Convalescent Adaptive Immunity Is Highly Heterogenous after SARS-CoV-2 Infection

The optimal detection strategies for effective convalescent immunity after SARS-CoV-2 infection and vaccination remain unclear. The objective of this study was to characterize convalescent immunity targeting the SARS-CoV-2 spike protein using a multiparametric approach. At the beginning of the pande...

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Main Authors: Balaji Pathakumari, Paige K. Marty, Maleeha Shah, Virginia P. Van Keulen, Courtney L. Erskine, Matthew S. Block, Pedro Arias-Sanchez, Patricio Escalante, Tobias Peikert
Format: Article
Language:English
Published: MDPI AG 2023-11-01
Series:Journal of Clinical Medicine
Subjects:
Online Access:https://www.mdpi.com/2077-0383/12/22/7136
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author Balaji Pathakumari
Paige K. Marty
Maleeha Shah
Virginia P. Van Keulen
Courtney L. Erskine
Matthew S. Block
Pedro Arias-Sanchez
Patricio Escalante
Tobias Peikert
author_facet Balaji Pathakumari
Paige K. Marty
Maleeha Shah
Virginia P. Van Keulen
Courtney L. Erskine
Matthew S. Block
Pedro Arias-Sanchez
Patricio Escalante
Tobias Peikert
author_sort Balaji Pathakumari
collection DOAJ
description The optimal detection strategies for effective convalescent immunity after SARS-CoV-2 infection and vaccination remain unclear. The objective of this study was to characterize convalescent immunity targeting the SARS-CoV-2 spike protein using a multiparametric approach. At the beginning of the pandemic, we recruited 30 unvaccinated convalescent donors who had previously been infected with COVID-19 and 7 unexposed asymptomatic controls. Peripheral blood mononuclear cells (PBMCs) were obtained from leukapheresis cones. The humoral immune response was assessed by measuring serum anti-SARS-CoV-2 spike S1 subunit IgG via semiquantitative ELISA, and T-cell immunity against S1 and S2 subunits were studied via IFN-γ enzyme-linked immunosorbent spot (ELISpot) and flow cytometric (FC) activation-induced marker (AIM) assays and the assessment of cytotoxic CD8<sup>+</sup> T-cell function (in the subset of HLA-A2-positive patients). No single immunoassay was sufficient in identifying anti-spike convalescent immunity among all patients. There was no consistent correlation between adaptive humoral and cellular anti-spike responses. Our data indicate that the magnitude of anti-spike convalescent humoral and cellular immunity is highly heterogeneous and highlights the need for using multiple assays to comprehensively measure SARS-CoV-2 convalescent immunity. These observations might have implications for COVID-19 surveillance, and the determination of optimal vaccination strategies for emerging variants. Further studies are needed to determine the optimal assessment of adaptive humoral and cellular immunity following SARS-CoV-2 infection, especially in the context of emerging variants and unclear vaccination schedules.
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spelling doaj.art-b8fad6e6152e42cb9a4123e6f2b763bc2023-11-24T14:49:36ZengMDPI AGJournal of Clinical Medicine2077-03832023-11-011222713610.3390/jcm12227136Convalescent Adaptive Immunity Is Highly Heterogenous after SARS-CoV-2 InfectionBalaji Pathakumari0Paige K. Marty1Maleeha Shah2Virginia P. Van Keulen3Courtney L. Erskine4Matthew S. Block5Pedro Arias-Sanchez6Patricio Escalante7Tobias Peikert8Division of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USADivision of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USADivision of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USADivision of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USADepartment of Immunology, Mayo Clinic, Rochester, MN 55905, USADepartment of Immunology, Mayo Clinic, Rochester, MN 55905, USADivision of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USADivision of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USADivision of Pulmonary and Critical Care Medicine, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USAThe optimal detection strategies for effective convalescent immunity after SARS-CoV-2 infection and vaccination remain unclear. The objective of this study was to characterize convalescent immunity targeting the SARS-CoV-2 spike protein using a multiparametric approach. At the beginning of the pandemic, we recruited 30 unvaccinated convalescent donors who had previously been infected with COVID-19 and 7 unexposed asymptomatic controls. Peripheral blood mononuclear cells (PBMCs) were obtained from leukapheresis cones. The humoral immune response was assessed by measuring serum anti-SARS-CoV-2 spike S1 subunit IgG via semiquantitative ELISA, and T-cell immunity against S1 and S2 subunits were studied via IFN-γ enzyme-linked immunosorbent spot (ELISpot) and flow cytometric (FC) activation-induced marker (AIM) assays and the assessment of cytotoxic CD8<sup>+</sup> T-cell function (in the subset of HLA-A2-positive patients). No single immunoassay was sufficient in identifying anti-spike convalescent immunity among all patients. There was no consistent correlation between adaptive humoral and cellular anti-spike responses. Our data indicate that the magnitude of anti-spike convalescent humoral and cellular immunity is highly heterogeneous and highlights the need for using multiple assays to comprehensively measure SARS-CoV-2 convalescent immunity. These observations might have implications for COVID-19 surveillance, and the determination of optimal vaccination strategies for emerging variants. Further studies are needed to determine the optimal assessment of adaptive humoral and cellular immunity following SARS-CoV-2 infection, especially in the context of emerging variants and unclear vaccination schedules.https://www.mdpi.com/2077-0383/12/22/7136SARS-CoV-2convalescent immunityT-cell immunityheterogenous immunitymultiparametric approach
spellingShingle Balaji Pathakumari
Paige K. Marty
Maleeha Shah
Virginia P. Van Keulen
Courtney L. Erskine
Matthew S. Block
Pedro Arias-Sanchez
Patricio Escalante
Tobias Peikert
Convalescent Adaptive Immunity Is Highly Heterogenous after SARS-CoV-2 Infection
Journal of Clinical Medicine
SARS-CoV-2
convalescent immunity
T-cell immunity
heterogenous immunity
multiparametric approach
title Convalescent Adaptive Immunity Is Highly Heterogenous after SARS-CoV-2 Infection
title_full Convalescent Adaptive Immunity Is Highly Heterogenous after SARS-CoV-2 Infection
title_fullStr Convalescent Adaptive Immunity Is Highly Heterogenous after SARS-CoV-2 Infection
title_full_unstemmed Convalescent Adaptive Immunity Is Highly Heterogenous after SARS-CoV-2 Infection
title_short Convalescent Adaptive Immunity Is Highly Heterogenous after SARS-CoV-2 Infection
title_sort convalescent adaptive immunity is highly heterogenous after sars cov 2 infection
topic SARS-CoV-2
convalescent immunity
T-cell immunity
heterogenous immunity
multiparametric approach
url https://www.mdpi.com/2077-0383/12/22/7136
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