Abstract
Background: COVID-19 mRNA vaccines elicit strong T and B cell responses to the SARS-CoV-2 spike glycoprotein in both SARS-CoV-2 naïve and experienced patients. However, it is unknown whether the post-vaccine CD4+ T cell responses seen in patients with a history of COVID-19 are due to restimulation of T cell clonotypes that were first activated during natural infection or if they are the result of new clones activated by the vaccine.
Methods: To address this question, we analyzed the SARS-CoV-2 spike glycoprotein-specific CD4+ T cell receptor repertoire before and after vaccination in 10 COVID-19 convalescent patients and 4 SARS-CoV-2 naïve healthy donor vaccine recipients. We used the viral Functional Expansion of Specific T cells (ViraFEST) assay to quantitatively identify specific SARS-CoV-2 and common cold coronavirus CD4+ T cell clonotypes post COVID-19 disease resolution and post mRNA SARS-CoV-2 vaccination.
Findings: We found that while some preexisting T cell receptor clonotypes persisted, the post-vaccine repertoire consisted mainly of vaccine-induced clones and was largely distinct from the repertoire induced by natural infection. Vaccination-induced clones led to an overall maintenance of the total number of SARS-CoV-2 reactive clonotypes over time through expansion of novel clonotypes only stimulated through vaccination. Additionally, we demonstrated that the vaccine preferentially induces T cells that are only specific for SARS-CoV-2 antigens, rather than T cells that cross-recognize SARS-CoV-2/common cold coronaviruses.
Interpretation: These data demonstrate that SARS-CoV-2 vaccination in patients with prior SARS-CoV-2 infection induces a new antigen-specific repertoire and sheds light on the differential immune responses induced by vaccination versus natural infection.
Funding: Bloomberg∼Kimmel Institute for Cancer Immunotherapy, The Johns Hopkins University, The Bill and Melinda Gates Foundation, NCI U54CA260492, NIH.
Keywords: CD4+ T cells; COVID-19; Coronavirus; SARS-CoV-2; mRNA vaccination.
【저자키워드】 COVID-19, SARS-CoV-2, mRNA vaccination, coronavirus, CD4+ T cells, 【초록키워드】 mRNA vaccination, Coronaviruses, Vaccine, immune response, vaccination, mRNA vaccine, SARS-COV-2 infection, spike glycoprotein, COVID-19 disease, T cell, mRNA, response, Patient, receptor, expansion, natural infection, T cell receptor, patients, CD4+ T cell, SARS-CoV-2 vaccination, SARS-CoV-2 antigens, B cell response, recipients, foundation, naïve, CD4+, common cold coronavirus, Specific, clone, Post-vaccine, reactive, healthy donor, Johns Hopkins University, stimulated, analyzed, identify, activated, question, demonstrated, elicit, induce, the vaccine, NIH, COVID-19 convalescent patient, Melinda Gate, the SARS-CoV-2, 【제목키워드】 SARS-COV-2 infection, T cell, Patient, SARS-CoV-2 vaccination, CD4+,