In May 2024, the University of Pennsylvania announced that its researchers have published research in Nature Communications that suggests potential in an experimental mRNA vaccine against avian influenza virus H5N1. The team believes that mRNA lipid nanoparticle (LNP) vaccines could be useful in the event of an influenza virus pandemic as they can be “rapidly” produced and “do not require the generation of egg-adapted vaccine seed stocks”. They therefore show that a monovalent mNRA-LNP vaccine that expresses 2.3.4.4b H5 is “immunogenic and protective in pre-clinical animal models”.
An increasing need
The authors state that highly pathogenic avian influenza (HPAI) H5 viruses of the A/goose/Guangdong/1996 (Gs/Gd) lineage “emerged in southeast Asia in 1996” and have “since spread geographically and diversified into several genetically distinct haemagglutinin (HA) clades”. Thanks to the long-distance migration of wild birds, these HPAI viruses have demonstrated “rapid transcontinental spread”. However, since 2020, Gs/GD lineage H5 viruses of clade 2.3.4.4b have “circulated at historically high levels” in both wild and domestic populations with “occasional human infections” and “increasing incidences” of spillover into mammals.
The study presents a monovalent mRNA-LNP encoding HA from a 2.3.4.4b virus, tested in mice and ferrets, to reveal that it is immunogenic and protective in these models. The team found that the vaccine “elicits robust antibody and CD8+ T cell responses in mice” and detected “high levels” of H5 antibodies 1 year after single vaccination. The vaccine also elicited neutralising antibodies and broadly binding HA stalk antibodies in both mice and ferrets. In challenge experiments the vaccinated ferrets cleared the virus “more rapidly” than unvaccinated controls, lost less weight, and displayed fewer clinical symptoms. All vaccinated animals survived, while the unvaccinated animals died after H5N1 challenge.
The researchers emphasise the importance of comparing the vaccine to other vaccine platforms. However, they highlight the “many potential benefits of mRNA-LNP based vaccines compared to inactivated vaccines” and reflect that the capacity to make mRNA-LNPs has “expanded widely” since the start of the COVID-19 pandemic.
“Notably, mRNA-LNP vaccines can be rapidly produced without first isolating and adapting viral strains that grow efficiently in fertilised chicken eggs or cell culture. It is now possible to start creating novel mRNA-LNP vaccines within hours of sequencing a new pandemic viral strain.”
More agility
Dr Scott Hensley, professor of Microbiology at the Perelman School of Medicine, worked with Dr Drew Weissman, Roberts Family professor in Vaccine Research and Director of Vaccine Research at Penn Medicine. Dr Hensley considered “previous influenza pandemics” such as the 2009 H1N1 pandemic, suggesting that “vaccines were difficult to manufacture and did not become available until after the initial pandemic waves subsided”.
“The mRNA technology allows us to be much more agile in developing vaccines; we can start creating an mRNA vaccine within hours of sequencing a new viral strain with pandemic potential.”
Dr Weissman commented that “before 2020, experts thought the influenza virus posed the greatest risk of causing a pandemic”. However, we had “limited options for creating a vaccine if that had happened”.
“COVID-19 showed us the power of mRNA-based vaccines as tools to protect humans from emerging viruses quickly, and we are better prepared now to respond to a variety of viruses with pandemic potential, including influenza.”
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