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, Liana; Caushi, Justina X.; Pardoll, Drew M.; Cox, Andrea L.; Smith, Kellie N.; Blankson, Joel N.

doi:10.1016/j.ebiom.2022.104048

Cited by 17 publications

(17 citation statements)

References 42 publications

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“…Other studies ( 27 , 28 ) have also observed that the S-specific T cell immunity does not seem to be boosted after vaccination. However, emerging data indicate that SARS-CoV-2 vaccination diversifies the CD4+ S-reactive T cell repertoire in patients with prior SARS-CoV-2 infection ( 29 , 30 ) or vaccine breakthrough infection with omicron ( 31 ). Furthermore, according to Röltgen et al.…”

Section: Discussionmentioning

confidence: 99%

Superior humoral immunity in vaccinated SARS-CoV-2 convalescence as compared to SARS-COV-2 infection or vaccination

Paniskaki

Konik²,

Anft

et al. 2022

Front. Immunol.

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Emerging variants of concern (VOC) raise obstacles in shaping vaccination strategies and ending the pandemic. Vaccinated SARS-CoV-2 convalescence shapes the current immune dynamics. We analyzed the SARS-CoV-2 VOC-specific cellular and humoral response of 57 adults: 42 convalescent mRNA vaccinated patients (C+V+), 8 uninfected mRNA vaccinated (C-V+) and 7 unvaccinated convalescent individuals (C+V-). While C+V+ demonstrated a superior humoral SARS-CoV-2 response against all analyzed VOC (alpha, delta, omicron) compared to C-V+ and C+V-, SARS-CoV-2 reactive CD4+ and CD8+ T cells, which can cross-recognize the alpha, delta and omicron VOC after infection and/or vaccination were observed in all there groups without significant differences between the groups. We observed a preserved cross-reactive C+V+ and C-V+ T cell memory. An inferior humoral response but preserved cross-reactive T cell memory in C+V- compared to C+V+ was observed, as well as an inferior humoral response but preserved cross-reactive T cell memory in C+V- compared to C-V+. Adaptive immunity generated after SARS-CoV-2 infection and vaccination leads to superior humoral immune response against VOC compared to isolated infection or vaccination. Despite the apparent loss of neutralization potential caused by viral evolution, a preserved SARS-CoV-2 reactive T cell response with a robust potential for cross-recognition of the alpha, delta and omicron VOC was detected in all studied cohorts. Our results may have implications on current vaccination strategies.

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Section: Discussionmentioning

confidence: 99%

Superior humoral immunity in vaccinated SARS-CoV-2 convalescence as compared to SARS-COV-2 infection or vaccination

Paniskaki

Konik²,

Anft

et al. 2022

Front. Immunol.

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“…A pre-vaccine TRB repertoire (at visit E01) was obtained from 34 participants immediately before vaccination, a median of 369 days (IQR 333-390) after symptom onset. Most participants had a TRB repertoire 2.5 to 4 weeks after mRNA dose 1 and prior to dose 2 at visit E02 (N = 52, median 19.5 days post dose 1, IQR [15][16][17][18][19][20][21][22][23][24] and after dose 2 at E03 (N = 53, median 24 days post dose 2, IQR 20-28). Forty-four persons had an mRNA booster (third dose) a median of 259 (IQR 230-283) days after primary vaccination, and a TRB repertoire at E05 (median 41.5 days after booster, IQR 26-69).…”

Section: Resultsmentioning

confidence: 99%

“…Clonal selection theory posits that naive T cell clonotypes proliferate in response to antigen exposure and persist as memory 17,18 . Thus, we hypothesized that in the context of hybrid immunity, repeated S antigen exposure from mRNA vaccination after COVID-19 would expand S-speci c T cell clonotypes from prior infection and potentially diversify S-speci c T cell memory 19,20 .…”

Section: Mainmentioning

confidence: 99%

CD8+ T cell clonotypes from prior SARS-CoV-2 infection predominate during the cellular immune response to mRNA vaccination

