6th International Influenza Meeting

Infection-induced heterosubtypic immunity against influenza virus correlates better with humoral than cellular immunity in TIV-vaccinated mice and benefits from innate immune activation.

Not scheduled

15m

Oral presentation

Description

Conventional influenza vaccines aim at the induction of virus-neutralizing antibodies. However, influenza vaccine efficiencies are often low. We investigated to what extent infection-permissive immunity provided by a seasonal trivalent inactivated influenza virus vaccine (TIV) could modulate disease and virus-induced host responses after infection with H1N1 virus that matches the vaccine. More than one TIV vaccination is needed to induce high serum HI titers efficiently in mice. However, single TIV administration already protected from vast morbidity after H1N1 infection, even in the presence of lung virus titers. Contrary to negative control mice, complete loss of alveolar macrophages, as well as pulmonary infiltration of Ly6c+ monocytes and release of pro-inflammatory cytokines and chemokines was prevented in TIV-vaccinated animals. We also show that induction of germinal center B cells and tissue-resident CD8+ T cells in the lung after H1N1 infection correlates with protection during reinfection with a lethal dose of a H3N2 virus but is negatively impacted by TIV vaccination. On the other hand, sera from TIV vaccinated animals that received H1N1 infection outperform sera from animals that either received H1N1 infection or a TIV vaccine, but not both, in an in vivo microneutralisation assay with H3N2 virus. Cross-protective sera were not able to inhibit red blood cell hemagglutination by H3N2 virus. These results suggest that, contrary to H1N1 virus-exposed non vaccinated animals, TIV vaccinated animals that were exposed to H1N1 virus rely more on cross-reactive serum antibodies than on cellular immunity for protection during lethal H3N2 reinfection. Finally, we show that innate immune activation through intranasal administration of Sendai virus defective interfering RNA, an antagonist of the innate RNA sensor RIG-I, can synergize with H1N1 virus- and/or TIV vaccine-induced pre-existing immunity to enhance protection during lethal H3N2 infection.