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December 16, 2021

An unrecognized immunity hero in the fight against omicron: T cells

Daily Briefing

    Although the omicron variant may be able to evade some vaccine-induced antibodies, immunologists and other experts say people who are vaccinated against Covid-19 are likely to be protected against severe disease and death due to other aspects of the immune system, such as T cells.

    The omicron variant: The 'good,' 'bad,' and 'ugly' scenarios

    Omicron may evade vaccine antibodies, early data suggests

    Early data has suggested that omicron is able to evade some forms of vaccine immunity, particularly neutralizing antibodies that help prevent symptomatic infection.

    According to The Atlantic, antibodies are "powerful but simple sentinels" that are produced by B cells. Antibodies target specific characteristics of a pathogen—such as the coronavirus's spike protein. And some antibodies, called neutralizing antibodies, attach to pathogens so they can't enter cells, thus preventing infection.

    However, antibody levels, which usually skyrocket after vaccination, begin to decrease over time, allowing pathogens more opportunities to infect the body. In addition, neutralizing antibodies are not usually effective against mutations, since they are trained to recognize only specific features of a virus.

    Fortunately, several experts say that other aspects of a person’s immune system will continue to offer protection even if antibodies begin to falter in the face of omicron. "It may be that our antibodies may not work as well, but the immune system has these backup plans that give us some resilience against omicron,” said John Wherry, director of the Institute for Immunology at the University of Pennsylvania.

    The backbone of the immune system: T cells

    If antibodies make up the immune system's first layer of defense, then T cells, which include helper T cells and killer T cells, make up the second layer. This second layer is primarily responsible for long-term immune protection.

    Helper T cells are important in coordinating the body's immune response after infection has occurred. These cells stimulate the production of antibodies and killer T cells. Killer T cells work to quickly destroy infected cells and halt the progression of disease.

    "T helper cells are like the generals of the immune system, and killer T cells are like the assassins," said Andrew Redd, a virologist at the National Institute of Allergy and Infectious Diseases (NIAID).

    Although T cells can't prevent infection, they can clear an infection that has already begun, according to Nature. Effective killer T cells likely mean the difference between a mild Covid-19 infection and a severe one that requires hospitalization.

    "If [killer T cells] are able to kill the virus-infected cells before they spread from the upper respiratory tract, it will influence how sick you feel," said Annika Karlsson, an immunologist at the Karolinska Institute in Sweden.

    T cells are also less likely to be affected by viral mutations, such as those seen on the omicron variant, according to several immunologists. In comparison to antibodies, which usually target only specific areas on a virus's surface, killer T cells target several different viral proteins. The proteins targeted by killer T cells can also vary widely from person to person, making it difficult for the virus to mutate to avoid T cell recognition.

    "That all makes it much more difficult for the virus to evade T-cell responses," said Azza Gadir, an immunologist and scientific advisor at Seed Health.

    Although some experts say that T-cell protection may drop slightly against the omicron variant, it likely won't be enough to significantly affect protection against severe illness and hospitalization.

    In addition, some early research suggests that T cells trained by vaccination or prior infection recognize most viral proteins from the omicron variant, with only a few exceptions. For example, a pre-print study from Redd and colleagues at NIAID found that of 52 coronavirus proteins, omicron had only one mutation in a protein targeted by T cells. Similar results were found in an earlier study of T cell responses against previous variants, including alpha, beta, and gamma.

    "[The data] suggests that T cell responses remain largely intact and should remain largely intact against omicron," Redd said.

    The importance of vaccination

    In general, many experts say that people vaccinated against Covid-19 are likely to be more susceptible to infection by the omicron variant than previous variants. However, vaccinated people will still be at a much lower risk of serious illness—a pattern that early studies from South Africa seem to support.

    The emergence of the omicron variant has further emphasized the necessity of Covid-19 vaccines, several experts said.

    "Even if the vaccine is not as effective against omicron, it's still going to be more effective than not being vaccinated," said Rachel Graham, an assistant professor in the department of epidemiology at the University of North Carolina at Chapel Hill. "It should, I hope, keep the majority of infected people from having to go to the hospital," she said.

    In addition, early data suggests that a booster dose of Pfizer-BioNTech's vaccine can improve antibody protection against the omicron variant, reducing the potential risk of infection.

    Overall, experts said that unless more people are vaccinated against Covid-19, new variants are likely to emerge. "If we can't get the world vaccinated, we're going to continue to see variants like omicron," Wherry said. "My big concern is the implications for whatever next variant comes in the future." (Wu, The Atlantic, 12/14; Chow, NBC News, 12/8; Ledford, Nature, 2/12; Stieg, CNBC, 12/2)

    The omicron variant: The 'good,' 'bad,' and 'ugly' scenarios

    future

    Since the news broke about the omicron variant, Advisory Board's Pamela Divack and Andrew Mohama pondered America's coronavirus future: What are the (relatively) "good," "bad," and "ugly" scenarios? In this piece, they've updated and mapped out the possibilities. 

    Read more

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