Coronavirus vaccines remain effective against variants
So far, COVID-19 vaccines have been effective against variants of the coronavirus. Scientists are monitoring the situation carefully, with updated or new vaccines a possibility in the future, if need be. Social media claims blaming vaccination for an impending variant “disaster” are hypothetical predictions that ignore life-saving benefits of the vaccines.
As we’ve written before, the fact that variants of the original SARS-CoV-2 virus have emerged is not surprising. Viruses mutate, randomly as they replicate and make errors as the genome is copied again and again.
A mutation is one change to the genetic sequence of a virus, while a variant is a distinct virus, typically with several mutations.
Most mutations don’t change the virus’s biology, clinical outcomes or how the body’s immune systems responds. But sometimes mutations can result in a competitive advantage for the virus, in its ability to replicate or transmit, for instance, or in how effectively immunity from a previous infection or a vaccine is able to fight the virus.
Dr. Adam Lauring, an associate professor in the department of microbiology & immunology at the University of Michigan Medical School, studies viral evolution. “Viruses are like people playing slot machines,” he explained to us. “Most of the time they lose when they’re making mutations.” But with the pandemic of SARS-CoV-2, “you have a lot of people playing the slot machines,” so the chances of someone “hitting the jackpot” and coming up with a new variant that has a competitive advantage are “much higher.”
Lauring said we need to have fewer people playing the slots — that is, fewer people getting infected and spreading the virus.
The good news is that, so far, the authorized vaccines have been largely effective against the variants that have most concerned scientists.
“So far, studies suggest that antibodies generated through vaccination with currently authorized vaccines recognize these variants,” the Centers for Disease Control and Prevention says about five “variants of concern” within the United States. “This is being closely investigated and more studies are underway.”
The CDC is using three classifications for variants.
A variant of interest is the lowest level and pertains to a variant that is associated with or predicted to affect transmission, effectiveness of antibodies, treatments or tests. There are eight such variants that the CDC is monitoring.
A variant of concern, the next level up, is one “for which there is evidence of an increase in transmissibility, more severe disease (e.g., increased hospitalizations or deaths), significant reduction in neutralization by antibodies generated during previous infection or vaccination, reduced effectiveness of treatments or vaccines, or diagnostic detection failures,” the CDC explains. There are five of those: B.1.1.7, which first emerged in the United Kingdom; B.1.351, initially identified in South Africa; P.1, first identified in Brazil; and B.1.427 and B.1.429, two variants identified in California in February.
There are no variants in the CDC’s top classification level: a variant of high consequence. To reach that level, there would need to be “clear evidence that prevention measures or medical countermeasures (MCMs) have significantly reduced effectiveness relative to previously circulating variants.”
While the authorized COVID-19 vaccines (from Pfizer/BioNTech, Moderna and Johnson & Johnson in the United States), were designed to protect against the original SARS-CoV-2 virus, whose genetic sequence was published in January, that’s not the virus the vaccines ultimately have confronted. Still, they worked extremely well. Clinical trials showed the Pfizer/BioNTech and Moderna vaccines had at least 94% efficacy in preventing symptomatic COVID-19, and the Johnson & Johnson vaccine, authorized more than two months later, had a 72% efficacy in preventing moderate to severe COVID-19 in the U.S.
We were on “version three or four of the virus” by the time the vaccines were rolled out, Dr. Michael Mina, an assistant professor of epidemiology at the Harvard T.H. Chan School of Public Health, said during an April 20 interview broadcast on Facebook Live. “We have pretty good evidence now to suggest that quite a number of them are more transmissible,” he said of the variants, which puts pressure on getting vaccines out quickly.
And while the effectiveness of the vaccines isn’t as strong for some variants that are circulating right now, Mina said, “it doesn’t seem hugely destructive. It’s not like these variants are able to completely break through people’s immune systems.”
Studies have found the vaccines “work very well” against the B.1.1.7 variant, Dr. Paul Offit, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia and a member of the Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee, told us. “More worrisome,” he said, are the other variants of concern, but even then, the vaccines, as well as natural immunity, protect against “severe, critical disease,” and “mild, moderate disease, but not as well.”
“That line hasn’t been crossed,” Offit said of protection against severe disease. To date, Offit said, we are not seeing a variant that evades the vaccines.
But in some corners of social media, predictions of a mass destruction scenario are circulating, painting widespread vaccination as the culprit for variants that won’t be able to be controlled by vaccines.
In an article on these claims, Jonathan Jarry, a science communicator for McGill University’s Office for Science and Society, writes: “[I]f we are concerned about the virus mutating to evade vaccine protection, the solution is to vaccinate as many people as quickly as possible and to eventually reformulate the vaccines to match variants of concern that acquire this ability.”
