Efficacy of live attenuated influenza vaccine in children 6 months to 17 years of age

Please cite this paper as: Belshe et al. (2010). Efficacy of live attenuated influenza vaccine in children 6 months to 17 years of age. Influenza and Other Respiratory Viruses 4(3), 141–145. Background  It has been suggested that live attenuated influenza vaccine (LAIV) may be less effective in older individuals because of prior wild‐type influenza infections. LAIV is currently approved in the United States, South Korea and Hong Kong for individuals 2–49 years of age. Objective  To examine data from previously published pediatric studies to determine the efficacy of LAIV in various age groups. Methods  Four studies in which the subject age range exceeded 36 months were identified: one 2‐year study comparing LAIV with placebo and three 1‐year studies comparing LAIV with trivalent inactivated influenza vaccine (TIV). Efficacy against any strain regardless of antigenic similarity to vaccine was analyzed by age; age groups were based on the study design and sample size. A logistic regression model was used to assess whether age, as a continuous variable, was an effect modifier on LAIV efficacy. Results  The efficacy of LAIV did not vary with age in children aged 15–84 months compared with placebo or in children aged 6 months to 17 years compared with TIV. Conclusions  The available data from prospective, randomized studies in children does not support the concept that prior repeated exposure to influenza, either through wild‐type infection or vaccination with live, attenuated or inactivated vaccines, reduces the efficacy of LAIV compared with placebo or TIV. The decreased immunologic responses to LAIV reported in older individuals or those with pre‐existing immunity do not appear to translate into reduced protection from influenza in children.     

Current status of live attenuated influenza vaccine in the United States for seasonal and pandemic influenza

Abstract A live attenuated influenza vaccine (LAIV) is currently approved in the United States for the prevention of influenza in individuals 2–49 years of age. This article summarizes the available data describing the safety and efficacy of LAIV for the prevention of influenza in both children and adults. LAIV is administered as an intranasal spray and has been shown to provide high levels of efficacy against influenza illness caused by both matched and mismatched strains in children and adults. In studies comparing LAIV and inactivated influenza vaccine in children, LAIV recipients experienced 35–53% fewer cases of culture‐confirmed influenza illness caused by antigenically matched strains. Protection through a second influenza season against antigenically matched strains has also been seen in children. In adults, definitive comparative studies of LAIV and inactivated vaccine have not been conducted and no statistically significant differences in efficacy have been demonstrated. The most common adverse reactions with LAIV include runny nose/nasal congestion in all age groups, fever >100°F in children, and sore throat in adults. Formulations of LAIV against pandemic influenza strains, including H5N1, H9N2, and H7N3, are currently being tested in preclinical and phase I clinical studies.     

An integrated, multistudy analysis of the safety of Ann Arbor strain live attenuated influenza vaccine in children aged 2-17 years

Please cite this paper as: Ambrose et al. (2011) An integrated, multistudy analysis of the safety of Ann Arbor strain live attenuated influenza vaccine in children aged 2–17 years. Influenza and Other Respiratory Viruses 5(6), 389–397. Background Trivalent, Ann Arbor strain, live attenuated influenza vaccine (LAIV) is approved in several countries for use in eligible children aged ≥2 years. Objective To describe the safety of Ann Arbor strain LAIV in children aged 2–17 years. Methods An integrated analysis of randomized, controlled trials of LAIV. Results A total of 4245 and 10 693 children received ≥1 dose of LAIV in year 1 of 6 trivalent inactivated influenza vaccine (TIV)‐controlled and 14 placebo‐controlled studies, respectively; 3212 children were revaccinated in year 2 of 4 placebo‐controlled studies. Compared with placebo for days 0–10 post‐vaccination, LAIV recipients exhibited increased runny/stuffy nose (+7%), headache (+7%), and tiredness/decreased activity (+2%) after dose 1; and a higher rate of decreased appetite (+4%) after year 2 revaccination. Compared with TIV, only runny/stuffy nose was increased (dose 1, +12%; dose 2, +4%). Compared with initial vaccination, LAIV reactogenicity was lower after dose 2 in year 1 and revaccination in year 2. Unsolicited adverse events (AEs) increased with LAIV in some comparisons were headache, nasal congestion/rhinorrhea, rhinitis, and pyrexia; ear pain and lower respiratory illness were decreased. There was no evidence of an increase in any potential vaccine‐related serious AE in LAIV recipients. Among children aged 2–17 years and specifically aged 24–35 months, there was no evidence that lower respiratory illness or wheezing illness occurred at a higher rate in LAIV recipients. Conclusion This analysis supports the safety of Ann Arbor strain LAIV in children aged 2–17 years and provides a consensus assessment of events expected after vaccination.     

