Pneumococcal colonization impairs mucosal immune responses to live attenuated influenza vaccine
Beatriz F. Carniel, Fernando Marcon, Jamie Rylance, Esther L. German, Seher Zaidi, Jesus Reiné, Edessa Negera, Elissavet Nikolaou, Sherin Pojar, Carla Solórzano, Andrea M. Collins, Victoria Connor, Debbie Bogaert, Stephen B. Gordon, Helder I. Nakaya, Daniela M. Ferreira, Simon P. Jochems, Elena Mitsi
Beatriz F. Carniel, Fernando Marcon, Jamie Rylance, Esther L. German, Seher Zaidi, Jesus Reiné, Edessa Negera, Elissavet Nikolaou, Sherin Pojar, Carla Solórzano, Andrea M. Collins, Victoria Connor, Debbie Bogaert, Stephen B. Gordon, Helder I. Nakaya, Daniela M. Ferreira, Simon P. Jochems, Elena Mitsi
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Research Article Immunology Vaccines

Pneumococcal colonization impairs mucosal immune responses to live attenuated influenza vaccine

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 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.

Authors

Beatriz F. Carniel, Fernando Marcon, Jamie Rylance, Esther L. German, Seher Zaidi, Jesus Reiné, Edessa Negera, Elissavet Nikolaou, Sherin Pojar, Carla Solórzano, Andrea M. Collins, Victoria Connor, Debbie Bogaert, Stephen B. Gordon, Helder I. Nakaya, Daniela M. Ferreira, Simon P. Jochems, Elena Mitsi

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Figure 2

LAIV increases frequency of influenza-specific TNF-α– and IFN-γ–producing CD4+ and TRM CD4+ T cells in the lung.

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LAIV increases frequency of influenza-specific TNF-α– and IFN-γ–producin...
Frequencies of cytokine-producing CD4+ and TRM CD4+ T cells were measured in human BAL samples by intracellular staining flow cytometry analysis with and without (mock) in vitro influenza antigen stimulation. Volunteers were divided by vaccine and colonization status in TIV/Spn– (n = 6), TIV/Spn+ (n = 8), LAIV/Spn– (n = 10), LAIV/Spn+ (n = 9), and unvaccinated (n = 8, 3 Spn– and 5 Spn+) groups. (A) Production of TNF-α by total CD4+ T cells in each group (paired unstimulated [mock] and stimulated condition [flu]). (B) Influenza-specific production of TNF-α by total CD4+ T cells (difference between influenza-stimulated and unstimulated) in each group. (C) Production of TNF-α by CD4+CD69+ T cells in each group. (D) Production of influenza-specific TNF-α by CD4+CD69+ T cells in each group. (E) Production of IFN- γ by total CD4+ T cells in each group. (F) Production of influenza-specific IFN-γ by CD4+ T cells in each group. (G) Production of IFN-γ by CD4+CD69+ T cells and (H) influenza-specific IFN-γ by CD4+CD69+ T cells in each group. Each individual dot represents a single volunteer, and the conditions from 1 individual are connected. Medians with IQR are depicted for influenza-specific responses (B, D, F, and H). *P < 0.05, **P < 0.01 by Wilcoxon’s test for comparisons within the same group and by Mann-Whitney U test for between-group comparisons.