TY - JOUR
T1 - Non-sterilizing, Infection-Permissive Vaccination With Inactivated Influenza Virus Vaccine Reshapes Subsequent Virus Infection-Induced Protective Heterosubtypic Immunity From Cellular to Humoral Cross-Reactive Immune Responses
AU - Choi, Angela
AU - Ibañez, Lorena I.
AU - Strohmeier, Shirin
AU - Krammer, Florian
AU - García-Sastre, Adolfo
AU - Schotsaert, Michael
N1 - Funding Information:
We want to acknowledge the Dean's Flow Cytometry Center of Research Excellence at the Icahn School of Medicine at Mount Sinai for assistance with flow cytometry. We also want to acknowledge excellent technical assistance by Richard Cadagan. Funding. These studies were partially funded by NIAID grant P01AI097092 to AG-S, by CRIP (Center for Research on Influenza Pathogenesis), an NIAID funded Center of Excellence for Influenza Research and Surveillance (CEIRS, contract # HHSN272201400008C) and by SEM CIVIC, an NIAID funded Sinai Emory Multi-Institutional Collaborative Influenza Vaccine Innovation Center (contract # 75N93019C00051) to AG-S and FK.
Publisher Copyright:
© Copyright © 2020 Choi, Ibañez, Strohmeier, Krammer, García-Sastre and Schotsaert.
PY - 2020/6/9
Y1 - 2020/6/9
N2 - Conventional influenza vaccines aim at the induction of virus-neutralizing antibodies that provide with sterilizing immunity. However, influenza vaccination often confers protection from disease but not from infection. The impact of infection-permissive vaccination on the immune response elicited by subsequent influenza virus infection is not well-understood. Here, we investigated to what extent infection-permissive immunity, in contrast to virus-neutralizing immunity, provided by a trivalent inactivated virus vaccine (TIV) modulates disease and virus-induced host immune responses after sublethal vaccine-matching H1N1 infection in a mouse model. More than one TIV vaccination was needed to induce a serum HI titer and provide sterilizing immunity upon homologous virus infection. However, single TIV administration provided infection-permissive immunity, characterized by lower viral lung titers and faster recovery. Despite the presence of replicating virus, single TIV vaccination prevented induction of pro-inflammatory cyto- and chemokines, alveolar macrophage depletion as well as the establishment of lung-resident B and T cells after infection. To investigate virus infection-induced cross-protective heterosubtypic immune responses in vaccinated and unvaccinated animals, mice were re-infected with a lethal dose of H3N2 virus 4 weeks after H1N1 infection. Single TIV vaccination did not prevent H1N1 virus infection-induced heterosubtypic cross-protection, but shifted the mechanism of cross-protection from the cellular to the humoral branch of the immune system. These results suggest that suboptimal vaccination with conventional influenza vaccines may still positively modulate disease outcome after influenza virus infection, while promoting humoral heterosubtypic immunity after virus infection.
AB - Conventional influenza vaccines aim at the induction of virus-neutralizing antibodies that provide with sterilizing immunity. However, influenza vaccination often confers protection from disease but not from infection. The impact of infection-permissive vaccination on the immune response elicited by subsequent influenza virus infection is not well-understood. Here, we investigated to what extent infection-permissive immunity, in contrast to virus-neutralizing immunity, provided by a trivalent inactivated virus vaccine (TIV) modulates disease and virus-induced host immune responses after sublethal vaccine-matching H1N1 infection in a mouse model. More than one TIV vaccination was needed to induce a serum HI titer and provide sterilizing immunity upon homologous virus infection. However, single TIV administration provided infection-permissive immunity, characterized by lower viral lung titers and faster recovery. Despite the presence of replicating virus, single TIV vaccination prevented induction of pro-inflammatory cyto- and chemokines, alveolar macrophage depletion as well as the establishment of lung-resident B and T cells after infection. To investigate virus infection-induced cross-protective heterosubtypic immune responses in vaccinated and unvaccinated animals, mice were re-infected with a lethal dose of H3N2 virus 4 weeks after H1N1 infection. Single TIV vaccination did not prevent H1N1 virus infection-induced heterosubtypic cross-protection, but shifted the mechanism of cross-protection from the cellular to the humoral branch of the immune system. These results suggest that suboptimal vaccination with conventional influenza vaccines may still positively modulate disease outcome after influenza virus infection, while promoting humoral heterosubtypic immunity after virus infection.
KW - TIV
KW - alveolar macrophage
KW - germinal center B cell
KW - heterosubtypic immunity
KW - influenza
KW - pre-existing immunity
KW - tissue-resident memory T cell
UR - http://www.scopus.com/inward/record.url?scp=85087020763&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2020.01166
DO - 10.3389/fimmu.2020.01166
M3 - Article
C2 - 32582220
AN - SCOPUS:85087020763
SN - 1664-3224
VL - 11
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 1166
ER -