B- and T-cell memory elicited by a seasonal live attenuated reassortant influenza vaccine: assessment of local antibody avidity and virus-specific memory T-cells using trogocytosis-based method

Please cite this paper as: Petukhova et al. (2011) B‐ and T‐cell memory elicited by a seasonal live attenuated reassortant influenza vaccine: assessment of local antibody avidity and virus‐specific memory T‐cells using trogocytosis‐based method. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750‐2659.2011.00279.x. Purpose The main purpose of vaccination is to generate immunological memory providing enhanced immune responses against infectious pathogens. The standard and most commonly used assay for influenza vaccine immunogenicity evaluation is a hemagglutination inhibition assay (HAI). It is clear now that HAI assay is unable to properly assess the proven protective immunity elicited by live attenuated influenza vaccines (LAIV). New methods need to be developed for more accurate LAIV immunogenicity assessment and prediction of vaccine efficacy among target populations. Objective Randomized placebo‐controlled study of memory B‐ and T‐cell responses to intranasal LAIV in young adults. Methods A total of 56 healthy young adults 18–20 years old received seasonal monovalent LAIV. Mucosal memory B‐cell responses were measured by IgA avidity assessment in nasal swabs. CD4 memory T cells in peripheral blood were examined by the expression of CD45RO marker and in functional test by the ability of virus‐specific T cells to maintain the trogocytosis with antigen‐loaded target cells. Results Intranasal LAIV immunization enhances mucosal IgA avidity even without reliable increases in antibody titers. At the day 21 after vaccination, up to 40% of subjects demonstrated significant increases in both total and virus‐specific CD4 memory T cells that were observed regardless of seroconversion rate measured by HAI assay. Conclusion The data suggest that immunogenicity of LAIV vaccines should be evaluated on the mucosal and cellular immunity basis. The assays applied could be used to support influenza clinical trials through preliminary screening of volunteers and subsequent measurement of anti‐influenza in immunity.     

Phenotypic changes in influenza-specific CD8+ T cells after immunization of children and adults with influenza vaccines

The effect of trivalent inactivated influenza vaccine (TIV) or live attenuated influenza vaccine (LAIV) on the phenotypes of circulating influenza-specific CD8+ T cells was analyzed by interferon (IFN)-gamma flow cytometry and tetramer staining. In adults, the expression of the T cell differentiation marker CD27 on virus-specific CD8+ T cells decreased after LAIV but increased after TIV. In children, expression of the cytotoxicity molecule perforin in influenza-specific CD8+ T cells increased after TIV but not after LAIV. Among children aged 6 months to 4 years who had not been vaccinated previously and who received 2 doses of TIV, CD27 expression decreased after each dose, whereas perforin expression increased after the second dose. These findings indicate that the phenotypic changes of influenza-specific CD8+ T cells differ depending on the type of vaccine and the age of the vaccinee. These differences are potentially affected by the different routes of vaccination and pathways of antigen presentation for TIV and LAIV.     

