Intranasal Live Attenuated Influenza Vaccine Research Articles

2610. Home Administration of Intranasal Live Attenuated Influenza Vaccine: A Review of Current Evidence and Potential for Meeting Vaccination Targets

Abstract Background During the 2010–2021 influenza seasons, vaccination coverage was below the 70% target for the United States at 33.4–58.6% among children and 50.2% among adults.[1, 2] The live attenuated influenza vaccine (LAIV) is currently approved for healthcare professional administration (HCPA); however, self- and home-administered LAIVs may provide an additional, effective option for vaccine administration, which could expand seasonal influenza vaccine accessibility. LAIV is a quadrivalent influenza vaccine administered intranasally, with comparable effectiveness to the inactivated influenza vaccine.[3] Broadening vaccine availability to multiple vaccination sites has been shown to increase vaccination rates by up to 22%.[4] Here we summarize the current evidence on self- and home-administered LAIV efficacy and safety, and potential applications for increasing community influenza vaccination accessibility. Methods Publications evaluating the efficacy, safety, and practicality of self- and home-administered LAIV were identified from a literature search with the following search string: (live attenuated influenza vaccine OR LAIV) AND (home administration OR self administration OR self immuni*). Results In three studies comparing LAIV self- and home administration to HCPA (Table), home administration was preferred by 64, 74, and 96% of participants. Sample sizes ranged from 41 children to 4561 patients receiving LAIV, with participants aged between 2.6 and 64 years old. A trial of 4561 patients comparing LAIV self- and home administration to HCPA groups found similar effectiveness against influenza-like illness, immunogenicity, and adverse events post-vaccination. Conclusion Evidence suggests that self- and home-administered LAIV could be safely and effectively offered, and may be preferable for a subset of the population, which could expand seasonal influenza vaccine accessibility.

Live attenuated influenza vaccine induces broadly cross-reactive mucosal antibody responses to different influenza strains in tonsils

Intranasal live attenuated influenza vaccine (LAIV) was used to stimulate tonsillar monocular cells (MNCs) following isolation. Haemagglutinin (HA) proteins of several influenza strains were used for the detection of HA-specific IgG, IgM and IgA antibodies using ELISA. Significant anti-sH1N1 HA IgG IgA and IgM antibody titres were detected in cell culture supernatants after stimulation (mean ± SE: 0.43 ± 0.09, mean ± SE: 0.23 ± 0.04 and mean ± SE: 0.47 ± 0.05 respectively, p < 0.01). LAIV stimulation of tonsillar MNCs induced significant IgG, IgA and IgM antibodies to the pH1N1 HA (mean ± SE:1.35 ± 0.12), (mean ± SE: 0.35 ± 0.06) and (mean ± SE: 0.58 ± 0.10) respectively, p < 0.01. Surprisingly, LAIV was shown to induce cross-reactive anti-aH5N1 HA antibodies (mean ± SE: 0.84 ± 0.20, p < 0.01) to avian influenza virus (aH5N1). Anti-H2N2 HA IgG antibody was also detected in the cell culture supernatants in a significant level after LAIV stimulation (mean ± SE: 0.93 ± 0.23, p < 0.01). High levels of anti-sH3N2 HA IgG antibody was discovered after LAIV stimulation of tonsillar MNCs, (mean ± SE: 1.2 ± 0.23p < 0.01). The current model of human nasal-associated lymphoid tissue (NALT) to evaluate B cells responses to LAIV was evident that it is a successful model to study future intranasal vaccines.

Cost-Effectiveness of Intranasal Live-Attenuated Influenza Vaccine for Children: A Systematic Review.

