Moderna’s omicron booster was only as good as current vaccine in monkey study

In a small group of monkeys, an omicron-specific version of Moderna's COVID-19 vaccine did not protect against the omicron variant better than Moderna's current, highly effective booster. This finding casts doubt on whether a switch to variant-specific doses is necessary.

The study was led by researchers at the National Institutes of Health and posted on a preprint server last Friday. The study has not been peer-reviewed or published in a scientific journal. It also has all the limitations of an animal study and only involved eight monkeys. The study's findings will have to be verified in human trials, which are currently underway.

Still, there's good reason to think the finding will hold up. As the authors of the study note, this isn't Moderna's first variant-specific booster. The company had previously developed a booster against the concerning variant beta. As with the omicron-specific booster, the beta-booster didn't outperform the original vaccine at protecting primates from beta. And that finding later held up in human trials.

"The nonhuman primate (NHP) model has... been largely predictive for what has been observed in humans in terms of protective efficacy," the authors write.

Moreover, the finding falls in line with the concept of "original antigenic sin" (aka antigenic imprinting). This idea suggests that, when the immune system is presented with a pathogen similar to one it has fought before, the encounter will activate the immune memory from the prior interaction. In other words, a response to an omicron-specific vaccine will build off the responses to prior versions of SARS-CoV-2 encountered.

That's exactly what the vaccine researchers saw in their new monkey study. After researchers gave all eight monkeys two standard doses of Moderna's vaccine, the humans boosted four of the simians with the current booster and the other four with an omicron-specific booster. Both boosters activated certain immune cells—called memory B cells—that were cross-reactive, meaning the cells targeted both the old version of SARS-CoV-2 and omicron. More specifically, regardless of which booster a monkey received, 70 percent to 80 percent of their memory B cells were dual-specific to the old virus and omicron. And, while the current booster also spurred responses that were specific only to the old virus, the omicron booster didn't seem to spur any omicron-specific B cell responses.

Equally good

Otherwise, boosting the monkeys with either of the vaccines led to the same strong increase in neutralizing antibodies against omicron. And, when the vaccinated and boosted monkeys were challenged with an omicron infection, both boosters protected the primates equally well from disease in their lower airways.

"Therefore, an Omicron boost may not provide greater immunity or protection compared to a boost with the current [Moderna] vaccine," the researchers concluded.

To be clear, that's not necessarily bad; the current boosters are providing strong protection against omicron. The latest real-world data reported by the Centers for Disease Control and Prevention found that boosters are 82 percent effective at preventing the need for urgent or emergency care from COVID-19 and 90 percent effective at preventing hospitalization from COVID-19. People who are vaccinated and boosted are five times less likely to get COVID-19 amid the omicron wave than unvaccinated people.

Still, Moderna is currently running a clinical trial on an omicron-specific booster dose to try to top those numbers. The company has said it expects it could distribute the booster later this year, possibly as a dose for the autumn in preparation for a cold-weather case surge. Vaccine maker Pfizer and partner BioNTech are also working on an omicron-specific vaccine that has entered clinical trials.

Whether or not the new monkey data will end up derailing those plans is unclear. The authors suggest that, if the findings do hold up in humans, there would be no need or advantage to switching to an omicron-specific booster for now. And even if omicron continues to be the dominant variant circulating, the authors argue that they would need further data to recommend replacing the current vaccine with an omicron-specific shot, particularly for currently unvaccinated children and infants. Data in mice, for instance, suggests that an omicron-specific vaccine may not provide the same cross-reactive protection against other variants. If that holds up in humans, a combination vaccine that targets multiple variants at once may be in order. Overall, a variant-specific booster may only be needed if a future variant evolves that can dodge current cross-reactive responses, the authors argue.

Correction: This story was updated to correct the likelihood of an omicron infection in people vaccinated and boosted compared with unvaccinated people. They are five times less likely, not 14.