WASHINGTON – A highly transmissible coronavirus variant first identified in South Africa was reported Thursday in the United States, hours before Maryland biotech company Novavax announced that its coronavirus vaccine was highly effective in preventing illness – except against that variant.
The Novavax data surprised and disappointed scientists, who said it is the latest sign that the new mutation-laden variants pose a challenge for vaccine makers and complicate the battle to crush the pandemic. The company’s results provide the first glimpse of how any coronavirus vaccine protects against two mutated versions of the virus that rapidly became dominant in the United Kingdom and South Africa and then spread across the world.
“The South African variant is looking like it’s going to be a far more complicating factor than we had hoped,” said Peter Jay Hotez, dean for the National School of Tropical Medicine at Baylor College of Medicine, who is developing a different coronavirus vaccine and said his team has already designed one against the South African variant.
The Novovax vaccine was highly effective – 89% – in a trial where the variant first identified in the United Kingdom, known as B.1.1.7., was highly prevalent. But its efficacy dropped to 49% in a smaller and less definitive South Africa trial, where the vast majority of infections were from a different variant that is spreading there, known as B. 1.351.
Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, said there was “good news and sobering news” in the Novovax data release.
“The good news is that it does have an impact on the South African strain, it does – no doubt,” Fauci said. But he called the drop in efficacy “significant” and said it was a wake-up call: “The viruses are going to continue to mutate, and we have to be nimble enough to keep up with them.”
Other experts cautioned against comparing trials too closely, because of differences in design and context. A 50 perfect effective vaccine, some noted, would have a powerful effect as the pandemic is raging and is similar to the efficacy of flu vaccine some years.
But the potentially ominous news for all the coronavirus vaccines, which are already rebooting to fight the variant identified in South Africa, came as public health officials received confirmation of what many have suspected – that all three major “variants of concern” identified by international science teams in recent weeks are present in the United States.
On Thursday, South Carolina officials disclosed the first two cases in the United States involving the B. 1.351 variant, and the patients’ lack of travel or a connection to one another suggests the variant is spreading in the community following an undetected introduction.
The state Department of Health and Environmental Control did not release the names of the people infected, stating only that they are adults, “one from the Lowcountry and one from the Pee Dee region.”
On Monday, Minnesota officials announced they had detected the P. 1 strain that has been spreading in Brazil and is linked to the disastrous surge in cases in the Amazonian city of Manaus, where hospitals are once again overwhelmed. The P. 1 variant shares several mutations with the B. 1.351 variant.
The widely publicized B.1.1.7 variant first seen in the United Kingdom has been detected in more than two dozen U.S. states.
Scientists are not surprised by these developments. The variants had gone undetected until now in the United States because of limited genomic surveillance of the virus. Efforts are being made to increase surveillance through partnerships among the Centers for Disease Control and Prevention and academic institutions and private companies.
There is no evidence the B. 1.351 variant is deadlier for the individual patient than more common strains. But if it is more transmissible, as scientists suspect based on preliminary data, the resulting boost to the infection rate would increase hospitalizations and deaths.
“At this time, we have no evidence that infections by this variant cause more severe disease. Like the UK and Brazilian variants, preliminary data suggests this variant may spread more easily and quickly than other variants,” the CDC said Thursday in a statement responding to the South Carolina cases.
The B. 1.351 variant contains a key mutation that appears to allow the virus to elude some of the onslaught of antibodies produced through vaccines or administered in drug therapies. At least one antibody therapy will not work against the new variants, and scientists are scrambling to create a new antibody that can block the mutation.
Laboratory studies in recent days have found that the mutation in the variant diminishes the ability of vaccine-induced antibodies to neutralize the virus. Whether that translates into decreased vaccine effectiveness has been uncertain, and the Novavax data provides one key data point, but vaccine makers are working on new vaccines and booster shots that could be used if immunity fails.
In the South African trial from Novavax, which included just 4,400 people, the vaccine was 49% effective, although the company underscored that when looking only at people not infected with HIV, the efficacy was 60%.
“I would also say that while 60 percent isn’t the 90 to 95 that we’re used to, it is pretty remarkable, and there were really two things happening in South Africa: One is the variant, but the second is just what appears to be the intensity of the transmission with other mitigating factors,” said Kathleen Neuzil, director of the Center for Vaccine Development at the University of Maryland School of Medicine.
