Safety Of Inactivated Influenza Vaccine Research Articles

Influenza vaccination during pregnancy and risk of selected major structural congenital heart defects, National Birth Defects Prevention Study 2006-2011.

Although results from studies of first-trimester influenza vaccination and congenital heart defects (CHDs) have been reassuring, data are limited for specific CHDs. We assessed associations between reported maternal influenza vaccination, 1 month before pregnancy (B1) through end of third pregnancy month (P3), and specific CHDs using data from a multisite, population-based case-control study. Analysis included 2,982 case children diagnosed with a simple CHD (no other cardiac involvement with or without extracardiac defects) and 4,937 control children without a birth defect with estimated delivery dates during 2006-2011. For defects with ≥5 exposed case children, we used logistic regression to estimate propensity score-adjusted odds ratios (aORs) and 95% confidence intervals (CIs), adjusting for estimated delivery year and season; plurality; and maternal age at delivery, race/ethnicity, low folate intake, and smoking and alcohol use during B1P3. Overall, 124 (4.2%) simple CHD case mothers and 197 (4.0%) control mothers reported influenza vaccination from 1 month before through the third pregnancy month. The aOR for any simple CHD was 0.97 (95% CI: 0.76-1.23). Adjusted ORs for specific simple CHDs ranged from 0.62 for hypoplastic left heart syndrome to 2.34 for total anomalous pulmonary venous return (TAPVR). All adjusted CIs included the null except for TAPVR. Although we cannot fully exclude that exposure misclassification may have masked risks for some CHDs, findings add to existing evidence supporting the safety of inactivated influenza vaccination during pregnancy. The TAPVR result may be due to chance, but it may help inform future studies.

Influenza vaccination during pregnancy and risk of selected major structural noncardiac birth defects, National Birth Defects Prevention Study 2006-2011.

To assess associations between influenza vaccination during etiologically-relevant windows and selected major structural non-cardiac birth defects. We analyzed data from the National Birth Defects Prevention Study, a multisite, population-based case-control study, for 8233 case children diagnosed with a birth defect and 4937 control children without a birth defect with delivery dates during 2006-2011. For all analyses except for neural tube defects (NTDs), we classified mothers who reported influenza vaccination 1 month before through the third pregnancy month as exposed; the exposure window for NTDs was 1 month before through the first pregnancy month. For defects with five or more exposed case children, we used logistic regression to estimate propensity score-adjusted odds ratios (aORs) and 95% confidence intervals (CIs), adjusting for estimated delivery year and season; plurality; maternal age, race/ethnicity, smoking and alcohol use, low folate intake; and, for NTDs, folate antagonist medications. There were 334 (4.1%) case and 197 (4.0%) control mothers who reported influenza vaccination from 1 month before through the third pregnancy month. Adjusted ORs ranged from 0.53 for omphalocele to 1.74 for duodenal atresia/stenosis. Most aORs (11 of 19) were ≤1 and all adjusted CIs included the null. The unadjusted CIs for two defects, hypospadias and craniosynostosis, excluded the null. These estimates were attenuated upon covariate adjustment (hypospadias aOR: 1.25 (95% CI 0.89, 1.76); craniosynostosis aOR: 1.23 (95% CI: 0.88, 1.74)). Results for several non-cardiac major birth defects add to the existing evidence supporting the safety of inactivated influenza vaccination during pregnancy. Under-reporting of vaccination may have biased estimates downward.

EASL position paper on the use of COVID-19 vaccines in patients with chronic liver diseases, hepatobiliary cancer and liver transplant recipients