Laboratory Biosafety: Summary of the NACI Supplemental Statement on Mammalian Cell Culture-Based Influenza Vaccines

BackgroundMammalian cell culture-based technology is an innovative technique for influenza vaccine manufacturing that may be a valuable alternative to overcome some of the problems and vulnerabilities associated with conventional egg-based influenza vaccine production. Flucelvax^® Quad (Seqirus, Inc.) is the first and only mammalian cell culture-based quadrivalent inactivated, subunit influenza vaccine (IIV4-cc) authorized for adult and pediatric use in Canada. The National Advisory Committee on Immunization (NACI) has not previously made a recommendation on cell culture-based influenza vaccines in any population.ObjectiveTo review the available evidence for the efficacy, effectiveness, immunogenicity, and safety of IIV4-cc, and to summarize the NACI recommendation regarding the use of Flucelvax Quad in Canada in adults and children.MethodsA systematic literature review on the vaccine efficacy, effectiveness, immunogenicity and safety of IIV4-cc in persons four years of age and older was performed. The systematic review’s methodology was specified a priori in a written protocol. The NACI evidence-based process was used to assess the quality of eligible studies, summarize and analyze the findings, and develop a recommendation regarding the use of Flucelvax Quad in adults and children. The proposed recommendation was then considered and approved by NACI in light of the available evidence.ResultsThirteen eligible studies were included in the evidence synthesis. In the four observational studies that assessed vaccine effectiveness of IIV4-cc, there were some data indicating potentially improved protection against influenza compared to conventional egg-based quadrivalent inactivated influenza vaccines (IIV4) or trivalent inactivated influenza vaccine (IIV3), particularly against A(H3N2) virus infection. There was also some evidence that IIV4-cc may be more effective than egg-based trivalent or quadrivalent influenza vaccines against non-laboratory confirmed influenza-related outcomes, but there is insufficient evidence for laboratory-confirmed outcomes. Two randomized controlled trials assessed the immunogenicity and safety of IIV4-cc compared with mammalian cell culture-based trivalent inactivated, subunit influenza vaccine (IIV3-cc). The IIV4-cc was well-tolerated and the reported solicited local and systemic adverse events were generally mild to moderate in intensity, self-limited and did not precipitate sequelae. One clinical review of cases and six peer-reviewed randomized controlled trials (four in adults and two in children) that reported on the safety of IIV3-cc were included in the review. The evidence on immunogenicity and safety was consistent across these studies and showed that there was no significant difference in adults and children four years of age and older who had received IIV3-cc or an egg-based IIV3.ConclusionNACI concluded that there is fair evidence (Grade B Evidence) that Flucelvax Quad is effective, safe, and has non-inferior immunogenicity to comparable vaccines, based on direct evidence in adults and children nine years of age and older. NACI recommends that Flucelvax Quad may be considered among the IIV4 offered to adults and children nine years of age and older (Discretionary NACI Recommendation).     

Absence of cross-reactive antibodies to influenza A (H1N1) 2009 before and after vaccination with 2009 Southern Hemisphere seasonal trivalent influenza vaccine in children aged 6 months-9 years: a prospective study

Please cite this paper as: McVernon et al. (2010) Absence of cross‐reactive antibodies to influenza A (H1N1) 2009 before and after vaccination with 2009 Southern Hemisphere seasonal trivalent influenza vaccine in children aged 6 months–9 years: a prospective study. Influenza and Other Respiratory Viruses 5(1), 7–11. Background Early outbreaks of the pandemic influenza A (H1N1) 2009 virus predominantly involved young children, who fuelled transmission through spread in homes and schools. Seroprevalence studies conducted on stored serum collections indicated low levels of antibody to the novel strain in this age group, leading many to recommend priority immunisation of paediatric populations. Objectives In a prospective study, we sought evidence of cross‐reactive antibodies to the pandemic virus in children who were naïve to seasonal influenza vaccines, at baseline and following two doses of the 2009 Southern Hemisphere trivalent influenza vaccine (TIV). Patients/Methods Twenty children were recruited, with a median age of 4 years (interquartile range 3–5 years); all received two age appropriate doses of TIV. Paired sera were collected pre‐ and post‐vaccination for the assessment of vaccine immunogenicity, using haemagglutination inhibition and microneutralisation assays against vaccine‐related viruses and influenza A (H1N1) 2009. Results Robust responses to H3N2 were observed regardless of age or pre‐vaccination titre, with 100% seroconversion. Fewer seroconverted to the seasonal H1N1 component. Only two children were weakly seropositive (HI titre 40) to the pandemic H1N1 strain at study entry, and none showed evidence of seroconversion by HI assay following TIV administration. Conclusions Administration of 2009 Southern Hemisphere TIV did little to elicit cross‐reactive antibodies to the pandemic H1N1 virus in children, in keeping with assay results on stored sera from studies of previous seasonal vaccines. Our findings support the recommendations for influenza A (H1N1) 2009 vaccination of children in preparation for the 2010 winter season.     

