Development of T-cell immunity in a liver and hematopoietic stem cell transplant recipient following coronavirus disease 2019 infection

Soni, Mithil; Migliori, Edoardo; Assal, Amer; Chan, Heather; Ciubotariu, Rodica; Pan, Jian B.; Cicero, Kara; Pereira, Marcus R.; Mapara, Markus Y.; Muranski, Pawel

doi:10.1016/j.jcyt.2021.05.005

Cited by 3 publications

(5 citation statements)

References 23 publications

(26 reference statements)

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“…Subject #1015 is a patient with active multiple myeloma who developed symptomatic COVID-19 at the beginning of the pandemic (March 2020) following a cycle of chemotherapy and subsequently underwent autologous SCT. Another IP Subject #1023 included in this experiment is a patient with history of erythropoietic protoporphyria (EPP), failed liver and hematopoietic stem cell transplant followed by the second liver and SCT rescue who experienced COVID-19 and was previously described in a case report ( 30 ).…”

Section: Resultsmentioning

confidence: 99%

“…1 mg/ml of brefeldin A (Golgi PLUG, BD Biosciences) and 1 mg/ml of Monensin (Golgi STOP, BD Biosciences), anti-CD28 1µl/ml and anti-CD49d 1µl/ml were added to each well, and plates were incubated for 5h at 37°C 5% CO2. Cells were stained for surface markers following the previously described protocol ( 30 ). Intracellular cytokine staining was performed per manufacturer’s instructions using Fixation/Permeabilization Solution Kit (BD Bioscience), resuspended in FACS buffer and analyzed by flow cytometry.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

The prospect of universal coronavirus immunity: characterization of reciprocal and non-reciprocal T cell responses against SARS-CoV2 and common human coronaviruses

Soni,

Migliori,

et al. 2023

Front. Immunol.

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T cell immunity plays a central role in clinical outcomes of Coronavirus Infectious Disease 2019 (COVID-19) and T cell-focused vaccination or cellular immunotherapy might provide enhanced protection for some immunocompromised patients. Pre-existing T cell memory recognizing SARS-CoV-2 antigens antedating COVID-19 infection or vaccination, may have developed as an imprint of prior infections with endemic non-SARS human coronaviruses (hCoVs) OC43, HKU1, 229E, NL63, pathogens of “common cold”. In turn, SARS-CoV-2-primed T cells may recognize emerging variants or other hCoV viruses and modulate the course of subsequent hCoV infections. Cross-immunity between hCoVs and SARS-CoV-2 has not been well characterized. Here, we systematically investigated T cell responses against the immunodominant SARS-CoV-2 spike, nucleocapsid and membrane proteins and corresponding antigens from α- and β-hCoVs among vaccinated, convalescent, and unexposed subjects. Broad T cell immunity against all tested SARS-CoV-2 antigens emerged in COVID-19 survivors. In convalescent and in vaccinated individuals, SARS-CoV-2 spike-specific T cells reliably recognized most SARS-CoV-2 variants, however cross-reactivity against the omicron variant was reduced by approximately 47%. Responses against spike, nucleocapsid and membrane antigens from endemic hCoVs were significantly more extensive in COVID-19 survivors than in unexposed subjects and displayed cross-reactivity between α- and β-hCoVs. In some, non-SARS hCoV-specific T cells demonstrated a prominent non-reciprocal cross-reactivity with SARS-CoV-2 antigens, whereas a distinct anti-SARS-CoV-2 immunological repertoire emerged post-COVID-19, with relatively limited cross-recognition of non-SARS hCoVs. Based on this cross-reactivity pattern, we established a strategy for in-vitro expansion of universal anti-hCoV T cells for adoptive immunotherapy. Overall, these results have implications for the future design of universal vaccines and cell-based immune therapies against SARS- and non-SARS-CoVs.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

The prospect of universal coronavirus immunity: characterization of reciprocal and non-reciprocal T cell responses against SARS-CoV2 and common human coronaviruses

Soni,

Migliori,

et al. 2023

Front. Immunol.

Self Cite

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show abstract

“…Subject #1015 was a patient with active multiple myeloma who developed symptomatic COVID-19 at the beginning of the pandemic (March 2020) following a cycle of chemotherapy and subsequently underwent autologous SCT. Subject #1023 is a patient with history of erythropoietic protoporphyria (EPP), failed liver and hematopoietic stem cell transplant followed by the second liver and SCT rescue who experienced COVID-19 and was previously described in a case report [38].…”

Section: This Was Further Underscored Upon Pearson Correlation Analys...mentioning

confidence: 99%

“…1 mg/mL of brefeldin A (Golgi PLUG, BD Biosciences) and 1 mg/mL of Monensin (Golgi STOP, BD Biosciences), anti-CD28 1ul/mL and anti-CD49d 1ul/mL were added to each well, and plates were incubated for 5h at 37°C 5% CO2. Cells were stained for surface markers following the previously described protocol [38]. Intracellular cytokine staining was performed by following the indication of Fixation/Permeabilization Solution Kit (BD Bioscience), incubating samples with cytokine master mix for 1h at 4ºC.…”

