Virus World

BACKGROUND

The safety and immunogenicity of the bivalent omicron-containing mRNA-1273.214 booster vaccine are not known.

METHODS

In this ongoing, phase 2–3 study, we compared the 50-μg bivalent vaccine mRNA-1273.214 (25 μg each of ancestral Wuhan-Hu-1 and omicron B.1.1.529 [BA.1] spike messenger RNAs) with the previously authorized 50-μg mRNA-1273 booster. We administered mRNA-1273.214 or mRNA-1273 as a second booster in adults who had previously received a two-dose (100-μg) primary series and first booster (50-μg) dose of mRNA-1273 (≥3 months earlier). The primary objectives were to assess the safety, reactogenicity, and immunogenicity of mRNA-1273.214 at 28 days after the booster dose.

RESULTS

Interim results are presented. Sequential groups of participants received 50 μg of mRNA-1273.214 (437 participants) or mRNA-1273 (377 participants) as a second booster dose. The median time between the first and second boosters was similar for mRNA-1273.214 (136 days) and mRNA-1273 (134 days). In participants with no previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the geometric mean titers of neutralizing antibodies against the omicron BA.1 variant were 2372.4 (95% confidence interval [CI], 2070.6 to 2718.2) after receipt of the mRNA-1273.214 booster and 1473.5 (95% CI, 1270.8 to 1708.4) after receipt of the mRNA-1273 booster. In addition, 50-μg mRNA-1273.214 and 50-μg mRNA-1273 elicited geometric mean titers of 727.4 (95% CI, 632.8 to 836.1) and 492.1 (95% CI, 431.1 to 561.9), respectively, against omicron BA.4 and BA.5 (BA.4/5), and the mRNA-1273.214 booster also elicited higher binding antibody responses against multiple other variants (alpha, beta, gamma, and delta) than the mRNA-1273 booster. Safety and reactogenicity were similar with the two booster vaccines. Vaccine effectiveness was not assessed in this study; in an exploratory analysis, SARS-CoV-2 infection occurred in 11 participants after the mRNA-1273.214 booster and in 9 participants after the mRNA-1273 booster.

CONCLUSIONS

The bivalent omicron-containing vaccine mRNA-1273.214 elicited neutralizing antibody responses against omicron that were superior to those with mRNA-1273, without evident safety concerns. (Funded by Moderna; ClinicalTrials.gov number, NCT04927065. opens in new tab.)

Published in NEJM (Sept.16, 2022):

https://doi.org/10.1056/NEJMoa2208343 

A 50-microgram dose increased antibodies by roughly 37-fold, and a full dose of 100 micrograms was even more powerful, the company said.  A booster shot of the Moderna coronavirus vaccine significantly raises the level of antibodies that can thwart the Omicron variant, the company announced on Monday. The news arrives as Omicron rapidly advances across the world, and most coronavirus vaccines seem unable to stave off infection from the highly contagious variant. Moderna’s results show that the currently authorized booster dose of 50 micrograms — half the dose given for primary immunization — increased the level of antibodies by roughly 37-fold, the company said. A full dose of 100 micrograms was even more powerful, raising antibody levels about 83-fold compared with pre-boost levels, Moderna said. Both doses produced side effects comparable to those seen after the two-dose primary series. But the dose of 100 micrograms showed slightly more frequent adverse reactions relative to the authorized 50-microgram dose. The results are based on laboratory tests that do not capture the full range of the body’s immune response against the virus. Although vaccines may not prevent infection from the variant, they are expected to prevent severe illness in the vast majority of people.