Introduction: The public health burden of seasonal influenza is significant, and influenza vaccination is the most effective preventive strategy. Nonetheless, the recommendation of influenza immunization in the pediatric population is still underrepresented. Our work aimed to assess the cost-effectiveness of pediatric influenza vaccination with the intranasal live-attenuated influenza vaccine (LAIV). Methods: We performed a systematic review of publications from PubMed/MEDLINE, Embase, and Scopus, covering the period from 1 January 2000 to 30 April 2022. We searched for economic evaluations that studied the impacts of LAIV among children or the pediatric population. Studies that considered incremental cost-effectiveness ratios (ICERs), in terms of cost per gain in life years, quality adjusted life years, or disability-adjusted life years, were covered. The Consensus Health Economic Criteria (CHEC) Extended Checklist was adopted to check the quality of the included studies. Results: Thirteen studies were included for the final review that were of good or excellent quality. The implementation of influenza vaccination with intranasal LAIV in the pediatric population was cost-effective when compared to the immunization strategies for the elderly and the high-risk groups alone or with no vaccination. The efficacy of LAIV for children, vaccination coverage, and the vaccine price were significant factors to the cost-effectiveness of influenza vaccination for children. Another significant contribution to the cost-effectiveness was the herd immunity arising from pediatric immunization against influenza. Conclusions: The implementation of influenza vaccination in the pediatric population with LAIV is cost-effective. Policymakers and health authorities may consider the evidence on the development of the pediatric influenza vaccination in their immunization schedules.

SARS-CoV-2 Vaccines: The Mucosal Immunity Imperative

SARS-CoV-2 Vaccines: The Mucosal Immunity Imperative

The effect of live attenuated influenza vaccine on pneumococcal colonisation densities among children aged 24–59 months in The Gambia: a phase 4, open label, randomised, controlled trial

SummaryBackgroundInfluenza and other respiratory viruses promote Streptococcus pneumoniae proliferation in the upper respiratory tract. We sought to investigate for what we believe is the first time, the effect of intranasal live attenuated influenza vaccine (LAIV) on nasopharyngeal S pneumoniae density in a low-income to middle-income country population with high pneumococcal carriage rates.MethodsIn an open-label, randomised, controlled trial in The Gambia, 330 healthy children aged 24–59 months were randomly assigned 2:1 to receive one trivalent LAIV dose at enrolment (day 0, intervention) or at the end of active follow-up (day 21, control). The investigator team were initially masked to block size and randomisation sequence to avoid allocation bias. Group allocation was later revealed to the investigator team. The primary outcome was PCR-quantified day 7 and 21 pneumococcal density. Asymptomatic respiratory viral infection at baseline and LAIV strain shedding were included as covariates in generalised mixed-effects models, to assess the effect of LAIV and other variables on pneumococcal densities. The study is registered at ClinicalTrials.gov, NCT02972957, and is closed to recruitment.FindingsBetween Feb 8 and April 12, 2017, and Jan 15 and March 28, 2018, of 343 children assessed for eligibility, 213 in the intervention group and 108 in the control group completed the study and were included in the final analysis. Although no significant differences were seen in pneumococcal carriage or density at each timepoint when comparing groups, changes from baseline were observed in the LAIV group. The baseline S pneumoniae carriage prevalence was high in both LAIV and control groups (75%) and increased by day 21 in the LAIV group (85%, p=0·0037), but not in the control group (79%, p=0·44). An increase in pneumococcal density from day 0 amounts was seen in the LAIV group at day 7 (+0·207 log10 copies per μL, SE 0·105, p=0·050) and day 21 (+0·280 log10 copies per μL, SE 0·105, p=0·0082), but not in the control group. Older age was associated with lower pneumococcal density (−0·015 log10 copies per μL, SE 0·005, p=0·0030), with the presence of asymptomatic respiratory viruses at baseline (+0·259 log10 copies per μL, SE 0·097, p=0·017), and greater LAIV shedding at day 7 (+0·380 log10 copies per μL, SE 0·167, p=0·024) associated with higher pneumococcal density. A significant increase in rhinorrhoea was reported in the LAIV group compared with the control group children during the first 7 days of the study (103 [48%] of 213, compared with 25 [23%] of 108, p<0·0001), and between day 7 and 21 (108 [51%] of 213, compared with 28 [26%] of 108, p<0·0001).InterpretationLAIV was associated with a modest increase in nasopharyngeal pneumococcal carriage and density in the 21 days following vaccination, with the increase in density lower in magnitude than previously described in the UK. This increase was accelerated when LAIV was administered in the presence of pre-existing asymptomatic respiratory viruses, suggesting that nasopharyngeal S pneumoniae proliferation is driven by cumulative mixed-viral co-infections. The effect of LAIV on pneumococcal density is probably similar to other respiratory viral infections in children. Our findings provide reassurance for the use of LAIV to expand influenza vaccine programmes in low-income to middle-income country populations with high pneumococcal carriage.FundingWellcome Trust.

