 0/14/28; (4) half dose AV7909 on Days 0/14/28; and (5) BioThrax vaccine on Days 0/14/28. Vaccinations in all groups were well tolerated. The incidences of adverse events (AEs) were 79% for AV7909 subjects and 65% for BioThrax subjects; 92% of AV7909 subjects and 87% of BioThrax subjects having AEs reported Grade 1-2 AEs. No serious AEs were assessed as potentially vaccine-related, and no AEs of potential autoimmune etiology were reported. There was no discernible pattern indicative of a safety concern across groups in the incidence or severity of reactogenicity events. Groups 2-4 achieved success for the primary endpoint, demonstrated by a lower 95% confidence limit of the percentage of subjects with protective toxin neutralizing antibody NF50 values (≥0.56) to be ≥40% at Day 63. Group 1 marginally missed the criterion (lower bound 95% confidence limit of 39.5%). Immune responses were above this threshold for Groups 1, 3 and 4 at Day 28 and all groups at Day 42. Further study of an AV7909 two-dose schedule given 2 weeks apart is warranted in light of the favorable tolerability profile and immunogenicity response relative to three doses of BioThrax vaccine, as well as preliminary data from nonclinical studies indicating similar immune responses correlate with higher survival for AV7909 than BioThrax vaccine. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Reactogenicity of infant whole cell pertussis combination vaccine compared with acellular pertussis vaccines with or without simultaneous pneumococcal vaccine in the Netherlands.

PubMed

David, Silke; Vermeer-de Bondt, Patricia E; van der Maas, Nicoline A T

2008-10-29

In addition to the routine enhanced passive safety surveillance of the Dutch National Vaccination Programme, RIVM (National Institute for Public Health and the Environment) started a large questionnaire study enrolling approximately 53,000 children from December 2003 until September 2007. We intended to establish accurate frequency estimates for several more severe adverse events and to compare the incidence rates of three different infant vaccines that were used consecutively. Whole cell pertussis (wP) DTP-IPV-Hib vaccine (NVI) was replaced by acellulair pertussis (aP) in 2005, first Infanrix-IPV-Hib (GSK) followed by Pediacel (Sanofi) in 2006. Pneumococcal vaccine, Prevenar (Wyeth), was added for children born from April 2006. Parents returned 28,796 questionnaires (response 54%), 15,069 for whole cell pertussis and 13,727 for acellular pertussis vaccine, including 4485 with pneumococcal vaccine. The OR for reported events was 3-6 for whole cell pertussis vaccine compared with acellular vaccine. This was true for prolonged crying for 3h and more after the first dose (1.5% versus 0.4%; 95 CI 1.1-1.9 and 95% CI 0.2-0.7, respectively), and very high fever of 40.5 degrees C and over following the fourth dose (0.8% versus 0.2%; 95% CI 0.5-1.1 and 0.06-0.3, respectively), while possible febrile convulsions were diagnosed only twice after the fourth dose in the whole cell vaccine group and one after acellular pertussis vaccine. Pallor was significantly more frequent after the first dose of whole cell pertussis than after acellulair pertussis vaccination (18.3% versus 3.4%; 95% CI 17.2-19.5 and 95% CI 2.8-4.0 respectively) Collapse after the first dose was rare in both vaccine groups (5 after whole cell vaccine and 1 after acellular vaccine). The addition of conjugated pneumococcal vaccine did not result in statistically significant increased rates of adverse events in the acellular vaccine group. Whole cell pertussis vaccine showed a significantly higher reactogenicity

Vaccine adjuvants: Why and how.

