tetano
Editor, Senior Moderator
EBioMedicine
. 2022 May 6;80:104048.
doi: 10.1016/j.ebiom.2022.104048. Online ahead of print.
SARS-CoV-2 vaccination diversifies the CD4+ spike-reactive T cell repertoire in patients with prior SARS-CoV-2 infection
Arbor G Dykema[SUP] 1 [/SUP], Boyang Zhang[SUP] 2 [/SUP], Bezawit A Woldemeskel[SUP] 3 [/SUP], Caroline C Garliss[SUP] 3 [/SUP], Rufiaat Rashid[SUP] 1 [/SUP], Timothy Westlake[SUP] 1 [/SUP], Li Zhang[SUP] 1 [/SUP], Jiajia Zhang[SUP] 1 [/SUP], Laurene S Cheung[SUP] 1 [/SUP], Justina X Caushi[SUP] 1 [/SUP], Drew M Pardoll[SUP] 1 [/SUP], Andrea L Cox[SUP] 4 [/SUP], Hongkai Ji[SUP] 2 [/SUP], Kellie N Smith[SUP] 5 [/SUP], Joel N Blankson[SUP] 6 [/SUP]
Affiliations
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.
. 2022 May 6;80:104048.
doi: 10.1016/j.ebiom.2022.104048. Online ahead of print.
SARS-CoV-2 vaccination diversifies the CD4+ spike-reactive T cell repertoire in patients with prior SARS-CoV-2 infection
Arbor G Dykema[SUP] 1 [/SUP], Boyang Zhang[SUP] 2 [/SUP], Bezawit A Woldemeskel[SUP] 3 [/SUP], Caroline C Garliss[SUP] 3 [/SUP], Rufiaat Rashid[SUP] 1 [/SUP], Timothy Westlake[SUP] 1 [/SUP], Li Zhang[SUP] 1 [/SUP], Jiajia Zhang[SUP] 1 [/SUP], Laurene S Cheung[SUP] 1 [/SUP], Justina X Caushi[SUP] 1 [/SUP], Drew M Pardoll[SUP] 1 [/SUP], Andrea L Cox[SUP] 4 [/SUP], Hongkai Ji[SUP] 2 [/SUP], Kellie N Smith[SUP] 5 [/SUP], Joel N Blankson[SUP] 6 [/SUP]
Affiliations
- PMID: 35533495
- DOI: 10.1016/j.ebiom.2022.104048
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.