mRNA Vaccine Defeats Infection for Key Protection Against COVID-19, Stanford Medicine Scientists Find | News Center

Most research on vaccine efficacy has focused on the ability of these products to generate antibodies, and their infection-blocking efficacy can be measured relatively easily in laboratory glassware. T cells have proven more difficult to study. But after decades of pioneering the search for killer T cells and their cousins, helper T cells, Davis has designed ever better ways to monitor more complex and subtle interactions with targets. and advocated, advancing the analysis.

Helper T cells are inherently more administrative than killer T cells and help induce antibody production by another immune cell type called B cells.

Davis suggests that the way T cells recognize antigens is different from the way antibodies recognize antigens, so T cells can be fooled or knocked down by minor variations in viral sequences (strain variants) than antibodies. said to be of low quality.

For the new study, Davis and his colleagues armed with cutting-edge techniques pioneered by Mallajosyula in Davis’ lab to alter levels of killer T cells specifically directed against SARS-infected cells. allowed us to accurately measure – CoV-2. The researchers examined three categories of SARS-CoV-2-naive people who received the first and second doses of the new mRNA vaccine, unvaccinated COVID-19 patients, and vaccinated people. Blood samples from study participants were analyzed. I had the virus before and am now recovered — at least apparently.

The researchers monitored the proliferation and activation of killer T cells specifically directed against SARS-CoV-2 in these individuals, drawing blood at several time points beginning on the day of first vaccination. The first day they showed symptoms.

Uninfected vaccinees had more than a 60-fold increase in levels of killer T cells targeting SARS-CoV-2. By 6 weeks after his first dose, his one-fifth of the killer T cells were SARS-CoV-2-specific.

Results for COVID-19 patients were even worse: mean levels of SARS-CoV-2-specific killer T cells were higher than those of uninfected patients, despite vaccines containing only part of the virus. less than one-tenth of those vaccinated. (The so-called spike protein that SARS-CoV-2 uses to stick to cells.) On the other hand, infection with the actual virus can generate killer T-cell responses against multiple components.

Recovery of SARS-CoV-2-specific responses to vaccination in COVID-19 patients was also delayed relative to responses in uninfected participants. Three weeks after the second dose of dual-dose mRNA vaccine therapy, killer T cells narrowly targeting SARS-CoV-2 were found in the blood of previously infected vaccinees compared to those in uninfected individuals. was less than one-seventh as high as blood. vaccination at the same time. Moreover, these cells appeared to be less belligerent, owing to signaling agents secreted by previously infected vaccinees than by uninfected vaccinees.

Helper T cells were not strongly affected by previous SARS-CoV-2 infection. In contrast to the face-to-face behavior of killer T cells, these cells have a more administrative role. This includes stimulating antibody production by other immune cells called B cells.

Antibody production remains robust upon reinfection in former SARS-CoV-2 patients, Davis said.

“But antibodies mostly only block infection. They cannot eradicate an established infection,” he said. “Only killer T cells can do that. We believe that the lack of functional killer T cells due to infection may be one of the factors contributing to the long-lasting outbreak of COVID. because these impaired killer T-cell populations fail to adequately clear all infected cells.

Researchers at Emory University contributed to this work.

This study was funded by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health (grant grants U19AI057229 and U01AI140498). Howard Hughes Medical Institute. Bill and Melinda Gates Foundation. Stanford Institute of Immunology, Transplantation and Infection. Sean N. Parker Center. and the Sunshine Foundation.