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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.

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“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.

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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.”

  • In the days of the 1st Smallpox inoculations in the late 18th century I don’t think many people, who agreed to receive the very risky and potentially life threatening inoculation and those that administered them cared whether there was a chance they would have – asymptomatic disease, a lower chance of severe Smallpox, or what percentage efficacy it had. People simply wanted to avoid – death, severe scarring, physical suffering, and social stigma that was caused by Smallpox until its eventual extirpation as a disease, because of the development and widespread use of inoculations which were the 1st form of vaccination practiced among populations.

    Initially actual live Smallpox samples from sick patients were used. These had a high failure rate(people became infected from the inoculation). But experimentation led to the use of simpler Cowpox samples in humans in the early 19th century for the inoculations. This was both successful and safe, even for 19th century standards. And since it was a simple process to repeat and produce it allowed the for successful mass vaccinations of whole countries.

    The point is – simple vaccines are needed that can be mass produced on a worldwide scale, with simple storage and other logistics requirements allowing for faster distribution to any location(no matter how rich or poor) in the World. The mRNA vaccines may sound more “high tech” and “cool”(like their storage freezers), but they are more complex, and that is not what is needed. The perceived higher efficacy of the Moderna and Pfizer/BioNTech vaccines was against older COVID variants and new limited trials are needed to confirm continued efficacy against the new ones.

  • All the very recent reporting on variants is scaring me

    1. There is no mention, typically, of the Manaus second epidemic. This article barely mentions it. Whatever the causes, new variant escaping natural immunity, or decline in natural immunity over time, we appear to be in the same boat as they are. Some say it’s a poor area in a poor country, but that is not an explanation at all.
    I have started to fear the Manaus epidemic is not being reported because it is just too scary – or, the authorities think it will cause people to get fatalistic and give up on masks, social distancing, etcetera, Whatever the motives, I see no reason the same thing can not happen here, BEFORE any new vaccines are available. IF they are even working on new vaccines against it, the media does not even tell you that.

    2. The efficacy of leading vaccines against the South African variant is never reported. Note, the article mentions efficacy of a vaccine was substantially lower IN South Africa, but does not tell us how much of that was due to the new variant escaping the vaccine. I note also, they do not report how much, if any, previous infection with the Wuhan variant protected from the South African variant.

    It would seem to be worthwhile for the world, which I guess means countries which can afford it, to send investigators to South Africa to vaccinate people, and find out what vaccines we currently have work best against the variant, and investigate reinfection rates.

    And what is being done about the Brazil variant?

  • If the “glass half full” medical technology story of 2020 was that effective vaccines could be developed, tested, and rolled out in under a year, I’m (perhaps quixotically) hopeful 2021 might herald even more profound achievement–deeper understanding of viral dynamics generally, leading to possibly far-reaching prevention options. (Cf. https://www.nature.com/articles/d41586-021-00241-6 )

  • PFE/BNTC and MRNA trial outcomes were based only on symptomatic results? If no Covid tests were done on ALL trial participants after their vaccinations, then the “results” missed all a-symptomatic infections. That amounts to bungling the trial outcome for benefit of the vaccine maker: we all know very well that a large percentage of Covid infected are a-symptomatic, and only tests can tell. If this was NOT done for either of the mRNA trials, then likely their efficacy is at the J & J level. That puts JNJ on top : one-shot, on a known effective platform, easy storage and handling, low-cost, no need to search for people (homeless, transient, etc) for second shots, far easier record keeping. As to effectiveness on variants/mutants, and duration of immunity : for all the Covid vaccines it simply is too early to tell, as there has not been the luxury of time for those kind of trials. But those details can be garnered – if all of us who get vaccinated (and we all should) get followed-up …..

  • If this pandemic is the result of a criminal act, how criminal does it go? Now, all the variants emerging. This make us doubt what we are really up to.

  • I will take homeopathy. Works simultaneously with “regular medicine”. Homeopathy had a very good performance in 1918. And I believe, based in limited but strong evidence, and in the way homeopathy works, it will also work for me now. I suggest you read “Homeopathy and Epidemics”.

  • I want to know more about the moderna 011m20a how do you
    Find out if this was really the vaccine or just a fake shot where people think they got the real vaccine but wasnt l forgot the word that it was called in the article.

    If you start have a running nose etc and feel cold after being vaccinated should a person be concern. No fever yet.
    Just curious l dont get my second dose to march 2 2021

  • It’s reassuring that in these articles (unlike much media coverage) there’s a degree of precision in the ‘naming of parts’.

    ‘Efficacy’ and ‘effective(ness)’ are related to each other, but they’re not the same thing. And vaccine experts say it’s crucial not to mix them up.

    ‘Efficacy’ is just a measurement made during a clinical trial.
    ‘Effectiveness’ is how well the vaccine works out in the real world.
    (Source: Naor Bar-Zeev, epidemiologist at the Johns Hopkins Bloomberg School of Public Health.)
    You can only determine ‘effectiveness’ after mass use of vaccines beyond the scope of the clinical trial.

    There’s a slogan amongst those engaged in disease control.
    ‘Vaccines don’t save lives. Vaccination programmes save lives.’

    When it comes to cutting down on infections, hospitalizations and deaths, rapid and extensive deployment of a vaccine (provided the vaccine is ‘adequately’ effective) matters more, probably, than its efficacy.

    And when commentators start quoting statistics (often after a bit of quick ‘Googling’) but in their remarks don’t realise that the word ‘data’ is a plural noun that takes a plural verb, I suspect they don’t have much of an background in the subject.

    • Well said-often it is just that the new variant is “scary” and vaccines “not as effective” without ALL the data.
      However I do think we need to stop thinking there will NEVER be deaths or severe disease from covid ever again even with 100% vaccination with 99% effectiveness-it seems this is the goal post that is CONSTANTLY getting moved-67% percent against all variants for symptomatic/severe disease is still GOOD. Bring it down to influenza level. Only reason we don’t constantly have flu numbers/deaths in our face every single day is we don’t count deaths daily like we are covid. CAn not wait until covid drops into the background as severe cases decrease dramatically.

  • I have a question about vaccines based upon bringing antigens to spike proteins and B.1.351 in particular. I understand a variant might emerge and escape a vaccine in part or in full by changing the protein in the spike to which antigens would react. However, presumably, some set of proteins in the spike exist there to bind or help bind to ACE2 and substituting different proteins for them might walk the virus off a least energy binding point with ACE2. It might therefore fail to stick some set of the times it might have before, or it might not bind as tightly, and this might interfere with completion of the life cycle. Are these factors understood in the biochemical dynamics of how SARS-CoV-2 binds to ACE2 via spike? Might a variant like B.1.351 not be as transmissible because, while it can escape the counter which a vaccinated individual poses, it had to do that by having a mutation which impairs its effectiveness?

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