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The hunt for a super coronavirus shot

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As global vaccination campaigns run to stay ahead of new variants of Covid-19, pioneering scientists have set out to calm fears of another pandemic by developing a single shot to protect against past, present and future coronaviruses.

Melanie Saville, director of vaccine research and development at the Coalition for Epidemic Preparedness Innovations, is among those leading the charge, after publishing a call for the creation of a vaccine that would be largely protective against all betacoronaviruses and potentially any new strain “that could hop from animal to human in the future”.

“[The] the strategy to move forward is around two key questions, “he told the Financial Times.” What should we do to end this pandemic and then what should we do to prevent the next pandemic? “

Sars-Cov-2, which has killed nearly 4m people in the last 18 months, is at least the third known betacoronavirus to be spread among humans in the last 20 years. The family of viruses, common in bats and rodents, also includes Sars-Cov-1, which killed more than 700 people in 2003, mainly in China and Hong Kong, and Mers-Cov, which was first identified. returned to Saudi Arabia and has resulted in more than 850 deaths since 2012.

Since Covid-19 is unlikely to be the last coronavirus to infect humans, the development of a vaccine capable of protecting it from all diseases has become a central focus for some scientists. And as Covid-19 has continued to move faster than originally anticipated – more recently with the rapid spread of the Delta variant, first identified in India – interest in its work has grown.

Scientists from OSE Immunotherapeutics in the French city of Nantes have used artificial intelligence to identify the epitopes of the virus targeted by its multivalent vaccine © Loic Venance / AFP via Getty Images

Within five years “multipurpose vaccines” that protect against different varieties of coronavirus “will keep the line at a very high level even against new variants,” Professor Chris Whitty, chief medical officer in England, told health officials. UK this month.

But the road to a so-called polyvalent or multivalent vaccination is fraught with challenges. Researchers have spent decades unsuccessfully researching a vaccine for HIV – a disease that often launches new strains – and the flu vaccine must always be updated every year.

The current culture of Covid-19 vaccines, many of which have proven to be highly effective against the original Sars-Cov-2 strain and its successive variants, have focused on the generation of antibodies to neutralize the spike protein that the virus uses to enter human cells. The difficulty with this approach, Saville explained, may be that “the virus evolves to bypass that immune response so … you need to update your vaccine constantly.”

Multivalent vaccines, on the other hand, are often intended to break down proteins in the virus that stimulate the immune system, known as epitopes, and specifically attack those epitopes in parts of the virus that do not mutate, even under it. ” evolutionary pressure, “according to Saville. Many such strokes also seek to stimulate the production – in addition to antibodies – of T cells, which, if developed gradually, are a crucial part of the immune response to Covid-19.

Paul Higham, chief executive of Valo Therapeutics, said that by looking at epitopes with “very, very low” mutation rates, his multivalent vaccine had been able to generate a T cell response that could work for Covid-19, Sars , Mers, and “Future coronavirus.” Higham hoped the Helsinki and Oxford society would have vaccination ready for clinical trials by the end of the year, adding that it could be available for public use “sometime in 2022.”

But developing vaccines capable of fighting many pathogens is extremely tough. “The more open the viruses are in terms of composition, in terms of sequence, the harder it is to find antibodies that act against [them], ”Explained Dennis Burton to the Scripps Research Institute in California, which has spent many years researching an HIV vaccine.

Information graphic explaining how epitopes may hold the key to a multivalent coronavirus vaccine

“For example, Sars-1 and Sars-2 are very similar and we find a lot of antibodies that act against the two viruses.” But to extend a shot to target even Mers, even less the event, plus several coronaviruses, was much more difficult, he said.

CEPI’s Saville believes that research into epitopes capable of providing protection against various coronaviruses will require the use of artificial intelligence – something that is increasingly being used in drug discovery to accelerate research and development.

John Lewis, executive director of Entos Pharmaceuticals, said his company had taken “a machine learning approach” to its multivalent vaccine. He partnered with a company specializing in AI with software that allowed him to identify “34 different epitopes from different coronavirus proteins” that would produce the most potent human T-cell response.

“We use pieces of proteins that are more than 90 percent similar between Sars-1 and Sars-2 and are also found in other types of coronaviruses where they appear to confer broad immunity,” he said. “They may not provide complete protection but they must provide partial protection against many different varieties.” Entos, based in Edmonton, Canada, hopes to begin human trials in the next two months.

OSE Immunotherapeutics, a French biotechnology company, has used an AI algorithm that it has already used to develop a cancer vaccine. The technology allowed them to identify 12 epitopes targeting 11 proteins, most of them in the virus, rather than on its surface. “As they are in the virus they do not mutate or change little,” explains Alexis Peyroles, executive director, adding that the same type of protein could be found in both Sars-1 and Mers.

The first phase of human testing of the jab began with results expected in September. OSE has already “freely planned” phase 2, aided by financial support from the French innovation bank, BPI France, and by a possible phase 3 process in 2022.

Peyroles said the vaccine could be particularly effective for people with suppressed immune systems who have not produced protective antibodies in response to currently available vaccines. But its wider use would be as a pan-coronavirus booster for everyone, easily adapted to account for new forms of the disease as they emerge. “We would have a base that would stop and then add or remove new epitopes based on the new coronavirus,” he said.

A Covid-19 information panel in Blackburn, in the north-west of England
Interest in the potential future of a multivalent vaccine has grown since Covid-19 continued to mutate faster than originally anticipated, more recently with the rapid spread of the Delta variant first identified in India © Oli Scarff / AFP via Getty Images

VBI Vaccines, based in Cambridge, Massachusetts, has taken a different approach. Like the current culture of Covid-19 vaccines, VBI jab is intended to spike protein, but has been known to generate a broader immune response. “When we vaccinated animals we made antibodies that could protect against Covid-19, Sars and Mers – it’s like making antibodies that can show red, yellow and blue,” said David Anderson, chief scientist.

“But the immune system is very flexible and you can teach it to see something that’s a little bit between red and yellow, or yellow and blue,‘ protein spike. ’So now they see a shade of orange or green, which shows that you have essentially broadened the immune response, ”he continued. “The idea is that these antibodies can now go after variants that will continue to mutate and emerge over time.”

There’s no precedent for the company’s “broad-spectrum approach,” but Anderson is optimistic. The coup received financial support from CEPI and the Canadian government with human trials planned for the second half of this year.

Jeff Baxter, executive director of VBI, said he could be with regulators to be considered in 12 to 14 months. “Science doesn’t always live as expected, and it constantly evolves as we learn more,” he said. “But it’s very exciting to think that maybe in two years, everyone could receive a booster of a multivalent pan-coronavirus vaccine.”


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