Administration Of Inactivated Influenza Vaccine Research Articles

The Safety of Maternal Influenza Vaccination and Infant Health Outcomes.

Influenza vaccination during pregnancy has been recommended for more than 70 years in the United States because of the high risk of complications resulting in hospitalization and mortality in pregnant women who acquire seasonal or pandemic influenza infection, particularly in the third trimester of pregnancy and during the postpartum period.1,2 Concerns regarding the safety of maternal immunization continue to be an important barrier to wide implementation and high rates of coverage for vaccines currently recommended for pregnant women, including influenza and pertussis vaccines.3 In this issue of Pediatrics, Foo et al4 report on their evaluation of potential adverse effects on long-term health outcomes for infants who were exposed to maternal influenza vaccination while in utero. Many studies conducted before, during, and after the 2009 influenza A (H1N1) pandemic consistently have shown that the administration of inactivated influenza vaccines during pregnancy is safe for the mother and is not associated with an increased risk of fetal or neonatal adverse outcomes such as stillbirth, preterm birth, low birth weight, or congenital anomalies.5,6 The potential long-term effects of fetal exposure to maternal vaccines are not often evaluated, as evidenced by the … Address correspondence to Flor M. Munoz, MD, Baylor College of Medicine and Texas Children’s Hospital, 1102 Bates Ave, Suite 1150, Houston, TX 77030. E-mail: florm{at}bcm.edu

Inactivated influenza vaccine and spontaneous abortion in the Vaccine Safety Datalink in 2012–13, 2013–14, and 2014–15

IntroductionA recent study reported an association between inactivated influenza vaccine (IIV) and spontaneous abortion (SAB), but only among women who had also been vaccinated in the previous influenza season. We sought to estimate the association between IIV administered in three recent influenza seasons and SAB among women who were and were not vaccinated in the previous influenza season. MethodsWe conducted a case-control study over three influenza seasons (2012–13, 2013–14, 2014–15) in the Vaccine Safety Datalink (VSD). Cases (women with SAB) and controls (women with live births) were matched on VSD site, date of last menstrual period, age group, and influenza vaccination status in the previous influenza season. Of 1908 presumptive cases identified from the electronic record, 1236 were included in the main analysis. Administration of IIV was documented in several risk windows, including 1–28, 29–56, and >56 days before the SAB date. ResultsAmong 627 matched pairs vaccinated in the previous season, no association was found between vaccination in the 1–28 day risk window and SAB (adjusted odds ratio (aOR) 0.9; 95% confidence interval (CI) 0.6–1.5). The season-specific aOR ranged from 0.5 to 1.7 with all CIs including the null value of 1.0. Similarly, no association was found among women who were not vaccinated in the previous season; the season-specific aOR in the 1–28 day risk window ranged from 0.6 to 0.7 and the 95% CI included 1.0 in each season. There was no association found between SAB and influenza vaccination in the other risk windows, or when vaccine receipt was analyzed relative to date of conception. ConclusionDuring these seasons we found no association between IIV and SAB, including among women vaccinated in the previous season. These findings lend support to current recommendations for influenza vaccination at any time during pregnancy, including the first trimester.

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.

Innovative Mucosal Vaccine Formulations Against Influenza A Virus Infections.

Despite efforts made to develop efficient preventive strategies, infections with influenza A viruses (IAV) continue to cause serious clinical and economic problems. Current licensed human vaccines are mainly inactivated whole virus particles or split-virion administered via the parenteral route. These vaccines provide incomplete protection against IAV in high-risk groups and are poorly/not effective against the constant antigenic drift/shift occurring in circulating strains. Advances in mucosal vaccinology and in the understanding of the protective anti-influenza immune mechanisms suggest that intranasal immunization is a promising strategy to fight against IAV. To date, human mucosal anti-influenza vaccines consist of live attenuated strains administered intranasally, which elicit higher local humoral and cellular immune responses than conventional parenteral vaccines. However, because of inconsistent protective efficacy and safety concerns regarding the use of live viral strains, new vaccine candidates are urgently needed. To prime and induce potent and long-lived protective immune responses, mucosal vaccine formulations need to ensure the immunoavailability and the immunostimulating capacity of the vaccine antigen(s) at the mucosal surfaces, while being minimally reactogenic/toxic. The purpose of this review is to compile innovative delivery/adjuvant systems tested for intranasal administration of inactivated influenza vaccines, including micro/nanosized particulate carriers such as lipid-based particles, virus-like particles and polymers associated or not with immunopotentiatory molecules including microorganism-derived toxins, Toll-like receptor ligands and cytokines. The capacity of these vaccines to trigger specific mucosal and systemic humoral and cellular responses against IAV and their (cross)-protective potential are considered.

