Study: T-Cell Responses Directed at Binding Domain of SARS-CoV-2 Increase Protection

Results of the analysis may help inform future COVID-19 vaccine development, investigators say.

T-cell responses that are directed against the receptor-binding domain of the SARS-CoV-2 spike proteins were associated with protection from the infection in vaccinated individuals with or without cancer but with lower T-cell responses observed in individuals with blood cancer, according to study results published in Cancer Discovery.

Investigators found that about 20% to 25% of the population, including both healthy individuals and those with cancer, had pre-existing SARS-CoV-2-specific T-cell responses.

Additionally, they observed that the types of cytokines released by memory T-cells were associated with protection against SARS-CoV-2 infection, while an imbalance of IL-2 and IL-5 cytokines was associated with higher susceptibility.

For example, an IL-2/IL-5 ratio of less than 1 could predict infection, regardless of cancer status. This suggests that the relative levels of cytokines released by T-cells could be predictors of susceptibility of infection.

Furthermore, investigators analyzed T-cells from individuals who had a primary infection, breakthrough infection post-vaccination, or reinfection with SARS-CoV-2. They found that those individuals did not react to the receptor-binding domain of the spike protein, even with an immune response against other regions of the viral genome.

The lack of reactivity to the spike receptor-binding domain could have made these individuals more susceptible to infection, investigators said.

Additionally, T-cell reactivity to the receptor-binding domain could even drive evolution of the spike protein and contribute to the emergence of new viral variants, investigators said.

Investigators also examined post-vaccination T-cell responses in healthy individuals, as well as in those with blood or solid cancers.

T-cell responses varied among this population, but individuals with blood cancer had significantly lower responses than did individuals with solid tumors or those who were cancer-free.

Approximately 10% of individuals with blood cancers had T-cells that were reactive to the receptor-binding domain compared with 49% and 34% of those who were cancer-free and those with solid tumors, respectively.

Additionally, investigators found that the vaccine-induced T-cell responses against the original, wild-type sequence of the spike receptor binding domain were poorly cross-reactive against those of the Alpha, Beta, and Delta variants.

“This may explain why the Omicron variant of SARS-CoV-2 is currently spreading among the vaccinees,” Laurence Zitvogel, MD, PhD, a professor at the Gustave Roussy Institute in Villejuif, France, said in a statement. “The available vaccines were developed against the original sequence of the receptor-binding domain and not against the mutated sequences found in the variants.”

In the study, blood samples were collected prior to infection with SARS-CoV-2, and various invitro experiments were preformed to assess how the polarity and repertoire of T-cell responses correlated with susceptibility to infection during subsequent waves of the COVID-19 pandemic.

Furthermore, T-cell polarity was assessed by identifying the types of cytokines released by T cells of each individual when exposed to a viral antigen. Investigators examined the makeup of each individual’s T-cell pool to determine the proportion of different T-cells.

Reference

T-cell responses may help predict protection against SARS-CoV-2 infection in individuals with and without cancer. EurekAlert. News release. February 18, 2022. Accessed February 18, 2022. https://www.eurekalert.org/news-releases/943715