The data have also not been published or reviewed by independent experts. Moderna said it was preparing a manuscript with the data that would be posted online. The pharmaceutical companies Pfizer and BioNTech announced earlier this month that a booster shot of their vaccine also increased the level of antibodies against Omicron. Moderna tested a third shot of several versions of its vaccine, each in 20 people. Before boosting, all the individuals had low levels of antibodies that can prevent Omicron infection. At Day 29, after receiving a third shot, the 50-microgram and 100-microgram doses of the current vaccine both sharply increased antibody levels. The company also tested “multivalent” booster shots that incorporate mutations seen in the Beta and Delta variants, many of which are also present in Omicron. Those continuing trials each have 300 to 600 people enrolled in them. The 50-microgram and 100-microgram doses of the multivalent boosters increased antibody levels to similarly high levels, Moderna said. Given how quickly Omicron is marching through the world, Moderna said, the company will focus its near-term efforts on extra shots of the original vaccine. It also plans to test a booster shot that is specific to the Omicron variant early next year and to include Omicron in a multivalent booster. “To respond to this highly transmissible variant, Moderna will continue to rapidly advance an Omicron-specific booster candidate into clinical testing in case it becomes necessary in the future,” said Stéphane Bancel, Moderna’s chief executive officer.

Moderna Press Release (Dec. 20, 2021):

https://investors.modernatx.com/news/news-details/2021/Moderna-Announces-Preliminary-Booster-Data-and-Updates-Strategy-to-Address-Omicron-Variant/default.aspx 

Background:

While Coronavirus disease 2019 (Covid-19) vaccines are highly effective, breakthrough infections are occurring. Booster vaccinations have recently received emergency use authorization (EUA) for certain populations but are restricted to homologous mRNA vaccines. We evaluated homologous and heterologous booster vaccination in persons who had received an EUA Covid-19 vaccine regimen. Methods: In this phase 1/2 open-label clinical trial conducted at ten U.S. sites, adults who received one of three EUA Covid-19 vaccines at least 12 weeks prior to enrollment and had no reported history of SARS-CoV-2 infection received a booster injection with one of three vaccines (Moderna mRNA-1273 100-mcg, Janssen Ad26.COV2.S 5x1010 virus particles, or Pfizer-BioNTech BNT162b2 30-mcg; nine combinations). The primary outcomes were safety, reactogenicity, and humoral immunogenicity on study days 15 and 29.

Results:

458 individuals were enrolled: 154 received mRNA-1273, 150 received Ad26.CoV2.S, and 154 received BNT162b2 booster vaccines. Reactogenicity was similar to that reported for the primary series. Injection site pain, malaise, headache, and myalgia occurred in more than half the participants. Booster vaccines increased the neutralizing activity against a D614G pseudovirus (4.2-76-fold) and binding antibody titers (4.6-56-fold) for all combinations; homologous boost increased neutralizing antibody titers 4.2-20-fold whereas heterologous boost increased titers 6.2-76-fold. Day 15 neutralizing and binding antibody titers varied by 28.7-fold and 20.9-fold, respectively, across the nine prime-boost combinations.

Conclusion:

Homologous and heterologous booster vaccinations were well-tolerated and immunogenic in adults who completed a primary Covid-19 vaccine regimen at least 12 weeks earlier.

Available as preprint in medRxiv (Oct. 13, 2021):

https://doi.org/10.1101/2021.10.10.21264827 

The authorization applies to people who received solid organ transplants and others with similarly compromised immune systems.  The Food and Drug Administration on Thursday authorized third doses of Pfizer-BioNTech’s and Moderna’s coronavirus vaccines for some people with weakened immune systems, giving physicians more leeway to protect those who did not respond enough to an initial series of shots. The authorization, in the form of updates to the existing emergency use authorizations for the two vaccines, applies to people who received solid organ transplants and others with similarly compromised immune systems, the F.D.A. said. The agency’s decision came a day before the Centers for Disease Control and Prevention’s independent advisory committee was set to consider and vote on whether to recommend the move. The committee is likely to give its approval, and the C.D.C. would follow with its own endorsement of the additional doses. “The F.D.A. is especially cognizant that immunocompromised people are particularly at risk for severe disease,” Dr. Janet Woodcock, the acting F.D.A. commissioner, said in a statement. “After a thorough review of the available data, the F.D.A. determined that this small, vulnerable group may benefit from a third dose of the Pfizer-BioNTech or Moderna Vaccines.”