The manufacturing process should remain the focus for severe febrile reactions in children administered an Australian inactivated influenza vaccine during 2010

Influenza vaccine safety is an ongoing issue. In 2010, inactivated trivalent influenza vaccines (TIVs), Fluvax^® and Fluvax Junior^® manufactured by CSL Biotherapies (‘CSL’), Parkville, Australia, were associated with a marked increase in febrile seizures (FS) in children <5 years old. Extensive investigations initially failed to identify a root cause. The company's researchers recently published two papers outlining their latest findings. Cytokine responses to TIV were measured in paediatric whole blood assays (WBA); NF‐κB activation was assessed using a HEK293 cell line reporter assay. CSL suggest that the combination of new influenza strains (H1N1 A/California/7/2009 and B/Brisbane/60/2008), increased complexes of viral RNA and lipid in the vaccine, and inherent sensitivities of some children <5 years old caused elevated inflammatory responses resulting in FS. Whilst the papers provide insight into pathogenesis, much remains unclear. The WBA were from only 10 ‘healthy’ children, potentially affecting generalisability of the results and reliability of these in vitro tests in assessing future influenza vaccine safety. Increased fever rates (without FS) found in CSL TIV studies between 2005 and 2010 suggest a long‐standing contribution to reactogenicity from the manufacturing process. More detailed comparisons with non‐CSL vaccines would have helped elucidate the relative contribution of patient/strain factors and the manufacturing process. The focus remains on manufacturing process differences as the key causative factor of elevated febrile responses. Studies underway, of modified vaccines in young children, will determine whether reactogenicity issues have been successfully addressed and whether CSL TIV can be relicensed in children <5 years of age.     

Safety and Immune Responses in Children After Concurrent or Sequential 2009 H1N1 and 2009-2010 Seasonal Trivalent Influenza Vaccinations

Background.?Administering 2 separate vaccines for seasonal and pandemic influenza was necessary in 2009. Therefore, we conducted a randomized trial of monovalent 2009 H1N1 influenza vaccine (2009 H1N1 vaccine) and seasonal trivalent inactivated influenza vaccine (TIV; split virion) given sequentially or concurrently in previously vaccinated children. Methods.?Children randomized to 4 study groups and stratified by age received 1 dose of seasonal TIV and 2 doses of 2009 H1N1 vaccine in 1 of 4 combinations. Injections were given at 21-day intervals and serum samples for hemagglutination inhibition antibody responses were obtained prior to and 21 days after each vaccination. Reactogenicity and adverse events were monitored. Results.?All combinations of vaccines were safe in the 531 children enrolled. Generally, 1 dose of 2009 H1N1 vaccine and 1 dose of TIV, regardless of sequence or concurrency of administration, was immunogenic in children ≥10 years of age; children <10 years of age required 2 doses of 2009 H1N1 vaccine. Conclusions.?Vaccines were generally well tolerated. The immune responses to 2009 H1N1 vaccine were adequate regardless of the sequence of vaccination in all age groups but the sequence affected titers to TIV antigens. Two doses of 2009 H1N1 vaccine were required to achieve a protective immune response in children <10 years of age. Clinical Trials Registration.?NCT00943202.     