Safety and Efficacy of Spray Intranasal Live Attenuated Influenza Vaccine: Systematic Review and Meta-Analysis.

Although influenza is a major public health concern, little is known about the use of spray live attenuated influenza vaccine (LAIV) among adults. For this reason, we conducted a systematic review and meta-analysis to investigate the efficacy and safety of LAIV, especially in adults with/without clinical conditions and children <2 years, with the final aim of possibly extending the clinical indications. PubMed/MEDLINE and Scopus were the two databases consulted through February 2021. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. A critical appraisal was conducted. Analyses were performed by using ProMeta3 software. Twenty-two studies were included, showing that LAIV was associated with a higher probability of seroconversion when compared with a placebo and considering the A/H1N1 serotype (pooled OR = 2.26 (95% CI = 1.12–4.54), p-value = 0.022; based on 488 participants, without heterogeneity (I2 = 0.0%)). The meta-analysis also confirmed no significant association with systemic adverse events. Only rhinorrhea, nasal congestion, and sore throat were significantly associated with LAIV compared to the placebo. Despite limited available evidence, LAIV has proved to be a safe and effective flu vaccination, also due to its very low invasiveness, and our review’s results can be considered a starting point for guiding future research and shaping forthcoming vaccination campaigns.

Long noncoding RNAs are involved in multiple immunological pathways in response to vaccination

Understanding the mechanisms of vaccine-elicited protection contributes to the development of new vaccines. The emerging field of systems vaccinology provides detailed information on host responses to vaccination and has been successfully applied to study the molecular mechanisms of several vaccines. Long noncoding RNAs (lncRNAs) are crucially involved in multiple biological processes, but their role in vaccine-induced immunity has not been explored. We performed an analysis of over 2,000 blood transcriptome samples from 17 vaccine cohorts to identify lncRNAs potentially involved with antibody responses to influenza and yellow fever vaccines. We have created an online database where all results from this analysis can be accessed easily. We found that lncRNAs participate in distinct immunological pathways related to vaccine-elicited responses. Among them, we showed that the expression of lncRNA FAM30A was high in B cells and correlates with the expression of immunoglobulin genes located in its genomic vicinity. We also identified altered expression of these lncRNAs in RNA-sequencing (RNA-seq) data from a cohort of children following immunization with intranasal live attenuated influenza vaccine, suggesting a common role across several diverse vaccines. Taken together, these findings provide evidence that lncRNAs have a significant impact on immune responses induced by vaccination.

Research progress in human infection with avian influenza H7N9 virus.

Since the identification of the novel reassortant avian influenza A (H7N9) virus in China in 2013, until Jun 30, 2017, the virus has caused five epidemic waves leading to a total of 1,552 human infections, with a fatality rate of about 40%. In the spring of 2017, highly pathogenic avian influenza (HPAI) H7N9 virus emerged and has caused 25 human infections. The HPAI H7N9 virus has some biological differences from the LPAI one, such as its multiple basic amino acid residues on HA leading to its independence on trypsin for replication. The pathogenicity of the HPAI H7N9 virus to experimental animals or humans is still unclear. A(H7N9) vaccine development for pandemic preparedness is ongoing, including the reassortment (H7N9/PR8) reverse genetic based vaccine, the virus like particle (VLP) vaccine, the intranasal live attenuated influenza vaccine (LAIV), the non-adjuvant Vero cell culture-derived inactivated whole-virus vaccine, the MDCK culture-derived vaccine, the H7 DNA vaccine and the recombinant replicative H7N9 virus (H7N9-53TM) vaccine. Five neuramidinase resistant sites of A(H7N9) virus isolated from patients have been reported. Some alternative drugs have been studied, such as DAS181 (Fludase), ribavirin, troglitazone and minocycline. Persistent surveillance and enhanced global control are essential to fight against human infections with A(H7N9) virus.

Perspectives from the Society for Pediatric Research: Decreased Effectiveness of the Live Attenuated Influenza Vaccine.

