Pneumococcal colonization impairs mucosal immune responses to Live Attenuated Influenza Vaccine in adults

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.

Streptococcus pneumoniae colonisation associates with impaired adaptive immune responses against SARS-CoV-2

“…Mice exposed to S. pneumoniae prior to influenza A exhibited reduced antiviral serum IgG with diminished virus neutralisation activity a month after infection 15 . A randomised controlled human study of experimental pneumococcus/influenza coinfection reported diminished IgA responses to influenza antigens associated with pneumococcal carriage 16 , resembling findings of the current study. Non-pneumococcal specific cleavage of mucosal IgA1 by pneumococcal IgA1 proteases 17 could be a potential mechanism which contributes to antiviral IgA reductions identified in both studies.…”

“…Recent reports demonstrated that SARS-CoV-2 virus is effective at avoiding or delaying the triggering of early innate immune responses, such as type I interferons (IFNs) in vitro 29 and in humans 30,31 . On the other hand, it has been shown that S. pneumoniae infection stimulates IFN-I production and upregulates the expression of IFN-stimulated genes in both mice and human studies 16,32 . Therefore, it is possible that pneumococcal colonisation interferes with the replication cycle of the virus 33,34 and contributes to host antiviral defences by governing the production of IFNs 35,36 .…”

“…We have previously observed similar findings of reduced IgA responses to a respiratory viral infection in Spn colonised subjects. For that study, mucosal IgA responses to influenza antigens but not IgG and IgM was reduced when subjects were experimentally colonised with pneumococcal serotype 6B three days before administration of live attenuated influenza vaccine (LAIV) 16 . Those findings in addition to the ones presented here implied the potential involvement of the pneumococcus IgA1 protease-a cell-associated enzyme which cleaves human IgA1, but not IgA2 17 -in the reduction of anti-viral mucosal IgA.…”

“…Antibody levels to SARS-CoV-2 and influenza antigens were quantified, as previously described 16,55 with minor modifications. Briefly, Nunc 96-well plates were coated with 1μg/ml SARS-CoV-2 antigen or 0.2 μg/ml TIV and stored at 4 o C overnight for at least 16h.…”

“…Lastly, we sought to assess whether pneumococcal carriage associated reduction in mucosal IgA to respiratory viruses could be due the activity of pneumococcus IgA1 protease as well as whether the order of infection of virus and pneumococcus was important. Consequently, we evaluated samples from our previous studies of live attenuated influenza virus vaccine (LAIV) and pneumococcus co-infections 11,16,18 to assess that.…”