Searching for a super shot of the Corona virus

As global vaccination campaigns race to stay ahead of the new variants of Covid-19, pioneering scientists have set out to ease fears of another pandemic by developing one-shot protection against past, present and future coronaviruses.

Melanie Savile, Director of Vaccine Research and Development at the Alliance for Epidemic Preparedness Innovations, is among those spearheading this mission, issuing a call to create a vaccine that broadly protects against all betacoron viruses and possibly any new strain “that might leap from animals to humans in the future.” “.

“[The] Moving forward with the strategy revolves around two main questions,” she 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?”

SARS-CoV-2, which has killed nearly 4 million people in the past 18 months, is at least the third beta-coronavirus that has spread to humans in the past 20 years. The family of viruses, common in bats and rodents, also includes SARS-Cove-1, which killed more than 700 people in 2003, mainly in China and Hong Kong, and Mers’ Cove, which was first identified and led to Saudi Arabia. In more than 850 deaths since 2012.

Given that 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 major focus for some scientists. And as Covid-19 continues to mutate faster than originally expected – most recently with the rapid spread of the delta variant, first identified in India – interest in their work has increased.

Scientists at OSE Immunotherapeutics in Nantes, France, used artificial intelligence to identify the epitopes of the virus targeted by its polyvalent vaccine © Loic Vitality / AFP via Getty Images

Within five years, Professor Chris Whitty, England’s chief medical officer, told UK health care staff this month that “multivalent vaccines” that protect against different types of coronavirus “will largely hold up against the new variants”.

But the path to a so-called polyvalent vaccine is fraught with challenges. Researchers have spent decades in vain searching for a vaccine for HIV – a disease that often causes new strains to emerge – and the flu vaccine still needs to be updated annually.

The current crop of Covid-19 vaccines, many of which have proven highly effective against the original Sars-Cov-2 strain and its later variants, have focused on generating antibodies to neutralize the spike protein that the virus uses to enter human cells. The difficulty with this approach could lie, Savile explained, that “the virus evolves to evade the immune response…You need to keep your vaccine up-to-date.”

In contrast, polyvalent vaccines often target pieces of a protein in the virus that stimulate the immune system, known as epitopes, and specifically attack those epitopes in parts of the virus that don’t mutate, even under “evolutionary pressure,” according to Savile. Many of these shots also seek to stimulate production – in addition to antibodies – of T cells, which have gradually emerged, an important part of the immune response to Covid-19.

Paul Higham, CEO of Valo Therapeutics, said that by targeting episodes with “very, very low” mutation rates, its polyvalent vaccine was able to generate a T-cell response that can work with Covid-19, Sars, Mers, and “coronaviruses.” future”. Higham hopes the vaccine will be ready for clinical trials by the end of the year at Helsinki and Oxford, adding that it could be available for public use “sometime in 2022.”

But developing vaccines capable of combating multiple pathogens is very difficult. “The further apart viruses are in terms of composition, in terms of their sequence, the more difficult it is to find antibodies that work against them. [them]explained Dennis Burton of the Scripps Research Institute in California, who has spent many years chasing a vaccine for HIV.

Diagram showing how epitopes could hold the key to a polyvalent coronavirus vaccine

“For example, Sars-1 and Sars-2 are quite similar and we find a lot of antibodies that will work against both viruses.” And expanding the shot to target Mers as well, he said, not to mention more diverse future coronaviruses, was more difficult.

CEPI’s Savile believes that finding epitopes capable of providing protection against diverse coronaviruses will require the use of artificial intelligence – something increasingly being deployed in drug discovery to accelerate research and development.

John Lewis, CEO of Entos Pharmaceuticals, said his company has taken a “machine learning approach” to a polyvalent vaccine. It partnered with an AI firm with software that allowed it to identify “34 different epitopes from different coronavirus proteins” that would produce the most effective 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 coronavirus where they seem to confer broad immunity,” he said. “It may not provide complete protection but it 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 biotech company, used the AI ​​algorithm it previously used to develop a cancer vaccine. The technology allowed her to identify 12 epitopes that target 11 proteins, most of which are inside the virus, rather than its surface. “Because they’re inside the virus, they don’t mutate or mutate much,” CEO Alexis Perolis explained, adding that the same type of proteins can be found in both SARS-1 and MERS.

Phase I human trials of the vaccine began with results expected in September. OSE is already working on “soft planning” for a second phase, with the help of financial support from France’s innovation bank, BPI France, and the possibility of a third phase trial in 2022.

Perols said the vaccine may be particularly effective for people with weakened immune systems who do not produce protective antibodies in response to currently available vaccines. But its widespread use would be a universal coronavirus booster for everyone, and it could easily be adapted to account for new forms of the disease as they emerge. “You will have a base that will stay and then add or remove new hovercraft based on the novel coronavirus,” he said.

Covid-19 dashboard in Blackburn, North West England
Interest in the future potential of a polyvalent vaccine has increased as Covid-19 continues to mutate faster than originally anticipated, 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, took a different approach. Like the current crop of Covid-19 vaccines, the VBI hit targets the spike protein but has been able to generate a broader immune response. “When we vaccinated the animals, we made antibodies that can protect against Covid-19, Sars and Mers – that’s like making antibodies that can see red, yellow and blue,” said David Anderson, chief scientific officer.

“But the immune system is very flexible and you can teach it to see something in 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.” “The idea is that these antibodies may now 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 shot has received financial support from both CEPI and the Canadian government, and human trials are expected to begin in the second half of this year.

VBI chief executive Jeff Baxter said the matter could be with regulators to consider in 12 to 14 months. “Science does not always go as you would expect, it is constantly evolving as we learn more,” he said. “But it’s very exciting to think that maybe in a couple of years everyone can have a multivalent pan-coronavirus booster.”

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