Evaluation of the safety of live attenuated influenza vaccine (LAIV) in children and adolescents with asthma and high-risk conditions: a population-based prospective cohort study conducted in England with the Clinical Practice Research Datalink

ObjectivesTo assess the safety of live attenuated influenza vaccine (LAIV) in children in high-risk groups.DesignNon-interventional cohort study.SettingEngland during 2013–2014 and 2014–2015 influenza seasons.ParticipantsLAIV recipients identified from the Clinical Practice Research...

Comparison of Safety and Immune Responses to Live-Attenuated Versus Inactivated Influenza Vaccine Administration in Breastfeeding Women and Their Infants

Comparison of Safety and Immune Responses to Live-Attenuated Versus Inactivated Influenza Vaccine Administration in Breastfeeding Women and Their Infants

Protective efficacy of CD4 memory T cells depends on route of administration of inactivated influenza vaccine (113.31)

Abstract Studies aimed at determining the impact route of influenza vaccination has on vaccine efficacy revealed reduced protection against influenza virus challenge afforded by intranasal delivery compared to subcutaneous delivery of inactivated H1N1 influenza A virus. Both vaccine routes induced similar anti-viral antibody titers, similar numbers of anti-viral CD4 T cells, and undetectable anti-viral CD8 T cell responses. Further analysis of vaccine-induced CD4 memory T cell responses revealed that CD4 memory T cells primed in the lung draining lymph nodes were defective in recruiting anti-viral CD8 effectors to the lungs during challenge infections compared to the recruitment of CD8 effectors to the lungs by peripherally primed CD4 memory T cells. Since the influx of anti-viral CD8 effector T cells to the airways during influenza virus infection is a key event for virus control and elimination, we assayed for the expression of type-1 chemoattractants in the respiratory tract of vaccinated mice following challenge infection and discovered reduced lung expression of chemoattractants in the presence of intranasally primed CD4 memory T cells. We also determined that the presence of intranasally primed CD4 memory T cells reduced the ability of pulmonary antigen presenting cells to stimulate CD8 effectors directly ex vivo. We are currently assessing whether route of influenza vaccination also impacts susceptibility to secondary bacterial pneumonia following influenza challenge.

Comparison of Adjuvant Efficacy of Chitosan and Aluminum Hydroxide for Intraperitoneally Administered Inactivated Influenza H5N1 Vaccine

A safe and effective adjuvant is important to develop vaccines against highly pathogenic avian influenza virus. Chitosan, a derivative from the natural amino polysaccharide chitin, has been proved to be an effective adjuvant for inactivated influenza virus vaccine. In this study, protective immunity in mice provided by chitosan-adjuvanted inactivated H5N1 vaccine was compared with that from an aluminum hydroxide-adjuvanted one. Mice were injected intraperitoneally once or twice with various dosages of inactivated vaccine alone or in combination with an adjuvant (chitosan or aluminum hydroxide). To test the immunization effect, mice were challenged with a lethal dose of H5N1 virus. The results showed that the adjuvanted vaccines were more effective than adjuvant-free ones in inducing humoral immune responses and protecting mice against lethal challenge. Chitosan was comparable to the alum adjuvant in efficacy. These findings indicated that chitosan might be a candidate adjuvant for parenteral administration of inactivated influenza vaccines.

Influenza — The Goal of Control

Annual administration of inactivated influenza vaccine to older adults has long been recommended by public health authorities.1 The risks of influenza-related complications, hospitalizations, and deaths increase with age, as does the prevalence of underlying medical conditions. Prospective, randomized, controlled studies have demonstrated that inactivated vaccine is protective against laboratory-confirmed influenza in young adults and, according to much more limited data, in older adults as well.2 Since the vaccine reduces the risk of influenza, it would be reasonable to expect that vaccination would also reduce the risks of influenza-related complications in recipients. Demonstrating this type of effect in a prospective, randomized, . . .