According to a recent World Health Organization estimate, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, which originated in China in 2019, has spread globally, infecting nearly 100 million people worldwide by January 2021. Patients with chronic liver diseases (CLD), particularly cirrhosis, hepatobiliary malignancies, candidates for liver transplantation, and immunosuppressed individuals after liver transplantation appear to be at increased risk of infections in general, which in turn translates into increased mortality. This is also the case for SARS-CoV-2 infection, where patients with cirrhosis, in particular, are at high risk of a severe COVID-19 course. Therefore, vaccination against various pathogens including SARS-CoV-2, administered as early as possible in patients with CLD, is an important protective measure. However, due to impaired immune responses in these patients, the immediate and long-term protective response through immunisation may be incomplete. The current SARS-CoV-2 pandemic has led to the exceptionally fast development of several vaccine candidates. A small number of these SARS-CoV-2 vaccine candidates have already undergone phase III, placebo-controlled, clinical trials in healthy individuals with proof of short-term safety, immunogenicity and efficacy. However, although regulatory agencies in the US and Europe have already approved some of these vaccines for clinical use, information on immunogenicity, duration of protection and long-term safety in patients with CLD, cirrhosis, hepatobiliary cancer and liver transplant recipients has yet to be generated. This review summarises the data on vaccine safety, immunogenicity, and efficacy in this patient population in general and discusses the implications of this knowledge on the introduction of the new SARS-CoV-2 vaccines.

Immune-mediated adverse events following influenza vaccine in cancer patients receiving immune checkpoint inhibitors.

The emergence of immune checkpoint inhibitors has transformed treatment paradigms for various malignancies. Patients with cancer are at increased risk of complications and hospitalizations from influenza; therefore, it is recommended that they receive inactivated influenza vaccination. However, efficacy and safety of inactivated influenza vaccination in patients receiving immune checkpoint inhibitors is uncertain. The objective of this prospective case series was to evaluate the incidence of immune-mediated adverse events (imAEs) following inactivated influenza vaccination in patients receiving immune checkpoint inhibitors. Changes in cytokine and chemokine levels were also evaluated. Patients receiving immune checkpoint inhibitors during the 2017-2018 influenza season were eligible for study participation. Peripheral blood samples were collected prior to administration of inactivated influenza vaccine and two post-vaccination time points. Evaluation of new or worsening imAEs occurred via patient questionnaire and review of medical records for 60 days following inactivated influenza vaccination. Baseline imAEs were evaluated from review of medical records for 60 days prior to inactivated influenza vaccination. Serum cytokines and chemokines were measured using a multiplex Luminex assay. Twenty-four patients were enrolled in this study. Seven patients experienced any grade imAE (one patient having 2) within 60 days following inactivated influenza vaccination. The majority were Grades 1-2, including rash (n = 3), hypothyroidism, myalgia, and colitis (n = 1 each). Two patients experienced severe imAEs (grade 3 nephritis and grade 4 diabetes). No significant changes (p > 0.05) in serum cytokine or chemokine concentrations were observed. Although small, our study suggests that inactivated influenza vaccine may be safely administered to patients receiving immune checkpoint inhibitors. The majority of imAEs following inactivated influenza vaccination were Grades 1-2 and did not require changes in immune checkpoint inhibitor therapy.

Safety of Inactivated Influenza Vaccine in Patients with Egg Allergy in Kurdistan Province, Iran

Most influenza vaccines are grown in embryonated eggs and residual egg proteins can cause allergic reactions in patients with egg allergy. The aim of the present study was to determine the safety of inactivated influenza vaccine in patients with egg allergy in Kurdistan Province, Iran. This case-control study was done on 876 patients referred to Kurdistan Asthma and Allergy Clinic, Sanandaj, Iran; 635 patients with egg allergy (cases) and 241 patients without egg allergy (controls) from 2012 to 2016. All of the patients were injected seasonal influenza vaccine. Side effects including anaphylactic shock, local reaction, vomiting, coughing, sneezing, wheezing, low blood pressure, redness and itching in the eyes, abdominal pain, dyspnea, oral/facial angioedema, swollen and itching of throat were checked by an allergist within 30 min after vaccination, and followed up to 24 h. Demographic and vaccination data were entered into the SPSS software and analyzed. Out of 876 patients, 460 (52.5%) were male. Patients' ages ranged from 6 months to 80 yr (mean 13.38 ± 15.22 SD). Overall, 63 patients with egg allergy had local reactions to vaccine. Difference of local reactions between case and control groups was statistically significant (P=0.001). No anaphylactic reactions were seen after vaccination. Although the risk of anaphylactic reactions to influenza vaccine in patients with egg allergy was rare, the vaccine should be administered by an allergist with precaution. The results of present study can be a confirmation of the existing evidences to prevent acute complications to influenza vaccine.