“We’re not facing eminent catastrophe,” Andrew Read, an evolutionary microbiologist and director of Pennsylvania State University’s Huck Institutes of the Life Sciences, told us when we asked him about such claims.
When vaccinated people are hospitalized, scientists can examine the virus, and if a variant is emerging that can’t be combated with the current vaccines, they can be tweaked. It “happens with seasonal flu all the time,” Read said.
Monitoring the emergence of variants is “very important,” he said, “but no reason for panic.”
What studies have found
Two types of studies have estimated the effectiveness of the authorized vaccines against the variants of concern: observational studies that look at infections and severity of disease in the real world as the vaccines have been administered, and lab studies that use blood samples from vaccinated people and those who have recovered from COVID-19 to measure how well their antibodies neutralize variants.
Several studies have suggested COVID-19 vaccines are highly effective against the B.1.1.7 variant, which first emerged in the U.K. in September and was identified in the U.S. in late December, shortly after the Pfizer/BioNTech and Moderna vaccines were authorized in the U.S. As of April 24, it was the most common variant circulating in the U.S., according to the CDC’s national genomic surveillance program.
A preprint, which has not yet been peer-reviewed, by U.K. researchers found that one dose of the Pfizer/BioNTech or AstraZeneca vaccine was highly effective in preventing hospitalization from COVID-19. The study, which relied on data for 5.4 million people in Scotland, about 99% of the population, was released in late February.
The first dose of the Pfizer vaccine was associated with an 85% reduced risk of hospitalization, while the AstraZeneca vaccine was associated with a 94% reduced risk, both measured 28 to 34 days after the first dose. The findings were comparable for those 80 years old or older. More than 1.3 million vaccines had been administered as of Feb. 18.
Similarly, observational studies in Israel of the Pfizer vaccine have suggested it protects against the B.1.1.7 variant.
A study published Feb. 24 in the New England Journal of Medicine evaluated vaccine effectiveness from Dec. 20 to Feb. 1 using a newly vaccinated group and an unvaccinated group, with 596,618 people in each group. It found the estimated effectiveness seven or more days after the second dose of the Pfizer shot was 92% for documented infection, 94% for symptomatic disease, 87% for hospitalization and 92% for severe disease.
The study found that up to 80% of the SARS-CoV-2 cultures were the B.1.1.7 variant days before the study extracted data.
Those findings were echoed by another study in Israel, published May 5 in The Lancet, that looked at data from Jan. 24 to April 3 and estimated the Pfizer vaccine effectiveness, seven days after the second dose, was 95.3% against infection and 91.5% against asymptomatic infection. The study estimated that 94.5% of infections were of the B.1.1.7 variant.
In Qatar, researchers used national databases on vaccinations, testing and clinical characteristics, and a study design that controlled for bias in whether people sought health care. Viral genome sequencing showed that half of COVID-19 cases in Qatar from Feb. 23 to March 18 were caused by the B.1.351 variant and nearly the other half by B.1.1.7. The researchers estimated the Pfizer vaccine effectiveness, two weeks or more after the second dose, against any infection of the B.1.1.7 variant at 89.5% and of the B.1.351 variant at 75%. Effectiveness against severe, critical or fatal disease from any variant was an estimated 97.4%.
The authors, who described the results in a May 5 letter to the New England Journal of Medicine, noted that while the effectiveness against the B.1.351 variant was about 20 percentage points lower than in the Pfizer clinical trial, the effectiveness against severe disease “was robust, at greater than 90%.”
The Johnson & Johnson vaccine’s clinical trial data also give an indication of its effectiveness against the B.1.351 and P.1 variants, since it included study sites in South Africa and Brazil, where those variants were identified in October and December and have spread. While the vaccine’s efficacy was lower in those countries than in the United States in the trial, the efficacy was still robust.
In the U.S. population, the J&J vaccine had 72% efficacy in preventing moderate to severe COVID-19 and 85.9% efficacy in preventing severe or critical COVID-19. In the South Africa population, those efficacy figures were 64% and 81.7%, respectively. In Brazil, where , efficacy was closer to that of the U.S. population: 68.1% in preventing moderate to severe disease and 87.6% in preventing severe or critical disease. The clinical trial included 44,325 people in the U.S., South Africa and Latin America, enrolled between late September and late December.
Lauring told us it was important to put these study figures in context. Even the lower efficacy against some variants is above the 50% threshold set by the Food and Drug Administration for the vaccines to gain authorization. “To date, the efficacy even against the variants appears to be higher than 50%,” he said.
