Synthetic Neuraminidase Vaccine Induces Cross-Species and Multi-Subtype Protection

The genetic diversity of influenza A virus is a major obstacle that makes vaccine effectiveness variable and unpredictable. <b>Objectives</b>: Current vaccines induce strain-specific immunity that oftentimes fail to protect against divergent strains. Our previous research explored synthe...

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Main Authors: Matthew J. Pekarek, Erika M. Petro-Turnquist, Nicholas E. Jeanjaquet, Kristine V. Hoagstrom, Enzo LaMontia-Hankin, Leigh Jahnke, Adthakorn Madapong, Eric A. Weaver
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Vaccines
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Online Access:https://www.mdpi.com/2076-393X/13/4/364
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Summary:The genetic diversity of influenza A virus is a major obstacle that makes vaccine effectiveness variable and unpredictable. <b>Objectives</b>: Current vaccines induce strain-specific immunity that oftentimes fail to protect against divergent strains. Our previous research explored synthetic centralized consensus (CC) vaccines to minimize immunogen-strain divergence and focused on the viral glycoprotein hemagglutinin. <b>Methods</b>: Recently, emerging evidence of neuraminidase (NA)-mediated immunity has shifted vaccine strategies, prompting our development of a CC NA type 1 (N1CC) vaccine based on ancestral N1 sequences and delivered using a human adenovirus type 5 vector <b>Results</b>: The N1CC vaccine elicited antibody responses with NA inhibition activity and induced NA-specific T-cell responses. In lethal influenza challenge models, N1CC fully protected mice from death against human, swine, and avian influenza H1N1 and H5N1 strains. <b>Conclusions</b>: These findings support NA as a protective immunogen and demonstrate the power and efficacy of a centralized consensus NA design.
ISSN:2076-393X