T cells are a key component of immune response to infections or cancer. In this immunofluorescence image, a killer T cell (blue) is engaging a target cell. A patch of signaling molecules (pink) gathers at the site of cell-cell contact. Granules that contain cytotoxic components (red) then travel to the contact site and kill the target. Credit: Alex Ritter, Jennifer Lippincott Schwartz and Gillian Griffiths, NIH.
A team of researchers in Italy has developed a new test to determine the optimal timing for administering booster vaccines against SARS-CoV-2.
Vaccines based on messenger RNA (mRNA) such as those against SARS-CoV-2, stimulate several types of immune cells. In addition to memory B cells, that promote the production of antibodies, they also stimulate CD4+ T cells, and CD8+ T cells that can kill infected cells, and are fundamental for protecting against infections. “The presence of antibodies does not tell us how much we are actually protected from infection and COVID-19, because they decrease over time” says Luigia Pace, a researcher at the Italian Institute for Genomic Medicine and at the Cancer Institute in Candiolo, near Turin, lead author of the paper.
The study1 followed 379 healthy subjects for 18 months, recruited from staff of a hospital in the Piedmont region of Italy. The researchers first collected blood samples before the first dose of a mRNA-based vaccine. Then they took further sample before the second dose, at week 3, week 6, month 3 and month 6 after the second dose, and finally 1 month after the booster dose. They looked specifically for B cell and T cell memory for the spike protein derived from original SARS-CoV-2 and from the beta, delta, and omicron variants.
The researchers classified participants as either high responders or low responders. High responders maintained higher level of B cells, CD4+ T cells and CD8+ T cells after 3 months than low responders. From three months onwards, the difference between the two groups in the immunological response was increasingly evident. T cells recognize many versions of the SARS-CoV-2 spike protein and compared to antibodies their activation is less affected by the mutations of the virus variants. “People in the first group have a greater ability to neutralize the virus than people in the second who will therefore need a booster sooner than high responders,” explains Pace. “This is very important, especially in the case of fragile subjects, in whom the level of preventive protection must be assessed, for example before a course of chemotherapy”.
The research team plans to evaluate the possibility of extending their findings to other mRNA vaccinations, such as those being tested for some types of cancer. “This would allow us to understand not only how patients respond to therapies, but also to make oncologic treatments more specific for each individual case,” says Pace. As for SARS-CoV-2, one of the next steps will be to standardize testing across all Italian analysis sites to generate diagnostic criteria that can be used across all institutions.
“It is an excellent work that deals with a crucial issue for the pandemic,” says Massimo Clementi, Director of the Laboratory of Microbiology and Virology of the Vita-Salute San Raffaele University of Milan, who was not involved in the study. “This study highlights some characteristics of both humoral and cell mediated immune responses. It is exactly what we want to study to make vaccines more and more efficient”.