The safety of inactivated influenza vaccines in pregnancy for birth outcomes: a systematic review

ABSTRACTPregnant women are at increased risk of morbidity and mortality from influenza and are recognized as a priority group for influenza vaccination. Despite this, uptake is often poor and one reason cited for this is concerns about safety. The objective of this study was to perform a systematic review of the safety of inactivated influenza vaccination (IIV) in pregnancy. Studies were included if they were: (i) observational or experimental design; (ii) included a comparator group comprising of unvaccinated pregnant women; (iii) comprised of either seasonal IIV or monovalent H1N1 IIV (including adjuvanted vaccines); and (iv) addressed one of the following outcomes: preterm birth (PTB), small for gestational age (SGA), fetal death (including stillbirth or spontaneous abortion), low birth weight (LBW) or congenital abnormalities. Two reviewers screened abstracts and titles and selected full texts for retrieval. Crude odds ratios were calculated from reported event rates, using binomial standard errors. Adjusted odds ratios, hazard ratios and relative rates were extracted as reported in each paper. After removal of duplicates and full text eligibility assessment, 40 studies remained. The aOR for PTB was 0.87 (0.78–0.96), for LBW 0.82 (0.76–0.89), congenital abnormality 1.03 (0.99–1.07), SGA 0.99 (0.94–1.04) and stillbirth 0.84 (0.65–1.08). This study contributes to the increasing body of safety data for IIV in pregnancy and reports a protective effect on PTB and LBW.

Do health care providers trust product monograph information regarding use of vaccines in pregnancy? A qualitative study.

Influenza immunization is recommended in pregnancy to prevent severe infections in pregnant women and newborns, yet vaccine uptake remains low. Studies suggest that cautionary language in vaccine product monographs regarding safety and use in pregnancy affects health care providers' perceptions of vaccine safety and how they counsel pregnant women. To conduct a qualitative analysis of health care provider perceptions of the safety of inactivated influenza vaccines and their recommendations for use in pregnancy based on product monograph language statements. Health care providers were recruited at two international health conferences and from teaching programs in Ethiopia, Ghana, Uganda, and Laos during September and October 2015. After reading the product monograph excerpts for three licensed inactivated influenza vaccines, participants completed a ten-item online survey with quantitative and qualitative components that captured perceptions of vaccine safety. Health care providers identified a lack of trust in manufacturers' and product monograph information. They perceived product monograph language as ambiguous and not "up-to-date" with current evidence. Health care providers wanted product monograph language that clearly conveyed evidence for the risks and benefits of the vaccine in an understandable manner. This study suggests that adopting best practices in the wording of product monographs would help to support evidence-based use of vaccines in pregnant women.

Immunogenicity and Safety of Inactivated Influenza Vaccine in Healthy Korean Children and Adolescent

목적: 인플루엔자 유행 예방에 대한 가장 효과적인 방법은 인플루엔자 백신이나 한국의 소아청소년을 대상으로 한 면역원성 및 안전성에 대한 자료가 많지 않다. 이에 본 연구는 국내에서 많이 사용되는 불활성화 3가 백신의 면역원성과 안전성을 확인하고자 하였다. 방법: 2008년 10월부터 12월까지 고려대학교 의료원 안산병원 소아청소년과에 인플루엔자 예방접종을 위해 내원한 건강한 소아청소년 중 임상시험 지원자 65명을 대상으로 하여 접종 전과 접종 후 30일째 혈구응집억제(hemagglutinin inhibition) 항체검사를 시행하고 접종 직후부터 접종 후 7일까지 국소반응과 전신반응을 포함한 이상반응을 관찰하여 기록하도록 하였다. 결과: 분할 인플루엔자 백신의 세 항원(H1N1, H3N2, B) 각각에 대한 접종 후 혈청보호율은 87.7%, 89.2%, 89.2% (≥70%)였으며 혈청전환율은 44.6%, 73.8%, 63.1% (≥40%), 혈청전환인자는 3.35, 7.18, 5.13 (>2.5)으로 Committee for Proprietary Medicinal Products (CPMP) 기준을 만족하였다. 전체 피험자 65명 중 48명(73.8%)이 백신 접종 후 이상반응을 보고하였으나 아나필락시스나 경련과 같은 심각한 이상반응은 없었다. 발적(29.2%), 동통(43.1%), 종창(41.5%)과 같은 국소반응을 보고한 피험자는 42명(64.6%)이었고, 권태(23.1%), 근육통(20.0%), 두통(10.8%), 관절통(10.8%), 오한(9.2%), 발열(7.7%) 등과 같은 전신반응을 보고한 피험자는 26명(40.0%)이었다. 결론: 6개월에서 18세까지의 소아청소년을 대상으로 한 불활성화 3가 백신의 면역원성과 안전성에 대한 연구 결과 H1N1, H3N2, B 항원 모두 CPMP 기준에 부합하여 적합한 면역원성이 있는 것으로 나타났으며, 국소반응 및 경미한 전신반응 이외에 심각한 이상반응은 보이지 않아 비교적 안전하다고 판단된다.