Lab-based studies measuring antibody responses have found the Moderna vaccine was equally effective against B.1.1.7 and less, but still significantly, effective against B.1.351, according to preprints. A March 9 preprint from researchers in California looked at the two variants of concern that emerged in California, finding they were more transmissible and had a “moderate resistance” to being neutralized by antibodies among recovered COVID-19 patients and Pfizer and Moderna vaccine recipients, though the resistance was lower among vaccinated individuals.
“Overall, the modest 2-fold decrease in neutralizing antibody titers in vaccine recipients to the B.1.429 variant is an indication of the robust neutralizing antibody responses elicited by mRNA vaccines in the face of variants under immune selection pressure,” the authors said.
Such studies don’t provide a real-world look at how people’s immune systems will respond to an infection. In addition to antibodies, T cells play a role in protecting against disease, and experts say that could blunt the impact of variants. But both the lab and observational studies have found reduced effectiveness against the B.1.351 variant.
Lab studies by Columbia University researchers, published by Nature in early March and a preprint posted in early April, found both the B.1.351 and P.1 variants were more resistant to antibody responses of the formerly infected and the vaccinated (with the Pfizer and Moderna vaccines). For the P.1 variant, “the magnitude of the loss was modest,” the researchers wrote. For B.1.351, that variant was “markedly more resistant” to neutralization by antibodies.
The authors of the March study cautioned that if “more critical mutations accumulate,” vaccination for COVID-19 could turn out to be similar to that for influenza, where the seasonal flu vaccine varies year to year, based on which strains are likely to spread. Mass vaccination would guard against that. “Such considerations require that we stop virus transmission as quickly as is feasible, by redoubling our mitigation measures and by expediting vaccine rollout,” they wrote.
Novavax phase 2b clinical trial data, published May 5, showed its vaccine candidate had 49% efficacy overall in South Africa. The company said all five cases of severe disease were in the placebo group.
Both Pfizer and Moderna are working on booster vaccines to specifically address the B.1.351 variant. But Phil Dormitzer, vice president and chief scientific officer of viral vaccines at Pfizer, told Reuters in February that the company wasn’t doing that “because we think that means that we’re going to need to change that vaccine.” Instead, “It’s primarily to learn how to change strain, both in terms of what we do at the manufacturing level, and especially what the clinical results are. So if a variant comes along for which there is clinical evidence of escape, we’re ready to respond very quickly,” he said.
What happens next
As Dormitzer’s quote shows, vaccine companies are ready to create boosters or new vaccines if needed to respond to new variants — if one emerges that significantly evades the protection from vaccines. Experts are carefully monitoring what happens with variants. But predicting the future is a shaky business.
Read, of Pennsylvania State University’s Huck Institutes of the Life Sciences, told us “we’re going to see some more evolution that’s associated with the vaccinated people.” But predicting what will happen “is very tricky.”
Evolutionary biologists are “good at explaining the past, not good at predicting the future,” and evolution “can go in all sort of directions.”
Yet such predictions, describing a “catastrophe” or “disaster” and blaming mass vaccination, are circulating online and on social media. The posts point to claims made by Geert Vanden Bossche, a self-described vaccine consultant, who holds a degree in veterinary medicine and the equivalent of a Ph.D. in virology. (The University of Hohenheim, Germany, confirmed the Ph.D. to us in an email.)
Vanden Bossche wrote an open letter to the World Health Organization in early March that says: “Why mass vaccination amidst a pandemic creates an irrepressible monster.” He warns of “viral immune escape” and calls for an end to mass vaccination.
In that letter and other documents, he says “there is at present massive evidence that viral immune escape is now threatening humanity.” He goes on to say that “it’s becoming increasingly difficult to imagine how the consequences of the extensive and erroneous human intervention in this pandemic are not going to wipe out large parts of our human population. One could only think of very few other strategies to achieve the same level of efficiency in turning a relatively harmless virus into a bioweapon of mass destruction.”
Vanden Bossche, who has been embraced by anti-vaccination websites, advocates using “natural killer” cell-based vaccines for which he says he is conducting research.
Offit told us such a vaccine would be “novel, a breakthrough.”
Those are cells of the innate immune system, as opposed to the adaptive immune system that remembers a virus and then mounts a response if exposed to the virus again. (For more, see this explanation from McGill’s Jarry.) “There is not a vaccine that’s ever been made on this planet that hasn’t had to elicit adaptive immunity in order to be protective,” Offit said, adding he’d like to see some evidence that stimulating natural killer cells “alone was capable of stopping a threat of a virus.”
There’s more — a lot more — in documents, an FAQ and responses to his critics that Vanden Bossche has posted online.
