Claudia Arevalo

"A multivalent nucleoside-modified mRNA vaccine that generates antibodies against 20 antigenically distinct influenza virus subtypes"

Claudia P. Arevalo, Marcus J. Bolton, Tyler Garretson, Kaela Parkhouse, Norbi Pardi, Scott E. Hensley

There are 18 different subtypes of influenza A virus and 2 lineages of influenza B virus. The H1N1 and H3N2 influenza A subtypes and 2 lineages of influenza B virus currently circulate in humans, and seasonal quadrivalent vaccines provide protection against these 4 types of viruses. The other 16 influenza A virus subtypes do not currently circulate in humans, but they have varying degrees of pandemic potential. It is important to develop new vaccines that elicit antibodies that can protect against all known influenza virus subtypes. Here, we developed a lipid nanoparticle-encapsulated, nucleoside-modified mRNA (mRNA-LNP) vaccine encoding 20 distinct hemagglutinin (HA) proteins from each of the influenza subtypes. Mice vaccinated with this vaccine produced antibodies that recognized all antigens encoded by the vaccine. The vaccine elicited antibodies that targeted epitopes in the HA head and stalk domains. Vaccinated mice survived following infection with a heterologous viral strain that was not included in the vaccine. Current studies are being completed to characterize B cell responses in vaccinated mice and to quantify the ratio of cross-reactive versus strain-specific serum antibodies after vaccination. Our studies suggest that mRNA-based vaccines may be useful for eliciting antibody responses against multiple antigens simultaneously, and might be a way to provide universal immunity against diverse influenza virus subtypes.