The variants first identified in the United Kingdom and South Africa are different but share a few concerning mutations. Most prominent among them is one called E484K, which affects the structure of a portion of the coronavirus spike protein that enables the virus to latch onto and enter cells. The spike protein is the target for many antibodies, both lab-generated ones used as drugs and those conjured by the immune system in response to a vaccine or natural infection.
David Ho, a professor of microbiology and immunology at Columbia University, compared the E484K mutation to having a lock changed, and then trying to use the same key to open the door.
Imagine there were jagged triangles at the top of the spike protein, he said, and that the antibody had a perfect fit to that jagged edge. With the mutation, the triangle tooth is modified significantly in its shape. Now, it’s a square. Suddenly, the antibody loses its ability to grab onto the virus, and the virus can escape and do its damage.
The most important near-term step the public can take is to try to stop the spread of the virus, scientists and public health officials have said – a message the CDC reiterated Thursday in its statement. Vaccinations are critical to suppression of the pandemic, but vaccines remain in short supply. In the meantime, people should adhere to non-pharmaceutical interventions such as social distancing and wearing masks.
“We know that viruses mutate to live and live to mutate,” Brannon Traxler, interim director of the South Carolina public health department, said in the statement released Thursday. “That’s why it’s critical that we all continue to do our part by taking small actions that make a big difference.”
She said the two people infected with the B. 1.351 variant were tested early in the month and are no longer contagious.
“We also are doing deeper dives into other histories they might have had or other exposures,” Traxler told reporters in a conference call. She added that, based on contact tracing so far, officials do not believe the people were engaged in activities leading to “widespread transmission.”
Companies that make vaccines and therapeutics are working to keep up with the mutations. The most immediate challenge involves the drugs called monoclonal antibodies. Because they deliver just one or two laboratory-brewed antibodies that latch on to the virus in specific areas, the wrong mutation may render them useless more easily than vaccines, which trigger a multifaceted immune response.
Many scientists believe, based on preliminary evidence, that the vaccines will still work in coming months, but companies that make the vaccines are preparing to evolve their recipes as the virus mutates.
“What we see now is worrisome, because there’s a substantial decline in activity against the strain from South Africa, and that likely applies to the strain from Brazil because of similar mutations,” Ho said. “It’s absolutely wrong to say this is gloom and doom, but it’s absolutely wrong to say it’s absolutely rosy. I think the truth is in the middle, and we need to be sufficiently concerned that we should be preparing for the worst-case scenario.”
This week, data released before publication from Ho’s lab showed that Eli Lilly’s monoclonal antibodies – one of which is authorized and one of which is experimental – would be eluded by the variants first identified in South Africa and Brazil. Lilly chief executive David Ricks told investors and media outlets Tuesday that the company was working on developing an antibody that would neutralize those mutant versions of the virus.
The B. 1.351 variant “is capturing the most attention and interest because it has so many mutations and changes in the spike protein, and would be predicted to disrupt binding of most antibodies,” Ricks said.
But in a sign of just how fast the situation is evolving, he said Tuesday that Lilly’s current antibodies were “predicted to be effective against more than 99 percent of all strains that we see in the United States today.” That was hours after it was disclosed that the Brazilian strain had been detected in Minnesota and two days before the South African strain was confirmed in South Carolina.
Scientists believe the antibody cocktail made by Regeneron Pharmaceuticals is still likely to be effective against the variant. Although the variant is likely to escape one part of its cocktail, the other component binds to an area that should not be affected by the current mutations, said Jason McLellan, a structural biologist at the University of Texas at Austin.
Christos Kyratsous, vice president of research at Regeneron, said the company is continually monitoring for new sequences and screening those against its library of antibodies to monitor when it becomes necessary to change or add on to the cocktail.
“Biologically, this is something I totally expected,” Kyratsous said. “There was the expectation from the beginning. . . . One reason we chose a cocktail [of antibodies] is to have an insurance policy, if one of the antibodies stops working or does not work as well. The cocktail will still work.”
Moderna announced Monday that it is working to develop and begin human tests of a vaccine specific to the South African variant, as a precaution. The company also will test a third booster shot of its current vaccine, to see whether boosting immunity to the original virus could protect against the variant.
– – –
The Washington Post’s Lena H. Sun contributed to this report.