Study shows how the fully vaccinated respond to a range of SARS-CoV-2 variants

Jan. 31, 2022

Scientists at La Jolla Institute for Immunology (LJI) have found that four COVID-19 vaccines (Pfizer-BioNTech, Moderna, J&J/Janssen, and Novavax) prompt the body to make effective, long-lasting T cells against SARS-CoV-2. These T cells can recognize SARS-CoV-2 variants of concern, including Delta and Omicron, according to a news release from the organization.

“The vast majority of T cell responses are still effective against Omicron,” says LJI Professor and study co-leader Alessandro Sette, Dr. Biol.Sci.

These data come from adults who were fully vaccinated but not yet boosted. The researchers are now investigating T cell responses in boosted individuals and people who have experienced “breakthrough” COVID-19 cases.

The study, published in Cell, also shows that fully vaccinated people have fewer memory B cells and neutralizing antibodies against the Omicron variant. This finding is in line with initial reports of waning immunity from laboratories around the world.

Without enough neutralizing antibodies, Omicron is more likely to cause a breakthrough infection. Fewer memory B cells means the body will then be slower to churn out additional neutralizing antibodies to fight the virus.

How T cells fight Omicron

The good news is that neutralizing antibodies and memory B cells are just two arms of the body’s adaptive immune response. In a person exposed to SARS-CoV-2, T cells do not prevent infection. Instead, T cells patrol the body and destroy cells that are already infected, which prevents a virus from multiplying and causing severe disease.

The LJI team believes the “second line of defense” from T cells helps explain why Omicron infections are less likely to lead to severe disease in fully vaccinated people. (The variant also appears to infect different tissues)

To know whether the vaccine-induced T cells they detected in their study were actually effective against variants such as Delta and Omicron, the scientists took a close look at how the T cells responded to different viral “epitopes.”

Every virus is made up of proteins that form a certain shape or architecture. A viral epitope is a specific landmark on this architecture that T cells have been trained to recognize. The current COVID-19 vaccines were designed to teach the immune system to recognize specific epitopes on the initial “Alpha” variant of SARS-CoV-2. As the virus has mutated, its architecture has changed, and the concern is that immune cells will no longer recognize their targets.

The new study shows that while the architecture of Omicron is different enough to evade some neutralizing antibodies and memory B cells, memory T cells still do a good job of recognizing their targets, even on the highly mutated Omicron variant. Overall, at least 83% of the CD4+ (helper) T cell responses and 85% of the CD8+ T cell responses stayed the same, no matter the vaccine or the variant.

The researchers emphasize that no one should count on T cell protection alone. The LJI study sheds light on immunity at the population level, but individual immune responses vary, and relying on one’s untested immune system to fight COVID is a roll of the dice.

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