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. 2016 Sep 19;11(9):e0162803.
doi: 10.1371/journal.pone.0162803. eCollection 2016.

Taxa of the Nasal Microbiome Are Associated with Influenza-Specific IgA Response to Live Attenuated Influenza Vaccine

Hannah M Salk  1 , Whitney L Simon  1 , Nathaniel D Lambert  1 , Richard B Kennedy  1 , Diane E Grill  2 , Brian F Kabat  2 , Gregory A Poland  1
Affiliations

Taxa of the Nasal Microbiome Are Associated with Influenza-Specific IgA Response to Live Attenuated Influenza Vaccine

Hannah M Salk et al. PLoS One. .

Abstract

Live attenuated influenza vaccine (LAIV) has demonstrated varying levels of efficacy against seasonal influenza; however, LAIV may be used as a tool to measure interactions between the human microbiome and a live, replicating virus. To increase our knowledge of this interaction, we measured changes to the nasal microbiome in subjects who received LAIV to determine if associations between influenza-specific IgA production and the nasal microbiome exist after immunization with a live virus vaccine. The anterior nares of 47 healthy subjects were swabbed pre- (Day 0) and post- (Days 7 and 28) LAIV administration, and nasal washes were conducted on Days 0 and 28. We performed next-generation sequencing on amplified 16s rRNA genes and measured mucosal influenza-specific IgA titers via enzyme-linked immunosorbent assay (ELISA). A significant increase in alpha diversity was identified (Observed, CHAO, and ACE) between Days 7 vs 0 (p-values = 0.017, 0.005, 0.005, respectively) and between Days 28 vs 0 (p-values = 0.054, 0.030, 0.050, respectively). Several significant associations between the presence of different microbial species, including Lactobacillus helveticus, Prevotella melaninogenica, Streptococcus infantis, Veillonella dispar, and Bacteroides ovatus, and influenza-specific H1 and H3 IgA antibody response were demonstrated. These data suggest that LAIV alters the nasal microbiome, allowing several less-abundant OTUs to establish a community niche. Additionally, specific alterations in the nasal microbiome are significantly associated with variations in influenza-specific IgA antibody production and could be clinically relevant.

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Conflict of interest statement

Dr. Poland is the chair of a Safety Evaluation Committee for novel investigational vaccine trials being conducted by Merck Research Laboratories. Dr. Poland offers consultative advice on vaccine development to Merck & Co. Inc., CSL Biotherapies, Avianax, Dynavax, Novartis Vaccines and Therapeutics, Emergent Biosolutions, Adjuvance, Seqirus, NewLink, Protein Sciences, GSK Vaccines, and Sanofi Pasteur. Dr. Poland holds two patents related to vaccinia and measles peptide research. Dr. Kennedy has grant funding from Merck Research Laboratories to study immune responses to mumps vaccine. These activities have been reviewed by the Mayo Clinic Conflict of Interest Review Board and are conducted in compliance with Mayo Clinic Conflict of Interest policies. This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and was conducted in compliance with Mayo Clinic Conflict of Interest policies. The other authors do not have any conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Changes in alpha diversity over time.
Observed OTUs, Day 7 vs. Day 0, p = 0.017 and Day 28 vs. Day 0, p = 0.005; Chao estimator, Day 7 vs. Day 0, p = 0.005 and Day 28 vs. Day 0, p = 0.030; ACE estimator, Day 7 vs. Day 0, p = 0.005 and Day 28 vs. Day 0, p = 0.050. There were no significant differences for Shannon’s Diversity Index. Box-and-whiskers plots showing four measures of Alpha Diversity of anterior nares microbial community for each study visit (Day 0, Day 7 and Day 28).
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Grants and funding

Research reported in this publication was supported by The Mayo Clinic Center for Individualized Medicine. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.