People infected with the earliest version of the omicron variant of the coronavirus, first identified in South Africa in November, may be vulnerable to reinfection with later versions of omicron even if they have been vaccinated and boosted, new findings suggest.

Vaccinated patients with omicron BA.1 breakthrough infections developed antibodies that could neutralize that virus plus the original SARS-CoV-2 virus, but the omicron sublineages circulating now have mutations that allow them to evade those antibodies, researchers from China reported on Friday in Nature.

Omicron BA.2.12.1, which is now causing most of the infections in the United States, and omicron BA.5 and BA.4, which account for more than 21% of new U.S. cases, contain mutations not present in the BA.1 and BA.2 versions of omicron.

Those newer sublineages “notably evade the neutralizing antibodies elicited by SARS-CoV-2 infection and vaccination,” the researchers found in test-tube experiments.

The monoclonal antibody drugs bebtelovimab from Eli Lilly and cilgavimab, a component of AstraZeneca’s Evusheld, can still effectively neutralize BA.2.12.1 and BA.4/BA.5, the experiments also showed.

But vaccine boosters based on the BA.1 virus, such as those in development by Pfizer/BioNTech and Moderna, “may not achieve broad-spectrum protection against new omicron variants,” the researchers warned.

Previous research that has not yet undergone peer review has suggested that unvaccinated people infected with omicron are unlikely to develop immune responses that will protect them against other variants of the coronavirus.

“My personal bias is that while there may be some advantage to having an omicron-specific vaccine, I think it will be of marginal benefit over staying current with the existing vaccines and boosters,” said Dr. Onyema Ogbuagu, an infectious diseases researcher at Yale School of Medicine in New Haven, Connecticut, who was not involved in the new study.

“Despite immune evasion, the expectation can be that vaccines will still protect against serious disease,” Ogbuagu said. “If you’re due for a booster, get a booster. What we’ve learned clinically is that it’s most important to stay up to date with vaccines” to maintain high levels of COVID-19 antibodies circulating in the blood.

Adolfo Garcia-Sastre, a microbiology and infectious diseases researcher at the Icahn School of Medicine at Mount Sinai in New York City, suggested that better protection might be seen with vaccines that target multiple strains of the virus or with intranasal vaccines that would increase protection from infection and transmission by generating immunity in the lining of the nose, where the virus first enters.

Garcia-Sastre, who was not involved in the research, said by the time one variant-specific vaccine becomes available, a new variant may well have taken over.
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