The good and the (potentially) bad: What scientists know about variants and Covid-19 vaccines

There is now real evidence that at least one coronavirus variant seems to elude some of the power of Covid-19 vaccines. What, exactly, that means for the pandemic is still being sussed out.

Even if the vaccines are less powerful against the variant, they still appear to protect people from the worst outcomes, like hospitalization or death. But the loss in efficacy against the B.1.351 variant in clinical trials suggested to some experts that the immunity the shots confer may not last as long against that form of the coronavirus. Or that the vaccines won’t be as powerful of a drag on transmission, the way scientists hope the shots will be for other versions of the virus.

More urgently, experts said, the disparate results serve as a warning flag that the world needs to step up its current vaccination campaigns and expedite efforts to envision what Covid-19 vaccines 2.0 might look like.

“It’s a huge relief to know that the vaccines still seem to protect against hospitalization and deaths,” said Emma Hodcroft, a molecular epidemiologist at the University of Bern. “The No. 1 thing at the moment is to try and reduce in any way the cost that this virus charges us as it spreads through societies. But it’s definitely true the loss in efficacy, it raises some worrying questions.”

Below, STAT lays out the good and the bad news about vaccines and the B.1.351 variant, and what may be coming next.

The good

Key questions about vaccines sometimes get reduced to whether they “work” or not against the different forms of the SARS-CoV-2 coronavirus. But that oversimplifies what clinical trials are measuring, what the vaccines might be able to do, and how much of this is a matter of degrees, not a yes-or-no answer.

The trials have generally been investigating whether the vaccines prevent symptomatic cases of Covid-19. But Covid-19 presents across a full spectrum, from asymptomatic infections to fatal ones, which is why some trials also include data specifically focused on the outcomes people most want to prevent: severe disease and death.

In a way, the first clinical trial results from Moderna and the Pfizer and BioNTech team, which both showed the respective vaccines were 90% or more protective against symptomatic disease, spoiled us for what we could expect for immunizations still going through trials. The achievements went way beyond what experts had hoped Covid-19 vaccines could hit.

So when Johnson & Johnson reported last week that its vaccine was, on average, 66% efficacious at blocking moderate and severe disease — a figure that ticked up to 72% when just looking at U.S. participants — many researchers sought to remind people that this was a result worth celebrating. The vaccine was 85% effective against severe disease cases no matter the infectious variant, and all the deaths and hospitalizations in the trial occurred among people who got the placebo, not the vaccine.

“People look at 72% and say well that’s not as good as 90%, but the fact is, if you look at serious disease, it was extremely effective in preventing serious disease, including hospitalizations and deaths,” Anthony Fauci, the head of the National Institute of Allergy and Infectious Diseases, told reporters this week.

The not so good

Simply, clinical trial data released last week for the J&J shot and another from Novavax showed the vaccines did not fare as well in South Africa, where the B.1.351 variant first emerged and has circulated at the highest levels.

The efficacy of the J&J shot against moderate or worse Covid-19 fell to 57% in South Africa, while Novavax reported its vaccine was 49% effective in South Africa at preventing symptomatic Covid-19. In a separate trial in the United Kingdom, Novavax’s shot was nearly 90% efficacious. (Another variant on the global radar, B.1.1.7, first emerged in the U.K., and while it is more transmissible, so far it doesn’t seem to have as significant of an impact on vaccines.)

Beyond the drop in protection, some experts said the results indicated the vaccines might be less powerful against B.1.351 in other ways, too.

Clinical trials haven’t shown whether any of the existing vaccines can slow the spread of any iteration of SARS-2, but many experts think the shots will offer some help in that arena, whether because they prevent some infections entirely, or because they make people who still contract the virus less contagious for a shorter time, or some combination of factors.

“When you think about vaccines, you think about the direct impacts on the person vaccinated, but you also think about the indirect effects,” like what it can do to spread, said evolutionary biologist Katia Koelle of Emory University.

But several experts told STAT the results from Novavax and J&J made them wonder if vaccines will have the same potential benefit on transmission against B.1.351 as they might on other forms. A less potent vaccine, even if it prevents severe disease, may not galvanize the immune system enough to block infection or reduce infectiousness as much.