The intranasal live attenuated influenza vaccine (LAIV), FluMist, has been widely appreciated by pediatricians, parents, and children alike for its ease of administration. However, concerns regarding lack of effectiveness in recent influenza seasons led to the CDC Advisory Committee on Immunization Practices (ACIP) recommendation to administer inactivated influenza vaccines (IIVs), and not LAIV, during the 2016-17 and 2017-18 seasons. Given that data from previous years demonstrated equivalent and even improved efficacy of LAIV compared with IIV, these recent data were surprising, raising many questions about the potential mechanisms underlying this change. This review seeks to summarize the history of LAIV studies and ACIP recommendations with a focus on the recent decrease in vaccine effectiveness (VE) and discordant results among studies performed in different countries. Decreased VE for A/H1N1pdm09 viruses represents the most consistent finding across studies, as VE has been low every season these viruses predominated since 2010-11. Potential explanations underlying diminished effectiveness include the hypothesis that prior vaccination, reduced thermostability of A/H1N1pdm09, addition of a fourth virus, or reduced replication fitness of A/H1N1pdm09 strains may have contributed to this phenomenon. Ongoing studies and potential alterations to LAIV formulations provide hope for a return of effective LAIV in future influenza seasons.

Live versus attenuated influenza vaccine uptake and post-vaccination influenza-like illness outcomes in HIV-infected US Air Force members

BackgroundAlthough clinical data is limited, guidelines recommend avoiding live attenuated intranasal influenza vaccine (LAIV) in HIV-infected persons. ObjectivesTo evaluate non-guideline LAIV use and resulting adverse effects in an HIV-infected population. Study designA retrospective analysis of influenza vaccination in US Air Force (USAF) members with HIV infection immunized between 2005 and 2015 was performed. Influenza vaccination history after HIV diagnosis was evaluated, including receipt of LAIV or inactivated influenza vaccine (IIV). The proportion with influenza-like illness (ILI) diagnoses within 30days after vaccination with IIV or LAIV was assessed by ICD-9 codes. Results437 patients met inclusion criteria, with 121 (27.7%) receiving at least one dose of LAIV and 316 (72.3%) receiving only IIV during follow-up. The mean number of LAIV doses received was 1.5±0.89 (range, 1–4) and the majority (n=50, 82%) received their first LAIV vaccination within the first year after HIV diagnosis. Patients were predominantly males and the LAIV group had a lower mean age at HIV diagnosis (27.5±6.6) compared to the IIV group (30±7.8; p <0.001). Overall, IIV was associated with ILI diagnosis within 30days of vaccination (X2 4.58; p=0.032), with 16 cases (94.1%) occurring in those who received IIV compared to 1 case (5.9%) in those who received LAIV. ConclusionAlthough over a quarter of USAF members received LAIV after HIV diagnosis, LAIV administration did not show an increased frequency of post-vaccine ILI diagnoses. Further education is needed to ensure that USAF members with HIV infection are vaccinated according to guideline recommendations, particularly newly diagnosed patients.

Adverse events following live-attenuated intranasal influenza vaccination of children with cystic fibrosis: Results from two influenza seasons.

Despite the approved use of live-attenuated intranasal influenza vaccine (LAIV) for seasonal immunization of patients with cystic fibrosis (CF), many questions remain unanswered regarding the timing, duration, and types of adverse events that occur following administration of this vaccine. In 2012 and 2013, 264 LAIV doses were administered to 198 patients aged 2-19 with CF. Vaccinees were followed prospectively for 55 days after vaccination (day 0) and information on adverse events was collected. Bayesian change-point analysis was used to identify the risk period following LAIV during which participants had a higher risk of reporting adverse events. Multivariable zero-inflated Poisson regression models were then used to estimate the adjusted incidence rate ratio (aIRR) and 95% credible interval (CrI) of reporting each adverse event in the risk period versus the control period. There was a higher risk of reporting serious adverse events (SAEs) (aIRR 1.45, 95% CrI (0.29, 5.17)) and solicited symptoms during days 0-6 of follow-up compared to control period days 7-55. However, most SAEs were not causally related to LAIV and the solicited symptom episodes were brief, usually lasting 1-2 days. There was no increased risk of antibiotic prescriptions for respiratory conditions in the risk vs. control periods (aIRR 0.48, 95% CrI (0.23, 0.91)). Adverse events were most common 0-6 days after LAIV administration but were generally benign and self-limiting. Pulmonary exacerbations did not increase in frequency.

