Bivalent vaccination with NA1 and NA2 neuraminidase virus-like particles is protective against challenge with H1N1 and H3N2 influenza A viruses in a murine model

• Type of Material: Article
• Authors: Zach Menne, Emory University; Vasilis C Pliasas, Emory-UGA Center; Richard Compans, Emory University; Sheniqua Glover, Auburn University; Constantinos S Kyriakis, Emory-UGA Center; Ioanna Skountzou, Emory University
• Language: English
• Date: 2021-08-07
• Publisher: ACADEMIC PRESS INC ELSEVIER SCIENCE
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2021 Elsevier Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.virol.2021.08.001
• Title of Journal or Parent Work: VIROLOGY
• Volume: 562
• Start Page: 197
• End Page: 208
• Grant/Funding Information: This work was supported by the National Institutes of Health (1R01 AI110680–04) and BAA-NIAID-DMID-NIH (HHSN272201400004C).
• Keywords: SUPPLEMENTATION; Science & Technology; Neuraminidase (NA); N1; IMMUNIZATION; Virus-like particle (VLP); UNITED-STATES; ANTIBODY-RESPONSES; HEMAGGLUTININ; INFECTION; Influenza virus vaccine; Virology; SEASONAL INFLUENZA; Life Sciences & Biomedicine; VIRAL NEURAMINIDASE; Influenza virus

Abstract

Neuraminidase (NA) is the second most abundant glycoprotein on the surface of influenza A viruses (IAV). Neuraminidase type 1 (NA1) based virus-like particles (VLPs) have previously been shown to protect against challenge with H1N1 and H3N2 IAV. In this study, we produced neuraminidase type 2 (NA2) VLPs derived from the sequence of the seasonal IAV A/Perth/16/2009. Intramuscular vaccination of mice with NA2 VLPs induced high anti-NA serum IgG levels capable of inhibiting NA activity. NA2 VLP vaccination protected against mortality in a lethal A/Hong Kong/1/1968 (H3N2) virus challenge model, but not against lethal challenge with A/California/04/2009 (H1N1) virus. However, bivalent vaccination with NA1 and NA2 VLPs demonstrated no antigenic competition in anti-NA IgG responses and protected against lethal challenge with H1N1 and H3N2 viruses. Here we demonstrate that vaccination with NA VLPs is protective against influenza challenge and supports focusing on anti-NA responses in the development of future vaccination strategies.