The hunt for the coronavirus super shot

As global vaccination campaigns rush to stay ahead of newer variants of Covid-19, pioneering scientists have set out to alleviate fears of another pandemic by developing a single shot to protect against the coronavirus past, present and future.

Melanie Saville, director of vaccine research and development at the Coalition for Epidemic Preparedness Innovations, is among those leading the charge, having called for the creation of a vaccine that would be broadly protective against all beta-coronaviruses and potentially any new strain “that could pass from animals to humans in the future”.

“[The] strategy for the future rests on two key questions, ”she told the Financial Times. “What must we do to end this pandemic and what must we 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 beta-coronavirus that has spread among humans in the past 20 years. The virus family, 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 has been identified for the first time in Saudi Arabia and has resulted in over 850 deaths since 2012.

Since Covid-19 is unlikely to be the last coronavirus to infect humans, developing a jab capable of protecting against all of these diseases has become a central goal for some scientists. And as Covid-19 has continued to mutate faster than initially expected – most recently with the rapid spread of the Delta variant, first identified in India – interest in their work has increased.

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

Within five years, the ‘versatile vaccines’ that protect against different varieties of coronavirus ‘will hold the line to a very large extent against even new variants,’ Professor Chris Whitty, Chief Medical Officer for England, told the UK. British health workers this month.

But the road to a so-called polyvalent or multivalent vaccine is strewn with pitfalls. Researchers have spent decades unsuccessfully researching a vaccine against HIV – a disease that frequently generates new strains – and the flu vaccine still needs to be updated every year.

The current crop 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 spike protein that the virus uses to enter human cells. The difficulty with this approach, explained Saville, may be that “the virus evolves to escape this immune response then. . . you have to constantly update your vaccine ”.

Multivalent vaccines, on the other hand, often target pieces of protein in the virus that boost the immune system, called epitopes, and specifically attack epitopes in parts of the virus that don’t mutate, even under “evolutionary pressure,” according to Saville. Many of these injections also seek to stimulate the production – in addition to antibodies – of T lymphocytes, which, it has 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 was able to generate a T cell response that could work for Covid-19, Sars, Seas and “future coronaviruses”. 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 “by 2022”.

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

Informational 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 work against both viruses. But extending a shot to target Mers as well, not to mention more diverse future coronaviruses, was much more difficult, he said.

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

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

“We use pieces of protein that are over 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. he declares. “They may not provide complete protection, but they should provide partial protection against many different varieties. Entos, based in Edmonton, Canada, hopes to begin human trials within the next two months.

OSE Immunotherapeutics, a French biotechnology company, used an AI algorithm it had previously deployed to develop a cancer vaccine. The technology allowed him 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 very little,” explained Alexis Peyroles, managing director, adding that the same type of proteins could be found in both Sars-1 and Mers.

Phase 1 human trials of the jab began with expected results in September. OSE is already “vaguely” planning phase 2, helped by financial support from the French innovation bank, BPI France, and a possible phase 3 trial in 2022.

Peyroles said the vaccine could be particularly effective for people with weakened immune systems who do not produce protective antibodies in response to currently available vaccines. But its wider use would be like a reminder of the pan-coronavirus for everyone, easily adaptable to take into account new forms of the disease as they arise. “You would have a base that would stay and then add or remove new epitopes based on the novel coronavirus,” he said.

A Covid-19 information board in Blackburn, North West England
Interest in the future potential of a multivalent vaccine has increased as Covid-19 continued to mutate faster than expected, most 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 crop of Covid-19 vaccines, the VBI jab targets the spike protein but has been able to generate a broader immune response. “When we immunized 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, scientific director.

“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, ‘spike proteins’. So now they see a shade of orange or green, which shows that you’ve basically expanded the immune response, ”he continued. “The idea is that these antibodies can now attack 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 CEPI and the Canadian government with human trials scheduled to begin in the second half of this year.

VBI chief executive Jeff Baxter said it could be reviewed by regulators in 12 to 14 months. “Science doesn’t always turn out the way you would expect and it is constantly evolving as we learn more,” he said. “But it’s very exciting to think that maybe in two years everyone could get a booster of a multivalent coronavirus vaccine.”

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