SARS-CoV-2 vaccination diversifies the CD4+ spike-reactive T cell repertoire in patients with prior SARS-CoV-2 infection
Arbor G. Dykema,
Boyang Zhang,
Bezawit A. Woldemeskel,
Caroline C. Garliss,
Rufiaat Rashid,
Timothy Westlake,
Li Zhang,
Jiajia Zhang,
Laurene S. Cheung,
Justina X. Caushi,
Drew M. Pardoll,
Andrea L. Cox,
Hongkai Ji,
Kellie N. Smith,
Joel N. Blankson
Affiliations
Arbor G. Dykema
Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA
Boyang Zhang
Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA
Bezawit A. Woldemeskel
Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA
Caroline C. Garliss
Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA
Rufiaat Rashid
Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA
Timothy Westlake
Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA
Li Zhang
Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA
Jiajia Zhang
Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA
Laurene S. Cheung
Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA
Justina X. Caushi
Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA
Drew M. Pardoll
Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA
Andrea L. Cox
Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD, USA; Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA
Hongkai Ji
Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA
Kellie N. Smith
Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA; Corresponding author at: Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD, USA.
Joel N. Blankson
Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA; Corresponding author at: Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA
Summary: 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.