Ford¹,

Mayer-Blackwell²,

Jing³

et al. 2022

Preprint

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Almost three years into the SARS-CoV-2 pandemic, hybrid immunity is highly prevalent worldwide and more protective than vaccination or prior infection alone. Given emerging resistance of variant strains to neutralizing antibodies (nAb), it is likely that T cells contribute to this protection. To understand how sequential SARS-CoV-2 infection and mRNA-vectored SARS-CoV-2 spike (S) vaccines affect T cell clonotype-level expansion kinetics, we identified and cross-referenced TCR sequences from thousands of S-reactive single cells against deeply sequenced peripheral blood TCR repertoires longitudinally collected from persons during COVID-19 convalescence through booster vaccination. Successive vaccinations recalled memory T cells and elicited antigen-specific T cell clonotypes not detected after infection. Vaccine-related recruitment of novel clonotypes and the expansion of S-specific clones were most strongly observed for CD8+ T cells. Severe COVID-19 illness was associated with a more diverse CD4+ T cell response to SARS-CoV-2 both prior to and after mRNA vaccination, suggesting imprinting of CD4+ T cells by severe infection. TCR sequence similarity search algorithms revealed myriad public TCR clusters correlating with human leukocyte antigen (HLA) alleles. Selected TCRs from distinct clusters functionally recognized S in the predicted HLA context, with fine viral peptide requirements differing between TCRs. Most subjects tested had S-specific T cells in the nasal mucosa after a 3rd mRNA vaccine dose. The blood and nasal T cell responses to vaccination revealed by clonal tracking were more heterogeneous than nAb boosts. Analysis of bulk and single cell TCR sequences reveals T cell kinetics and diversity at the clonotype level, without requiring prior knowledge of T cell epitopes or HLA restriction, providing a roadmap for rapid assessment of T cell responses to emerging pathogens.

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“…This approach produces a skewed T cell response that is enhanced against immunodominant epitopes ( 51 ) while also being targeted at less-dominant S-derived epitopes in vaccine recipients compared to convalescent individuals ( 78 ). In the aftermath of natural infection, the resulting CD8 + T cell clones are likely to recognize a broader set of viral epitopes that are not encountered in vaccines ( 76 ), and this T cell repertoire also demonstrates a higher rate of cross-recognition of epitopes from common-cold coronaviruses ( 79 ). Nevertheless, the repertoire induced by S protein-based vaccines is generally capable of protecting against existing variants as well as emerging variants of concern (VOCs) ( 80 – 82 ).…”

Section: Vaccine-induced T Cell Response and Tcr Repertoirementioning

confidence: 99%

Architecture of the SARS-CoV-2-specific T cell repertoire

et al. 2023

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The T cell response plays an indispensable role in the early control and successful clearance of SARS-CoV-2 infection. However, several important questions remain about the role of cellular immunity in COVID-19, including the shape and composition of disease-specific T cell repertoires across convalescent patients and vaccinated individuals, and how pre-existing T cell responses to other pathogens—in particular, common cold coronaviruses—impact susceptibility to SARS-CoV-2 infection and the subsequent course of disease. This review focuses on how the repertoire of T cell receptors (TCR) is shaped by natural infection and vaccination over time. We also summarize current knowledge regarding cross-reactive T cell responses and their protective role, and examine the implications of TCR repertoire diversity and cross-reactivity with regard to the design of vaccines that confer broader protection against SARS-CoV-2 variants.

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

Cited by 17 publications

References 42 publications

Superior humoral immunity in vaccinated SARS-CoV-2 convalescence as compared to SARS-COV-2 infection or vaccination

Superior humoral immunity in vaccinated SARS-CoV-2 convalescence as compared to SARS-COV-2 infection or vaccination

CD8+ T cell clonotypes from prior SARS-CoV-2 infection predominate during the cellular immune response to mRNA vaccination

Architecture of the SARS-CoV-2-specific T cell repertoire

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