PubMed

Christensen, Dennis

2016-10-02

Novel vaccine strategies include the so-called subunit vaccines, which encompass only the part of the pathogen to which immune recognition results in protection. The high purity of these vaccines make adverse events less likely, but it also makes the vaccines less immunogenic and therefore potentially less effective. Vaccine adjuvants that increase and modulate the immunogenicity of the vaccine are therefore added to solve this problem. Besides aluminum salts, which have been used in vaccines for 90 years, a number of novel vaccine adjuvants have been included in licensed vaccines over the last 30 years. Increasing insight into immunological mechanisms and how to manipulate them has replaced empirical with rational design of adjuvants, leading to vaccine adjuvants with increased and customized immunogenicity profiles without compromising vaccine safety.

Safety and Immunogenicity of 3 Formulations of an Investigational Respiratory Syncytial Virus Vaccine in Nonpregnant Women: Results From 2 Phase 2 Trials

PubMed Central

Beran, Jiři; Lickliter, Jason D; Schwarz, Tino F; Johnson, Casey; Chu, Laurence; Domachowske, Joseph B; Van Damme, Pierre; Withanage, Kanchanamala; Fissette, Laurence A; David, Marie-Pierre; Maleux, Koen; Schmidt, Alexander C; Picciolato, Marta; Dieussaert, Ilse

2018-01-01

Abstract Background Respiratory syncytial virus (RSV) causes bronchiolitis and pneumonia in neonates and infants. RSV vaccination during pregnancy could boost preexisting neutralizing antibody titers, providing passive protection to newborns. Methods Two observer-blinded, controlled studies (RSV F-020 [clinical trials registration NCT02360475] and RSV F-024 [NCT02753413]) evaluated immunogenicity and safety of an investigational RSV vaccine in healthy, nonpregnant 18–45-year-old women. Both studies used a licensed adult formulation of combined tetanus toxoid-diphtheria toxoid-acellular pertussis (Tdap) vaccine as a control. RSV F-020 evaluated immunogenicity and safety: participants were randomized (1:1:1:1) to receive 1 dose of RSV–prefusion F protein (PreF) vaccine containing 30 µg or 60 µg of nonadjuvanted RSV-PreF, 60 µg of aluminum-adjuvanted RSV-PreF, or Tdap. RSV F-024 evaluated safety: participants were randomized 1:1 to receive 1 dose of 60 µg of nonadjuvanted RSV-PreF or Tdap. Results Both studies showed similar reactogenicity profiles for RSV-PreF and Tdap. No serious adverse events were considered vaccine related. In RSV F-020, geometric mean ratios of RSV-A neutralizing antibody levels at day 30 versus prevaccination were 3.1–3.9 in RSV-PreF recipients and 0.9 in controls. Palivizumab-competing antibody concentrations increased >14-fold in RSV-PreF recipients on day 30. RSV antibody titers waned after day 30 but remained well above baseline through day 90. Conclusions All formulations of RSV-PreF boosted preexisting immune responses in 18–45-year old women with comparable immunogenicity. The RSV-PreF safety profile was similar to that of Tdap vaccine. PMID:29401325

Immunogenicity and safety results from a randomized multicenter trial comparing a Tdap-IPV vaccine (REPEVAX®) and a tetanus monovalent vaccine in healthy adults

PubMed Central

Laurichesse, Henri; Zimmermann, Ulrich; Galtier, Florence; Launay, Odile; Duval, Xavier; Richard, Patrick; Sadorge, Christine; Soubeyrand, Benoit