Fluwatchers A Crowdsourcing Approach: Summary of the National Advisory Committee on Immunization (NACI) Seasonal Influenza Vaccine Statement for 2021–2022

BackgroundSeveral influenza vaccines are authorized in Canada and the evidence on influenza immunization is continually evolving. The National Advisory Committee on Immunization (NACI) provides recommendations regarding the use of seasonal influenza vaccines annually to the Public Health Agency of Canada (PHAC).ObjectiveTo summarize NACI recommendations regarding the use of seasonal influenza vaccines for 2021–2022 and to highlight new recommendations.MethodsAnnual influenza vaccine recommendations are developed by NACI''s Influenza Working Group for consideration and approval by NACI. The development of the recommendations is based on the NACI evidence-based process.ResultsThe following new recommendations were made: 1) Influvac^® Tetra may be considered as an option among the standard dose quadrivalent inactivated influenza vaccines (IIV4-SD) offered to adults and children three years of age and older; 2) Fluzone High Dose Quadrivalent (IIV4-HD) may be considered an option for individuals 65 years of age and older who are currently recommended to receive Fluzone^® High Dose (trivalent); and 3) Flucelvax^® Quad may be considered amongst the quadrivalent influenza vaccines offered to adults and children nine years of age and older for annual influenza immunization. Guidance for use of influenza immunizations during the coronavirus disease 2019 pandemic is also highlighted.ConclusionNACI continues to recommend that an age-appropriate influenza vaccine should be offered annually to anyone six months of age and older who does not have contraindications to the vaccine. Vaccination should be offered as a priority to people at high risk of influenza-related complications or hospitalization, people capable of transmitting influenza to those at high risk of complications, and others as indicated.     

Influenza: epidemiology, clinical features, therapy, and prevention

Influenza A and B are important causes of respiratory illness in all age groups. Influenza causes seasonal outbreaks globally and, less commonly, pandemics. In the United States, seasonal influenza epidemics account for >200,000 hospitalizations and >30,000 deaths annually. More than 90% of deaths occur in the elderly population. Interestingly, in the novel 2009 H1N1 influenza pandemic, attack rates were highest among children and young adults. Fewer than 10% of cases occurred in adults >60 years old, likely because preexisting antibodies against other H1N1 viruses afforded protection. Despite concerns about a high lethality rate with the novel 2009 H1N1 strain, most illnesses caused by the 2009 H1N1 viruses were mild (overall case fatality rate <0.5%). Clinical features of influenza infection overlap with other respiratory pathogens (particularly viruses). The diagnosis is often delayed due to low suspicion and the limited use of specific diagnostic tests. Rapid diagnostic tests are widely available and allow detection of influenza antigen in respiratory secretions within 1 hour; however, sensitivity ranges from 50 to 90%. Neuraminidase inhibitors (NAIs) (eg, oseltamivir and zanamivir) are effective for treating influenza A or B and for prophylaxis in selected adults and children. Resistance to NAIs is rare, but influenza strains resistant to oseltamivir have been detected. Vaccines are the cornerstone of influenza control. Currently, trivalent inactivated vaccine (TIV) and live attenuated influenza vaccine (LAIV) are available. These agents reduce mortality and morbidity in high-risk patients (i.e., the elderly or patients with comorbidities), and expanding the use of vaccines to healthy children and adults reduces the incidence of influenza, pneumonia, and hospitalizations due to respiratory illnesses in the community.     

Live attenuated influenza vaccine is safe and immunogenic in immunocompromised ferrets

Patients undergoing chemotherapy for cancer are highly susceptible to influenza virus infection. Prevention of influenza virus infection is complicated in the immunocompromised host because of suboptimal responses to the trivalent inactivated influenza vaccine (TIV). A new, live attenuated influenza vaccine (LAIV; FluMist) may offer a more effective alternative to TIV, but the safety of this LAIV in immunocompromised patients must first be established. In the present study, FluMist was administered to ferrets immunocompromised by treatment with dexamethasone and cytarabine. Ferrets exhibited no signs or symptoms attributable to FluMist, and nasal clearance of LAIV strains from immunocompromised ferrets was similar to that from control ferrets. Serum antibody responses against the vaccinating strains were analyzed as a measure of vaccine efficacy. Antibody titers to all 3 vaccine strains in immunocompromised ferrets were similar to those seen in mock-treated control ferrets, as assessed by microneutralization assay. These findings support the potential use of this vaccine in immunocompromised humans.     

The safety and efficacy of quadrivalent live attenuated influenza vaccine in Japanese children aged 2‐18 years: Results of two phase 3 studies

Background

Quadrivalent live attenuated influenza vaccine (Q/LAIV) has not been assessed in Japanese children.

