Claudia Arevalo and colleagues have developed a mRNA lipid nanoparticle vaccine that contains antigens from all 20 known subtypes of influenza A and B viruses, a strategy that may 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 against disease symptoms and death after infection with both antigenically matched and mismatched strains of influenza. Even with increased global surveillance, it is difficult to predict which flu strain will cause the next flu pandemic, making a universal vaccine important.
The approach by Arevalo et al. differs from previous attempts to craft a universal flu vaccine by including antigens specific to each subtype, rather than just a smaller set of antigens shared among subtypes. Following on 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 mostly stable four months after vaccination in the mice. 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 regarding the regulation and approval pathway of such a vaccine that targets viruses of pandemic potential but are not currently in human circulation.”
Arevalo, C.P., et al. (2022) A multivalent nucleoside-modified mRNA vaccine against all known influenza virus subtypes. Science. doi.org/10.1126/science.abm0271.