2012-01-01

In adults with a tetanus-prone injury, combined vaccines such as Tdap-IPV (REPEVAX®) can boost immunity against several diseases simultaneously. This Phase IIIb, parallel-group, open-label trial compared antibody responses to Tdap-IPV and tetanus monovalent vaccine (TMV; Vaccin Tétanique Pasteur® or Tetavax®) against tetanus toxoid 10 and 28 d post-vaccination. Between July and December 2009, four centers in France and five in Germany recruited healthy adults who had received a tetanus-containing vaccine 5−10 y previously. Participants were randomized 1:1 to receive at the first visit a single dose (0.5 mL) of Tdap-IPV or TMV, with follow-up visits at Day 10 and Day 28. Outcomes: per protocol (PP) population immunogenicity at Day 10 (primary) and at Day 28 (secondary); safety throughout the study. Of 456 adults randomized, 223 received Tdap-IPV and 233 received TMV (PP population: 183 and 199 participants, respectively). All participants receiving Tdap-IPV and 99.0% receiving TMV had an anti-tetanus antibody concentration ≥ 0.1 IU/mL, confirming non-inferiority of Tdap-IPV to TMV (95% confidence interval of the difference: –1.2, 3.6). Number of adverse events reported was comparable in each group. Injection-site reactions were reported by 76.6% participants receiving Tdap-IPV and 74.6% receiving TMV. Systemic events (e.g., malaise, myalgia and headache) were reported in 47.7% and 39.7% of the Tdap-IPV and the TMV groups, respectively. Tdap-IPV is effective and well-tolerated for use in the management of tetanus-prone injuries in emergency settings in persons for whom a booster against diphtheria, pertussis and poliomyelitis is also needed. ClinicalTrials.gov identifier: NCT00928785. Research sponsored by Sanofi Pasteur MSD. PMID:23032160

Intussusception after monovalent rotavirus vaccine-United States, Vaccine Adverse Event Reporting System (VAERS), 2008-2014.

PubMed

Haber, Penina; Parashar, Umesh D; Haber, Michael; DeStefano, Frank

2015-09-11

In 2006 and 2008, two new rotavirus vaccines (RotaTeq [RV5] and Rotarix [RV1]) were introduced in the United States. US data on intussusception have been mostly related to RV5, with limited data on RV1. We assessed intussusception events following RV1 reported to the Vaccine Adverse Event Reporting System (VAERS), a US national passive surveillance system, during February 2008-December 2014. We conducted a self-controlled risk interval analysis using Poisson regression to estimate the daily reporting ratio (DRR) of intussusception after the first 2 doses of RV1 comparing average daily reports 3-6 versus 0-2 days after vaccination. We calculated the excess risk of intussusception per 100,000 vaccinations based on DRRs and background rates of intussusception. Sensitivity analyses were conducted to assess effects of differential reporting completeness and inaccuracy of baseline rates. VAERS received 108 confirmed insusceptible reports after RV1. A significant clustering was observed on days 3-8 after does1 (p=0.001) and days 2-7 after dose 2 (p=0.001). The DRR comparing the 3-6 day and the 0-2 day periods after RV1 dose 1 was 7.5 (95% CI=2.3, 24.6), translating to an excess risk of 1.6 (95% CI=0.3, 5.8) per 100,000 vaccinations. The DRR was elevated but not significant after dose 2 (2.4 [95% CI=0.8,7.5]). The excess risk ranged from 1.2 to 2.8 per 100,000 in sensitivity analysis. We observed a significant increased risk of intussusception 3-6 days after dose 1 of RV1. The estimated small number of intussusception cases attributable to RV1 is outweighed by the benefits of rotavirus vaccination. Published by Elsevier Ltd.

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

PubMed

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 in<5-year-old patients between Zagreb 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.

[Current events in vaccination].

PubMed

Aubert, M; Aumaître, H; Beytout, J; Bloch, K; Bouhour, D; Callamand, P; Chave, C; Cheymol, J; Combadière, B; Dahlab, A; Denis, F; De Pontual, L; Dodet, B; Dommergues, M-A; Dufour, V; Gagneur, A; Gaillat, J; Gaudelus, J; Gavazzi, G; Gillet, Y; Gras-le-Guen, C; Haas, H; Hanslik, T; Hau-Rainsard, I; Larnaudie, S; Launay, O; Lorrot, M; Loulergue, P; Malvy, D; Marchand, S; Picherot, G; Pinquier, D; Pulcini, C; Rabaud, C; Regnier, F; Reinert, P; Sana, C; Savagner, C; Soubeyrand, B; Stephan, J-L; Strady, C