Viral interference and the live-attenuated intranasal influenza vaccine: Results from a pediatric cohort with cystic fibrosis

ABSTRACT Background: The objective of this study was to explore the effects of viral co-detection in individuals recently vaccinated with the live-attenuated intranasal influenza virus vaccine (LAIV) on the detection of influenza RNA. Methods: Before the 2013–2014 influenza season, nasal swabs were obtained from 59 pediatric participants with cystic fibrosis (CF) and 17 of their healthy siblings immediately before vaccination and 4 times during the week of follow-up. Real-time RT-PCR assays were used to detect influenza RNA. Co-detection of a non-influenza respiratory virus (NIRV) at the time of vaccination was determined by a multiplex RT-PCR assay. Differences in the proportions and rates of influenza detection and their 95% credible intervals (CrI) were estimated. Results: Influenza RNA was detected in 16% fewer participants (95% CrI: −7, 39%) throughout follow-up in the NIRV-positive group compared with the NIRV-negative group (59% vs. 75%). This was also observed in participants with CF alone (66% vs. 74%; RD = 8% 95% CrI: −16, 33%) as well as in healthy participants only (75% vs. 30%; RD = 45%, 95% CrI: −2, 81%). Influenza was detected in NIRV-negative subjects for 0.49 d more compared with NIRV-positive subjects (95% CrI: −0.37, 1.26). Conclusion: The observed proportion of subjects in whom influenza RNA was detected and the duration of detection differed slightly between NIRV- positive and −negative subjects. However, wide credible intervals for the difference preclude definitive conclusions. If true, this observed association may be related to a recent viral respiratory infection, a phenomenon known as viral interference.

A Feasibility Trial of Home Administration of Intranasal Vaccine by Parents to Eligible Children

PurposeIntranasal vaccines are being developed for protection against many different infectious agents. The currently available intranasal live attenuated influenza vaccine (LAIV) is only approved for administration by medical personnel. We conducted a pilot study to investigate the feasibility of training parents to give LAIV to their own children. MethodsSubjects were recruited from several sources: a university-based outpatient clinic, university employee e-mail announcement, and direct referrals from study subjects. After confirming eligibility to receive LAIV, consented parents were trained by viewing a video with the study staff. LAIV was provided in a cooler with instructions to vaccinate within 24 hours. Telephone follow-up was conducted to confirm proper administration and to assess parental attitudes about home administration. At season’s end, immunization registry and hospital records were reviewed to confirm no additional doses were given. FindingsTwenty-seven families with 41 children were enrolled. All participants successfully administered LAIV to their children, and all preferred or strongly preferred home administration to an office visit for getting vaccinated. Two families stated that without this option they would not have otherwise vaccinated their children. Adverse events were minor. All patients had their state vaccine registries accurately updated and none received duplicate doses. Upon review, no reimbursement was received for vaccination. ImplicationsHome administration of intranasal LAIV was successful and well received. This option could be used in the future for LAIV or other intranasal vaccines as a way to increase vaccination rates and convenience for parents. ClinicalTrials.gov identifier: NCT01938170.

Influenza Virus Detection Following Administration of Live-Attenuated Intranasal Influenza Vaccine in Children With Cystic Fibrosis and Their Healthy Siblings.

Background. We aimed to explore the detection profile of influenza viruses following live-attenuated intranasal influenza vaccination (LAIV) in children aged 2–19 years with and without cystic fibrosis (CF). Methods. Before the 2013–2014 influenza season, flocked nasal swabs were obtained before vaccination and 4 times in the week of follow-up from 76 participants (nCF: 57; nhealthy: 19). Influenza was detected by reverse transcription polymerase chain reaction (RT-PCR) assays. A Bayesian hierarchical logistic regression model was used to estimate the effect of CF status and age on influenza detection. Results. Overall, 69% of the study cohort shed influenza RNA during follow-up. The mean duration of RT-PCR detection was 2.09 days (95% credible interval [CrI]: 1.73–2.48). The odds of influenza RNA detection on day 1 following vaccination decreased with age in years (odds ratio [OR]: 0.82 per year; 95% CrI: 0.70–0.95), and subjects with CF had higher odds of influenza RNA detection on day 1 of follow-up (OR: 5.09; 95% CrI: 1.02–29.9). Conclusion. Despite the small sample size, our results indicate that LAIV vaccine strains are detectable during the week after LAIV, mainly in younger individuals and vaccinees with CF. It remains unclear whether recommendations for avoiding contact with severely immunocompromised patients should differ for these groups.

