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

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

San Diego

Congreso; 11th Vaccine Congress; 2017

Vaccine Elsevier

Conventional influenza vaccines aim at the induction of virus-neutralizingantibodies. This requires vaccine efficiencies that are not always reported forvaccinees. We investigated to what extent infection-permissive immunity, incontrast to virus-neutralizing immunity, provided by a classical influenzavirus vaccine (trivalent inactivated virus vaccine, TIV) could modulate diseaseand virus-induced host immune responses after homologous H1N1 infection. Methods: Balb/c mice were vaccinated intramuscularly once or twice with trivalentinactivated virus vaccine (TIV, equivalent of 3ug HA). Three weeks afterimmunization, mice were challenged sublethally with homologous H1N1 virus. Lungvirus titers were quantified at different days post infection. At 7dpi, we alsoquantified alveolar macrophages in vaccinated and control-vaccinated animals.For rechallenge experiments, mice were infected with H1N1 or H3N2 virus fourweeks after primary challenge. Cross-reactive CD8+ T cell responses directedagainst the influenza nucleoprotein were measured at different days post primaryand secondary infection. The effect of vaccination on DbNP366-specific CD8+ Tcell, as well as B cell responses in lung tissue was investigated post-secondaryinfection.Results:More than one TIV vaccination is needed to induce a serum HI titer andfully prevent onset of morbidity upon virus infection. However, single TIVadministration correlated with lower viral lung titers and faster recoveryafter homologous challenge. Contrary to negative control mice, completeabolishment of alveolar macrophages was prevented in TIV-vaccinated animals.TIV vaccination also affects levels of pulmonary B and T cell levels afterinfection. In the absence of detectable virus neutralization antibodies,induction of  cross-reactive NP-specific CD8+ T cells by virus infectionis still observed in TIV vaccinated animals which correlates with protectionagainst subsequent challenge with hetero(sub)typic H1N1 and H3N2 virus.Discussion: These results suggest that suboptimal vaccinationwith conventional influenza vaccines may still positively modulate diseaseoutcome, allowing induction of hetero(sub)typic immunity by virus infection