Low-dose Moderna mRNA-1273 vaccination led to a durable and functional T cell and antibody response comparable to natural infection in a small trial, researchers report. The SARS-CoV-2 mRNA vaccines have been extraordinary successes. Still, scientists seek to better understand the immunology of these vaccines. Pre-existing cross-reactive memory CD4+ T cells that recognize SARS-CoV-2 have been found in ~50% of individuals pre-pandemic, though scientists are still trying to understand the extent and impact of this cross-immunity, including for the way it may influence the efficacy of vaccine regimens. One approach to test the relevance of such T cells in a controlled fashion is in the context of a vaccine trial, as individuals in a clinical trial are all exposed to a well-defined dose of antigen at a specific time. Exposure to a low antigen dose may be more sensitive to influence by cross-reactive memory. Here, Jose Mateus et al. report the results of a clinical trial comparing patients who received a low antigen dose (25-µg) of the mRNA-1273 (Moderna) COVID-19 vaccine, as compared to those who received the emergency use authorization (EUA)–approved 100-µg mRNA-1273 COVID-19 vaccine and as compared to SARS-CoV-2-infected individuals. Studying these subjects’ immune profiles 7 months from the initial immunization, the authors found that the low-dose Moderna vaccine generated long-lived T cell immunity that was equivalent between younger and older patients, and which could be enhanced by the presence of cross-reactive T cells. Moreover, antibody and T cell responses induced by the low-dose vaccine were comparable to natural infection and about half those seen with high-dose vaccination.
Low-dose mRNA-1273 COVID-19 vaccine generates durable memory enhanced by crossreactive T cells
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