鶏卵アレルギーと接種量が増量となったインフルエンザワクチンの安全性に関する検討

鶏卵アレルギーと接種量が増量となったインフルエンザワクチンの安全性に関する検討

小児におけるインフルエンザHA ワクチン接種量変更による 効果と安全性の検討

We examined the efficacy and safety of inactivated influenza vaccine when the amount of HA influenza vaccination in children was increased to the dose recommended by the WHO. The purpose of this study was to obtain basic evidence to review the vaccination dose in Japanese children. HA influenza vaccine produced by the Research Foundation for Microbial Diseases of Osaka University (Biken) licenced in Japan was administered through vaccination at the international dose, and split HA influenza vaccine produced by Sanofi Pasteur corp. (Sanofi) was used as control. Children from 6 months to less than 13 years of age were registered, and vaccinated with doses of 0.25 mL or 0.5 mL. Clinical symptoms during the influenza season were monitored to investigate vaccine efficacy, and information on adverse reactions was collected to evaluate safety profile. Paired serum HI and NT antibody titers were measured at pre first dose and post second dose of vaccination. Both HI and NT antibody titers for H1N1 subtype were satisfactory elevated after administration of both vaccines. Elevation of the NT antibody titer for the H3N2 subtype was observed for both vaccines, but the H3N2 HI antibody titer for the Biken vaccine was not so high. For the subtype B virus, the NT titer had a better response than the HI titer for both vaccines. As only the H1N1 virus was prevalent in the area during the study period, we performed factor analysis concerning influenza contraction only for the H1N1 antibody titer. An HI titer of 1 : 40 or more at post-vaccination was a significant factor to lower the risk of influenza contraction. The relative risk for fever among children with an HI titer of 1 : 20 or less was significantly higher than those with an HI titer of 1 : 40 or more. Children with a higher HI titer had better prevention against fever, so that both vaccines were considered to be effective. As for the appearance of adverse reactions, both vaccines were considered to be safe. From the above-mentioned results, vaccination with the Japanese Biken vaccine at an international dose was thought to be an effective and safe procedure.

Immunogenicity and safety of inactivated influenza vaccines in primed populations: A systematic literature review and meta-analysis

Several inactivated influenza vaccine formulations for systemic administration in man are currently available for annual (seasonal) immunization: split virus and subunit (either plain-aqueous, or virosomal, or adjuvanted by MF59). From a literature search covering the period 1978–2009, 33 articles could be identified, which described randomized clinical trials comparing at least two of the four vaccine formulations with respect to serum hemagglutination inhibition (HI) antibody response, local and systemic vaccine reactions and serious adverse events after vaccination, and employing seasonal vaccine components and doses. In total, 9121 vaccinees of all ages, either healthy or with underlying diseases, were involved. Most vaccinees were primed or had been vaccinated in previous years. For immunogenicity, homologous post-vaccination geometric mean HI titers (GMTs) were analyzed by a random effects model for continuous data. Unreported standard deviations (SD) were addressed by imputing assumed SD-values. Age and health state of the vaccinees appeared to have little influence on the outcome. The immunogenicity of split, aqueous and virosomal subunit formulations were similar, with geometric mean ratio values (GMR, quotient of paired GMT-values) varying around one (0.93–1.24). The MF59-adjuvanted subunit vaccine induced, on average, larger antibody titers than the non-adjuvanted vaccine formulations, but the absolute increase was small (GMR-values varying between 1.25 and 1.40). Vaccine reactions were analyzed using a random effects model for binary data. Local and systemic reactogenicity was similar among non-adjuvanted formulations. The adjuvanted subunit formulation was more frequently associated with local reactions than the non-adjuvanted formulations (rate ratio: 2.12, significant). Systemic reactions were similar among all vaccine formulations. The original articles emphasized the mild and transient character of the vaccine reactions and the absence of serious vaccine-related adverse events. This adequate amount of evidence led to the conclusion that all the currently available inactivated influenza vaccine formulations are safe, well tolerated and similarly effective to control seasonal influenza outbreaks across primed populations and age ranges.

