Vaccines seem to work well against coronavirus variants. It’s also complicated

The question about how Covid-19 vaccines stand up to coronavirus variants often gets distilled to: Do they work?

The simplest answer is yes. People who’ve received one of the highly powerful vaccines don’t need to be too worried about the variants for now, experts say.

But the complete answer is more complicated.

The real question isn’t whether the vaccines work, but how well they do. Even the best vaccines allow some “breakthrough infections” — infections in people who’ve been immunized. And there are outstanding questions about how the continued emergence of variants — such as the one that’s popped up in India and appears to be helping fuel the explosion in cases there — will shape the Covid-19 pandemic into the future and potentially affect vaccine strategies.

It’s also helpful to specify what you’re talking about. Different countries are deploying different vaccines, and different variants have different tricks up their genetic codes. Clinical trials generally measured how well the vaccines prevented symptomatic Covid-19, but just as relevant are such questions as, how well do the vaccines protect against severe disease, hospitalization, and death? Do they block infections entirely, even those without symptoms? And even if people still contract the virus, does being immunized make them less infectious?

“There’s no simple, one-line sound bite,” said John Moore, a professor of microbiology and immunology at Weill Cornell Medical College.

Below, STAT outlines the latest on some of the vaccines’ performance against the variants, what’s known about the variant of concern in India, and how the continued emergence of variants will shape the future of Covid-19.

The variants and vaccines

Two variants have raised the most concern in terms of evading immunity: B.1.351 and P.1, which were first identified in South Africa and Brazil, respectively, and which share some of the same genetic changes that partially cloak the viruses from the immune system’s fighters.

In clinical trials, some of the vaccines lost efficacy against B.1.351, though certain trials also showed the immunizations could provide enough protection to generally guard against severe disease. (It’s typically easier for vaccines to prevent the worst outcomes of an infection than to prevent mild cases or block infection entirely.)

B.1.351 and some of its mutations also showed in lab experiments some ability to “escape” the antibodies generated by vaccines that are found in the blood, or serum, of people who’d been immunized. Experts cautioned, however, that what could be gleaned from those studies was limited, both because they only examined one aspect of the body’s broad immune response and because the vaccines elicit such strong antibody responses that people can afford to lose some of that potency without reverting to a sitting-duck state.

“They give people a huge amount of antibody, so even if you have a fivefold reduction in reactivity in your serum to some of these variants, you’re still left with a bunch of antibodies that can bind and block” the virus, said Richard Webby, an infectious disease expert at St. Jude Children’s Research Hospital, citing the mRNA vaccines in particular.

Since then, real-world studies with some of the vaccines have backed up those findings, indicating that while B.1.351 may cause more breakthrough infections than other forms of the virus, the vaccines are still widely protecting people from it, including most powerfully against serious disease and death.

A study out of Israel, which has used the two-dose Pfizer vaccine, found that B.1.351 was the culprit behind a higher rate of breakthrough infections, indicating it was skating past immune protection more frequently than other forms of the coronavirus. The number of those infections, however, was low, and Israel has managed to greatly suppress its Covid-19 epidemic through widespread vaccination.

Another study last week out of Qatar, which has also used the Pfizer vaccine, estimated the effectiveness of the vaccine against any B.1.351 infection was about 75% — a strong result, if a drop from its performance in clinical trials before the emergence of B.1.351. Overall, however, the vaccine was 97.4% effective against severe, critical, or fatal disease caused by any variant that was circulating in the country, including B.1.351. “The reduced protection against infection with the B.1.351 variant did not seem to translate into poor protection against the most severe forms of infection,” the researchers wrote.

Studies indicate P.1 has roughly the same or even less ability to evade immunity as B.1.351, giving researchers confidence that the vaccines can generally stand up to that variant as well. A rapid and broad deployment of initial vaccine doses, combined with enhanced restrictions on businesses, is credited with helping quell a P.1-driven outbreak this spring in British Columbia.

“There’s a degree of reduction of efficacy, but it’s going to be manageable” with the high-performing vaccines, Moore said. “It’s why we call these ‘variants of concern,’ and not ‘variants of mass panic.’”

