A study has provided new information on a vital subset of immune system cells necessary for successful vaccination against the SARS-CoV-2 pandemic virus.
The study, led by researchers at New York University Grossman School of Medicine and the New York Genome Center, focused on T cells that, along with B cells, form the human immune system’s response to invading viruses and bacteria. T cells marked with the surface protein CD8 generate chemicals that directly kill infected cells. B cells secrete antibodies that neutralize and mark contaminated cells for elimination from the body.
Vaccines expose patients to a small amount of invading bacteria to generate responses such as activation of B and T cells, so that the system is ready for the invader if it is encountered again. The COVID-19 mRNA vaccines were based on RNA, a genetic material used to code for the spike protein the virus needs to attach to human cells. When mRNA instructions are injected, the spike is generated and the immune response is activated.
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In the rush to create vaccines against SARS-CoV-2, clinical trials relied primarily on antibody levels, when efficient diagnostics were available, to determine whether patients’ immune responses to mRNA vaccine candidates were protective. However, clinical protection was observed as early as ten days after the initial vaccine dose, long before neutralizing antibodies could be produced. T cells were thought to be at least as important in this protection, but normal methods for tracking them were too slow, so careful examination of CD8 T cell responses was discontinued.
The study published in Nature Immunology describes a rapid (high-throughput) approach to tracking T cell responses, demonstrates that they are critical for the early protection provided by mRNA vaccines against COVID-19, and identifies the T cell subsets most responsible for it.
“Our study identified markers for CD8 T cells that arise from mRNA vaccination and closely follow successful vaccination, which have previously been difficult to quantify at the population level,” said first study co-author Rabi Upadhyay, MD, assistant professor in the Department of Medicine at NYU Langone Health and the faculty of its Perlmutter Cancer Center.
“Although our study looks at mRNA vaccination against coronavirus, the antigen-specific CD8 T cell subpopulations we discovered represent key features of immune responses more broadly and may help us study T cells in other diseases.”
For the current study, the research team analyzed gene expression over time in individual T cells collected before and after immunization with the mRNA vaccine produced by BioNTech and Pfizer against SARS-CoV-2.
The researchers found distinct subsets of CD8 T cells that reliably multiplied (proliferated) 21 days after the original vaccination, specifically targeting and attacking key proteins (antigens) that make up the pandemic virus.
By looking at the genetic makeup of the most effective T cells, the researchers observed that cells lacking a surface protein called KLRG1, which stands for coinhibitory lectin-like killer cell receptor G1, were the most likely to multiply rapidly after mRNA. vaccination and specifically attack.
When the study authors verified these profiles in patients hospitalized with COVID-19, those with the most “properly programmed” T cells (lacking KLRG1 but expressing other markers such as CD38 and HLA-DR) were the most likely to successfully recover from their infections.
In the years since the pandemic began, mRNA vaccines, first used against the virus, are now in clinical trials in which they direct the body’s immune system to attack cancer cells.
By clarifying T cell markers (e.g., KLRG1, CD38, HLA-DR) and the timing of CD8 T cells emerging in the blood after vaccination, the new work may allow clinical teams to determine which Patients are responding to vaccines within days or weeks, the authors say.
That compares to the more than two months that oncologists must currently wait after mRNA vaccination to perform CT scans to assess whether their patients with lung, breast or prostate cancer responded to an mRNA vaccine.
If validated in this context and dramatically shorten those wait times, the new profiling methods promise to help patients transition more quickly to other treatments if necessary, the researchers say.
Additionally, the study authors reference a recent study led by a different research team that found that T cells with very similar attributes, again involving KLRG1, CD38, and HLA-DR, were the most effective at attacking cancer cells. after treatment with an immune system. system triggering drug (immunotherapy), just as they were the most effective in attacking the SARS-CoV-2 virus in the current study.
“It is notable that the T cell attributes found after treatment with an effective immunotherapy mirrored those we found in patient recovery from COVID-19,” said co-author Dan Littman, MD, PhD, Helen L. and Martin S. Kimmel Professor of Molecular Immunology in the Department of Cell Biology at NYU Langone. “This pattern suggests that close monitoring of antigen-specific CD8 T cell subpopulations will be critical for future efforts to design treatments and vaccines against viruses or tumors.”
This story has been published from a news agency feed without modifications to the text. Only the headline has been changed.
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