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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

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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 5

LAIV vaccination increases levels of antibody against influenza in serum and nasal wash, with impaired nasal production caused by S. pneumoniae colonization.

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LAIV vaccination increases levels of antibody against influenza in serum...
(A) IgG titers to influenza, measured by ELISA, in serum of LAIV (n = 36) and TIV (n = 36) vaccinated subjects at baseline (8 days prevaccination) and D24 (24 days after vaccination). (B) FC (D24/baseline) of paired IgG titers to influenza in serum following TIV or LAIV vaccination. TIV/Spn– (n = 20), TIV/Spn+ (n = 16), LAIV/Spn– (n = 18), and LAIV/Spn+ (n = 18). (C) IgA and (D) IgG titers against influenza measured by ELISA in nasal wash of TIV (n = 40) and LAIV (n = 80) vaccinated subjects at baseline (8 days before vaccination) and D24 (24 days after vaccination). (E) FC (D24/baseline) of paired IgA and (F) IgG titers against influenza in nasal wash following vaccination with TIV/Spn– (n = 21), TIV/Spn+ (n = 19), LAIV/Spn– (n = 37), and LAIV/Spn+ (n = 43). Medians with IQR are shown. *P < 0.05, ***P < 0.001, ****P < 0.0001 by Wilcoxon’s test for comparisons within the same group and by Mann-Whitney U test for comparisons between groups.

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