Objectives

Evaluate safety and efficacy of Q/LAIV in Japanese children.

Patients/methods

Two phase 3 studies were conducted in the 2014‐2015 influenza season. Study 1 was an open‐label, uncontrolled single arm, multicenter study of Q/LAIV safety in subjects aged 2‐6 years. Study 2 was a randomized, double‐blind, placebo‐controlled multicenter study of Q/LAIV safety and efficacy; subjects aged 7‐18 years were randomized 2:1 to receive Q/LAIV or placebo. Primary efficacy endpoint was laboratory‐confirmed symptomatic influenza infection caused by vaccine‐matched strains; secondary endpoint evaluated efficacy against all strains regardless of match. Both studies reported solicited symptoms, adverse events (AEs), and serious AEs.

Results

In Study 1, 100 subjects received Q/LAIV. In Study 2, 1301 subjects received Q/LAIV (n = 868) or placebo (n = 433). Treatment‐emergent AEs occurred in 42% of subjects in Study 1, and in 24.3% of subjects in the Q/LAIV arm and in 25.9% of subjects in the placebo arm in Study 2. In Study 2, a single infection by a vaccine‐matched strain was reported in the placebo arm, resulting in a vaccine efficacy estimate of 100% (95% CI: ?1875.3, 100.0); efficacy for all strains regardless of match to the vaccine was 27.5% (95% CI: 7.4, 43.0).

Conclusions

Quadrivalent live attenuated influenza vaccine did not meet its primary efficacy endpoint as only a single infection by a vaccine‐matched strain was detected; however, efficacy for the secondary endpoint, all strains regardless of match, was achieved. Q/LAIV was generally well tolerated in the Japanese pediatric population.

     

Universal Live-Attenuated Influenza Vaccine Candidates Expressing Multiple M2e Epitopes Protect Ferrets against a High-Dose Heterologous Virus Challenge

The development of an influenza vaccine with broad protection and durability remains an attractive idea due to the high mutation rate of the influenza virus. An extracellular domain of Matrix 2 protein (M2e) is among the most attractive target for the universal influenza vaccine owing to its high conservancy rate. Here, we generated two recombinant live attenuated influenza vaccine (LAIV) candidates encoding four M2e epitopes representing consensus sequences of human, avian and swine influenza viruses, and studied them in a preclinical ferret model. Both LAIV+4M2e viruses induced higher levels of M2e-specific antibodies compared to the control LAIV strain, with the LAIV/HA+4M2e candidate being significantly more immunogenic than the LAIV/NS+4M2e counterpart. A high-dose heterosubtypic influenza virus challenge revealed the highest degree of protection after immunization with LAIV/HA+4M2e strain, followed by the NS-modified LAIV and the classical LAIV virus. Furthermore, only the immune sera from the LAIV/HA+4M2e-immunized ferrets protected mice from a panel of lethal influenza viruses encoding M genes of various origins. These data suggest that the improved cross-protection of the LAIV/HA+4M2e universal influenza vaccine candidate was mediated by the M2e-targeted antibodies. Taking into account the safety profile and improved cross-protective potential, the LAIV/HA+4M2e vaccine warrants its further evaluation in a phase I clinical trial.     

Virus-Vectored Influenza Virus Vaccines

Despite the availability of an inactivated vaccine that has been licensed for >50 years, the influenza virus continues to cause morbidity and mortality worldwide. Constant evolution of circulating influenza virus strains and the emergence of new strains diminishes the effectiveness of annual vaccines that rely on a match with circulating influenza strains. Thus, there is a continued need for new, efficacious vaccines conferring cross-clade protection to avoid the need for biannual reformulation of seasonal influenza vaccines. Recombinant virus-vectored vaccines are an appealing alternative to classical inactivated vaccines because virus vectors enable native expression of influenza antigens, even from virulent influenza viruses, while expressed in the context of the vector that can improve immunogenicity. In addition, a vectored vaccine often enables delivery of the vaccine to sites of inductive immunity such as the respiratory tract enabling protection from influenza virus infection. Moreover, the ability to readily manipulate virus vectors to produce novel influenza vaccines may provide the quickest path toward a universal vaccine protecting against all influenza viruses. This review will discuss experimental virus-vectored vaccines for use in humans, comparing them to licensed vaccines and the hurdles faced for licensure of these next-generation influenza virus vaccines.     

