Claudia Arevalo and colleagues have developed an mRNA lipid nanoparticle vaccine containing antigens from all 20 known subtypes of influenza A and B viruses, a strategy that could serve as the basis for universal flu vaccines. Their vaccine produced high levels of cross-reactive and subtype-specific antibodies in mice and ferrets and could protect animals from disease symptoms and death after infection with both antigen-matched and unmatched flu strains. Even with more global scrutiny, it is difficult to predict which flu strain will cause the next flu pandemic, making a universal vaccine important. Arevalo et al.’s approach differs from previous attempts to create a universal flu vaccine by including antigens specific to each subtype, rather than just a smaller set of antigens shared among subtypes. Following the success of mRNA vaccines against SARS-CoV-2, the researchers prepared 20 different nanoparticle-encapsulated mRNAs, each encoding a different hemagglutinin antigen – a highly immunogenic flu protein that helps the virus enter cells. Antibody levels remained largely stable in the mice four months after vaccination. Multivalent protein vaccines produced using more traditional methods elicited fewer antibodies and were less protective compared to the multivalent mRNA vaccine in the animals. In a related Perspective, Alyson Kelvin and Darryl Falzarano discuss the results, noting that “questions remain about the regulation and approval pathway of such a vaccine targeting viruses with pandemic potential but not currently in human circulation .”
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