Low-Dose mRNA-1273 COVID-19 Vaccine Generates Durable Memory Enhanced by Cross-reactive T Cells

Vaccination and infection are two different paths to immunity. Understanding human immune responses to SARS-CoV-2 RNA vaccines is of interest for a panoply of reasons. mRNA vaccines have demonstrated impressive protection from COVID-19; however, durability of immunity has been a major unknown. 

Given evidence that antibodies, CD4+ T cells, and CD8+ T cells can each participate in protective immunity against COVID-19, we measured acute and memory SARS-CoV-2 Spike-specific antibodies, CD4+ T cells and CD8+ T cells in the blood of subjects who received a low dose (25-µg) or standard dose (100-µg) mRNA-1273 COVID-19 vaccine. Vaccine-generated spike-specific memory CD4+ T cells 6 months post-boost were comparable in quantity and quality to COVID-19 cases, including the presence of T follicular helper cells and IFNγ-expressing cells. Spike-specific CD8+ T cells were generated in 88% of subjects, with equivalent memory at 6 months post-boost compared to COVID-19 cases. Lastly, subjects with pre-existing cross-reactive CD4+ T cell memory had increased CD4+ T cell and antibody responses to the vaccine, demonstrating the biological relevance of SARS-CoV-2–cross-reactive CD4+ T cells. In summary, the 25-µg-dose of mRNA-1273 vaccine induces durable and functional T cell and antibody memory at comparable magnitude to natural infection. This work expands our understanding of immune memory to mRNA vaccine in humans, the biological relevance of crossreactive T cells, and possible timing of boosters. 
 

Learning Objectives:

1. Discuss the durability of mRNA vaccine induced immunity.

2. Break down impact of pre-existing crossreactive memory on immune responses to SARS-CoV-2 proteins.