The authorization of the third doses kicks off what promises to be a busy next stretch for federal vaccine regulators — and a new phase of the nation’s inoculation drive. By the start of next month, the agency is expected to grant full approval to Pfizer-BioNTech’s vaccine. That will most likely prompt a wave of vaccination mandates from companies and organizations that waited to require vaccination until the F.D.A. fully cleared a vaccine.  At the same time, government scientists and regulators are grappling with whether more Americans will need booster shots, a hotly debated move that many scientists argue is not yet supported by data. Other countries such as Israel and Germany have implemented booster policies. “Other individuals who are fully vaccinated are adequately protected and do not need an additional dose of Covid-19 vaccine at this time,” Dr. Woodcock said in her statement Thursday, adding that the agency was “actively engaged in a science-based, rigorous process with our federal partners to consider whether an additional dose may be needed in the future.” The United States is the latest country to begin offering third doses to those with weaker immune systems. France has offered additional vaccine doses to certain people with poor immune responses since April, and Germany and Hungary recently followed suit.

Moderna Inc (MRNA.O) said on Wednesday early human trial data shows that a third dose of either its current COVID-19 shot or an experimental new vaccine candidate increases immunity against variants of COVID-19 first found in Brazil and South Africa.  The booster shots, given to volunteers previously inoculated with Moderna's two-dose vaccine regimen, also boosted antibodies against the original version of COVID-19, Moderna said. The early data comes from a 40-person trial testing both Moderna's existing shot and a version developed to protect against the South African variant of COVID-19 called mRNA-1273.351. Moderna is also studying a shot that combines both the new and existing vaccine. The results show that while booster shots of either version of the vaccine increased antibodies against all of the variants of COVID-19 tested in the trial, the new booster had a bigger response against the South African variant than the original vaccine.

"We are encouraged by these new data, which reinforce our confidence that our booster strategy should be protective" against the newer variants of COVID-19, Stephane Bancel, Moderna's chief executive officer, said in a statement. Both booster shots were well tolerated, with side effects similar to what volunteers in previous studies experienced from the second dose of its vaccine, Moderna said. The new variants of COVID-19 first discovered in South Africa and Brazil are thought to be more resistant to existing vaccines. Both variants have been detected in the United States but comprise only a small fraction of U.S. cases so far, according to federal data last updated in April. Moderna’s study is looking at levels of antibodies in participants’ blood that combat COVID-19, an early indication that they will be protected against the virus. It first announced it was studying ways to protect against the variants of COVID-19 in February.  Moderna expects to share additional data soon on another potential booster shot that mixes its existing COVID-19 vaccine with the newly developed shot. The U.S. government scientists at the National Institute of Allergy and Infectious Diseases (NIAID) is conducting a separate early stage study of mRNA-1273.351, Moderna said.

Moderna's Press Release (May 5, 2021):

https://investors.modernatx.com/news-releases/news-release-details/moderna-announces-positive-initial-booster-data-against-sars-cov 

