Vaccine-induced pre-existing immunity modulates both innate and adaptive immune components following influenza virus infection

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

Paris

Congreso; Vaccine Congress 2017; 2017

International Society of Vaccines (ISV)

In this work we investigated how pre-existing immunityprovided by influenza vaccination can affect the outcome of sequentialinfections with influenza viruses of different subtypes. We took advantage ofdifferent efficiencies of intramuscular vaccination with trivalent inactivatedvirus vaccine (TIV). TIV vaccination in the quadriceps muscles of Balb/c miceresults in low HA-specific humoral antibody levels as assessed by ELISA andinhibition of hemagglutination. It can also modulate disease followingsublethal infection, which correlates with protection of alveolar macrophagesand control of virus replication. Host immune responses like cross-reactive Tcell responses and pulmonary infiltration of myeloid cells following virusinfection are still allowed and correlate with protection against reinfectionwith a heterotypic virus. Vaccination with the same TIV in the hamstringmuscles is more efficient in induction of HA-specific humoral immunity, whichcorrelates with better but not full protection during subsequent infection. TIVvaccination allowed but affected establishment of germinal center formation inboth lung and draining lymph nodes and interfered with establishment of lungresident mucosal CD8+ T cells after vaccine-matched H1N1 infection. Thisrestriction of cellular immune responses at the lung mucosal sites resulted inreduced protection during subsequent infection with a vaccine-mismatched H3N2influenza infection. Vaccine-induced humoral immune responses are boosted byH1N1 infection and provide protection during reinfection with H3N2 virus in theabsence of overt detectable lung resident CD8+ T cells and reduced germinalcenter B cells. Vaccine-induced influenza-specific CD8+ T cells in theperiphery are recruited to lungs immediately after infection, but fail to turninto long term mucosal tissue resident T cells as observed in non-vaccinatedanimals. Finally we show that an innate stimulus delivered at the mucosalsurface can delay onset of morbidity during reinfection but relies onpre-existing immunity in order to be protective.