Live Attenuated Flu Vaccine Offers No Extra Community Benefit

Intranasal live attenuated influenza vaccine has been more immunogenic than intramuscular inactivated vaccine among children in clinical trials. This finding has led to the assumption that the live vaccine also should be a more powerful inducer of herd immunity. Canadian researchers studied the community-wide performance of both vaccines in 52 rural Hutterite colonies — tiny religious settlements composed …

Live Attenuated Versus Inactivated Influenza Vaccine in Hutterite Children

Whether vaccinating children with intranasal live attenuated influenza vaccine (LAIV) is more effective than inactivated influenza vaccine (IIV) in providing both direct protection in vaccinated persons and herd protection in unvaccinated persons is uncertain. Hutterite colonies, where members live in close-knit, small rural communities in which influenza virus infection regularly occurs, offer an opportunity to address this question. To determine whether vaccinating children and adolescents with LAIV provides better community protection than IIV. A cluster randomized blinded trial conducted between October 2012 and May 2015 over 3 influenza seasons. (ClinicalTrials.gov: NCT01653015). 52 Hutterite colonies in Alberta and Saskatchewan, Canada. 1186 Canadian children and adolescents aged 36 months to 15 years who received the study vaccine and 3425 community members who did not. Children were randomly assigned according to community in a blinded manner to receive standard dosing of either trivalent LAIV or trivalent IIV. The primary outcome was reverse transcriptase polymerase chain reaction-confirmed influenza A or B virus in all participants (vaccinated children and persons who did not receive the study vaccine). Mean vaccine coverage among children in the LAIV group was 76.9% versus 72.3% in the IIV group. Influenza virus infection occurred at a rate of 5.3% (295 of 5560 person-years) in the LAIV group versus 5.2% (304 of 5810 person-years) in the IIV group. The hazard ratio comparing LAIV with IIV for influenza A or B virus was 1.03 (95% CI, 0.85 to 1.24). The study was conducted in Hutterite communities, which may limit generalizability. Immunizing children with LAIV does not provide better community protection against influenza than IIV. The Canadian Institutes for Health Research.

Estimates of the Public Health Impact of a Pediatric Vaccination Program Using an Intranasal Tetravalent Live-Attenuated Influenza Vaccine in Belgium.

Our objectives were to estimate the public health outcomes of vaccinating Belgian children using an intranasal tetravalent live-attenuated influenza vaccine (QLAIV) combined with current coverage of high-risk/elderly individuals using the trivalent inactivated vaccine. We used a deterministic, age-structured, dynamic model to simulate seasonal influenza transmission in the Belgian population under the current coverage or after extending vaccination with QLAIV to healthy children aged 2-17years. Differential equations describe demographic changes, exposure to infectious individuals, infection recovery, and immunity dynamics. The basic reproduction number (R 0) was calibrated to the observed number of influenza doctor visits/year. Vaccine efficacy was 80% (live-attenuated) and 59-68% (inactivated). The 10-year incidence of symptomatic influenza was calculated with different coverage scenarios (add-on to current coverage). Model calibration yielded R 0=1.1. QLAIV coverage of 75% of those aged 2-17years averted 374,000 symptomatic cases/year (57% of the current number), 244,000 of which were among adults (indirect effect). Vaccinating 75% of those aged 2-11years and 50% of those aged 12-17years averted 333,200 cases/year (213,000 adult cases/year). Vaccinating only healthy children aged 2-5years generated direct protection but limited indirect protection, even with 90% coverage (40,800 averted adult cases/year; -8.4%). Targeting all children averted twice as many high-risk cases as targeting high-risk children only (8485 vs. 4965/year with 75% coverage). Sensitivity analyses showed the robustness of results. The model highlights the direct and indirect protection benefits when vaccinating healthy children with QLAIV in Belgium. Policies targeting only high-risk individuals or the youngest provide limited herd protection, as school-age children are important influenza vectors in the community.

Live Attenuated Influenza Vaccine in Children Induces B-Cell Responses in Tonsils.

