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

doi:10.1016/j.ebiom.2022.104048

SARS-CoV-2 vaccination diversifies the CD4+ spike-reactive T cell repertoire in patients with prior SARS-CoV-2 infection

EBioMedicine. 2022 Jun:80:104048. doi: 10.1016/j.ebiom.2022.104048. Epub 2022 May 6.

Authors

Affiliations

¹ Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
² Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
³ Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
⁴ Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD, USA; Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
⁵ Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA. Electronic address: ksmit228@jhmi.edu.
⁶ Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA. Electronic address: jblanks@jhmi.edu.

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.

MeSH terms

Antibodies, Viral
CD4-Positive T-Lymphocytes
COVID-19 Vaccines
COVID-19*
Common Cold*
Humans
SARS-CoV-2
Vaccination
Viral Vaccines*

Substances

Antibodies, Viral
COVID-19 Vaccines
Viral Vaccines

Abstract

MeSH terms

Substances

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