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

Presented at: Coronavirus Series
  • Daniela Weiskopf, PhD

    Research Assistant Professor, Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI)


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. 

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