Unvaccinated Omicron survivors do not build immunity to other strains

Researchers have discovered that in unvaccinated people, infection with the Omicron variant of SARS-CoV-2 (novel coronavirus) does not provide much long-term immunity against other variants.

The research was conducted at Gladstone Institutes and University of California San Francisco (UCSF) and was published in Nature journal.

The researchers used mice and blood samples from donors infected with the Omicron variant, and realised that this variant creates only a weak immune response. So how do humans react? 

Well, if they were vaccinated, even though their immune response was weak, the infection still boosted their overall protection against a variety of coronavirus strains. Yet if they were not vaccinated, the immune response was negligible, and did not offer enough protection against other strains.

“In the unvaccinated population, an infection with Omicron might be roughly equivalent to getting one shot of a vaccine,” says Melanie Ott, MD, PhD, director of the Gladstone Institute of Virology and co-senior author of the new work. “It confers a little bit of protection against Covid-19, but it’s not very broad.”

“This research underscores the importance of staying current with your vaccinations, even if you have previously been infected with the Omicron variant, as you are still likely vulnerable to re-infection,” says co-senior author Jennifer Doudna, PhD, who is a senior investigator at Gladstone, a professor at UC Berkeley, founder of the Innovative Genomics Institute, and an investigator of the Howard Hughes Medical Institute.

Weaker yet highly infectious variant

The Omicron variant of SARS-CoV-2 took the world by storm in late 2021 and early 2022. People who get infected with it suffer from less severe symptoms than Delta and other variants of concern. Yet scientists did not know at the beginning why the symptoms were less severe, or how a weaker infection might act upon long-term immunity against the coronavirus.

“When the Omicron variant first emerged, a lot of people wondered whether it could essentially act as a vaccine for people who didn’t want to get vaccinated, eliciting a strong and broad-acting immune response,” says Irene Chen, co-first author of the new study and graduate student in Ott’s lab. Other first authors, according to a news release, are Rahul Suryawanshi, PhD, a Gladstone staff research scientist, and Tongcui Ma, PhD, scientist in the Roan Lab at Gladstone.

In order to find out the outcome of an Omicron infection, the researchers turned to mice. The Omicron variant led to far fewer symptoms in mice compared to other strains of the coronavirus, including the Delta variant. Yet they were able to detect the virus in airway cells, even though it was at lower levels. Likewise, it was possible for Omicron to infect isolated human cells but it replicated less than other variants.

The researchers summed up their findings about the immune response generated by Omicron infections. They found that in mice infected with the Omicron variant, even though they displayed milder symptoms, their immune systems came up with the T cells and antibodies typically seen in response to other viruses.

“We demonstrated in this study that the lower pathogenicity of Omicron is not because the virus cannot take hold,” says Nadia Roan, PhD, an associate investigator at Gladstone.

So the researchers had to find other explanations for why Omicron infections are different from other variant infections in terms of symptoms and immunity, “including the lower replication seen with omicron or the types of antibodies that the immune system generates in response to the virus,” the news release explains.

Does not protect against other variants

The researchers collected blood samples from mice infected with three coronavirus variants: ancestral (WA1),  Delta, and Omicron. They wanted to see how the immune response against Omicron fared over time. Then they measured the capacity of mice immune cells and antibodies to recognise five different viral variants: ancestral (WA1), Alpha, Beta, Delta, Omicron.

If the animals had been uninfected by the coronavirus, their blood could not neutralise any of the five virus variants – that is, block the ability for them to replicate. “Samples from  WA1-infected animals could neutralise Alpha, and, to a lesser degree, the Beta and Delta virus –– but not Omicron,” the news release notes. “Samples from Delta-infected mice could neutralise Delta, Alpha and, to a lesser degree, the Omicron and Beta virus.”

One detail that stood out: blood from Omicron-infected mice could only neutralise the Omicron variant. This time the researchers went further than just testing mice blood – they drew blood from 10 unvaccinated people who had been infected with Omicron, and discovered that their blood couldn’t neutralise the other variants either. However, when they tested the blood of 11 unvaccinated people who had been infected with the Delta variant, their blood could neutralise Delta and just like as seen in mice, the other variants, although not as much.

The researchers did not only draw blood from unvaccinated people but involved vaccinated people as well in the study. Their results differed from those from unvaccinated people: vaccinated subjects with confirmed Omicron or Delta breakthrough infections all showed the ability to neutralise all five variants tested, creating a more protective immune system for the vaccinated patients.

“When it comes to other variants that might evolve in the future, we can’t predict exactly what would happen, but based on these results, I’d suspect that unvaccinated people who were infected with Omicron will have very little protection,” says Ott. “But 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 individuals’ decisions on vaccination, but also for the design of future COVID-19 vaccines that confer broad protection against many variants,” says Charles Chiu, MD, PhD, a professor of infectious diseases at UCSF and a co-senior author of the work.