Immunogenicity of a quadrivalent Ann Arbor strain live attenuated influenza vaccine delivered using a blow‐fill‐seal device in adults: a randomized,active‐controlled study

Please cite this paper as: Sheldon et al. (2013) Immunogenicity of a quadrivalent Ann Arbor strain live attenuated influenza vaccine delivered using a blow‐fill‐seal device in adults: a randomized, active‐controlled study. Influenza and Other Respiratory Viruses 7(6), 1142–1150. Background  Influenza B strains from two distinct lineages (Yamagata and Victoria) have cocirculated over recent years. Current seasonal vaccines contain a single B lineage resulting in frequent mismatches between the vaccine strain and the circulating strain. An Ann Arbor strain quadrivalent live attenuated influenza vaccine (Q/LAIV) containing B strains from both lineages is being developed to address this issue. Objectives  The goal of this study was to evaluate whether Q/LAIV administered intranasally as a single dose to a single nostril, using a blow‐fill‐seal (BFS) delivery system had a similar immunogenicity and safety profile compared with the licensed trivalent vaccine delivered using the Accuspray device. Patients/Methods  Adults aged 18–49 years were randomized to receive one intranasal dose of Q/LAIV delivered using a BFS device (Q/LAIV‐BFS; n = 1202) or one of two trivalent live attenuated influenza vaccines (T/LAIV) containing one of the corresponding B strains (total T/LAIV, n = 598). Primary endpoints were the post‐vaccination strain‐specific serum hemagglutination inhibition antibody geometric mean titers for each strain. Secondary immunogenicity endpoints, safety, and acceptability of the BFS device were also assessed. Results  Q/LAIV was immunogenically non‐inferior to T/LAIV for all four influenza strains. Secondary immunogenicity outcomes were consistent with the primary endpoint. Solicited symptoms and AEs were comparable in both groups. Subjects considered the BFS device to be acceptable. Conclusions  Immune responses to vaccination with Ann Arbor strain Q/LAIV‐BFS were non‐inferior to those with T/LAIV. Q/LAIV may confer broader protection against seasonal influenza B by targeting both major influenza B lineages.     

Immunization with live influenza viruses in an experimental model of allergic bronchial asthma: infection and vaccination

Background Asthmatics in particular have a need for influenza vaccines because influenza infection is a frequent cause of hospitalization of patients with bronchial asthma. Currently, only inactivated influenza vaccines are recommended for influenza prevention in asthma sufferers. Objective The aim of our study was to analyze and compare the effects of influenza infection and vaccination with live attenuated influenza vaccine (LAIV) on different phases of experimental murine allergic bronchial asthma (acute asthma and remission phase) and on subsequent exposure to allergen in sensitized animals. Methods Ovalbumin (OVA)‐specific serum IgE levels, IL‐4 production by spleen and lung lymphocytes, and histological changes in the lungs of mice infected with pathogenic virus or LAIV were studied at two phases of OVA‐induced bronchial asthma (acute asthma and remission). Results Infection with pathogenic virus both in acute asthma and remission led to asthma exacerbation associated with the production of OVA‐specific IgE, IL‐4 and significant inflammatory infiltration in airways. Infection, even after complete virus clearance, induced the aggravation of lung inflammation and IgE production in asthmatic mice additionally exposed to OVA. Immunization with LAIV at remission did not enhance allergic inflammatory changes in the lung, OVA‐specific IgE or IL‐4 production. Then after additional OVA exposure, histological and immunological changes in these mice were the same as in the control group. Conclusions Influenza infection provokes asthma exacerbation regardless of the disease phase. Immunization with LAIV during the remission phase of bronchial asthma is safe and does not interfere upon subsequent contact of asthma sufferers with allergen.