Last winter, the Omicron variant swept across the country, triggering a spate of COVID-19 cases. Now, a few months later, those affected are left with a nagging question: how protected am I against future variants? This question is particularly relevant because another variant, BA.2.12.1, is causing a recent spike in the number of cases. Now a team of researchers may have an answer.
New research shows that infection with the Omicron variant of SARS-CoV-2 in unvaccinated people provides little long-term immunity against other variants. In experiments with mice and blood samples from donors infected with Omicron, the team found that the Omicron variant induces only a weak immune response. In vaccinated individuals, this response, while weak, helped bolster overall protection against a variety of COVID-19 strains. However, in those without prior vaccination, the immune response did not provide broad, robust protection against other strains.
“In the unvaccinated population, an infection with Omicron can be roughly equivalent to getting one shot of a vaccine,” says Melanie Ott, MD, PhD, director of the Gladstone Institute of Virology. “It offers a little bit of protection against COVID-19, but it’s not very broad.”
This research was published in Nature in the paper, “Limited Immunity to Different Variants of SARS-CoV-2 Omicron Without Vaccination.”
As the Omicron variant of SARS-CoV-2 spread around the world in late 2021 and early 2022, scientists were initially unsure how the variant, which appeared to result in a weaker infection, enhances long-term immunity against COVID-19. could affect. †
“When the Omicron variant first showed up, many people wondered if it could essentially act as a vaccine for people who didn’t want to be vaccinated, eliciting a strong and broad-based immune response,” said Irene Chen, a graduate student. . in Ott’s lab.
To find the answer, the team of researchers examined the effect of Omicron in mice. Compared to an ancestral strain of SARS-CoV-2 and the Delta variant, Omicron resulted in far fewer symptoms in the mice. However, the virus was detected in airway cells, albeit at lower levels. Similarly, Omicron was able to infect isolated human cells, but replicated less than other variants.
The team then characterized the immune response generated by Omicron infections. In mice infected with Omicron, despite the milder symptoms, the immune system generated the T cells and antibodies usually seen in response to other viruses.
“We showed in this study that Omicron’s lower pathogenicity is not due to the virus’s inability to take hold,” said Nadia Roan, PhD, associate researcher at Gladstone.
That leaves other reasons that could explain why Omicron differs from other variants in terms of symptoms and immunity, including the lower replication seen with Omicron or the antibodies generated.
To measure how the immune response to Omicron progressed over time, the researchers collected blood samples from mice infected with the ancestral, Delta, or Omicron variants of SARS-CoV-2 and measured the ability of their immune cells and antibodies to recognize five different viral viruses. variants – ancestral (WA1), Alpha, Beta, Delta and Omicron.
Blood from uninfected animals was unable to neutralize the viruses. Samples from WA1-infected animals can neutralize alpha and, to a lesser extent, beta and delta viruses, but not Omicron. Samples from Delta-infected mice could neutralize Delta, Alpha and, to a lesser extent, Omicron and Beta viruses. However, blood from Omicron-infected mice could neutralize only the Omicron variant.
The team confirmed these results with blood from ten unvaccinated people infected with Omicron – their blood was unable to neutralize other variants. When they tested blood from 11 unvaccinated people infected with Delta, the samples were able to neutralize Delta and, as seen in mice, the other variants to a lesser extent.
When they repeated the experiments with blood from vaccinated people, the results were different: vaccinated individuals with confirmed Omicron or Delta breakthrough infections all showed the ability to neutralize all tested variants, yielding higher protection.
“When it comes to other variants that could evolve in the future, we can’t predict exactly what would happen, but based on these results, I suspect that unvaccinated people infected with Omicron will have very little protection,” said Otto. “On the contrary, vaccinated individuals are likely to be more broadly protected against future variants, especially if they had a breakthrough infection.”
“Our results may be useful not only to inform individual decisions about vaccination, but also to design future COVID-19 vaccines that provide broad protection against many variants,” said Charles Chiu, MD, PhD, professor of infectious diseases at UCSF .
“This research underscores the importance of staying up to date with your vaccinations, even if you have been previously infected with the Omicron variant, as you are likely still vulnerable to reinfection,” said co-senior author Jennifer Doudna, PhD. , a senior investigator at Gladstone, a professor at UC Berkeley, and a Howard Hughes Medical Institute investigator.
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