Social media posts and Vanden Bossche, in his letter, highlight his former employment at Gavi, an international partnership for vaccinations and immunization, and the Bill & Melinda Gates Foundation. Both confirmed to us that he worked there: from 2015 to 2016 at Gavi and from 2008 to 2011 at the Gates Foundation. A spokesperson for Gavi noted it was a temporary position helping with implementation of the Ebola vaccine program; Vanden Bossche’s work there “had nothing to do with vaccine research.”
Experts we spoke to said Vanden Bossche is wrong to claim “there is at present massive evidence that viral immune escape is now threatening humanity.”
There is concern about viral immune escape, or what’s called an escape variant or escape mutant — as we described above, scientists are monitoring variants of SARS-CoV-2 and vaccine effectiveness. But experts disputed the idea that life-saving vaccines should be withheld based on a theoretical or hypothetical possibility that a variant might emerge that evades vaccine-induced immunity, or natural immunity for that matter.
“We have a proven vaccine to prevent severe disease,” Read said. Holding back “a life-saving vaccine because of theoretical predictions … doesn’t strike me as the right way to go.”
Read, whose research on Marek’s disease in chickens was cited among Vanden Bossche’s supporting materials on his website, said the vaccine for Marek’s is a “good example where the evolution did undermine the vaccines,” but it took 10 years for that to happen. The vaccine was changed and the problem “went away.”
The vaccines actually failed twice, but “failing here is still not a bad thing,” Read explained. Vaccine escape was happening, but the vaccine still protected the chickens. Farmers experienced losses in their flocks, but it wasn’t catastrophic. “The industry was still much better off vaccinating than not vaccinating,” he said. And the third generation of the vaccine has been working for 30 to 40 years.
Before the COVID-19 pandemic, Read and colleague David Kennedy wrote an analysis in 2018 of vaccine resistance and how it was “less of a concern” than resistance to drugs. In six cases of vaccine resistance Read and Kennedy examined, “the pronounced health benefits associated with vaccination have largely been sustained,” they wrote. “Thus, we contend that vaccine resistance is less of a concern than drug resistance because it is less likely to evolve and when it does, it is less harmful to human and animal health and well-being.”
To be clear, a vaccine doesn’t cause a virus to mutate. As we explained, mutations occur randomly as the virus replicates. But if mutations lead to a variant that’s more infectious or isn’t controlled by natural immunity or vaccine-induced immunity, it could well become the dominant variant. It spreads because it can.
The University of Michigan’s Lauring, who studies mutation rates, said in general SARS-CoV-2 appears to be “accumulating mutations a little bit slower than flu but probably higher than we would like compared to other viruses.” Because the virus is spreading widely in many parts of the world, it “provides more opportunity for evolution to happen” — like the slot machine analogy.
Lauring also told us that while some variants are not recognized as well by vaccine-stimulated antibodies, that’s different from “whether someone is protected by the vaccine. … We don’t know what degree of change in the virus actually leads to vaccine failure.”
And, he said, it’s not clear what level of vaccine effectiveness would prompt a need to update the vaccines. We “might be able to make a lot of headway” even with vaccination that’s 60% to 70% effective.
The seasonal flu vaccine effectiveness hit 60% once in the last 11 years. The average over that time was 43.4%. “If we had a flu vaccine that was 60% effective, we’d be ecstatic,” Lauring said.
The suggestion that the vaccines have driven the emergence of variants “doesn’t make scientific sense,” Lauring said. “They all arose before there was widespread vaccination.”
“What’s really important is that you’ve got to consider the relative risk here,” Matthew Ferrari, director of the Center for Infectious Disease Dynamics and an associate professor of biology at Penn State, told us.
A mutation that escapes immunity can arise whether there’s a vaccination scenario or a no-vaccination scenario, he explained. The same selective pressure exists when people are infected by the virus. But when there’s no vaccination, lots of people will get sick. The benefit of vaccination is that people don’t get sick.
“In a no-vaccination setting, you still get that same risk” — the risk that a variant will escape immunity — “and tons of people get sick and die,” Ferrari said.
If scientists did start to see variants that evaded the vaccine, “we’ll start to notice that,” Read said, and “vaccine companies will be all over it.”
“What we don’t really want,” Harvard’s Mina said in April, is to have “so many different variants and each of them are escaping immunity in slightly different ways.” One solution is to create “more universal vaccines” that “could protect against multiple, different lineages.”
But the potential need for new vaccines in the future doesn’t mean there’s any reason to hold back on vaccination now. The authorized vaccines are “very safe, very potent vaccines,” Read said. He “can’t see an evolutionary scenario where you could possibly justify not using these things now.”