Infection-permissive immunity against influenza virus provided by vaccination prevents loss of alveolar macrophages and modulates virus-induced cross-reactive immune responses during subsequent influenza infections.

CHOI A; MORALES MINA JA; SPITAELS J; IBAÑEZ LI ; GARCÍA-SASTRE A; SCHOTSAERT M

Texas

Simposio; Keystone Symposia on Molecular and Cellular Biology; 2018

Keytone

Introduction:Conventional influenzavaccines aim at the induction of virus-neutralizing antibodies. This requiresvaccine efficiencies that are not always reported for vaccinees. Weinvestigated to what extent infection-permissive immunity, in contrast tovirus-neutralizing immunity, provided by a classical influenza virus vaccine(trivalent inactivated virus vaccine,TIV) could modulate disease andvirus-induced host immune memory responses after homologous H1N1 infection. Methods:Balb/c mice were vaccinated intramuscularlyonce or twice with trivalent inactivated virus vaccine (TIV, equivalent of 3ugHA). Three weeks after immunization, mice were challenged sublethally withhomologous H1N1 virus. Lung virus titers were quantified at different days postinfection as well as dynamics of different pulmonary myeloid cell populationswere monitored. For rechallenge experiments, mice were infected with H3N2 virusfour weeks after primary challenge. The effect of vaccination on tissueresident memory CD8+ T cells, as well as on germinal center B cell responses inlung tissue and lymph nodes and cross-reactive sera was investigated andcorrelated with protection during secondary heterosubtypic infection.Results: More than one TIVvaccination is needed to induce a serum HI titer and fully prevent onset ofmorbidity upon virus infection. However, single TIV administration correlatedwith lower viral lung titers and faster recovery after homologous challenge.Contrary to negative control mice, complete abolishment of alveolar macrophageswas prevented in TIV-vaccinated animals. TIV vaccination also affects levels ofpulmonary B and T cell levels after infection. In the absence of detectablevirus neutralization antibodies, TIV vaccination shifts virus-induced broadheterosubtypic cross-protection from the cellular to the humoral branch of theimmune system.Discussion:These results suggestthat suboptimal vaccination with conventional influenza vaccines may stillpositively modulate disease outcome, allowing but modulating induction ofheterosubtypic immunity by virus infection.