mRNA vaccine-induced T cells respond identically to SARS-CoV-2 variants of concern but differ in longevity and homing properties depending on prior infection status.

Vaccination is one of the best ways to prevent severe COVID-19. Two doses of mRNA vaccine protect against serious illness caused by the coronavirus SARS-CoV-2. They do this, in part, by encouraging the immune system to make specialised proteins known as antibodies that recognise the virus. Most of the vaccine research so far has focussed on these antibodies, but they are only one part of the immune response. Vaccines also activate immune cells called T cells. These cells have two main roles, coordinating the immune response and killing cells infected with viruses. It is likely that they play a key role in preventing severe COVID-19. There are many kinds of T cells, each with a different role. Currently, the identity and characteristics of the T cells that protect against COVID-19 is unclear. Different types of T cells have unique proteins on their surface. Examining these proteins can reveal details about how the T cells work, which part of the virus they recognise, and which part of the body they protect. A tool called cytometry by time of flight allows researchers to measure these proteins, one cell at a time. Using this technique, Neidleman, Luo et al. investigated T cells from 11 people before vaccination and after their first and second doses. Five people had never had COVID-19 before, and six had already recovered from COVID-19. Neidleman, Luo et al. found that the T cells recognizing SARS-CoV-2 in the two groups differed. In people who had never had COVID-19 before, the second dose of vaccine improved the quality and quantity of the T cells. The same was not true for people who had already recovered from COVID-19. However, although their T cells did not improve further after a second vaccine dose, they did show signs that they might offer more protection overall. The proteins on the cells suggest that they might last longer, and that they might specifically protect the nose, throat and lungs. Neidleman, Luo et al. also found that, for both groups, T cells activated by vaccination responded in the same way to different variants of the virus. This work highlights the importance of getting both vaccine doses for people who have never had COVID-19. It also suggests that vaccination in people who have had COVID-19 may generate better T cells. Larger studies could show whether these patterns remain true across the wider population. If so, it is possible that delivering vaccines to the nose or throat could boost immunity by mimicking natural infection. This might encourage T cells to make the surface proteins that allow them to home to these areas.