A next-generation avian influenza (bird flu) vaccine that uses artificial intelligence (AI) to provide complete protection against highly transmissible viral variants in animal experiments has been developed. The universal vaccine is designed so that a single formulation can provide sustained immunity against a broad range of viral variants.

A research team led by Professor Jonathan Heeney of the Department of Veterinary Medicine at the University of Cambridge, together with DIOSynVax, a Cambridge spin-out company, has developed a new avian influenza vaccine that offers protection against a wide spectrum of variants rather than targeting a single specific variant. The team reported on 5 November (local time) in the international journal Cell Reports Medicine that the vaccine demonstrated far superior protective efficacy compared with existing vaccines.

Avian influenza viruses parasitize the organs of infected birds. Every year, they are transmitted across continents by migratory birds traveling long distances, and spread among wild animals and livestock worldwide, posing a threat to global public health. Humans can also be infected. Variants that spread in North America caused only mild illness in humans, but people infected with variants circulating in Southeast Asia suffered severe disease, with high mortality rates. In particular, pigs have the same type of viral receptors in their respiratory tracts as humans, so if avian influenza adapts to pigs, its ability to infect humans may increase.

Like the coronavirus that causes coronavirus disease 2019 (COVID-19), avian influenza viruses are also ribonucleic acid (RNA) viruses. RNA viruses can rapidly acquire mutations that allow them to evade the immune system and existing vaccines, or to gain the ability to transmit to humans.

Vaccines currently in use are produced and stockpiled against specific, already-identified viral variants. The research team designed an AI-based vaccine capable of broad protection by predicting not only existing variants but also potential variants that could emerge in the near future.

To this end, the team compiled all avian influenza genome sequence data contained in global surveillance programs that collect viral specimens from wild animals, livestock, and individuals infected with avian influenza. Using AI, they integrated this vast dataset and designed a “super-antigen” that incorporates core structures commonly found across all viruses. Antigens, which are the active ingredients in vaccines, induce immune responses so that the body’s immune system can fight off invading pathogens.

To select the optimal vaccine candidates from among the super-antigens designed by AI, the researchers first verified in cultured cells in the laboratory whether the antigens were properly produced and expressed, then selected the best candidates and conducted animal experiments.

The selected vaccine provided complete protection for mice and ferrets exposed to different avian influenza variant viruses. By contrast, existing avian influenza vaccines protected only about half of the animals when administered, as they were designed to respond to specific single variants and therefore had minimal protective power against diverse variants. With the technology developed by the research team, vaccines can be designed to provide proactive protection even when new viral variants emerge. Until now, responses to avian influenza virus variants have been reactive, initiated only after a variant is identified. This has meant that vaccine designs had to be updated each time a new variant appeared.

The team is also developing a universal seasonal influenza vaccine that maintains immunity across multiple flu seasons, as well as a single vaccine that can prevent Ebola, Marburg, and Lassa fever at once. According to early research results on the influenza vaccine, antigens designed in 2018 have remained effective even seven years later, up to the present.

The researchers stated, “AI-based vaccine design has the potential to induce broad herd immunity before a pandemic occurs,” adding, “It can also alleviate the heavy burden on healthcare budgets by addressing the need for frequent vaccine reformulation.”

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