Universal protection against influenza viruses by multi-subtype neuraminidase and M2 ectodomain virus-like particle.

Annual influenza vaccination is recommended to update the variable hemagglutinin antigens. 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), and M2e antibodies as well as interferon-gamma secreting T cell responses. Mice vaccinated with m-cNA-M2e VLP were protected against influenza A (H1N1, H5N1, H3N2, H9N2, H7N9) and influenza B (Yamagata and Victoria lineage) viruses containing substantial antigenic variations. Protective immune contributors include cellular and humoral immunity as well as antibody-dependent cellular cytotoxicity. 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 A and B viruses potentially in both young and aged populations by inducing multi-NA subtype and M2e immunity with a single VLP entity. Author summary: Current influenza vaccine is based on strain-specific neutralizing immunity to hemagglutinin (HA). The effectiveness of seasonal vaccine is unpredictable and could be below 20% due to continuous changes in HA. Thereby, influenza remains a high risk to human health worldwide. Here, we developed a universal influenza vaccine candidate displaying consensus multi-neuraminidase (NA) subtypes and M2 ectodomain (M2e) tandem repeat. A single vaccine entity inducing immunity to conserved M2e and multi subtype NA proteins was found to be effective in conferring broad cross protection against antigenically diverse influenza A and B viruses in young and aged mice. This study provides impactful insight into developing a universal influenza vaccine in young and aged populations. [ABSTRACT FROM AUTHOR]