Abstract
SARS-CoV-2 vaccines pose as the most effective approach for mitigating the COVID-19 pandemic. High-degree efficacy of SARS-CoV-2 vaccines in clinical trials indicates that vaccination invariably induces an adaptive immune response. However, the emergence of breakthrough infections in vaccinated individuals suggests that the breadth and magnitude of vaccine-induced adaptive immune response may vary. We assessed vaccine-induced SARS-CoV-2 T cell response in 21 vaccinated individuals and found that SARS-CoV-2–specific T cells, which were mainly CD4+ T cells, were invariably detected in all individuals but the response was varied. We then investigated differentiation states and cytokine profiles to identify immune features associated with superior recall function and longevity. We identified SARS-CoV-2–specific CD4+ T cells were polyfunctional and produced high levels of IL-2, which could be associated with superior longevity. Based on the breadth and magnitude of vaccine-induced SARS-CoV-2 response, we identified 2 distinct response groups: individuals with high abundance versus low abundance of SARS-CoV-2–specific T cells. The fractions of TNF-α– and IL-2–producing SARS-CoV-2 T cells were the main determinants distinguishing high versus low responders. Last, we identified that the majority of vaccine-induced SARS-CoV-2 T cells were reactive against non-mutated regions of mutant S-protein, suggesting that vaccine-induced SARS-CoV-2 T cells could provide continued protection against emerging variants of concern.
Highlights
COVID-19 infection is a critical public health issue, and mRNA-based vaccines, mRNA-1273 (Moderna) and BNT162b2 (BioNtech/Pfizer), harboring modified RNAs spanning the whole length of spike (S-) protein, are highly effective in inducing protective cellular and humoral immunity conferring protection against COVID-19
To quantify the response against the mutated regions of S-protein of Alpha and Beta variants in COVID-19 mRNA vaccine recipients, we stimulated the PB mononuclear cells (PBMCs) in parallel with 2 different SARS-CoV-2 peptide pools spanning only the mutated S-protein regions of Alpha and Beta variants (Figure 1B) and 2 reference peptide pools containing the S-protein regions of Alpha and Beta variants as controls
We only detected a miniscule fraction of reactive CD8+ T cells in 3 individuals, and CD4+ T cells were not reactive against S-protein after coculture (Supplemental Figure 1, B and C). These findings indicate that SARS-CoV-2–specific CD4+ and CD8+ T cells in vaccinated individuals emerged after vaccination since SARS-CoV-2–specific CD4+ and CD8+ T cells were detectable in every vaccine recipient
Summary
COVID-19 infection is a critical public health issue, and mRNA-based vaccines, mRNA-1273 (Moderna) and BNT162b2 (BioNtech/Pfizer), harboring modified RNAs spanning the whole length of spike (S-) protein, are highly effective in inducing protective cellular and humoral immunity conferring protection against COVID-19. High efficacy of mRNA-1273 and BNT162b2 vaccines in clinical trials suggests that mRNA-based vaccines induce a protective immune response in every individual, and correlative studies in these trials mostly relied on assessment of presence and titers of SARS-CoV-2–specific neutralizing antibodies [1, 2]. Determining the breadth and durability of adaptive immunity, cellular immune response against SARS-CoV-2, in vaccinated individuals could be of great importance since it could provide valuable insights into durability of vaccine-induced cellular immune response, infection risk, and the need for booster shots. It will be critical from a public health perspective to determine whether vaccinated individuals develop long-term memory T cell immunity against SARS-CoV-2
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