The U.S. Food and Drug Administration cleared a path for millions more Americans to receive Covid-19 vaccine booster shots, as the nation looks to bolster its defenses and prevent another virus surge.  The agency said in a statement on Wednesday that Moderna Inc. vaccine recipients 65 and over can receive a third shot, as can adults 18 and up who are at high risk of severe Covid or with frequent institutional or occupational exposure to the virus that causes the disease. Additionally, all J&J recipients 18 and older are eligible for a booster shot at least two months after receiving their first dose. The agency also allowed each of the available Covid vaccines to be used as a booster dose for eligible individuals following completion of a primary vaccination with a different vaccine.  The moves will mean the U.S. has a bigger toolkit to try to limit a potential winter virus rebound. The summer’s delta-variant fueled spike in infections helped increase urgency to make boosters available, and health officials across the U.S. are eager to forestall a rebound in cases that could cripple hospitals and disrupt work and school this winter. FDA officials indicated they would also move quickly to expand eligibility for booster shots as more data become available or if breakthrough cases start to rise in younger adults. “We will not hesitate to drop this age range as we see that that benefit clearly outweighs the risk,” said Peter Marks, the head of the agency’s Center for Biologics Evaluation and Research, during a media briefing following the announcement. The clearances came after a panel of expert advisers to the FDA unanimously backed the Moderna and J&J booster regimens in two days of meetings last week. Regulators have now signed off on boosters for all three coronavirus vaccines available in the U.S.  Last month, the FDA said people 65 and over and others who are at heightened risk of severe Covid were eligible for a booster dose of the vaccine developed by Pfizer Inc. and BioNTech SE. Moderna shares climbed 0.8% in after-hours trading in New York, while J&J shares gained 0.4% and Pfizer shares rose 0.2%. U.S.-traded shares of Germany-based BioNTech gained 0.9%.

Smaller Dose

The Moderna booster shot authorized by the FDA is half the dose that is given in the initial two-shot series, and it should be given at least six months after the initial inoculation, regulators said.  The FDA said that a single booster dose of the Pfizer vaccine may be given at least 6 months after completing the primary series to people 18 to 64 with frequent institutional or occupational exposure to the coronavirus. In permitting mixing and matching, the FDA is allowing J&J vaccine recipients to receive an additional dose of any cleared vaccine after two months. Likewise, recipients of Moderna and Pfizer who are eligible for a booster would receive their booster, including J&J’s shot, at least six months after their initial immunization regimen. Marks said during the call with reporters that different combinations produce different antibody levels in the short term, but it isn’t clear what that means in terms of actual long-term protection. Seen as a convenient, effective alternative to two-shot messenger RNA vaccines, J&J’s single-shot immunization has seen far less use in the U.S., in part because it isn’t as effective. The drugmaker has also experienced manufacturing problems that limited the shot’s distribution.  The decision to allow mixing will create greater flexibility and is beneficial to global public health, Paul Stoffels, J&J’s chief scientific officer, said in a statement.  Before the Moderna and J&J booster shots can be administered, the Centers for Disease Control and Prevention’s Advisory Panel on Immunization Practices will make further recommendations about who should receive them. The panel is scheduled to discuss boosters on Thursday.  The next big milestone for the U.S. immunization effort looms next week, when the FDA advisory panel is expected to weigh Pfizer’s proposed Covid vaccine for children ages 5 to 11. If authorized, it could begin to roll out to pediatricians’ offices and drugstores as soon as next month.

— With assistance by Jeannie Baumann, and Riley Griffin

FDA Press Release (Oct. 20, 2021) available at:

https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-takes-additional-actions-use-booster-dose-covid-19-vaccines 

A new study from La Jolla Institute for Immunology (LJI) scientists helps answer the question: how long does immunity against COVID-19 last in vaccinated people?  As they report in Science, a low dose of the Moderna vaccine lasts for at least six months, and there is no indicator that vaccinated people will need a booster shot. "This time point is critical because that is when true immune memory has formed," says LJI Research Assistant Professor Daniela Weiskopf, Ph.D., who co-led the study with LJI Professors Alessandro Sette, Dr.Biol.Sci., and Shane Crotty, Ph.D. In fact, while the Moderna COVID-19 vaccine (mRNA-1273) led to strong CD4+ (helper) T cell, CD8+ (killer) T cell and antibody responses for at least six months after clinical trial participants were fully vaccinated, it is likely that the immune response could last much longer. The researchers also show that this strong immune memory lasted in all age groups tested, including in people over age 70, a demographic especially vulnerable to severe COVID-19.  "The immune memory was stable, and that was impressive," adds Crotty. "That's a good indicator of the durability of mRNA vaccines."

