Improved influenza vaccine responses after expression of multiple viral glycoproteins from a single mRNA

Rebecca A. Leonard, Kaitlyn N. Burke, Rachel L. Spreng, Andrew N. Macintyre, Ying Tam, Mohamad-Gabriel Alameh, Drew Weissman and Nicholas S. Heaton ()
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Rebecca A. Leonard: Duke University School of Medicine Durham
Kaitlyn N. Burke: Duke University School of Medicine Durham
Rachel L. Spreng: Duke University School of Medicine
Andrew N. Macintyre: Duke University School of Medicine
Ying Tam: Acuitas Theraputics
Mohamad-Gabriel Alameh: Perelman School of Medicine
Drew Weissman: Perelman School of Medicine
Nicholas S. Heaton: Duke University School of Medicine Durham

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-52940-z

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