| Daily Briefing

What experts know—and don't—about Covid-19 vaccines and new coronavirus variants

New research suggests that at least one of the recently discovered variants of the novel coronavirus may be able to sidestep immunity provided by Covid-19 vaccines, Andrew Joseph reports for STAT News. But what does that really mean for vaccine efficacy? Here's what scientists know—and don't know—so far.

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What scientists know so far

Covid-19 vaccines are largely effective at preventing severe cases of Covid-19

Whether or not a Covid-19 vaccine "works" is sort of a misleading question, because the way the vaccines respond to the novel coronavirus "is a matter of degrees, not a yes-or-no answer," Joseph writes.

So far, clinical trials on Covid-19 vaccines have examined whether the vaccines prevent symptomatic cases of Covid-19, as well as hospitalizations and deaths from the disease. Joseph notes that the first late-stage clinical trial results on Covid-19 vaccines manufactured by Pfizer and BioNTech, as well as Moderna, showed the two vaccines were at least 90% effective at preventing symptomatic Covid-19. According to Joseph, those results shifted public perception to thinking that around 90% effectiveness against symptomatic Covid-19 should be the benchmark for such vaccines when, in fact, those results "went way beyond what experts had hoped Covid-19 vaccines could hit."

That's why recent results from Johnson & Johnson's (J&J) Phase III clinical trials, which showed the vaccine candidate was 66% effective at preventing moderate and severe cases of Covid-19 across a few countries and 72% effective among just American participants, were received less enthusiastically by the public, Joseph reports. But J&J's results were still good news, he writes.

For one, Joseph notes that J&J's trial found its vaccine candidate was 85% effective at preventing severe cases of Covid-19. Also, every death and hospitalization from Covid-19 that occurred during the trial happened among participants in the placebo group, meaning none occurred among participants who received the experimental 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 death," Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases and chief medical advisor to the White House's Covid-19 response team, said.

But the vaccines appear less effective against new coronavirus variants

However, recent clinical trial data on J&J's Covid-19 vaccine candidate and an experimental Covid-19 vaccine being developed by Novavax found that those vaccine candidates weren't as effective at preventing symptomatic Covid-19 in South Africa, where the B.1.351 coronavirus variant was first discovered, when compared with the experimental vaccines' efficacy in countries without the variant.

Research suggests that B.1.351 could be less susceptible to current Covid-19 vaccines because it contains a mutation called E484K, which occurs on a part of the novel coronavirus's spike protein that's instrumental in attaching the virus to ACE2 receptors. Specifically, some studies have shown that viruses with the E484K mutation are not recognized as well by antibodies as viruses without the mutation, meaning coronavirus variants with the E484K mutation—such as B.1.351 and other recently identified variants with the mutation—could potentially bypass immune protection.

That appeared to the be case, to some extent, in clinical trials in South Africa on J&J's and Novavax's experimental Covid-19 vaccines, with data showing the vaccine candidates' efficacy was 57% for J&J and 49% for Novavax in those trials.

Results from clinical trials on Moderna's vaccine as well as Pfizer's and BioNTech's vaccine were released before the troubling new coronavirus variants were identified, so there's no clinical trial data showing how effective they are against the variants. However, the drugmakers have since tested the effectiveness of neutralizing antibodies from people who've been vaccinated against the new variants, and they've found that their vaccines, too, appear less effective against B.1.351 or certain mutations within the variant.

That said, experts say that, given how effective Moderna's and Pfizer's/BioNTech's vaccines are overall, even a drop in effectiveness for those vaccines still means the vaccines perform relatively well.

"There's a lot of headroom in the mRNA vaccines," Linda-Gail Bekker, deputy director of the Desmond Tutu HIV Centre at the University of Cape Town, said. With the B.1.351 variant, "even if there is a little bit of ding there, we would still be in a very good space."

The unknowns

There are still some unknowns about the vaccines, however, which might have implications for how well they stop the novel coronavirus pandemic and emerging variants of the virus.

For instance, researchers aren't yet sure how effective the Covid-19 vaccines are at slowing transmission of the novel coronavirus.

"When you think about vaccines, you think about the direct impacts on the person vaccinated, but you also think about the indirect effects," such as how the vaccine affects viral spread, Katia Koelle, an evolutionary biologist at Emory University, said.

However, Joseph reports, many experts believe the vaccines will help slow the virus's spread, either by entirely preventing infection, by making people who contract the virus less contagious for a period of time, or through a combination of factors.

But when it comes to the new variants, some experts are wondering whether the vaccines' reduced efficacy at preventing severe cases of Covid-19 will also mean that the vaccines are less likely to slow transmission of the new variants.

"If everyone is vaccinated, then maybe that's not a big deal, because you've just got a cold going around," Emma Hodcroft, a molecular epidemiologist at the University of Bern, 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."

Further, as it stands, the length of immune protection provided by Covid-19 vaccines isn't yet fully known, Joseph reports. Still, experts also are wondering whether immunity developed from the vaccines may wane more quickly against the B.1.351 and similar new variants than it would against earlier variants of the novel coronavirus, Joseph reports.

"When we're looking at four months down from vaccination, six months down from vaccination, these [efficacy] numbers could be even worse," Kristian Andersen, an infectious diseases expert at Scripps Research Institute, said.

Overall, Andersen said the data researchers have available so far should signal to the scientific community that they need to prepare for a scenario in which the B.1.351 and similar variants can "escape" protection provided by vaccines in a way that hasn't yet been shown in clinical trial data.

"If we sit around and wait until we have all the perfect data—showing do you or do you not get people with severe diseases? Does it help control transmission? All these things—if we sit around and wait, and we're wrong, that's bad," Andersen said (Joseph, STAT News, 2/5).







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