Reactogenicity and immunogenicity of an inactivated influenza vaccine administered by intramuscular or subcutaneous injection in elderly adults

In many countries there is no clear recommendation regarding the preferred route of administration of inactivated influenza vaccines. In a randomised, observer blind study of 720 elderly subjects, a split, trivalent influenza vaccine was significantly more immunogenic for both A strains (H3N2 and H1N1, p = 0.0016 and 0.003, respectively) when given intramuscularly compared to subcutaneously. This difference was due entirely to a gender effect, with females in the intramuscular (IM) group having a significantly greater serological response than females in the subcutaneous (SC) group for both of these strains. Similar results were seen with local adverse effects. These data suggest that vaccination practices that ensure intramuscular injection are required for optimal administration of influenza vaccines in the elderly.

Influenza Vaccination in Children With Asthma: Randomized Double-Blind Placebo-Controlled Trial

Bueving HJ, Bernsen RM, de Jongste JC, et al. Am J Respir Crit Care Med. 2004;169:488–493To investigate if influenza vaccination in children with asthma prevents asthma exacerbations provoked by influenza infectionSubjects were asthmatic children aged 6 to 18 years who had no other chronic illness. There were 347 children assigned to the vaccine group and 349 assigned to the placebo group.The primary outcome was the number of asthma exacerbations associated with virologically proven influenza infection. Study subjects and their families scored daily symptoms in a diary, and when symptoms reached a predefined level, a pharyngeal swab for influenza was taken. The symptom diary was maintained from the day after administration of inactivated influenza vaccine or placebo on approximately November 1 until April 1 of the following year. Secondary outcomes included the duration and severity of the asthma exacerbations, adverse effects of vaccination, and the number, duration, and severity of all asthma exacerbations. Influenza virus–specific antibody titers were measured before vaccination, 14 to 21 days afterward, and at the end of the influenza season.In each group, 344 participants provided diary data for the primary outcome. The groups were generally similar in baseline characteristics, with almost 90% of children having used maintenance medication for asthma in the previous 12 months. There were 486 reports of symptom scores that met the predefined criteria for an asthma exacerbation (vaccine group: 251; placebo group: 235), with 42 of the resultant throat swabs testing positive for influenza (vaccine group: 24; placebo group: 18). The difference in the number of asthma exacerbations was not significant (95% confidence interval: 34% reduction to 161% increase). There were no significant differences found between the 2 groups for any of the secondary outcomes measured. Antibody levels 14 to 21 days after vaccination were increased only in the vaccine group. However, when comparing the 14- to 21-day titers to those at the end of the season, ∼23% of subjects in the placebo group and 10% in the vaccine group had a fourfold increase in influenza-specific titers.The authors concluded that influenza vaccination was not more effective than placebo in reducing the number of asthma exacerbations caused by influenza infections in children.Current guidelines that recommend the use of influenza vaccination in asthmatics are based on epidemiologic evidence. A recent Cochrane review on influenza vaccination in asthmatics found insufficient evidence to make conclusions about the risks or benefits of influenza vaccination, primarily because of a lack of randomized trials. Although this study was a randomized trial, the low attack rate of influenza (∼6% of subjects tested positive by pharyngeal swab) makes it difficult to draw conclusions from the results. The study’s sample size was calculated based on the assumption of a 30% influenza attack rate, leaving it significantly underpowered to detect an effect at such a low attack rate. If the question of efficacy of influenza vaccine in reducing asthma morbidity is ever to be answered convincingly, a large randomized trial, probably over several influenza seasons, will be needed.

