The hunt for a super feature of coronavirus

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

Melanie Saville, director of vaccine research and development at the Coalition for Epidemic Preparedness Innovations, is one of the people in charge, as she has launched a call for the creation of a vaccine that would be broadly protective against all vaccines. betacoronavirus and possibly any new strain “that may jump from animals to humans in the future”.

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

Sars-Cov-2, which has killed nearly 4 million people in the past 18 months, is at least the third so-called betacoronavirus to have spread among humans in the past 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, first identified in Arabia. Saudi Arabia and in more than 850 deaths since 2012.

Given that Covid-19 is unlikely to be the last coronavirus to infect humans, the development of a punch capable of protecting against all of these diseases has become a central focus for some scientists. And, as Covid-19 has continued to mutate faster than initially expected (more recently with the rapid spread of the Delta variant, first identified in India), interest in its work has increased.

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

In five years, “multipurpose vaccines” that protect against different varieties of coronavirus “will keep the line even against new variants,” said Professor Chris Whitty, chief English doctor, this month.

But the road to the so-called multipurpose or multivalent vaccine is fraught with challenges. Researchers have spent decades unsuccessfully searching for an HIV vaccine, a disease that often launches new strains, and the flu still needs to be updated annually.

The current culture of Covid-19 vaccines, many of which have been shown to be highly effective against the original Sars-Cov-2 strain and its later variants, has focused on generating antibodies to neutralize the ear protein that the virus uses to enter human cells. The difficulty with this approach, Saville explained, may be that “the virus evolves to escape this immune response. . . the vaccine needs to be constantly updated. ”

In contrast, multivalent vaccines often target pieces of virus protein that stimulate the immune system, known as epitopes, and specifically attack these epitopes in parts of the virus that do not mutate, even under “evolutionary pressure,” according to Saville. Many of these prey also seek to stimulate the production of T cells, as well as antibodies, which have gradually emerged, are a crucial part of the immune response to Covid-19.

Paul Higham, CEO of Valo Therapeutics, said that by targeting 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 “Futures coronavirus”. Higham hoped the Helsinki and Oxford-based company would have the vaccine 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 multiple pathogens is extremely hard. “The more separated the viruses are in terms of their composition, in terms of their sequence, the more difficult it is to find antibodies that act against [them]Dennis Burton told the Scripps Research Institute in California, which has been pursuing an HIV vaccine for many years.

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

“For example, Sars-1 and Sars-2 are quite similar and we find many antibodies that will act against both viruses.” But extending a shot to target Mers as well, let alone future more diverse coronaviruses, was much more difficult, he said.

Saville, of CEPI, believes that finding epitopes capable of protecting against various coronaviruses will require the use of artificial intelligence, which is increasingly being deployed in drug discovery to accelerate research and development.

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

“We are using pieces of protein that are more than 90% similar between Sars-1 and Sars-2 and that are also found in other types of coronavirus where they appear to confer broad immunity,” he said. “They may not provide complete protection, but they should provide partial protection against many different varieties.” Entos, based in Edmonton, Canada, expects to begin human testing in the next two months.

OSE Immunotherapeutics, a French biotechnology company, has used an artificial intelligence algorithm that it previously deployed to develop a cancer vaccine. The technology allowed him to identify 12 epitopes targeting 11 proteins, most within the virus, rather than on its surface. “Because they are inside the virus, they don’t mutate or mutate very little,” explained Alexis Peyroles, executive director, adding that the same type of proteins could be found in both Sars-1 and Mers.

Phase 1 trials with punch humans have begun, with results expected in September. OSE is already “vaguely planning” the second phase, aided by financial support from French innovation bank BPI France, and a possible Phase 3 trial in 2022.

Peyroles said the vaccine could be especially effective for people with suppressed immune systems who did not produce protective antibodies in response to currently available vaccines. But its wider use would be a pan-coronavirus boost for everyone, easily adaptable to account for new forms of the disease as they arose. “You would have a base that would be maintained and then add or remove new epitopes based on the new coronavirus,” he said.

A Covid-19 information forum in Blackburn, North West England
Interest in the future potential of a multivalent vaccine has increased as Covid-19 has continued to mutate faster than originally expected, more recently with the rapid spread of the Delta variant first identified in India © Scarff / AFP oils via Getty Images

VBI Vaccines, based in Cambridge, Massachusetts, has taken a different approach. Like current Covid-19 vaccine culture, the VBI sting targets the ear protein, but it has been able 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 see 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 is a little bit between red and yellow, or yellow and blue,‘ tip proteins. ’So now they see an orange or green hue. , which shows that you have essentially expanded the immune response, “he continued. “The idea is that these antibodies can go after variants that will continue to mutate and emerge over time.”

There is no precedent for the company’s “broad-spectrum approach,” but Anderson is optimistic. The shooting has received financial support from both CEPI and the Canadian government, and human testing is expected to begin during the second half of this year.

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

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