Bird Flu Vaccine Developed Using AI Outperforms Current Stockpiled Vaccines in Preclinical Tests

Researchers at the University of Cambridge and at the University of Cambridge spin-out DIOSynVax reported on the development of a broad-spectrum bird flu vaccine that in animal trials provided complete protection against globally circulating, diverse H5Nx variants of the disease. Current pandemic preparedness relies on stockpiling vaccines against individual virus variants that have already emerged. The Cambridge team’s approach uses AI-guided engineering to create broadly protective vaccines intended to remain effective across a wide range of existing and future variants.

The team’s study, described in Cell Reports Medicine, found the new digitally engineered multi-antigen mRNA vaccine to be superior to bird flu vaccines currently stockpiled by many governments for use in the event of a human outbreak. Their preclinical trial results showed that the existing vaccines tested protected only around 50% of animals exposed to multiple H5N1 bird flu variants, compared with complete protection achieved by the team’s new vaccine, DVX-panH5Nx.

The results demonstrate the potential of AI-guided vaccine design in developing broad protective population immunity ahead of evolving biological threats. The researchers say the vaccine represents the third success with their AI-guided technique for designing vaccines against highly infectious viruses that threaten animal and human health. The new study in addition demonstrates that the team’s ‘plug and play’ approach can be used to create safe, highly effective vaccines for a plethora of infectious diseases threatening animal and human health globally.

“Rather than providing immunity to a single variant of bird flu, our new broad-spectrum vaccine is protective against a huge range of variants,” said Professor Jonathan Heeney, PhD, in the Lab of Viral Zoonotics, University of Cambridge’s Department of Veterinary Medicine. “It’s designed to anticipate viral evolution, rather than reacting to it … These new-generation vaccines are a game changer for national biosecurity and more resilient public health. They mean we can be prepared to respond immediately to virus epidemics and pandemics, rather than the current scenario of always being on the back foot and responding with a strain which will have changed.”

In their paper, titled “Broad vaccine protection against globally diverse influenza A H5Nx viruses,” senior and corresponding author Heeney and colleagues stated, “Compared to WHO candidate vaccine viruses (CVVs), DVX-panH5Nx confers superior protection against antigenically distinct H5N1 challenges spanning two decades of viral evolution, demonstrating that computationally designed multivalent antigen vaccines can overcome natural influenza diversification and provide a scalable strategy for pre-pandemic preparedness.”

Bird flu is an RNA vaccine (as are the coronaviruses that cause COVID-19) that is spreading in animals around the world and is currently considered a significant threat to global public health, the authors noted. “Influenza A H5Nx viruses continue to diversify and undergo gene reassortment as they infect avian and mammalian hosts worldwide,” they wrote. RNA viruses represent a particular threat to human health because they can mutate rapidly into new strains that can jump from animals to humans and evade our immune systems—and our existing vaccines.

“It’s when bird flu adapts to live in the airways of mammals that we start to get really nervous,” said Heeney, “not only because of the impact on animal health but because of the threat to humans. If we can make better animal vaccines, then we can better protect human health as well.”

The decades-old approach to vaccine design has been largely reactive, responding to pathogens after they have emerged. The team’s goal is to create broadly protective vaccines for both animals and humans, helping reduce opportunities for pathogens to emerge, adapt, and spread. Their new class of universal vaccines is future proofed. The vaccines not only protect against many variants simultaneously, but potentially against related viruses that haven’t yet emerged and spilt over to humans.

To design the new bird flu vaccine, Heeney and team collected the genetic sequence data of all the bird flu viruses logged by surveillance programs around the world, which take virus samples from wildlife, livestock, and humans infected with bird flu. They built an AI tool to integrate the huge amount of genetic data and use it to design a range of “super-antigens” which contain the antigen features common to this whole group of viruses. These were screened in cells to select the best one for the vaccine, which was then tested in animal trials.

“… we engineered a broadly protective, multi-antigen panH5Nx vaccine using computational and structure-guided HA, NA, and M2 antigens, capturing global H5Nx diversity,” the team noted. Heeney added, “Using AI vastly speeds up the process of vaccine design, and then we can test the vaccine candidates in the lab to make sure they’re robust and safe.”

In vivo tests showed that the new DVX-panH5Nx vaccine completely protected mice and ferrets against a range of genetically distinct H1N1 variants—all of which have caused human infections and represent potential pandemic threats. “By integrating HA, NA, and M2 antigens representing global H5Nx diversity, we demonstrated that broad, cross-clade protection could be achieved using a single vaccine formulation,” the researchers commented. “… the broad immunogenicity of DVX-panH5Nx translated into complete protection against lethal heterologous challenges in mice and superior survival in ferrets.”

In comparison, only half the animals survived these same viruses when immunized with the World Health Organization’s existing bird flu vaccine. The bird flu vaccine stockpiled by governments is based on representative virus isolates identified through the World Health Organization’s pandemic influenza preparedness program. It was designed to protect against one specific strain of the disease, but the study found it provides minimal protection against other strains in circulation.

“Here, we present a mechanistically informed, digitally engineered mRNA vaccine, DVX-panH5Nx, designed to anticipate viral evolution rather than reacting to it with single isolate-based vaccines,” the investigators reported. They suggest that their collective data “… support a shift in pandemic influenza preparedness toward broadly protective, digitally designed, multi-antigen vaccines that reflect global viral diversity.”

The next step is to test the new bird flu vaccine in human clinical trials, so that it can be ready to be given to humans immediately, when needed. The team is also working on a seasonal flu vaccine that would provide broad-spectrum protection over several flu seasons. Preliminary results show that the vaccine antigen they designed in 2018 is still effective after seven years.

Earlier this year the team announced that their broad-spectrum coronavirus vaccine had proved safe in human trials, and published results showing their broad-spectrum influenza vaccine protects against both human and swine flu viruses.

In their newly released paper the team concluded, “Leveraging genomic surveillance data from animal reservoirs and human spillover events, with structural insights and immune correlates, offers a powerful framework not only for next-generation pre-pandemic H5Nx vaccines but also for improving seasonal influenza vaccines and developing more effective broadly protective vaccines against other rapidly evolving RNA viruses.”

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