Comparing Moderna vaccine to natural immunity

The researchers compared recovered COVID-19 patients to vaccine trial participants who received a 25-microgram dose of the Moderna vaccine during the phase 1 clinical trials (supported by the National Institute of Allergy and Infectious Diseases, National Institutes of Health).  "We wanted to see if a quarter of the dose is able to induce any immune response," says study first author Jose Mateus Triviño, Ph.D., a postdoctoral fellow at LJI. "We had the opportunity to receive the samples from the original Moderna/ NIH phase 1 trial participants who had received two 25-microgram injections of the vaccine, 28 days apart." This vaccine dose is a quarter of the 100-microgram Moderna dose given emergency authorization by the Food and Drug Administration (FDA). While researchers don't know whether this smaller dose is as effective as the standard dose, this new study shows that the T cell and antibody response in the smaller dose group is still strong. In fact, the researchers found that the Moderna vaccine spurs an adaptive immune response to the SARS-CoV-2 spike protein (a key target) nearly identical to the immune system's response to a natural SARS-CoV-2 infection. "The response is comparable," says Weiskopf. "It's not higher and it's not lower." The new study does not show that a lower dose of the Moderna vaccine provides the same protection as the standard dose. "It would take a clinical trial to tell you how protective the lower dose is," says Crotty.

Common cold viruses do prep the immune system

The new research also shows the power of "cross-reactive" T cells. In a 2020 Science study, the LJI team showed that T cells in people who had recovered from common cold coronaviruses could respond to the novel coronavirus, SARS-CoV-2. At the time, they didn't know whether this cross-reactivity could actually protect against COVID-19.  "Understanding the role of cross-reactive T cells is important because T cells play an important role in the control and resolution of COVID-19 infections," says Sette. For the new study, the researchers found that people with cross-reactive T cells had significantly stronger CD4+ T cell and antibody responses to both doses of the vaccine. "If you have this immune reactivity, your immune system may kick in faster against the virus," says Sette. "And multiple studies have shown that how quickly the immune system reacts is key."

Moderna vaccine activates "killer" T cells 

The team also filled in an important gap in COVID-19 vaccine research. Until now, many studies had shown an effective CD4+ T cell response to the Moderna vaccine, but CD8+ T cell data was lacking.  "We know naturally infected and recovered people develop excellent CD8+ T cell responses against SARS-CoV-2; however, there was concern about the generation of CD8+ T cells by mRNA vaccines," says Mateus Triviño.  The new study shows a strong CD8+ T cell response to the low dose Moderna vaccine, similar to the response after a patient fights a natural SARS-CoV-2 infection, says Sette, a renowned T cell expert. "We see a robust CD8+ T cell response—and we showed that using multiple assays," adds Weiskopf.

Coming up:

Will this same vaccine durability hold true for the other types of COVID-19 vaccines? Weiskopf and her colleagues are investigating. In the meantime, Weiskopf says real-world data suggest immune memory does last.  "The people in the hospitals are the ones not vaccinated," she says. The researchers are also interested in how the durability of the Moderna vaccine compares with other COVID-19 vaccines in use.

Research cited published in Science (Sept. 14, 2021):

https://doi.org/10.1126/science.abj9853 

Moderna Inc (MRNA.O) said on Thursday its COVID-19 shot was about 93% effective through six months after the second dose, showing hardly any change from the 94% efficacy reported in its original clinical trial. However, it said it still expects booster shots to be necessary ahead of the winter season as antibody levels are expected to wane. It and rival Pfizer Inc (PFE.N) and BioNTech SE (22UAy.DE) have been advocating a third shot to maintain a high level of protection against COVID-19.  During a second-quarter earnings call, Moderna CEO Stephane Bancel said that the company would not produce more than the 800 million to 1 billion doses of the vaccine that it has targeted this year. "We are now capacity constrained for 2021, and we are not taking any more orders for 2021 delivery," he said.  Moderna shares fell 3.6% to around $403.87 in pre-market trading after closing at $419.05 on Wednesday. The Moderna data compares favorably to that released by Pfizer and BioNTech last week in which they said their vaccine's efficacy waned around 6% every two months, declining to around 84% six months after the second shot. Both the Moderna and Pfizer-BioNTech vaccines are based on messenger RNA (mRNA) technology. The comment comes as public health officials across the world debate whether additional doses are safe, effective and necessary even as they grapple with the fast-spreading Delta variant of the coronavirus. Meanwhile, Pfizer is planning to seek authorization for a third shot later this month, and some countries like Israel have begun or plan to start administering a booster shot to older or vulnerable people.

