Dataset Information

Molecular-level analysis of the serum antibody repertoire in young adults before and after seasonal influenza vaccination.

ABSTRACT: Molecular understanding of serological immunity to influenza has been confounded by the complexity of the polyclonal antibody response in humans. Here we used high-resolution proteomics analysis of immunoglobulin (referred to as Ig-seq) coupled with high-throughput sequencing of transcripts encoding B cell receptors (BCR-seq) to quantitatively determine the antibody repertoire at the individual clonotype level in the sera of young adults before and after vaccination with trivalent seasonal influenza vaccine. The serum repertoire comprised between 40 and 147 clonotypes that were specific to each of the three monovalent components of the trivalent influenza vaccine, with boosted pre-existing clonotypes accounting for ?60% of the response. An unexpectedly high fraction of serum antibodies recognized both the H1 and H3 monovalent vaccines. Recombinant versions of these H1 + H3 cross-reactive antibodies showed broad binding to hemagglutinins (HAs) from previously circulating virus strains; several of these antibodies, which were prevalent in the serum of multiple donors, recognized the same conserved epitope in the HA head domain. Although the HA-head-specific H1 + H3 antibodies did not show neutralization activity in vitro, they protected mice against infection with the H1N1 and H3N2 virus strains when administered before or after challenge. Collectively, our data reveal unanticipated insights regarding the serological response to influenza vaccination and raise questions about the added benefits of using a quadrivalent vaccine instead of a trivalent vaccine.

SUBMITTER: Lee J

PROVIDER: S-EPMC5301914 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Molecular-level analysis of the serum antibody repertoire in young adults before and after seasonal influenza vaccination.

Lee Jiwon J Boutz Daniel R DR Chromikova Veronika V Joyce M Gordon MG Vollmers Christopher C Leung Kwanyee K Horton Andrew P AP DeKosky Brandon J BJ Lee Chang-Han CH Lavinder Jason J JJ Murrin Ellen M EM Chrysostomou Constantine C Hoi Kam Hon KH Tsybovsky Yaroslav Y Thomas Paul V PV Druz Aliaksandr A Zhang Baoshan B Zhang Yi Y Wang Lingshu L Kong Wing-Pui WP Park Daechan D Popova Lyubov I LI Dekker Cornelia L CL Davis Mark M MM Carter Chalise E CE Ross Ted M TM Ellington Andrew D AD Wilson Patrick C PC Marcotte Edward M EM Mascola John R JR Ippolito Gregory C GC Krammer Florian F Quake Stephen R SR Kwong Peter D PD Georgiou George G

Nature medicine 20161107 12

Molecular understanding of serological immunity to influenza has been confounded by the complexity of the polyclonal antibody response in humans. Here we used high-resolution proteomics analysis of immunoglobulin (referred to as Ig-seq) coupled with high-throughput sequencing of transcripts encoding B cell receptors (BCR-seq) to quantitatively determine the antibody repertoire at the individual clonotype level in the sera of young adults before and after vaccination with trivalent seasonal influ ...[more]

PMID: 27820605

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Project description:In advance of a large influenza vaccine effectiveness (VE) cohort study among older adults in Thailand, we conducted a population-based, cross-sectional survey to measure vaccine coverage and identify factors associated with influenza vaccination among older Thai adults that could bias measures of vaccine effectiveness.We selected adults ?65 years using a two-stage, stratified, cluster sampling design. Functional status was assessed using the 10-point Vulnerable Elders Survey (VES); scores ?3 indicated vulnerability. Questions about attitudes towards vaccination were based on the Health Belief Model. The distance between participants' households and the nearest vaccination clinic was calculated. Vaccination status was determined using national influenza vaccination registry. Prevalence ratios (PR) and 95% confidence intervals (CIs) were calculated using log-binomial multivariable models accounting for the sampling design.We enrolled 581 participants, of whom 60% were female, median age was 72 years, 41% had at least one chronic underlying illness, 24% met the criteria for vulnerable, and 23% did not leave the house on a daily basis. Influenza vaccination rate was 34%. In multivariable models, no variable related to functional status was associated with vaccination. The strongest predictors of vaccination were distance to the nearest vaccination center (PR 3.0, 95% CI 1.7-5.1 for participants in the closest quartile compared to the furthest), and high levels of a perception of benefits of influenza vaccination (PR 2.8, 95% CI 1.4-5.6) and cues to action (PR 2.7, 95% CI 1.5-5.1).Distance to vaccination clinics should be considered in analyses of influenza VE studies in Thailand. Strategies that emphasize benefits of vaccination and encourage physicians to recommend annual influenza vaccination could improve influenza vaccine uptake among older Thai adults. Outreach to more distant and less mobile older adults may also be required to improve influenza vaccination coverage.

Dataset Information

Molecular-level analysis of the serum antibody repertoire in young adults before and after seasonal influenza vaccination.

Publications

Molecular-level analysis of the serum antibody repertoire in young adults before and after seasonal influenza vaccination.

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