2011-11-01

The annual meeting of the Infectious Disease Society of America (IDSA) ; which brought together nearly 5000 participants from over 80 countries in Vancouver, Canada, October 21 to 24, 2010 ; provided a review of the influenza (H1N1) 2009 pandemic, evaluated vaccination programmes and presented new vaccines under development. With 12,500 deaths in the United States in 2009-2010, the influenza (H1N1) 2009 pandemic was actually less deadly than the seasonal flu. But it essentially hit the young, and the toll calculated in years of life lost is high. The monovalent vaccines, whether live attenuated or inactivated with or without adjuvants, were well tolerated in toddlers, children, adults and pregnant women. In order to protect infants against pertussis, family members are urged to get their booster shots. The introduction of the 13-valent Pneumococcal conjugated vaccine in the beginning of 2010 may solve - but for how long ? - the problem of serotype replacement, responsible for the re-increasing incidence of invasive Pneumococcal infections observed in countries that had introduced the 7-valent vaccine. The efficacy of a rotavirus vaccine has been confirmed, with a reduction in hospitalization in the United States and a reduction in gastroenteritis-related deaths in Mexico. In the United States, vaccination of pre-adolescents against human papillomavirus (HPV) has not resulted in any specific undesirable effects. Routine vaccination against chicken pox, recommended since 1995, has not had an impact on the evolution of the incidence of shingles. Vaccination against shingles, recommended in the United States for subjects 60 years and over, shows an effectiveness of 55 %, according to a cohort study (Kaiser Permanente, Southern California). Although some propose the development of personalized vaccines according to individual genetic characteristics, the priority remains with increasing vaccine coverage, not only in infants but also in adults and the elderly. Vaccine

[Current events in vaccination].

PubMed

Aubert, M; Aumaître, H; Beytout, J; Bloch, K; Bouhour, D; Callamand, P; Chave, C; Cheymol, J; Combadière, B; Dahlab, A; Denis, F; De Pontual, L; Dodet, B; Dommergues, M A; Dufour, V; Gagneur, A; Gaillat, J; Gaudelus, J; Gavazzi, G; Gillet, Y; Gras-le-Guen, C; Haas, H; Hanslik, T; Hau-Rainsard, I; Larnaudie, S; Launay, O; Lorrot, M; Loulergue, P; Malvy, D; Marchand, S; Picherot, G; Pinquier, D; Pulcini, C; Rabaud, C; Regnier, F; Reinert, P; Sana, C; Savagner, C; Soubeyrand, B; Stephan, J L; Strady, C

2011-05-01

The annual meeting of the Infectious Disease Society of America (IDSA); which brought together nearly 5000 participants from over 80 countries in Vancouver, Canada, October 21 to 24, 2010; provided a review of the influenza (H1N1) 2009 pandemic, evaluated vaccination programmes and presented new vaccines under development. With 12,500 deaths in the United States in 2009-2010, the influenza (H1N1) 2009 pandemic was actually less deadly than the seasonal flu. But it essentially hit the young, and the toll calculated in years of life lost is high. The monovalent vaccines, whether live attenuated or inactivated with or without adjuvants, were well tolerated in toddlers, children, adults and pregnant women. In order to protect infants against pertussis, family members are urged to get their booster shots. The introduction of the 13-valent Pneumococcal conjugated vaccine in the beginning of 2010 may solve--but for how long?--the problem of serotype replacement, responsible for the re-increasing incidence of invasive Pneumococcal infections observed in countries that had introduced the 7-valent vaccine. The efficacy of a rotavirus vaccine has been confirmed, with a reduction in hospitalization in the United States and a reduction in gastroenteritis-related deaths in Mexico. In the United States, vaccination of pre-adolescents against human papillomavirus (HPV) has not resulted in any specific undesirable effects. Routine vaccination against chicken pox, recommended since 1995, has not had an impact on the evolution of the incidence of shingles. Vaccination against shingles, recommended in the United States for subjects 60 years and over, shows an effectiveness of 55%, according to a cohort study (Kaiser Permanente, Southern California). Although some propose the development of personalized vaccines according to individual genetic characteristics, the priority remains with increasing vaccine coverage, not only in infants but also in adults and the elderly. Vaccine

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

PubMed

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

Assessment of the Safety and Immunogenicity of 2 Novel Vaccine Platforms for HIV-1 Prevention: A Randomized Trial.