Immunogenicity and safety of a trivalent inactivated influenza vaccine

Background Trivalent inactivated influenza vaccines (TIV) containing antigens of two influenza A strains, A(H1N1) and A(H3N2), and one influenza B strain, are the standard {onnulation for influenza prevention. The vaccines must be updated annually to provide optimal protection against the predicted prevalent strains for the next influenza season.Objective To assess the immunogenidty and safety of the inactivated influenza vaccine (Flubio®) in adolescents and adults, 28 days after a single dose.Methods In this experimental, randomized, single-blind, bridging study, we included 60 healthy adolescents and adults. A single, 0.5 mL dose was administered intramuscularly in the deltoid muscle of the left ann. Blood samples were obtained before and 28 days after immunization. Standardized hemagglutination inhibition (HI) test was used to assess antibody response to influenza antigens.Results From January to February 2010, a total of 60 adolescents and adults enrolled in the study, but two participants did not provide the required blood samples. One hundred percent of the subjects had an anti-influenza titer ≥ 1:40 HI units to all three strains, A/Brisbane/59/2007 (H1N1), A/Uruguay/716/2007 (H3N2), and B/Brisbane/60/2008 (P=1.000) after immunization. The Geometric Mean Titers (GMT) after immunization increasedfor all strains: A/Brisbane, 76.4 to 992.7, A/Uruguay, 27.6 to 432.1, and B/Brisbane, 19.9 to 312.7. Twenty eight days after immunization, we found a 4 times increase in antibody titers in 75.8% of the subjects for A/Brisbane, 84.5% for A/Uruguay, and 77.6% for B/Brisbane. We also observed that 100% of seronegative subjects converted to seropositive for all 3 strains. All vaccines were well-tolerated. There were no serious adverse events reported during the study.Conclusion In adolescents and adults, the Flubio® vaccine was immunogenic and safe.

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

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

Inactivated influenza vaccine is safe for children and adults with stable asthma

(2001) N Engl J Med 345, 1529. American Lung Association Asthma Clinical Research Centers. . The safety of inactivated influenza vaccine in adults and children with asthma. . Nov 22;...

The inactivated trivalent split-virus influenza vaccine was safe in stable asthma

Source Citation American Lung Association Asthma Clinical Research Centers. The safety of inactivated influenza vaccine in adults and children with asthma. N Engl J Med. 2001 Nov 22;345:1529-36. 11...

Drug distribution for a large crossover trial of the safety of inactivated influenza vaccine in asthmatics

We report on the drug packaging, masking, and distribution procedures for a large double-masked, randomized, controlled, crossover trial. The Study of Inactivated Influenza Vaccine in Asthmatics was performed to evaluate whether influenza vaccination was safe for asthmatics. Nineteen clinical centers enrolled 2032 participants from 15 September to 30 November 2000. The participants were assigned individual kits with two syringes (placebo and vaccine); the order of injection was randomly assigned. All participants enrolled in the trial received the first injection and 2009 participants received the second injection. Five participants received their injections in the wrong order; we have no evidence that any participant received an injection from the wrong kit. Challenges faced by the trial were a manufacturing shortage of vaccine, the lack of a commercially available placebo, short time periods for planning and startup, and a diverse set of clinical centers. Utilizing individual syringe kits, using the same identification for patient, kit, and drug assignment, and dispensing drug from a central facility helped to successfully meet these challenges.