Multivalent next generation influenza virus vaccines protect against seasonal and pre-pandemic viruses

Abstract

Each year, new influenza virus vaccine formulations are generated to keep up with continuously circulating and mutating viral variants. A next-generation influenza virus vaccine would provide long-lasting, broadly-reactive immune protection against current and future influenza virus strains for both seasonal and pre-pandemic viruses. Next generation immunogens were designed using computationally optimized broadly reactive antigen (COBRA) methodology to protect against a broad range of strains over numerous seasons. Novel HA and NA amino acid sequences were derived from multilayered consensus sequence alignment for multiple subtypes of influenza. This multivalent formulation was hypothesized to elicit broadly protective immune responses against both seasonal and pre-pandemic influenza viruses. Mice were vaccinated with multivalent mixtures of HA and NA (H1, H2, H3, H5, H7, N1, N2) proteins. Multivalent COBRA vaccinations elicited antibodies that recognized a broad panel of strains and vaccinated mice were protected against viruses representing multiple subtypes. This is a promising candidate for a universal influenza vaccine that elicits protective immune responses against seasonal and pre-pandemic strains over multiple seasons.

A Single Dose of Inactivated Influenza Virus Vaccine Expressing COBRA Hemagglutinin Elicits Broadly-Reactive and Long-Lasting Protection

“…In this study, ferrets were used to further assess these vaccine candidates because the mouse-influenza model has some limitations. Typically, mice are resistant to infection by most human influenza strains (28), therefore, mouse-adapted strains are often required for viral challenge (29). Moreover, mice do not show similar clinical symptoms as humans and they poorly transmit viruses between mice (30).…”