Cell Study Confirms COVID-19 Vaccines Elicit Durable T Cell Responses Effective Against Omicron Variant

January 31, 2022/BioValleyBIOON/---In a new study, researchers from La Jolla, USAImmunologyResearchers at the institute found that four COVID-19 vaccines (Pfizer-BioNTech, Moderna, J&J/Janssen, and Novavax) prompt the human body to produce effective, long-lasting T cells to combat SARS-CoV-2. These T cells can recognize concerning SARS-CoV-2 variants, including the Delta and Omicron variants. The relevant findings were published online in the journal Cell on January 23, 2022, under the title "SARS-CoV-2 vaccination induces immunological T cell memory able to cross-recognize variants from Alpha to Omicron."

"Dr. Alessandro Sette, co-corresponding author of the paper and professor at the La Jolla Institute for Immunology, said, 'The vast majority of T cell responses remain effective against the Omicron variant.' Dr. Shane Crotty, co-corresponding author of the paper and professor at the La Jolla Institute for Immunology, added, 'These T cells won't prevent you from getting infected, but in many cases, they are likely to keep you from getting severely ill.' Co-corresponding author of the paper and professor at the La JollaImmunology"This is true for all types of vaccines we have studied, and it remains so within six months after vaccination," said Dr. Alba Grifoni, a lecturer at the institute.

These data come from fully vaccinated adults who have not yet received a booster shot. The authors are now studying the T-cell responses in people who have received a booster shot and in COVID-19 patients who have experienced "breakthrough infections."

Image source: Cell, 2022, doi:10.1016/j.cell.2022.01.015.

This new study also shows that fully vaccinated individuals have fewer memory B cells and neutralizing antibodies against the Omicron variant. This finding is consistent with preliminary reports of waning immunity from laboratories around the world. Without sufficient neutralizing antibodies, the Omicron variant is more likely to cause breakthrough infections. Fewer memory B cells mean the body will subsequently be slower to produce additional neutralizing antibodies to fight the virus.

Co-first author of the paper, La JollaImmunology"Most neutralizing antibodies, which are antibodies that work well against SARS-CoV-2, bind to an area known as the receptor-binding domain (RBD). Our research shows that the 15 mutations present in the RBD of the Omicron variant can significantly reduce the binding ability of memory B cells compared to variants like Alpha, Beta, and Delta," said Dr. Camila Coelho, a lecturer at the institute.

How T Cells Combat the Omicron Variant

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 have already been infected, thereby preventing the virus from multiplying and causing severe disease.

These authors believe that the "second line of defense" from T cells helps explain why Omicron variant infections are less likely to cause severe disease in fully vaccinated individuals. (The variant also seems to infect different tissues).

To understand whether the vaccine-induced T-cell responses detected in this study are truly effective against SARS-CoV-2 variants such as the Delta and Omicron variants, the authors closely examined the T-cell responses to different viral "epitopes."

Each virus is composed of proteins that form a specific shape or structure. Viral epitopes are the specific sites on this structure that T cells are trained to recognize. Current COVID-19 vaccines are designed to teach the immune system to recognize specific epitopes on the original Alpha variant of SARS-CoV-2. As the virus mutates, its structure changes, raising concerns that immune cells may no longer recognize their targets.

This new study shows that while the structure of the Omicron variant is different enough to evade some neutralizing antibodies and memory B cells, memory T cells can still recognize their targets well, even on the highly mutated Omicron variant. Overall, at least 83% of CD4+ (helper) T cell responses and 85% of CD8+ T cell responses remain unchanged, regardless of the vaccine or SARS-CoV variant.

Crotty pointed out that memory B cells that do bind to the Omicron variant may also help protect people from severe disease. Crotty said, "Vaccinated individuals have memory CD4+ T cells, CD8+ T cells, and memory B cells to help fight off infection. If the virus breaches the first line of defense provided by initial antibodies, having multiple layers of defense could be a significant advantage."

Omicron Variant Still Poses a Threat

These authors emphasized that no one should rely solely on T-cell protection. This study reveals population-level immunity, but individual immune responses vary widely, and counting on an untested personal immune system to fight COVID-19 is a gamble.

Alison Tarke, co-first author of the paper and a graduate student in the Sette lab, said, "I urge people to still be cautious and continue wearing masks. You could be one of the few whose immune response has declined." Sette added, "This study also highlights the importance of getting booster shots."

Sette Lab and Crotty Lab have been collaborating on COVID-19 research since early 2020. With Sette Lab's expertise in T cells and Crotty Lab's expertise in vaccine design and B cell responses, this collaboration has led to critical insights into pre-existing SARS-CoV-2 immunity, vaccine responses, and severe COVID cases.

Grifoni said that they are now studying two pressing issues. First, they want to see what the T-cell, B-cell, and antibody responses look like after receiving a COVID-19 booster vaccine. Second, they are examining what the immune response looks like following breakthrough infections. (Bioon.com)

References:

Alison Tarke et al. SARS-CoV-2 vaccination induces immunological T cell memory able to cross-recognize variants from Alpha to Omicron. Cell, 2022, doi:10.1016/j.cell.2022.01.015.