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SARS-CoV-2 vaccination diversifies the CD4+ spike-reactive T cell repertoire in patients with prior SARS-CoV-2 infection.
Dykema, Arbor G; Zhang, Boyang; Woldemeskel, Bezawit A; Garliss, Caroline C; Rashid, Rufiaat; Westlake, Timothy; Zhang, Li; Zhang, Jiajia; Cheung, Laurene S; Caushi, Justina X; Pardoll, Drew M; Cox, Andrea L; Ji, Hongkai; Smith, Kellie N; Blankson, Joel N.
  • Dykema AG; Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
  • Zhang B; Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
  • Woldemeskel BA; Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
  • Garliss CC; Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
  • Rashid R; Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
  • Westlake T; Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
  • Zhang L; Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
  • Zhang J; Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
  • Cheung LS; Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
  • Caushi JX; Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
  • Pardoll DM; Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
  • Cox AL; Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University, Baltimore, MD, USA; Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
  • Ji H; Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
  • Smith KN; 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.
  • Blankson JN; Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, MD, USA. Electronic address: jblanks@jhmi.edu.
EBioMedicine ; 80: 104048, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1821212
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Viral Vaccines / Common Cold / COVID-19 Type of study: Experimental Studies / Prognostic study / Randomized controlled trials Topics: Long Covid / Vaccines Limits: Humans Language: English Journal: EBioMedicine Year: 2022 Document Type: Article Affiliation country: J.ebiom.2022.104048

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Viral Vaccines / Common Cold / COVID-19 Type of study: Experimental Studies / Prognostic study / Randomized controlled trials Topics: Long Covid / Vaccines Limits: Humans Language: English Journal: EBioMedicine Year: 2022 Document Type: Article Affiliation country: J.ebiom.2022.104048