PubMed

Baden, Lindsey R; Karita, Etienne; Mutua, Gaudensia; Bekker, Linda-Gail; Gray, Glenda; Page-Shipp, Liesl; Walsh, Stephen R; Nyombayire, Julien; Anzala, Omu; Roux, Surita; Laher, Fatima; Innes, Craig; Seaman, Michael S; Cohen, Yehuda Z; Peter, Lauren; Frahm, Nicole; McElrath, M Juliana; Hayes, Peter; Swann, Edith; Grunenberg, Nicole; Grazia-Pau, Maria; Weijtens, Mo; Sadoff, Jerry; Dally, Len; Lombardo, Angela; Gilmour, Jill; Cox, Josephine; Dolin, Raphael; Fast, Patricia; Barouch, Dan H; Laufer, Dagna S

2016-03-01

A prophylactic HIV-1 vaccine is a global health priority. To assess a novel vaccine platform as a prophylactic HIV-1 regimen. Randomized, double-blind, placebo-controlled trial. Both participants and study personnel were blinded to treatment allocation. (ClinicalTrials.gov: NCT01215149). United States, East Africa, and South Africa. Healthy adults without HIV infection. 2 HIV-1 vaccines (adenovirus serotype 26 with an HIV-1 envelope A insert [Ad26.EnvA] and adenovirus serotype 35 with an HIV-1 envelope A insert [Ad35.Env], both administered at a dose of 5 × 1010 viral particles) in homologous and heterologous combinations. Safety and immunogenicity and the effect of baseline vector immunity. 217 participants received at least 1 vaccination, and 210 (>96%) completed follow-up. No vaccine-associated serious adverse events occurred. All regimens were generally well-tolerated. All regimens elicited humoral and cellular immune responses in nearly all participants. Preexisting Ad26- or Ad35-neutralizing antibody titers had no effect on vaccine safety and little effect on immunogenicity. In both homologous and heterologous regimens, the second vaccination significantly increased EnvA antibody titers (approximately 20-fold from the median enzyme-linked immunosorbent assay titers of 30-300 to 3000). The heterologous regimen of Ad26-Ad35 elicited significantly higher EnvA antibody titers than Ad35-Ad26. T-cell responses were modest and lower in East Africa than in South Africa and the United States. Because the 2 envelope inserts were not identical, the boosting responses were complex to interpret. Durability of the immune responses elicited beyond 1 year is unknown. Both vaccines elicited significant immune responses in all populations. Baseline vector immunity did not significantly affect responses. Second vaccinations in all regimens significantly boosted EnvA antibody titers, although vaccine order in the heterologous regimen had a modest effect on the immune response

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

Code of Federal Regulations, 2010 CFR

2010-04-01

... guinea pigs, the test shall be satisfied if the product provides satisfactory results using either the subcutaneous or intraperitoneal injection of 5.0 milliliters of inactivated influenza vaccine into each guinea pig. The requirements for general safety for inactivated influenza vaccine shall not be considered to...

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

PubMed

Fox, Christopher B; Haensler, Jean

2013-07-01

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

Vaccine-preventable diseases, vaccines and Guillain-Barre' syndrome.

