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

CHOI A; IBAÑEZ LI; SPITAELS J; KRAMMER F; GARCÍA-SASTRE A; SCHOTSAERT, M.

New York

Congreso; 11th Annual CEIRS Network Meeting; 2018

CEIRS

Conventional influenza vaccines aim at the inductionof virus-neutralizing antibodies. However, influenza vaccine efficiencies areoften low. We investigated to what extent infection-permissive immunityprovided by a seasonal trivalent inactivated influenza virus vaccine (TIV)could modulate disease and virus-induced host responses after infection withH1N1 virus that matches the vaccine. More than one TIV vaccination is needed toinduce high serum HI titers efficiently in mice. However, single TIVadministration already protected from vast morbidity after H1N1 infection, evenin the presence of lung virus titers. Contrary to negative control mice,complete loss of alveolar macrophages, as well as pulmonary infiltration ofLy6c+ monocytes and release of pro-inflammatory cytokines and chemokines wasprevented in TIV-vaccinated animals. We also show that induction of germinalcenter B cells and tissue-resident CD8+ T cells in the lung after H1N1infection correlates with protection during reinfection with a lethal dose of aH3N2 virus but is negatively impacted by TIV vaccination. On the other hand,sera from TIV vaccinated animals that received H1N1 infection outperform serafrom animals that either received H1N1 infection or a TIV vaccine, but not both,in an in vivo microneutralisationassay with H3N2 virus. Cross-protective sera were not able to inhibit red bloodcell hemagglutination by H3N2 virus. These results suggest that, contrary toH1N1 virus-exposed non vaccinated animals, TIV vaccinated animals that wereexposed to H1N1 virus rely more on cross-reactive serum antibodies than oncellular immunity for protection during lethal H3N2 reinfection. Finally, weshow that innate immune activation through intranasal administration of Sendaivirus defective interfering RNA, an antagonist of the innate RNA sensor RIG-I,can synergize with H1N1 virus- and/or TIV vaccine-induced pre-existing immunityto enhance protection during lethal H3N2 infection.