BOOSTER CANDIDATES 

Separately, Moderna said its studies of three different booster candidates induced robust antibody responses against variants, including the Gamma, Beta and Delta variants. "Our COVID-19 vaccine is showing durable efficacy of 93% through six months, but recognize that the Delta variant is a significant new threat so we must remain vigilant," Bancel said.  It said neutralizing antibody levels following the boost approached those observed after the second shot. For this year, Moderna has signed vaccine contracts worth $20 billion in sales. It has agreements for $12 billion in 2022, with options for another roughly $8 billion in sales and expects to produce between 2 billion and 3 billion doses next year. The company, however, has not been able to keep pace with the much larger Pfizer, which expects to manufacture as many as 3 billion doses this year and 2021 sales to top $33.5 billion. Moderna's vaccine was authorized for emergency use in adults in the United States in December and has since been cleared for emergency or conditional use in adults in more than 50 countries.  The company expects to finish its submission for full approval with the U.S. Food and Drug Administration this month. It posted second-quarter sales of $4.4 billion, slightly above expectations of $4.2 billion drawn from 10 analysts polled by Refinitiv. Its COVID-19 shot is the firm's first authorized product and sales were just $67 million a year earlier. Moderna earned $2.78 billion, or $6.46 a share, beating quarterly expectations of $5.96 a share. 

Reporting by Michael Erman in New Jersey and Manas Mishra in Bengaluru; editing by Kirsten Donovan, Edwina Gibbs and Arun Koyyur

Current vaccines likely still work, scientists say, but their power may be declining. News from U.S. manufacturer Moderna that its COVID-19 vaccine is still “expected to be protective” against a virus variant first detected in South Africa came as a relief to scientists and the public. But the 25 January announcement included a caveat: Antibodies triggered by the vaccine appear to be a little less potent against the new variant, named B.1.351, than the one the vaccine was developed for. So researchers were perhaps even more relieved to hear the company will start development of booster shots tailored to B.1.351 and other variants. “These are exactly the steps that I hoped to see,” says virologist Trevor Bedford of the Fred Hutchinson Cancer Research Center. “It may well not be necessary to have a vaccine update in the fall, but taking these steps now is the right course of action.” Other vaccinemakers are also contemplating updates. Scientists have grown increasingly concerned that new coronavirus variants may worsen the pandemic. B.1.1.7, first detected in England and now spreading globally, has been shown to be more transmissible; on 22 January, the U.K. government said it may be deadlier as well. B.1.351 and a very similar variant named P.1 that originated in Brazil’s Amazonas state are suspected of evading immunity in people who were vaccinated or previously infected. Now, researchers from Moderna and the Vaccine Research Center at the U.S. National Institutes of Health have tested the potency of antibodies from eight people who had received the company’s vaccine against a retrovirus modified to express the mutated spike proteins of B.1.351 and B.1.1.7. In a preprint, they report that antibodies neutralized the virus in both cases. But for B.1.351, the levels needed were six times higher than for virus expressing the original protein.

