The world could be on the verge of having two more vaccines to fight the COVID-19 pandemic, but virus variants popping up worldwide are forcing vaccine-makers to develop boosters for a disease that’s constantly changing and could remain active for years.
Vaccines made by Moderna Inc. and the Pfizer Inc.-BioNTech SE partnership are already in use. Meanwhile, new studies show that two more — from Johnson & Johnson and Novavax Inc. — pack potent punches against early forms of the virus, potentially paving the way for quick authorizations in the U.S. for J&J’s vaccine and in the U.K. for Novavax’s shot.
Now comes the bad news: Mutations that likely confer partial resistance to vaccines and antibody treatments are now prevalent in both South Africa and Brazil, and they are threatening to spread worldwide. The J&J shot was found in a late-stage trial to be 72% effective in the U.S., but that fell to 57% in studies done in South Africa. Novavax’s shot, 89% effective in the U.K., was only 49% effective in South Africa.
Even before these results, laboratory tests on other vaccines suggested the shots would likely be less potent against the new South Africa variant. But what that meant in terms of illness in the real world was unclear. The new results offer a clear indication that vaccines won’t work as well against at least one of the emerging mutations.
“Now we have the real world clinical consequences, and we can see that we are going to be challenged,” said Anthony Fauci, the top U.S. infectious disease expert, on a conference call on Friday.
The first step is to know when mutations are around. In another Friday briefing, Centers for Disease Control and Prevention Director Rochelle Walensky said the U.S. is now asking each state to send at least 750 samples a week to be sequenced to determine what mutations may be spreading.
She warned that the existing U.S. system to detect different mutations is too slow for public health interventions to contain them.
“By the time someone has symptoms, gets a test, has a positive result and we get the sequence, our opportunity for doing real case control and contact tracing is largely gone,” Walensky said. “We should be treating every case as if it’s a variant during this pandemic right now.”
Peter Marks, director of the U.S. Food and Drug Administration’s Center for Biologics Evaluation and Research, said the agency is seeking to finalize a playbook with the industry to address mutations.
If the agency feels the virus has drifted enough to require a different sequence, it will require small trials to make sure the vaccines produce an immune response, he said. The first few studies may have to go through an advisory committee, according to Marks, but the agency is looking to streamline the process as much as possible and may require less data over time.
“We would intend to be pretty nimble with this,” Marks said on an American Medical Association webinar, “so we get these variants covered as quickly as possible because it is clear they can spread pretty quickly.”
Both Pfizer and Moderna — makers of the only two vaccines authorized for emergency use in the U.S. — have said their existing shots should produce enough antibodies against the South Africa mutation to make their vaccines effective.
The J&J vaccine has the potential to be the next authorized in the U.S. The drug giant plans to file with the FDA for an emergency-use authorization this week. The company’s top scientist said this month he expects a clearance in March.
The Novavax shot, meanwhile, is likely to get its first approval in the U.K., and the company is discussing with U.S. regulators whether trial data from other countries could be part of the shot’s review, Chief Executive Officer Stan Erck said. Novavax is still recruiting patients for a trial in the U.S. and Mexico, Erck said in an interview on Bloomberg Television.
The South African variant, or B.1.351, has already spread quickly across the African continent, and has been seen in at least 24 countries outside of Africa. It was found in the U.S. last week in two cases in South Carolina and another in Maryland. Meanwhile, a highly transmissible variant hailing from the U.K., which first surfaced Dec. 29 in the U.S., has spread to 29 states in less than a month, and U.S. health officials warn it could quickly become dominant.
While nations worldwide are seeking to contain the spread of the variants with travel restrictions, history suggests that’s a near impossibility.
The South Africa trial results are “most sobering,” said Eric Topol, director of the Scripps Research Translational Institute in San Diego. “We see an unequivocal drop-off in efficacy.”
That means the world must now divert attention to work on a new, adjusted vaccine or booster shot that works better on the South Africa strain, while it is still ramping up injections of the first shots, according to Topol.
“We are having enough struggle getting the first round of vaccines in,” he said.
The bottom line from scientists: This is a fight that could go for a long time. Vaccines that work well now may fade in the future unless booster shots are devised, something vaccine makers are already starting to work on. And it could be that COVID-19 morphs into something akin to influenza, requiring periodic booster shots over the years to keep it at bay.
“The implications are really worrisome,” said Peter Hotez, the dean of the National School of Tropical Medicine at Baylor College of Medicine, in an interview Thursday after the Novavax results were announced. “All the vaccine-makers now have to make decisions” on how to proceed.
Drugmakers could start working on new, so-called bivalent vaccines, a combined shot that contains two components to stimulate the immune system against both the original strain and the South Africa variant, Hotez said. Or they could keep their existing vaccines, he said, and customize booster shots to generate antibodies against the new variants.
Race to vaccinate
So far, Pfizer, Moderna and J&J have all said they’re in the process of developing booster shots or other approaches against the South Africa variant. In the meantime, it’s now a race to vaccinate the U.S. and Europe before the South Africa and Brazil variants become more common or, worse yet, new mutations develop that make the virus more resistant.
Fauci, in statements at the New York Press Club on Friday, said the thing that keeps him up at night is having “a mutant, where it really escapes everything.”
He said it was “concerning that you need to stay ahead of these mutants, and essentially crush this outbreak so that there’s no more replication. And when there’s no more replication you’re not going to have any mutations.”
In laboratory results reported before the new Novavax and Johnson & Johnson trial data was in, researchers from the Aaron Diamond AIDS Research Center at Columbia University found that the Pfizer and Moderna vaccines were “6.5 to 8.6-fold” less potent against the South Africa mutation.
“Looking at our results you cannot say this would doom the vaccine. That would be wrong. But I think it is equally wrong to say everything is rosy,” said virologist David Ho, who leads the lab. “We allowed the virus to infect 100 million people already, so that is 100 million chances for mutation.”