Influenza M2 virus-like particles confer a broader range of cross protection to the strain-specific pre-existing immunity

Immunity in humans with annual vaccination does not provide effective protection against antigenically distinct strains. As an approach to improve cross-protection in the presence of pre-existing strain-specific immunity, we investigated the efficacy of heterologous and heterosubtypic protection in previously vaccinated mice at earlier times after subsequent immunization with conserved-antigenic target influenza M2 ectodomain (M2e) virus-like particle vaccine (M2e5 x VLP). Immunization of mice with HI NI split vaccine induced virus specific antibodies to homologous influenza virus but did not provide heterosubtypic hemagglutination inhibiting antibody responses and cross-protection. However, subsequent M2e5 x VLP immunization induced an M2e specific antibody response as well as interferon-gamma (IFN-gamma) producing cells in systemic and mucosal sites. Upon lethal challenge with H3N2 or H5N1 subtype influenza viruses, subsequently immunized mice with M2e5 x VU' were well protected against heterosubtypic influenza viruses. These results provide evidence that non-seasonal immunization with M2e5 x VLP, an experimental candidate for universal vaccine, is a promising approach for broadening the cross-protection even in the presence of strain-specific immunity. (C) 2014 Elsevier Ltd. All rights reserved.