Inactivated influenza vaccination for people with spinal cord injury

Trautner BW, Atmar RL, Hulstrom A, Darouiche RO. Inactivated influenza vaccination for people with spinal cord injury. Arch Phys Med Rehabil 2004;85:1886-9. Objective To examine the antibody responses of people with spinal cord injury (SCI) to the commercially available trivalent influenza vaccine. Design Prospective trial of patients and controls. Setting Veterans Affairs medical center. Participants Forty people with SCI and 40 able-bodied subjects. Intervention Intramuscular administration of inactivated influenza vaccine. Main outcome measures Antibody responses were determined by using the standard hemagglutination-inhibition test before and 4 weeks after vaccination. Serum antibody responses were assessed as follows: (1) percentage of each cohort achieving a 4-fold or greater rise in antibody titer, (2) percentage of each cohort achieving a postvaccination antibody titer of 32 or more, and (3) postvaccination geometric mean antibody titers. Results The serum antibody responses to each vaccine antigen were similar for the SCI and the control cohorts for the 3 outcomes. Neither the time since injury (≤1y vs >1y) nor the level of injury (paraplegia vs quadriplegia) affected the vaccine antibody responses in the SCI cohort. Subjects older than 65 years had lower postvaccination serum antibody levels than those younger than 65 years ( P<.05). Conclusions People with SCI responded to influenza vaccination in a manner similar to able-bodied subjects and would be expected to benefit from vaccination.

Mucosal Delivery of Inactivated Influenza Vaccine Induces B-Cell-Dependent Heterosubtypic Cross-Protection against Lethal Influenza A H5N1 Virus Infection

Influenza vaccines that induce greater cross-reactive or heterosubtypic immunity (Het-I) may overcome limitations in vaccine efficacy imposed by the antigenic variability of influenza A viruses. We have compared mucosal versus traditional parenteral administration of inactivated influenza vaccine for the ability to induce Het-I in BALB/c mice and evaluated a modified Escherichia coli heat-labile enterotoxin adjuvant, LT(R192G), for augmentation of Het-I. Mice that received three intranasal (i.n.) immunizations of H3N2 vaccine in the presence of LT(R192G) were completely protected against lethal challenge with a highly pathogenic human H5N1 virus and had nasal and lung viral titers that were at least 2,500-fold lower than those of control mice receiving LT(R192G) alone. In contrast, mice that received three vaccinations of H3N2 vaccine subcutaneously in the presence or absence of LT(R192G) or incomplete Freund's adjuvant were not protected against lethal challenge and had no significant reductions in tissue virus titers observed on day 5 post-H5N1 virus challenge. Mice that were i.n. administered H3N2 vaccine alone, without LT(R192G), displayed partial protection against heterosubtypic challenge. The immune mediators of Het-I were investigated. The functional role of B and CD8+ T cells in Het-I were evaluated by using gene-targeted B-cell (IgH-6(-/-))- or beta2-microglobulin (beta2m(-/-))-deficient mice, respectively. beta2m(-/-) but not IgH-6(-/-) vaccinated mice were protected by Het-I and survived a lethal infection with H5N1, suggesting that B cells, but not CD8+ T cells, were vital for protection of mice against heterosubtypic challenge. Nevertheless, CD8+ T cells contributed to viral clearance in the lungs and brain tissues of heterotypically immune mice. Mucosal but not parenteral vaccination induced subtype cross-reactive lung immunoglobulin G (IgG), IgA, and serum IgG anti-hemagglutinin antibodies, suggesting the presence of a common cross-reactive epitope in the hemagglutinins of H3 and H5. These results suggest a strategy of mucosal vaccination that stimulates cross-protection against multiple influenza virus subtypes, including viruses with pandemic potential.

Cross-protection against influenza virus infection in mice vaccinated by combined nasal/subcutaneous administration

The effects of a combination of intranasal (i.n.) and subcutaneous (s.c.) administration of inactivated influenza vaccine for priming and boosting on the cross-protection against antigenically drifted virus challenge were examined in Balb/c mice. Mice were primed through the i.n. or s.c. route with a CTB ∗-A/Kumamoto/37/79 (H1N1) combined vaccine (CTB ∗: cholera toxin B subunit supplemented with 0.2% of the holotoxin) and boosted through the i.n. or s.c. route with another drift virus vaccine, A/Bangkok/10/83 (H1N1), 4 weeks later. Two weeks after boosting, the mice were challenged with a third drift virus, A/Yamagata/120/86 (H1N1). The combination of i.n. priming and i.n. boosting afforded the highest cross-protection, while combinations of s.c. priming and i.n. or s.c. boosting afforded little cross-protection. In parallel with the protective activity, anti-A/Yamagata haemagglutinin-reactive IgA and IgG antibodies were detected in nasal and bronchoalveolar wash specimens. These results suggest that cross-protection against a variant virus challenge is most favourably provided by i.n. priming with the CTB ∗ combined vaccine and i.n. boosting with the vaccine, which optimally induces cross-protective IgA and IgG antibodies.