1. Improved influenza vaccine responses after expression of multiple viral glycoproteins from a single mRNA.
- Author
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Leonard RA, Burke KN, Spreng RL, Macintyre AN, Tam Y, Alameh MG, Weissman D, and Heaton NS
- Subjects
- Animals, Female, Mice, Male, Hemagglutinin Glycoproteins, Influenza Virus immunology, Hemagglutinin Glycoproteins, Influenza Virus genetics, Humans, Mice, Inbred BALB C, Influenza B virus immunology, Influenza B virus genetics, Influenza A virus immunology, Influenza A virus genetics, Influenza, Human prevention & control, Influenza, Human immunology, Influenza, Human virology, Glycoproteins immunology, Glycoproteins genetics, Viral Proteins immunology, Viral Proteins genetics, Antigens, Viral immunology, Antigens, Viral genetics, Vaccination methods, Ferrets, Influenza Vaccines immunology, Influenza Vaccines administration & dosage, Neuraminidase immunology, Neuraminidase genetics, Antibodies, Viral immunology, Orthomyxoviridae Infections prevention & control, Orthomyxoviridae Infections immunology, Orthomyxoviridae Infections virology, RNA, Messenger genetics, RNA, Messenger metabolism, RNA, Messenger immunology
- Abstract
Influenza viruses cause substantial morbidity and mortality every year despite seasonal vaccination. mRNA-based vaccines have the potential to elicit more protective immune responses, but for maximal breadth and durability, it is desirable to deliver both the viral hemagglutinin and neuraminidase glycoproteins. Delivering multiple antigens individually, however, complicates manufacturing and increases cost, thus it would be beneficial to express both proteins from a single mRNA. Here, we develop an mRNA genetic configuration that allows the simultaneous expression of unmodified, full-length NA and HA proteins from a single open reading frame. We apply this approach to glycoproteins from contemporary influenza A and B viruses and, after vaccination, observe high levels of functional antibodies and protection from disease in female mouse and male ferret challenge models. This approach may further efforts to utilize mRNA technology to improve seasonal vaccine efficacy by efficiently delivering multiple viral antigens simultaneously and in their native state., (© 2024. The Author(s).)
- Published
- 2024
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