As new Covid-19 task force gets underway, threat looms of vaccine, monoclonal antibody-resistant variants
Hours before President Biden’s Covid-19 team gave their first virtual press conference, the famed AIDS researcher David Ho delivered concerning news in a new pre-print: SARS-CoV-2 B.1.351, the variant that emerged in South Africa, is “markedly more resistant” to antibodies from convalescent plasma and vaccinated individuals.
The news for several monoclonal antibodies, including Eli Lilly’s bamlanivimab, was even worse: Their ability to neutralize was “completely or markedly abolished,” Ho wrote. Lilly’s antibody cocktail, which was just shown to dramatically reduce the risk of hospitalizations or death, also became far less potent.
The B1.351 variant has yet to be seen in the US, new CDC director Rochelle Walensky assured reporters, but the variants nonetheless took up a substantial portion of the first Covid-19 briefing, as Walensky and NIAID director Anthony Fauci outlined steps the US would take as they became more common in the country and as the virus continues to mutate, potentially in ways that make them yet more resistant to vaccines and antibodies.
The B.1.1.7 variant, now dominant in the UK and growing in the US, hasn’t been able to significantly elide vaccines or monoclonal antibodies, Fauci said. There’s growing evidence, though, that the variant common in South Africa can avoid monoclonals and some antibodies produced by vaccines.
Because the Pfizer and Moderna vaccines are so effective, Fauci said, potency can drop considerably without impacting efficacy, and there are no data to suggest the vaccine isn’t still protective.
“However,” he said, “given that as a fact now, we have to be concerned about what further evolution of this might be.”
So far, the only tests for whether vaccines and monoclonal antibodies can neutralize new variants have been in vitro studies — test tube experiments where the antibodies are mixed with a fake version of SARS-CoV-2 the experimenter checks to see whether the virus still managed to infect cells. Those experiments, conducted both by companies and in academic labs, have been encouraging for B.1.1.7 and discouraging for B.1.351.
The new Ho paper, for example, conducted in collaboration with the NIH and Regeneron, showed 10 out of 12 antibodies were equally effective against B.1.1.7 and two were only slightly less effective, while vaccine efficacy fell 2-fold. The B.1.351 variant, though, almost entirely avoided five of the monoclonal antibodies, while vaccine efficacy fell 6.5-fold for Pfizer and 8.6-fold for Moderna.
Soon, though, the US is likely to get data on how the vaccine works against the different variants in the real world, Fauci said. J&J conducted their pivotal vaccine trial around the world, including in South Africa and Brazil, where another variant, called P.1, has spread. Their results should come “within the next few days,” Fauci said.
“What we will see was the relative efficacy against the wild type virus that is predominantly in the US, as well as the South African isolate,” Fauci said. It “will inform us of where we would go, if the eventuation occurs that we do have that particular lineage seed itself in the United States.”
In the meantime, vaccine and antibody developers have been preparing for that potential. Moderna developed a vaccine designed specifically for B.1.351 and has said they will start Phase I trials using both the new vaccine and the original as a booster shot. Pfizer and Novavax said they are also drawing up contingency plans.
The Ho paper pointed antibody developers, who are more acutely threatened by a mutating virus than vaccine companies, to a potential solution. Although Eli Lilly’s main antibody did little against the new variant, Regeneron’s combo still successfully neutralized it, pointing to the potential importance of combination strategies.
Still, a combo isn’t necessarily a panacea, as shown by the low potency Ho found for Lilly’s cocktail. The Indianapolis-based Big Pharma announced this morning, though, that they began experimentally dosing patients with a combination of bamlanivimab and an antibody Vir and GSK are co-developing. In a statement, GSK noted that the two antibodies bind to different epitopes, or sub-units, of the virus.
Vir could also emerge as a winner in the hunt for an effective single antibody. Relying on an antibody that also neutralizes the original SARS virus, they long positioned themselves as developing the best antibody should the virus mutate. Although their potency was reduced against B.1.351, it still effectively neutralized the variant. A large trial of the antibody is due to read out in the coming weeks.
Responding to the new strains, however, will require the US to properly monitor the genomes of viruses entering the country and to track how the virus evolves within the country. So far, the US has lagged considerably in sequencing viruses, officials acknowledged at the briefing, ranking 43rd in the world according to one count.
The new health officials promised that would improve, noting that Biden’s new stimulus and relief bill includes funds for genomic surveillance.
“It is essential as part of the American rescue plan,” said Jeffrey Zients, coordinator of Biden’s Covid-19 response.
Fauci added that sequencing will be supplemented with continual studies to test whether antibodies from vaccines neutralize new variants and when it’s time to push forward modified vaccines or antibodies.
“All of that is going on,” he said, “literally as we speak.”
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