M2e-based universal vaccine protects against Influenza A virus challenge and enhances heterosubtypic immunity during subsequent infections

MICHAEL SCHOTSAERT; TINE YSENBAERT; KATRIJN NEYT; LORENA ITATI IBAÑEZ; PIETER BOGAERT; BART LAMBRECHT; WALTER FIERS; XAVIER SAELENS

Muenster

Congreso; 3rd International Meeting Influenza FluResearchNet; 2012

FluResearchNet

However, due to sequence drift or shift, the virus escapes neutralizing immunity. Infectionwith a seasonal influenza virus correlates with protection against a subsequent infection witha heterotypic or heterologous virus, and this heterosubtypic immunity (HSI) very often isaccompanied by the activation of an antiviral T-cell response. Vaccination with licensedinactivated vaccines protects against a homologous infection but also impairs the inductionof cellular HSI. We demonstrated that Matrix 2 protein ectodomain (M2e)-based vaccines notonly protect against influenza A virus challenge but also allow the induction of cellular HSI inmice. Vaccination with a recombinant M2e-virus like particle (M2e-VLP) strongly reducedmorbidity and virus replication after a sublethal H3N2 infection and protects from mortalityfollowing a lethal challenge with pandemic H1N1 virus. Vaccination with whole inactivatedvirus (WIV) also protected mice against the homologous sublethal H3N2 infection but failedto protect against a subsequent lethal heterologous pandemic H1N1 challenge. Contrary tovaccination with WIV, vaccination with M2e-VLP followed by a sublethal infection with H3N2virus resulted in the induction of a qualitative and functional cellular immune response and inthe induction of iBALT. We hereby showed that, contrary to vaccination with WIV,vaccination with M2e-VLP universal vaccine does not only protect against challenge withviruses from different subtypes, but also permits the induction of cellular immunity inducedby encounters with influenza virus.