Abstract
Understanding the mechanisms and impact of booster vaccinations are essential in the design and delivery of vaccination programs. Here we show that a three dose regimen of a synthetic peptide vaccine elicits an accruing CD8 + T cell response against one SARS-CoV-2 Spike epitope. We see protection against lethal SARS-CoV-2 infection in the K18-hACE2 transgenic mouse model in the absence of neutralizing antibodies, but two dose approaches are insufficient to confer protection. The third vaccine dose of the single T cell epitope peptide results in superior generation of effector-memory T cells and tissue-resident memory T cells, and these tertiary vaccine-specific CD8 + T cells are characterized by enhanced polyfunctional cytokine production. Moreover, fate mapping shows that a substantial fraction of the tertiary CD8 + effector-memory T cells develop from re-migrated tissue-resident memory T cells. Thus, repeated booster vaccinations quantitatively and qualitatively improve the CD8 + T cell response leading to protection against otherwise lethal SARS-CoV-2 infection.
【초록키워드】 SARS-CoV-2, Vaccine, vaccination, Neutralizing antibodies, spike, SARS-COV-2 infection, peptide, CD8, vaccine dose, T cell, memory T cells, understanding, epitope, mechanism, T cell response, cytokine production, booster vaccination, K18-hACE2, dose, epitope peptide, fraction, repeated, Transgenic mouse, IMPROVE, develop, approach, characterized, absence, elicit, dose regimen, 【제목키워드】 vaccination, SARS-COV-2 infection, T cell, murine model, epitope,