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Use of equine H3N8 hemagglutinin as a broadly protective influenza vaccine immunogen.
Abstract: Development of an efficacious universal influenza vaccines remains a long-sought goal. Current vaccines have shortfalls such as mid/low efficacy and needing yearly strain revisions to account for viral drift/shift. Horses undergo bi-annual vaccines for the H3N8 equine influenza virus, and surveillance of sera from vaccinees demonstrated very broad reactivity and neutralization to many influenza strains. Subsequently, vaccinating mice using the equine A/Kentucky/1/1991 strain or recombinant hemagglutinin (HA) induced similar broadly reactive and neutralizing antibodies to seasonal and high pathogenicity avian influenza strains. Challenge of vaccinated mice protected from lethal virus challenges across H1N1 and H3N2 strains. This protection correlated with neutralizing antibodies to the HA head, esterase, and stem regions. Vaccinated ferrets were also protected after challenge with H1N1 influenza A/07/2009 virus using whole viral or HA. These data suggest that equine H3N8 induces broad protection against multiple influenzas using a unique antigen that diverges from other universal vaccine approaches.
© 2024. The Author(s).
Publication Date: 2024-12-19 PubMed ID: 39702334PubMed Central: PMC11659547DOI: 10.1038/s41541-024-01037-1Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
Overview
- This research investigated the potential of using the equine influenza virus H3N8 hemagglutinin (HA) protein as a broadly protective vaccine against multiple influenza strains.
- Vaccines based on the equine H3N8 HA showed broad immune responses and protection across diverse influenza subtypes in animal models, suggesting a promising approach for universal flu vaccines.
Background and Motivation
- Influenza vaccines currently in use have limitations including variable efficacy and the need for yearly updates due to viral mutation (antigenic drift and shift).
- A universal influenza vaccine that offers broad protection against many strains and subtypes would greatly improve disease control but remains elusive.
- Horses routinely receive bi-annual vaccines for equine influenza, specifically the H3N8 strain, providing a readily available source of broadly reactive immunogens.
Research Aims
- To assess whether the equine influenza virus H3N8 HA protein can induce broadly neutralizing antibodies effective against multiple influenza A strains.
- To evaluate the efficacy of vaccination with equine H3N8 whole virus or recombinant HA in animal models including mice and ferrets.
Experimental Approach
- Serum samples from vaccinated horses were examined to determine the antibody breadth and neutralization capacity against various influenza strains.
- Mice were vaccinated with either the full equine A/Kentucky/1/1991 virus or recombinant H3N8 HA protein.
- Post-vaccination, mice sera were tested for neutralizing antibody responses against seasonal human influenza strains and highly pathogenic avian influenza strains.
- Vaccinated mice were challenged with lethal doses of H1N1 and H3N2 viruses to test protection efficacy.
- Ferrets, an established influenza model closer to humans, were vaccinated and then challenged with H1N1 A/California/07/2009 to evaluate protective immunity using both whole virus and HA protein vaccinations.
Key Findings
- Horses vaccinated against equine H3N8 produced sera with broad neutralizing activity to many influenza subtypes beyond the equine strains.
- Mice vaccinated with equine H3N8 induced broadly reactive neutralizing antibodies that targeted multiple functional regions of HA: the head, esterase, and stem domains.
- The vaccinated mice showed protection from lethal viral challenges with human seasonal influenza strains H1N1 and H3N2, indicating cross-subtype efficacy.
- Vaccinated ferrets also demonstrated protection following challenge with the pandemic H1N1 virus, confirming translational potential in a model more similar to humans.
- This broad protective effect contrasts with many current universal vaccine candidates focused primarily on the HA stem or other conserved motifs, suggesting the equine H3N8 HA is a unique immunogen.
Conclusions and Implications
- The equine H3N8 HA protein represents a promising immunogen for developing broadly protective or universal influenza vaccines.
- Its ability to induce neutralizing antibodies to multiple domains of the HA protein and provide cross-protection against diverse influenza strains offers advantages over existing vaccine approaches.
- Future studies could explore the mechanism of this broad immunity and evaluate the safety and efficacy in humans to move towards universal flu vaccine development.
- This research supports leveraging animal-adapted influenza strains as novel antigen sources for combating human influenza virus diversity.
Cite This Article
APA
Verhoeven D, Sponseller BA, Crowe JE, Bangaru S, Webby RJ, Lee BM.
(2024).
Use of equine H3N8 hemagglutinin as a broadly protective influenza vaccine immunogen.
NPJ Vaccines, 9(1), 247.
https://doi.org/10.1038/s41541-024-01037-1 Publication
Researcher Affiliations
- Department of Veterinary Microbiology and Preventive Medicine, Iowa State University, Ames, IA, USA. davidver@iastate.edu.
- Department of Veterinary Microbiology and Preventive Medicine, Iowa State University, Ames, IA, USA.
- Department of Veterinary Clinical Service, Iowa State University, Ames, IA, USA.
- Department of Pediatrics, Vanderbilt Vaccine Center, Nashville, TN, USA.
- Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN, USA.
- Department of Pediatrics, Vanderbilt Vaccine Center, Nashville, TN, USA.
- Department of Infectious Diseases, St. Jude's Children's, Memphis, TN, USA.
- Department of Chemistry, Coastal Carolina University, Conway, SC, USA.
Conflict of Interest Statement
Competing interests: The vaccine used in this study is based on a veterinary vaccine (FluAvert) manufactured by Merck Sharp & Dohme LLC. However, Merck was not involved in the planning or execution of this study. D.V. and B.S. have a patent granted for the use of A/equine/Kentucky/91 for use as a universal influenza vaccine and are developing it for use for our company Syntherna. J.E.C. has served as a consultant for Luna Labs USA, Merck Sharp & Dohme Corporation, Emergent Biosolutions, a former member of the Scientific Advisory Boards of Gigagen (Grifols), of Meissa Vaccines, and BTG International, is founder of IDBiologics and receives royalties from UpToDate. The laboratory of J.E.C. received unrelated sponsored research agreements from AstraZeneca, Takeda Vaccines, and IDBiologics during the conduct of the study.
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Citations
This article has been cited 2 times.- Wang L, Xie Q, Yu P, Zhang J, He C, Huang W, Wang Y, Zhao C. Research Progress of Universal Influenza Vaccine.. Vaccines (Basel) 2025 Aug 15;13(8).
- Siddoway AC, Van Zanten A, Verhoeven D, Wannemuehler MJ, Mallapragada SK, Narasimhan B. Equine influenza antigen-based particle vaccine protects mice against homologous and heterosubtypic viral challenges.. Acta Biomater 2025 Sep 1;203:578-590.
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