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PLoS One. 2018 Jan 11;13(1):e0190868. doi: 10.1371/journal.pone.0190868. eCollection 2018.

Intranasal vaccination with M2e5x virus-like particles induces humoral and cellular immune responses conferring cross-protection against heterosubtypic influenza viruses.

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Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia, United States of America.
Animal and Plant Quarantine Agency, Gimcheon, Gyeongsangbukdo, Republic of Korea.


Current influenza vaccines do not provide broad cross-protection. Here, we report that intranasal vaccination with virus-like particles containing the highly conserved multiple ectodomains of matrix protein 2 (M2e5x VLP) of influenza virus induces broad cross-protection by M2-specific humoral and cellular immune responses. M2e5x VLP intranasal vaccination prevented severe weight loss, attenuated inflammatory cytokines and cellular infiltrates, and lowered viral loads, and induced germinal center phenotypic B and plasma cells. In addition, depletion studies demonstrate the protective roles of CD4 and CD8 T cells induced by M2e5x VLP intranasal vaccination. Thus, this study provides evidence that mucosal delivery of M2e5x VLP vaccine provides cross-protection by inducing humoral and cellular immune responses.

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