A similar study by virologist David Ho of Columbia University, under review at Nature and posted as a preprint on bioRxiv, found that the serum of 22 people vaccinated with Moderna’s vaccine or a similar one from Pfizer was six to nine times less potent against B.1.351, and serum from 20 previously infected people was 11 to 33 times less potent. Researchers in South Africa, meanwhile, have found that antibodies from six recovered patients were six to 200 times less effective at neutralizing B.1.351. Such drops sound alarming, but the vaccines produced by Pfizer and Moderna trigger very high levels of antibodies, which likely compensates for the decline in potency, says Florian Krammer, a vaccine researcher at the Icahn School of Medicine at Mount Sinai. Besides, antibodies are only one part of the immune response; the vaccines also trigger T cells. Krammer is “quite optimistic” that both vaccines will still protect against B.1.351 and P.1. “However, this is worrisome for vaccines that are not as potent in inducing neutralizing antibodies as the two mRNA [messenger RNA] vaccines.” Others agree the results don’t spell doom yet. “Given the high starting point, it’s conceivable [vaccine efficacy] could drop only slightly,” Bedford says. Immunity is not binary, adds Jeremy Farrar, head of the Wellcome Trust: “It doesn’t suddenly turn on and turn off.” A drop in antibody potency could have more subtle effects, such as immunity waning a bit faster, he says. The results with sera from recovered patients also suggest the risk of reinfection with COVID-19 may be rising, especially for people who produced low levels of antibodies during their first encounter with the virus, says Stephen Goldstein, a virologist at the University of Utah. “Most of these people I expect to still have good protection from serious disease. It’s on a spectrum, though.”

Moderna says it will start phase I trials of two booster strategies: a third dose of its current vaccine, or of a slightly different one in which the mRNA has been tweaked to incorporate B.1.351’s mutations. They may be given to volunteers 6 to 12 months after the initial immunization, Moderna Chief Medical Officer Tal Zaks said in a call with investors. Pfizer, in an email to Science, wrote that it, too, is “laying the groundwork to respond quickly if a future variant of SARS-CoV-2 is unresponsive to existing vaccines.” Novavax, which is in late-stage trials with a vaccine based the spike protein, says it is “testing sera against the new strains.” Georgetown University virologist Angela Rasmussen says it’s “very wise” to start to prepare boosters now. “It’s also wise to begin thinking about how they will be distributed,” she adds. “For example, will they be allocated to regions with evidence that B.1.351 is circulating?” Regulators still need to spell out what trials they would require for updated vaccines. At a press conference on Monday, World Health Organization official Bruce Aylward said work to define a regulatory pathway was “kicking off right now.” Scientists also need to agree on faster ways to address any concerns about immune escape variants, says Farrar, and standardize the way they test antibodies’ potency: “We need harmonization of the assays, so we can compare the results and it doesn’t matter which lab you’re in.” Animal experiments need to be coordinated as well. Vincent Munster, a virologist at the U.S. National Institute of Allergy and Infectious Diseases, says he has already vaccinated hamsters and will challenge them with virus variants in the next couple of weeks. “These studies take a lot of coordination and we are discussing the need for a more planned approach to prepare for other novel variants emerging,” Munster says.

The most timely answers on B.1.351 may come from humans, however. Efficacy trials of several vaccines, including the Pfizer one, are ongoing in South Africa; Tulio de Oliveira, a virologist at the University of KwaZulu-Natal, says researchers are now sequencing the virus from 150 study participants who became infected. “We’re going have the results in 36 hours,” he says. But only after the trial is unblinded next week will researchers know how many of these infections occurred in people who received the vaccine instead of a placebo. Ho’s paper also sheds some light on how B.1.351 escapes the immune response. The team produced retroviruses with spike proteins incorporating each of B.1.351’s nine mutations separately, as well as all at once. A mutation named E484K accounted for much of the effect, they found. “E484K is really the bad boy here,” Goldstein says. Brazil’s P.1 variant has the same mutation, which might be a sign that the virus has few other tricks to evade immunity, he says: “The virus has a lot of room to evolve but not infinite room. We may have come upon one of the worst possible mutations already.” But other researchers say the plethora of recent changes is a warning sign that the coronavirus may have more surprises in store—and that the world needs to administer existing vaccines as fast as possible. “I think we need to stop the virus from replicating however we can,” Ho says. “Otherwise, it will keep accumulating more mutations.”