Section: Intracellular Cytokine Staining Assaymentioning

confidence: 99%

The prospect of universal coronavirus immunity: a characterization of reciprocal and non-reciprocal T cell responses against SARS-CoV2 and common human coronaviruses

Soni

Migliori

et al. 2023

Preprint

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T cell immunity plays a central role in clinical outcomes of Coronavirus Infectious Disease 2019 (COVID-19). Therefore, T cell-focused vaccination or cellular immunotherapy might provide enhanced protection for immunocompromised patients. Pre-existing T cell memory recognizing SARS-CoV2 antigens antedating COVID-19 infection or vaccination, may have developed as an imprint of prior infections with endemic non-SARS human coronaviruses (hCoVs) OC43, HKU1, 229E, NL63, pathogens of common cold. In turn, SARS-CoV2-primed T cells may recognize emerging variants or other hCoV viruses and modulate the course of subsequent hCoV infections. Cross-immunity between hCoVs and SARS-CoV2 has not been well characterized. Here, we systematically investigated T cell responses against the immunodominant SARS-CoV2 spike, nucleocapsid and membrane proteins and corresponding antigens from alpha and beta hCoVs among vaccinated, convalescent, and unexposed subjects. Broad T cell immunity against all tested SARS-CoV2 antigens emerged in COVID-19 survivors. In convalescent and in vaccinated individuals, SARS-CoV2 spike-specific T cells reliably recognized most SARS-CoV2 variants, however cross-reactivity against the omicron variant was reduced by approximately 50%. Responses against spike, nucleocapsid and membrane antigens from endemic hCoVs were more extensive in COVID-19 survivors than in unexposed subjects and displayed cross-reactivity between alpha and beta hCoVs. In some, non-SARS hCoV-specific T cells demonstrated a prominent non-reciprocal cross-reactivity with SARS-CoV2 antigens, whereas a distinct anti-SARS-CoV2 immunological repertoire emerged post-COVID-19, with relatively limited cross-recognition of non-SARS hCoVs. Based on this cross-reactivity pattern, we established a strategy for in-vitro expansion of universal anti-hCoV T cells for adoptive immunotherapy. Overall, these results have implications for the future design of universal vaccines and cell-based immune therapies against SARS- and non-SARS-CoVs.

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“…In brief, cryopreserved PBMCs were pulsed with overlapping 15-aminoacid long peptide libraries spanning the full length of S1, S2, M and NP antigens (final concentration of 1 mg/mL) and expanded for 14 days in AIM V medium (Thermo Fisher Scientific, Waltham, MA, USA) supplemented with inactivated 5% human serum, IL-7 at 10 ng/mL and IL-2 at 30 IU/mL (PeproTech, Rocky Hill, NJ, USA). Final cultures were restimulated with indicated peptide mixes for 6 h in the presence of brefeldin A and monensin A (BD Biosciences, San Jose, CA, USA) per the manufacturer’s instructions followed by intracellular cytokine staining and flow cytometry to quantify antigen-specific T cell response ( 9 ). Gating strategy for the analyzing antigen specific T cells has been shown in Supplementary Figure 1A .…”

Section: Diagnostic Assessment and Therapeutic Interventionmentioning

confidence: 99%

Case Report: Kinetics and durability of humoral and cellular response of SARS-CoV-2 messenger RNA vaccine in a lung and kidney transplant recipient

et al. 2023

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We present a case report of a 63-year-old female health care worker who is 15 years status post double lung transplant and six years status post living related donor kidney transplant who is healthy on a chronic immunosuppression regimen including prednisone, mycophenolate, and tacrolimus who received the SARS-CoV-2 mRNA vaccine (Pfizer-BioNTech BNT162b2) primary series and had poor initial humoral response to the COVID-19 mRNA vaccine, then demonstrated a robust, sustained immune response against S1 and S2 antigens for over seven months after receiving the recommended vaccine doses, including booster dose, without developing COVID-19 or other serious adverse events. Her immune response to vaccination indicates effective formation of anti-spike T cell memory despite chronic immunosuppression. This case report provides a comprehensive characterization of her immune response to this SARS-CoV-2 vaccination series. As vaccine effectiveness data is updated, and as better understanding of immune response including hybrid immunity emerges, these findings may reassure that recipients of SOTs may be capable of durable immune responses to emerging variants of SARS-CoV-2.

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Development of T-cell immunity in a liver and hematopoietic stem cell transplant recipient following coronavirus disease 2019 infection

Cited by 3 publications

References 23 publications

The prospect of universal coronavirus immunity: characterization of reciprocal and non-reciprocal T cell responses against SARS-CoV2 and common human coronaviruses

The prospect of universal coronavirus immunity: characterization of reciprocal and non-reciprocal T cell responses against SARS-CoV2 and common human coronaviruses

The prospect of universal coronavirus immunity: a characterization of reciprocal and non-reciprocal T cell responses against SARS-CoV2 and common human coronaviruses

Case Report: Kinetics and durability of humoral and cellular response of SARS-CoV-2 messenger RNA vaccine in a lung and kidney transplant recipient

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