PubMed

Principi, Nicola; Esposito, Susanna

2018-06-04

Guillain-Barré syndrome (GBS) is an acute, immune-mediated polyradiculoneuropathy. Infections and vaccines have been hypothesized to play a role in triggering GBS development. These beliefs can play a role in reducing vaccination coverage. In this report, data concerning this hypothesis are discussed. It is shown that an association between vaccine administration and GBS has never been proven for most of debated vaccines, although it cannot be definitively excluded. The only exception is the influenza vaccine, at least for the preparation used in 1976. For some vaccines, such as measles/mumps/rubella, human papillomavirus, tetravalent conjugated meningococcal vaccine, and influenza, the debate between supporters and opponents of vaccination remains robust and perception of vaccines' low safety remains a barrier to achieving adequate vaccination coverage. Less than 1 case of GBS per million immunized persons might occur for these vaccines. However, in some casesimmunization actually reduces the risk of GBS development. In addition, the benefits of vaccination are clearly demonstrated by the eradication or enormous decline in the incidence of many vaccine-preventable diseases. These data highlight that the hypothesized risks of adverse events, such as GBS, cannot be considered a valid reason to avoid the administration of currently recommended vaccines. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

PubMed

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

2016-07-01

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

Safety, reactogenicity and immunogenicity of a novel pneumococcal protein-based vaccine in adults: a phase I/II randomized clinical study.

PubMed

Leroux-Roels, Geert; Maes, Cathy; De Boever, Fien; Traskine, Magali; Rüggeberg, Jens U; Borys, Dorota

2014-11-28

New vaccines containing highly conserved Streptococcus pneumoniae proteins such as pneumolysin toxoid (dPly) and histidine-triad protein D (PhtD) are being developed to provide broader protection against pneumococcal disease. This study evaluated the safety, reactogenicity and immunogenicity of different pneumococcal protein-containing formulations in adults. In a phase I double-blind study (www.clinicaltrials.gov: NCT00707798), healthy adults (18-40 years) were randomized (1:2:2:2:2:2:2) to receive two doses of one of six investigational vaccine formulations 2 months apart, or a single dose of the control 23-valent pneumococcal polysaccharide vaccine (23PPV; Pneumovax23™, Sanofi Pasteur MSD) followed by placebo. The investigational formulations contained dPly alone (10 or 30 μg), or both dPly and PhtD (10 or 30 μg each) alone or combined with the polysaccharide conjugates of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV; Synflorix™, GlaxoSmithKline Vaccines). Two groups primed with a formulation containing dPly and PhtD (10 or 30 μg each) continued to the follow-up phase II study (NCT00896064), in which they received a booster dose at 5-9 months after primary vaccination. Of 156 enrolled and vaccinated adults, 146 completed the primary immunization and 43 adults received a booster dose. During primary and booster vaccination, for any formulation, ≤ 8.9% of doses were followed by grade 3 solicited local or general adverse events. No fever >39.5°C (oral temperature) was reported. Unsolicited adverse events considered causally related to vaccination were reported following ≤ 33.3% of investigational vaccine doses. No serious adverse events were reported for adults receiving investigational vaccine formulations. Formulations containing dPly with or without PhtD were immunogenic for these antigens; polysaccharide conjugate-containing formulations were also immunogenic for those 10 polysaccharides

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

PubMed

Dixon, Graham; Clarke, Christopher

2013-04-01

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

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

PubMed Central

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

2017-01-01

Background 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. Methods 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. Results 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 (<1%) with 38% occurring in immunocompromised individuals. All reports of disseminated HZ confirmed by PCR as VZV Oka/Merck vaccine-strain were in individuals with immunosuppressive conditions and/or therapy at the time of vaccination. Conclusions The safety profile of ZVL, following 10 years of post-marketing use, was favorable and consistent with that observed in clinical trials and post-licensure studies. PMID:29174682

Vaccines for the common cold.

PubMed

Simancas-Racines, Daniel; Guerra, Claudia V; Hidalgo, Ricardo

2013-06-12