What Will it Take to Make Covid-19 Vaccines Variant-Proof?

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Last week, two more pharmaceutical firms backed by the US federal government’s Operation Warp Speed program announced preliminary results from large-scale clinical trials of their Covid-19 vaccines. And both had very welcome results to report. Mostly.

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According to Johnson & Johnson’s press release, the company’s single shot was 85 percent effective in preventing severe forms of the disease across the 44,000 people enrolled in each of three trials in the United States, Latin America, and South Africa. But when it came to fending off more mild cases of coronavirus infection, the vaccine worked best in the US, where it was 72 percent protective compared to just 57 percent in South Africa. (The shot’s efficacy in Latin America was 66 percent.)

It was the same story with Novavax, a much smaller, Maryland-based company. In its 15,000-person United Kingdom trial, the vaccine demonstrated 89 percent efficacy against mild, moderate, and severe cases of Covid-19; in the company’s smaller study in South Africa, the efficacy rate fell to about 50 percent.

The dramatic difference likely comes down to the particular versions of the coronavirus circulating in different locations. Late last year, around the time that both Novavax and Johnson & Johnson were launching their South African trials, scientists in Durban uncovered a new cluster of cases, all united by a unique constellation of mutations in the gene for the virus’s spike protein. That variant, known as B.1.351, quickly expanded across the country, becoming the dominant strain in just a few weeks’ time and fueling a massive surge in new infections.

Since B.1.351’s initial discovery, scientists around the world have been sprinting to better understand its mutations. A series of non-peer-reviewed studies posted as preprints in recent weeks found that one in particular, called E484K, made it much harder for antibodies found in the blood of recovered Covid-19 patients and immunized people to recognize version B.1.351 of the virus. Based on those lab experiments, scientists had a strong suspicion that the current class of authorized vaccines would still work against that strain—but maybe just not as well. Data gathered from the Novavax and Johnson & Johnson trials now seems to be bolstering that hunch.

“This is a wake-up call to all of us,” Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases, said at a White House press briefing on Friday. He acknowledged that the virus is changing more quickly than once thought, and that the variants now spreading around the world won’t be the end of its evolution. “That means that we as a government, companies, all of us in this together, will have to be nimble to be able to adjust readily, to make versions of the vaccine that are specifically directed toward whatever mutation is prevalent at any given time,” he continued.

B.1.351 is one of at least three variants—including one first found in the UK and another in Brazil—thought to spread more easily than earlier forms of the coronavirus, though it’s not yet clear how much more transmissible each one is, and to what extent they can cause reinfections. What is apparent to scientists and public health experts is that the US, and indeed the world, is now in a race to vaccinate as many people as possible before these problematic mutations gain a foothold. But at the same time, parallel efforts to develop and distribute multi-variant vaccines to tackle all the existing strains must also begin. How will that actually work?

Executives from both Pfizer and Moderna, the first companies to have Covid-19 vaccines authorized by the US Food and Drug Administration, have said they are retooling their shots to boost protection against these new mutations, just as a precaution. Moderna has gone so far to begin preparing for a Phase I study of a B.1.351-specific booster dose that would be given as a follow-up to people who already received the original vaccine.

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