A University of Cambridge team has had a third success with their AI-guided technique for designing vaccines against highly infectious viruses that threaten animal and human health.
Their new broad-spectrum bird flu vaccine gave complete protection against globally circulating, diverse variants of the disease in animal trials.
The study found the vaccine is far superior to bird flu vaccines currently stockpiled by many governments for use in the event of a human outbreak. In the study, those vaccines protected only around 50% of animals exposed to multiple bird flu variants, compared with complete protection achieved by the team's new vaccine.
Developed by the University of Cambridge and spin-out DIOSynVax Ltd, this is the latest in a series of new vaccines made in an entirely new way. Their active ingredient is designed to give lasting protection from thousands of virus variants in a single vaccine.
The new study proves 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. It's designed to anticipate viral evolution, rather than reacting to it," said Professor Jonathan Heeney in the Lab of Viral Zoonotics, University of Cambridge's Department of Veterinary Medicine, who led the work.
Bird flu is spreading in animals around the world and currently considered a significant threat to global public health. Although some human infections with the North American variants have been mild, other variants in south-east Asia have caused severe disease and high mortality in humans.
Like the coronaviruses that caused COVID-19, and many other emerging infectious diseases, bird flu is an RNA virus. 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.
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.
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.
"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," said Heeney.
The results demonstrate the potential of AI-guided vaccine design in developing broad protective population immunity ahead of evolving biological threats. This aligns closely with the emerging national and international focus on biosecurity, following the UK government's recent £100 million investment in national AI biosecurity.
The study is published today in the journal Cell Reports Medicine .
An entirely new way to design vaccines
The active ingredient in a vaccine, called an antigen, triggers the body's immune system to produce a protective response. This trains the body to fight off future infection by a pathogen containing this specific antigen.
To design the bird flu vaccine, the team collected the genetic sequence data of all the bird flu viruses logged by surveillance programmes 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.
"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," said Heeney.
This new class of universal vaccines is future-proofed. They not only protect against many variants simultaneously, but potentially against related viruses that haven't yet emerged and spilt over to humans.
A superior bird flu vaccine
In the new study, the DIOSynVax vaccine completely protected mice and ferrets against a range of genetically distinct variants of the virus causing bird flu - all of which have caused human infections and represent potential pandemic threats. In comparison, only half the animals survived these same viruses when immunised with the World Health Organisation'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 programme. 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.
The decades-old approach to vaccine design has been largely reactive, responding to pathogens after they have emerged. Traditional vaccines are designed to give protection to specific virus strains or variants that have already been detected in humans. But since viruses are constantly mutating, by the time the vaccines are manufactured and distributed, they have limited protection and must be updated regularly to try and keep up.
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.
A highly adaptable technology
Emerging RNA viruses like bird flu can spread quickly between livestock, wildlife, and people. 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.
In October the team, together with partners at the Universities of Regensburg and Southampton, received £4.28 million from UK Research and Innovation (UKRI) and Defra as part of a national biosecurity investment aimed at tackling future disease outbreaks, shortening response times and reducing risks internationally and in the UK.
The funding will enable the team to continue development of their single vaccine against the viruses causing Lassa fever, Marburg, and Ebola – some of the most dangerous in the world. Ebola has an average fatality rate of around 50%, and there is no approved Marburg vaccine or antiviral treatment.
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.
The need for frequent reformulation is a fundamental limitation of current vaccines, and the reason why flu and Covid jabs are currently needed every year by millions around the world – at a huge cost to health services.
Bird flu: a highly mobile virus
Bird flu is carried in the guts of infected birds and, due to many species flying long distances as they migrate each year, it can easily be carried halfway across the world and deposited as infectious droppings. This year it was detected for the first time in animals in Australia and New Zealand.
"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."
Pigs and humans have the same receptors for the virus in their respiratory tract, which means that a bird flu virus infecting pigs could increase the virus' ability to infect humans too. And with the speed at which humans travel across the world, a highly infectious strain emerging in one place could quickly be everywhere.
