Moderna believes it could update its coronavirus vaccine without a big new trialAntonio Regaladoon January 14, 2021 at 12:00 am

Covid vaccines reprogrammed to aim at emerging new strains of the virus could reach the market quickly, without going through large clinical trials, according to officials at Moderna Therapeutics and the US government.

As researchers identify mutated versions of the coronavirus that causes covid-19, there’s concern that the germ could evade approved vaccines and new shots could be necessary.

But new shots could come to market in just a few months. The reason: no need for big studies to prove they work.

Moderna’s chief medical officer, Tal Zaks, said that “scientifically” it would be possible to formulate a new vaccine and expect it to work without testing it again in tens of thousands of volunteers. He added that bringing a quickly updated shot to market would “depend on regulators.”

Zaks made the comments during a question and answer session at the J.P. Morgan health-care conference on January 11.

Researchers are scrutinizing new versions of the virus that have been appearing as it spreads and mutates. There is concern that some mutations, including one seen in cases in South Africa and Brazil, could allow the pathogen to overcome existing immunity, gained because someone has received a vaccine or previously had covid-19.

“With these mutants coming out, you just wonder where it’s going to go now. It keeps me up at night,” Peter Marks, the US Food and Drug Administration official who conceived the US vaccine program Operation Warp Speed, said in a December broadcast on WebMD.

Moderna says laboratory studies indicate that its current vaccine, first authorized in the US in December, should protect against all the major variants now being tracked, including one in the UK that is believed to be more transmissible, so there is no reason to change the inoculation yet.

“From what we have seen so far, the variants being described … don’t alter the ability of neutralizing antibodies elicited by vaccination to neutralize the virus,” Zaks said, adding that he believed protection conferred by vaccination “should last at least a year.”

“Our technology is very well suited to actually rapidly deploy a vaccine based on the new variant. But based on the data we have seen today, we don’t see a need for it,” he said.

The company’s novel vaccine, along with one from Pfizer and BioNTech, involves packaging genetic instructions for the “spike” protein of the coronavirus into minuscule fatty nanoparticles. Injected into a person’s arm, cells begin to read that information and make the spike molecule, setting off an immune response that, trials show, leads to protection against severe covid in the large majority of people.

The technology’s flexibility is that the genetic information—messenger RNA—can easily be rewritten and revised, making it possible to target the latest mutant forms of the virus. The other ingredients—salts, sugars, and the lipid nanoparticles—would not have to be changed.

Last spring, it took Moderna only six weeks to devise and manufacture initial lots of its vaccine, which it delivered to the National Institutes of Health for initial tests on animals. There is no reason it can’t be done again. “Technically it is possible to make a new vaccine mimicking the new strain in a few weeks,” Uğur Şahin, founder and CEO of BioNTech, which uses similar technology, said during a press event in December.

What took longer was tests in humans, including a huge study by Moderna and the National Institutes of Health involving more than 30,000 volunteers that lasted from July to November. In that study, half of the participants got the vaccine and half got a dummy shot, giving researchers an unbiased view of how well it worked.

“With the mRNA vaccine, we know how they work … it’s not going to have to be another 30,000-patient clinical trial,” Marks said. “We will have a way of evolving here.”

If the big trials can be skipped, that suggests the timeline to bring a new shot to market would be shortened by at least four months, if not more. Several other vaccines, including ones from Johnson & Johnson and Novavax, have not yet completed their large phase 3 trials needed to win the nod from regulators, in part because they began later.

The idea of updating a vaccine to keep up with a changing pathogen isn’t new. Influenza vaccines are also changed each year to match changes in the virus. Each updated vaccine undergoes more limited tests on people to assess whether they cause the expected immune responses. Flu vaccines are not always very effective, however, especially if there is a mismatch between the strain used in the vaccine and the one that ends up circulating that year.

The fear the public and vaccine companies are grappling with now is the growing evidence that the covid-19 virus will keep mutating and changing its shape, a phenomenon called “antigenic drift.” The result could be evolved forms that today’s vaccines don’t protect against as well.

“Unfortunately, this virus is starting to look like it wants to become, like, Flu Two, or Son-of-Flu,” Marks said in December. “What is good about flu is it set up a very nice paradigm [for updating vaccines].”

On January 12, Brazilian researchers described a new variant circulating in Manaus, the capital of Brazil’s Amazonas state. That city has had among the world’s highest rates of covid-19. Estimates are that two-thirds of the population was infected by summer, and so researchers expected the virus to burn out, without many new people to infect.

Instead, though, cases in Manaus are rising again, leading the Brazilian researchers to wonder if their new strain has an “increased propensity for reinfection of individuals.” They say “is essential to rapidly investigate.”

Moderna says it is also looking to real-world events outside the laboratory where countless trillions of copies of the virus are at this moment reproducing in the bodies of millions of people.

“My definition of when to get worried is when we see real clinical data that suggests people who have been sick or immunized are getting reinfected with new variants,” says Zaks. “We are keeping our fingers on the pulse, just like many others.”

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