An investigational messenger RNA (mRNA) vaccine encoding hemagglutinin antigens from all 20 known influenza A virus subtypes and B virus lineages protected mice and ferrets from a wide range of matched and mismatched virus strains in a recent study.
The vaccine was developed on the same nucleic acid–based platforms behind the COVID-19 mRNA vaccines. The mRNA platforms make it possible to incorporate many more antigens than protein-based multivalent vaccine technologies can. This could make the new approach effective against a broader range of potential pandemic influenza strains circulating in animal reservoirs, the study’s authors wrote in Science.
To ensure that each encoded antigen generated an immune response to its target strain, the authors first tested the antigens individually in 20 separate mRNA vaccines. Each individual vaccine induced antibodies in mice that were reactive against the target strains, as well as antibodies that were cross-reactive to some degree against other strains.
Next, mice were injected with the multivalent mRNA vaccine that encoded all 20 strain-specific antigens. The rodents produced antibodies to all the strains for at least 4 months. The multivalent vaccine also boosted existing H1N1 antibodies in mice previously infected with that influenza strain, while inducing new antibodies against the other 19 strains.
When challenged with a variety of matched and mismatched influenza viruses 28 days after vaccination, mice that received the multivalent vaccine lost less weight, showed fewer clinical symptoms, and were less likely to die than mice that received a single-strain vaccine that did not target the challenge virus. Mice injected with a 19-strain vaccine that lacked the H1N1 antigen were highly susceptible to 1 H1N1 virus sample but survived infection with virus from another sample. The multivalent vaccine also protected ferrets against an antigenically mismatched avian H1N1 virus, according to the report.
According to the authors, the results suggest that the multivalent mRNA flu vaccine protects against matched antigens by inducing neutralizing antibodies, and against mismatched antigens with some other mechanism, such as antibody–mediated cell toxicity.
“This provides a pathway to a universal influenza vaccine,” wrote the authors of a commentary accompanying the study.
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