Perturbations of the T-cell receptor repertoire in response to SARS-CoV-2 in immunocompetent and immunocompromised individuals

Delmonte, Ottavia M.; Oguz, Cihan; Dobbs, Kerry; Myint-Hpu, Katherine; Palterer, Boaz; Abers, Michael S.; Draper, Deborah; Truong, Meng; Kaplan, Ian M.; Gittelman, Rachel M.; Zhang, Yu; Rosen, Lindsey B.; Snow, Andrew L.; Dalgard, Clifton L.; Burbelo, Peter D.; Imberti, Luisa; Sottini, Alessandra; Quiros-Roldan, Eugenia; Castelli, Francesco; Rossi, Camillo; Brugnoni, Duilio; Biondi, Andrea; Bettini, Laura Rachele; D’Angio, Mariella; Bonfanti, Paolo; Anderson, Megan V.; Saracino, Annalisa; Chironna, Maria; Di Stefano, Mariantonietta; Fiore, Jose Ramon; Santantonio, Teresa; Castagnoli, Riccardo; Marseglia, Gian Luigi; Magliocco, Mary; Bosticardo, Marita; Pala, Francesca; Shaw, Elana; Matthews, Helen; Weber, Sarah E.; Xirasagar, Sandhya; Barnett, Jason; Oler, Andrew J.; Dimitrova, Dimana; Bergerson, Jenna R.E.; McDermott, David H.; Rao, V. Koneti; Murphy, Philip M.; Holland, Steven M.; Lisco, Andrea; Su, Helen C.; Lionakis, Michail S.; Cohen, Jeffrey I.; Freeman, Alexandra F.; Snyder, Thomas M.; Lack, Justin; Notarangelo, Luigi D.

doi:10.1016/j.jaci.2023.12.011

Cited by 3 publications

(2 citation statements)

References 80 publications

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“…This suggests that IEI cohorts may also have developed cross-reactive T-cells following vaccination, which potentially protect them against severe disease after infection with an emerging SARS-CoV-2 variant. The advantageous role of COVID-19 mRNA vaccination in patients with IEIs was also recently demonstrated in another study that examined the breadth and epitope specificity of SARS-CoV-2-specific T cell receptor clonotypes ( 37 ).…”

Section: Discussionmentioning

confidence: 79%

Immunogenicity of COVID-19 booster vaccination in IEI patients and their one year clinical follow-up after start of the COVID-19 vaccination program

van Leeuwen,

Grobben,

GeurtsvanKessel

et al. 2024

Front. Immunol.

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PurposePrevious studies have demonstrated that the majority of patients with an inborn error of immunity (IEI) develop a spike (S)-specific IgG antibody and T-cell response after two doses of the mRNA-1273 COVID-19 vaccine, but little is known about the response to a booster vaccination. We studied the immune responses 8 weeks after booster vaccination with mRNA-based COVID-19 vaccines in 171 IEI patients. Moreover, we evaluated the clinical outcomes in these patients one year after the start of the Dutch COVID-19 vaccination campaign.MethodsThis study was embedded in a large prospective multicenter study investigating the immunogenicity of COVID-19 mRNA-based vaccines in IEI (VACOPID study). Blood samples were taken from 244 participants 8 weeks after booster vaccination. These participants included 171 IEI patients (X-linked agammaglobulinemia (XLA;N=11), combined immunodeficiency (CID;N=4), common variable immunodeficiency (CVID;N=45), isolated or undefined antibody deficiencies (N=108) and phagocyte defects (N=3)) and 73 controls. SARS-CoV-2-specific IgG titers, neutralizing antibodies, and T-cell responses were evaluated. One year after the start of the COVID-19 vaccination program, 334 study participants (239 IEI patients and 95 controls) completed a questionnaire to supplement their clinical data focusing on SARS-CoV-2 infections.ResultsAfter booster vaccination, S-specific IgG titers increased in all COVID-19 naive IEI cohorts and controls, when compared to titers at 6 months after the priming regimen. The fold-increases did not differ between controls and IEI cohorts. SARS-CoV-2-specific T-cell responses also increased equally in all cohorts after booster vaccination compared to 6 months after the priming regimen. Most SARS-CoV-2 infections during the study period occurred in the period when the Omicron variant had become dominant. The clinical course of these infections was mild, although IEI patients experienced more frequent fever and dyspnea compared to controls and their symptoms persisted longer.ConclusionOur study demonstrates that mRNA-based booster vaccination induces robust recall of memory B-cell and T-cell responses in most IEI patients. One-year clinical follow-up demonstrated that SARS-CoV-2 infections in IEI patients were mild. Given our results, we support booster campaigns with newer variant-specific COVID-19 booster vaccines to IEI patients with milder phenotypes.

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Section: Discussionmentioning

confidence: 79%

Immunogenicity of COVID-19 booster vaccination in IEI patients and their one year clinical follow-up after start of the COVID-19 vaccination program

van Leeuwen,

Grobben,

GeurtsvanKessel

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…We collected four public TCR-seq sample cohorts 27 , 79 , 80 , 81 with HLA genotype information available. We compiled them into a mixed cohort totaling 1,208 individuals.…”

Section: Methodsmentioning

confidence: 99%

Quantifiable TCR repertoire changes in prediagnostic blood specimens among patients with high-grade ovarian cancer

Yu,

Pan,

et al. 2024

Cell Reports Medicine

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T-cell receptor sequencing in interrogating antigen-specific T-cell responses to foreign and self-antigens

Johansson,

Kwok

2024

Journal of Allergy and Clinical Immunology

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Perturbations of the T-cell receptor repertoire in response to SARS-CoV-2 in immunocompetent and immunocompromised individuals

Cited by 3 publications

References 80 publications

Immunogenicity of COVID-19 booster vaccination in IEI patients and their one year clinical follow-up after start of the COVID-19 vaccination program

Immunogenicity of COVID-19 booster vaccination in IEI patients and their one year clinical follow-up after start of the COVID-19 vaccination program

Quantifiable TCR repertoire changes in prediagnostic blood specimens among patients with high-grade ovarian cancer

T-cell receptor sequencing in interrogating antigen-specific T-cell responses to foreign and self-antigens

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