Abstract
Abstract Annual influenza vaccination is recommended to update the variable hemagglutinin antigens. [add more scientific justification for why NA + M2e immunity will be important?] Here, we first designed a virus-like particle (VLP) displaying consensus multi-neuraminidase (NA) subtypes (cN1, cN2, B cNA) and M2 ectodomain (M2e) tandem repeat (m-cNA-M2e VLP). Vaccination of mice with m-cNA-M2e VLP induced broad NA inhibition (NAI), M2e antibodies as well as interferon-gamma secreting T cell responses. Mice vaccinated with m-cNA-M2e VLP were protected against multi strains of different subtypes (H1N1, H5N1, H3N2, H9N2, H7N9) influenza A viruses containing substantial antigenic variations. From the T cell depletion and passive transfer experiments, we found that immunization of mice with m-cNA-M2e VLP induced cellular and humoral immune components contributing to broader cross protection. Also, surrogate effector assay indicated antibody-dependent cellular cytotoxicity as an additional protective immune contributor. Furthermore, comparable cross protection by m-cNA-M2e VLP vaccination was induced in aged mice. This study supports a novel strategy of developing a universal vaccine against influenza viruses potentially in both young and aged populations by inducing multi-NA subtype and M2e immunity with a single VLP entity. Supported by grants from NIH/NIAID (AI093772, AI154656, AI147042)
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