While most of the attention in terms of vaccine effects has focused on B.1.351 and P.1, sometimes nonevents are worth noting as well. The other variant of concern is B.1.1.7, which emerged in the United Kingdom and is not only much more transmissible than other forms of the virus, but also causes severe disease at higher rates. The vaccines, however, are continuing to work exceptionally well against the variant, both protecting individual people and snuffing out transmission, which helps explain why case counts are tumbling now in the United States, even as B.1.1.7 has become dominant.

“It is clear that [B.1.1.7] is not an antibody-resistant virus,” Moore said.

Another variant of concern enters the arena

Another variant entirely, called B.1.617, appears to be helping fuel India’s devastating spring Covid-19 surge. And if the alphabet soup of different variant and mutation names wasn’t already causing enough headaches, there are different sublineages of the variant that have their own characteristics.

One of the subtypes is somewhat resistant to vaccine-elicited antibodies, though perhaps not to the same extent as B.1.351, according to two preprinted studies. Such concerns, along with some evidence that B.1.617 is more transmissible, led the World Health Organization this week to designate it as a variant of concern.

But the authors of those studies also found that the level of immunity generated should still be broadly protective against the most serious outcomes. As researchers wrote in one, “extensive vaccination will likely protect against moderate to severe disease and will reduce transmission of B.1.617,” if perhaps not as quickly as it would suppress other, less threatening variants. (More transmissible variants require a higher percentage of people to be protected before their circulation tapers off.)

“There are a number of reports from India saying that although there’s infection in people who’ve been vaccinated, there is protection against severe disease,” said Ravi Gupta, the senior author of the paper and a professor of clinical microbiology at the University of Cambridge. “So on an individual level, vaccination is still fantastic and works. But in terms of controlling transmission, there may be a degree of compromise.”

Separately, researchers are still trying to confirm whether B.1.617 (or its subtypes) is indeed more transmissible than earlier forms of the virus, and if it is, how it compares to something like B.1.1.7. The variant has taken off in India, but its ascendance coincided with a rollback in mitigation efforts and the snowballing prevalence of outbreak-driving B.1.1.7.

B.1.617 “did not cause the entire situation we’re seeing in India,” said infectious disease expert Kristian Andersen of Scripps Research Institute. “It might well add it to it. Does it play a 5% role? Does it play a 70% role? I don’t know.”

What it means going forward

The particulars of variants — whether those already on the world’s radar, or the ones that could appear if the virus continues to transmit — will shape the future of the Covid-19 pandemic, which is why it’s crucial for scientists and public health authorities to keep up with them.

“Should an individual who is vaccinated be concerned about being infected by something like P.1 in the short term and getting sick from it?” Andersen said. “The answer to that is no. The vaccines remain highly effective when it comes to these variants. The question is, what might we expect a year from now?”

Some scientists think that people eventually will need vaccine boosters, and that the vaccines might need to be tweaked to better match the evolving virus. Among the questions that will influence when and how that might occur: How long does vaccine-generated protection last, and will the waning process accelerate in the presence of certain variants? If immunity starts to wane, will people still generally be protected from the worst outcomes, even if they’re more vulnerable to infection?

While those questions can’t be answered yet, work is in progress to prepare for the possibility of boosters. Vaccine makers, for example, are testing refined recipes for their shots. Moderna last week unveiled data showing a booster bolstered antibody levels against B.1.351 and P.1, and that another booster designed specifically against B.1.351 elicited even stronger defenses.

There’s some evidence that even a booster of the existing vaccines might be enough to handle variants should an extra shot become necessary. A preprint study published this week found that people who recovered from Covid-19 and then received an mRNA vaccine had long-lasting and broad immunity against the coronavirus and its variants. An extra shot could act like that additional exposure, the researchers suggested, writing that such a strategy “could cover most circulating variants of concern.”

“Depending potentially on the vaccination protocol, the vaccines are good enough to deal” with B.1.351 and other variants, said virologist Theodora Hatziioannou of Rockefeller University, an author of the study. “At least,” she added, “the variants we’ve seen up to now.” 

The unknown future of the virus and its evolution means that scientists will continue to be on the lookout for variants that could throw a wrench in the global response, said Sharon Peacock, the executive director of the Covid-19 Genomics UK Consortium.

“This is something that we’re just going to need to keep doing for the foreseeable future.”