Pneumococcal colonization impairs mucosal immune responses to live attenuated influenza vaccine
Carniel, Beatriz F.; Marcon, Fernando; Rylance, Jamie; German, Esther L.; Zaidi, Seher; Reiné, Jesus; Negera, Edessa; Nikolaou, Elissavet; Pojar, Sherin; Solórzano, Carla; Collins, Andrea M.; Connor, Victoria; Bogaert, Debbie; Gordon, Stephen B.; Nakaya, Helder I.; Ferreira, Daniela M.; Jochems, Simon P.; Mitsi, Elena
(2021) JCI Insight, volume 6, issue 4, pp. 1 - 17
(Article)
Abstract
Influenza virus infections affect millions of people annually, and current available vaccines provide varying rates of protection. However, the way in which the nasal microbiota, particularly established pneumococcal colonization, shape the response to influenza vaccination is not yet fully understood. In this study, we inoculated healthy adults with live Streptococcus
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pneumoniae and vaccinated them 3 days later with either tetravalent-inactivated influenza vaccine (TIV) or live attenuated influenza vaccine (LAIV). Vaccine-induced immune responses were assessed in nose, blood, and lung. Nasal pneumococcal colonization had no impact upon TIV-induced antibody responses to influenza, which manifested in all compartments. However, experimentally induced pneumococcal colonization dampened LAIV-mediated mucosal antibody responses, primarily IgA in the nose and IgG in the lung. Pulmonary influenza-specific cellular responses were more apparent in the LAIV group compared with either the TIV or an unvaccinated group. These results indicate that TIV and LAIV elicit differential immunity to adults and that LAIV immunogenicity is diminished by the nasal presence of S. pneumoniae. Therefore, nasopharyngeal pneumococcal colonization may affect LAIV efficacy.
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Keywords: Adaptive Immunity, Adolescent, Adult, Antibodies, Viral/blood, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cytokines, Double-Blind Method, Female, Humans, Immunity, Mucosal, Immunoglobulin A/immunology, Influenza Vaccines/immunology, Influenza, Human/immunology, Lung/immunology, Male, Middle Aged, Nasopharynx/immunology, Orthomyxoviridae Infections/prevention & control, Pneumococcal Vaccines/immunology, Streptococcus pneumoniae, Vaccines, Attenuated/immunology, Young Adult, General Medicine, Clinical Trial, Research Support, Non-U.S. Gov't, Randomized Controlled Trial, Journal Article
ISSN: 2379-3708
Publisher: The American Society for Clinical Investigation
Note: Funding Information: The authors would like to thank the Data Monitoring and Safety Committee (Brian Faragher, Christopher Green, and Robert C. Read). We would also like to thank all the volunteers for their participation in the clinical trial and the Clinical Research Network in the North West Coast for their continued support, as well as the clinical team members for helping to collect the samples and Dessi Loukov for helpful review of the manuscript. This work was funded by grants from the Bill & Melinda Gates Foundation (OPP1117728) (to DMF) and Medical Research Council grants (MR/M011569/1) (to SBG). Flow cytometric acquisition was performed on a BD LSRII funded by Wellcome Trust Multi-User Equipment grant (104936/Z/14/Z). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: © 2021, Carniel et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.
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