Omicron vs. T cells: Why scientists are banking on the immune system’s ‘memory’

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It’s a worrying convergence: falling antibody levels and a new variant.

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Scientists have warned that a coronavirus virus like Omicron, which appears to be able to dodge some of the protective antibodies generated by vaccines, could be a major setback in the pandemic. But as the world awaits more data on the heavily mutated version, experts say there are some early but encouraging signs that our immune system has assembled a variety of tools to fight COVID-19.

“Our antibodies may not work as well, but the immune system has these backup plans that give us some resilience against omicrons,” said E. John Varys, director of the Institute of Immunology at the University of Pennsylvania.

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There is some early indication that booster shots may be needed to counteract the drop in antibodies with Omicron. Pfizer-BioNtech announced Wednesday that the third dose provides comparatively stronger protection against Omicron as the company’s initial two-dose regimen did against the original strain of the virus.

Yet even if antibody levels are low against the variant, the immune system can be primed to “remember” the virus from vaccines or previous infections. The focus now is whether the parts of the immune system that power this long-term protection – mainly T cells – will hold up against the omicrons.

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If so, the immune response after infection can accelerate and protect people from the worst effects of the virus.

More research is needed, but the ability of the body’s immune system to recall the virus will likely be important no matter how severe the current wave of infections around the world is. It will also help scientists better characterize the Omicron variant, including the risk of breakthrough infection in vaccinated individuals and the potential for re-infection in those who were ill with a previous strain.

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In South Africa, where the first major outbreak of the variant was reported, Omicron is seeing a sharp increase in cases. Although it is still early, the increase in infections has not yet been associated with serious illness or hospitalization.

South Africa has limited access to vaccines, and thus its population has a significantly lower vaccination rate than the United States and Europe but a high level of natural immunity from infection in previous waves of epidemics.

Very said that if hospitalization rates remain relatively low when Omicron’s outbreak, it could indicate that the immune system is still building a strong response against this latest variant. But he said it’s too soon to know for sure, as hospitalizations and deaths can lag behind infections by weeks, and researchers are still racing to understand the basics of Omicron, as Delta et al. How contagious it is compared to previously identified variants.

However, there is increasing evidence that the mutation of the oomicron in the spike protein of the coronavirus may help prevent neutralizing antibodies produced by vaccines. These antibodies usually bind to specific targets with spike proteins and prevent the virus from getting into cells, but high enough mutations can disrupt this biological mechanism.

Yet antibodies are just one part of how the immune system organizes protective immunity.

“Antibodies are your first line of defense,” Very said. “But we have other cells that can recognize the virus in a completely different way.”

Specifically, there are two types of so-called T cells that are designed to lie in wait until foreign invaders are detected. One type, known as T helper cells, coordinates the body’s various immune responses. The second, called cytotoxic T cells or killer T cells, are designed to recognize and eliminate tiny snippets of viruses inside cells.

“T helper cells are like immune system generals, and killer T cells are like killers,” said Andrew Rad, a virologist at the National Institute of Allergy and Infectious Diseases.

Because T cells do not target specific regions on the surface of the virus the way antibodies do, they are less affected when a pathogen undergoes mutation, Rad said.

In a pre-print study that has yet to be peer-reviewed, Rad and his colleagues examined whether mutations in the omicron effectively changed the snippets of virus that killer T cells could recognize. The researchers looked at 52 fragments of the virus, which were identified early last year from 30 patients infected with Kovid and have since recovered. They found only one mutation in a segment that T cells recognize, and only two of the 30 people studied.

Conclusion a. were similar to Separate NIAID Study Published in March by Rad and colleagues found that T cell responses were largely unaffected by mutations in the previous three variants: alpha, which was first detected in the United Kingdom in late 2020; beta, which was first reported in South Africa in December 2020; and Gamma, which was first detected in Brazil in January.

“This suggests that T cell responses are largely intact and should remain largely intact against Omicron,” Rad said.

This means that even if antibody levels are reduced, most people who are vaccinated – With two doses of Pfizer-BioEntech or Moderna Vaccines or one shot of the Johnson & Johnson vaccine – or natural immunity, they can be protected from becoming seriously ill if they test positive for Omicron.

“I expect most infected people to stop going to the hospital,” said Rachel Graham, an assistant professor in the department of epidemiology at the University of North Carolina at Chapel Hill.

In addition to T cells, the body also has cells known as memory cells, which can remember pathogens and rapidly activate immune responses. For example, some memory cells can increase the production of antibodies, while others can jump-start killer T cells.

It is this complex interplay of biological mechanisms and responses that fuels optimism among some experts that the immune system can bank on more than one weapon in its arsenal to fight off omicrons and other forms.

Graham said the situation underscores the importance of thorough vaccination because even low antibody levels can provide some protection, especially in people who have also received a booster shot.

“Even if the vaccine isn’t as effective against Omicron, it’s still going to be more effective than not being vaccinated,” she said.

Preliminary data showed that the Pfizer-BioEntech vaccine appears to be less effective against Omicron, but the company announced Wednesday that the third dose offers stronger protection against the variant. More results on the vaccine’s effectiveness are expected in the coming weeks.

But beyond vaccines and antibodies, collecting data on T cell responses is hard enough, Rad said.

Unlike testing for antibodies, a relatively simple procedure that can be done with a blood sample, studying T cells requires purifying white blood cells from a sample and testing all of those potential areas. where T cells can recognize the responses to be measured. Wherry said this is not only expensive but very laborious, and the process, which involves the transfer of the resulting data through reams, cannot be automated in any way.

“It’s easily a week or more of work to analyze T cell responses in 10 or a dozen people, whereas in a day you can analyze antibody responses from thousands of people,” Veri said.

But with the coronavirus still circulating around the world, opening up the possibility for other new forms to emerge, it will remain essential for scientists to keep track of how the body’s immune response changes as the virus evolves.

“If we can’t get the world vaccinated, we’re going to continue to see variants like Omicron,” Veri said. “My big concern is the implications of whatever next version comes out in the future.”



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