“If everyone is vaccinated, then maybe that’s not a big deal, because you’ve just got a cold going around,” Hodcroft said. “But if you’ve got a partially vaccinated population, that means you still have some susceptible people, where if a vaccinated person passes it on to a non-vaccinated person, they could still be in danger of being hospitalized or dying.”

The potentially bad

Experts also raised the question of whether the vaccines might lose more of their power against the variant faster than they would against other SARS-2 iterations. How long the protection elicited by any of the existing vaccines lasts, against any version of the virus, remains an open question. Essentially, researchers have to track vaccinated people and watch when their immunity wanes. But a weaker response could start to dissipate faster.

“When we’re looking at four months down from vaccination, six months down from vaccination, these numbers could be even worse,” Kristian Andersen, an infectious diseases expert at Scripps Research Institute, said about the differing efficacy levels by variant.

Andersen said the Novavax and J&J results should serve as a rallying cry for the global scientific community — including vaccine makers and regulators — to prepare, in case the B.1.351 variant or some other form of SARS-2 is able to “escape” immune protection in ways the trial data do not yet show. He said people shouldn’t assume that because the vaccines appeared to guard against severe disease from B.1.351 during the trial, that people will carry that protection for a long period.

“If we sit around and wait until we have all the perfect data — showing do you or do you not get people with severe disease? Does it help control transmission? All these things — if we sit around and wait, and we’re wrong, that’s bad,” he said.

What about the other vaccines?

The clinical trials of the two vaccines authorized in the U.S. — the Moderna and Pfizer-BioNTech products — were completed before particular variants of concern took off, so there are not clinical data on how the shots stack up against B.1.351.

Instead, scientists have studied in lab experiments how well neutralizing antibodies taken from people who’ve been vaccinated fend off the variants. So far, the companies have reported drops in the antibodies’ potency against B.1.351 or select mutations in the variant, but the message from them and other scientists has been that the shots produce such sky-high levels of defense that they can withstand some loss of response without really changing how well they protect people.

“There’s a lot of headroom in the mRNA vaccines,” Linda-Gail Bekker, the deputy director of the Desmond Tutu HIV Centre at the University of Cape Town, told reporters this week, referring to the mRNA technology with which both vaccines are made. With B.1.351, “even if there is a little bit of ding there, we would still be in a very good space.”

But scientists caution that it’s difficult to extrapolate what such lab experiments mean for the real world. The experiments only look at neutralizing antibodies, while the immune response includes other types of antibodies as well as fighters like T cells. With that thinking, it’s possible that the real immune response from vaccines is even more robust against mutations than the lab data show.

But the drop in neutralizing antibody power in the experiments, combined with the drop in efficacy in the Novavax and J&J trials, leads some experts to think that if the Moderna or Pfizer vaccines were put up against B.1.351 in trials, they might also see declines in efficacy.

What needs to happen now

Right now, B.1.351 accounts for just a fraction of global Covid-19 infections. But already, researchers are exploring ways to update vaccines to better target it or other worrisome variants that crop up. Vaccine makers have announced they’re studying strain-specific boosters or next-generation vaccines that could target multiple variants, and regulators have said they’re considering how to green light tweaked vaccines without requiring the full package of trials that new products have to fulfill.

B.1.351 is not the only variant that researchers worry could evade the immune response. Another variant, called P.1 and identified first in Brazil, shares some of the same mutations. There is preliminary evidence that both variants can slip past the protection generated after an initial Covid-19 case and reinfect people more easily than other SARS-2 types.

But the clinical trial results do not change the imperative to vaccinate as many people as quickly as possible with the shots that are available, experts stress. If anything, they add to the pressure to pick up the global pace. The shots protect people from Covid-19. And, if they can help drive down cases — which steps communities and individuals take to slow the spread of the virus will also do — they will prevent people from getting sick and dying, and decrease the likelihood that other potentially dangerous variants emerge.

“We need to vaccinate even faster and even more,” Andersen said. “The vaccines are still effective.”

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