Background. Tonsils play a key role in eliciting immune responses against respiratory pathogens. Little is known about how tonsils contribute to the local immune response after intranasal vaccination. Here, we uniquely report the mucosal humoral responses in tonsils and saliva after intranasal live attenuated influenza vaccine (LAIV) vaccination in children.Methods. Blood, saliva, and tonsils samples were collected from 39 children before and after LAIV vaccination and from 16 age-matched, nonvaccinated controls. Serum antibody responses were determined by a hemagglutination inhibition (HI) assay. The salivary immunoglobulin A (IgA) level was measured by an enzyme-linked immunosorbent assay. Antibody-secreting cell (ASC) and memory B-cell (MBC) responses were enumerated in tonsils and blood.Results. Significant increases were observed in levels of serum antibodies and salivary IgA to influenza A(H3N2) and influenza B virus strains as early as 14 days after vaccination but not to influenza A(H1N1). Influenza virus–specific salivary IgA levels correlated with serum HI responses, making this a new possible indicator of vaccine immunogenicity in children. LAIV augmented influenza virus–specific B-cell responses in tonsils and blood. Tonsillar MBC responses correlated with systemic MBC and serological responses. Naive children showed significant increases in MBC counts after LAIV vaccination.Conclusions. This is the first study to demonstrate that LAIV elicits humoral B-cell responses in tonsils of young children. Furthermore, salivary IgA analysis represents an easy method for measuring immunogenicity after vaccination.

Perfluoroalkyl substance serum concentrations and immune response to FluMist vaccination among healthy adults

Perfluoroalkyl substances (PFAS) were shown to be immunotoxic in laboratory animals. There is some epidemiological evidence that PFAS exposure is inversely associated with vaccine-induced antibody concentration. We examined immune response to vaccination with FluMist intranasal live attenuated influenza vaccine in relation to four PFAS (perfluorooctanoate, perfluorononanoate, perfluorooctane sulfonate, perfluorohexane sulfonate) serum concentrations among 78 healthy adults vaccinated during the 2010–2011 influenza season. We measured anti-A H1N1 antibody response and cytokine and chemokine concentrations in serum pre-vaccination, 3 days post-vaccination, and 30 days post-vaccination. We measured cytokine, chemokine, and mucosal IgA concentration in nasal secretions 3 days post-vaccination and 30 days post-vaccination. Adults with higher PFAS concentrations were more likely to seroconvert after FluMist vaccination as compared to adults with lower PFAS concentrations. The associations, however, were imprecise and few participants seroconverted as measured either by hemagglutination inhibition (9%) or immunohistochemical staining (25%). We observed no readily discernable or consistent pattern between PFAS concentration and baseline cytokine, chemokine, or mucosal IgA concentration, or between PFAS concentration and change in these immune markers between baseline and FluMist-response states. The results of this study do not support a reduced immune response to FluMist vaccination among healthy adults in relation to serum PFAS concentration. Given the study's many limitations, however, it does not rule out impaired vaccine response to other vaccines or vaccine components in either children or adults.

H7N9 Live Attenuated Influenza Vaccine Is Highly Immunogenic, Prevents Virus Replication, and Protects Against Severe Bronchopneumonia in Ferrets

Avian influenza viruses continue to cross the species barrier, and if such viruses become transmissible among humans, it would pose a great threat to public health. Since its emergence in China in 2013, H7N9 has caused considerable morbidity and mortality. In the absence of a universal influenza vaccine, preparedness includes development of subtype-specific vaccines. In this study, we developed and evaluated in ferrets an intranasal live attenuated influenza vaccine (LAIV) against H7N9 based on the A/Leningrad/134/17/57 (H2N2) cold-adapted master donor virus. We demonstrate that the LAIV is attenuated and safe in ferrets and induces high hemagglutination- and neuraminidase-inhibiting and virus-neutralizing titers. The antibodies against hemagglutinin were also cross-reactive with divergent H7 strains. To assess efficacy, we used an intratracheal challenge ferret model in which an acute severe viral pneumonia is induced that closely resembles viral pneumonia observed in severe human cases. A single- and two-dose strategy provided complete protection against severe pneumonia and prevented virus replication. The protective effect of the two-dose strategy appeared better than the single dose only on the microscopic level in the lungs. We observed, however, an increased lymphocytic infiltration after challenge in single-vaccinated animals and hypothesize that this a side effect of the model.