AUTHOR=La Rosa Corinna , Chiuppesi Flavia , Park Yoonsuh , Zhou Qiao , Yang Dongyun , Gendzekhadze Ketevan , Ly Minh , Li Jing , Kaltcheva Teodora , Ortega Francisco Sandra , Gutierrez Miguel-Angel , Ali Haris , Otoukesh Salman , Amanam Idoroenyi , Salhotra Amandeep , Pullarkat Vinod A. , Aldoss Ibrahim , Rosenzweig Michael , Aribi Ahmed M. , Stein Anthony S. , Marcucci Guido , Dadwal Sanjeet Singh , Nakamura Ryotaro , Forman Stephen J. , Al Malki Monzr M. , Diamond Don J. 

TITLE=Functional SARS-CoV-2-specific T cells of donor origin in allogeneic stem cell transplant recipients of a T-cell-replete infusion: A prospective observational study

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1114131

DOI=10.3389/fimmu.2023.1114131

ISSN=1664-3224

ABSTRACT=<p>In the current post-pandemic era, recipients of an allogeneic hematopoietic stem cell transplant (HCT) deserve special attention. In these vulnerable patients, vaccine effectiveness is reduced by post-transplant immune-suppressive therapy; consequently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) is often associated with elevated morbidity and mortality. Characterizing SARS-CoV-2 adaptive immunity transfer from immune donors to HCT recipients in the context of immunosuppression will help identify optimal timing and vaccination strategies that can provide adequate protection to HCT recipients against infection with evolving SARS-CoV-2 variants. We performed a prospective observational study (NCT04666025 at <uri xlink:href="https://ClinicalTrials.gov" xmlns:xlink="http://www.w3.org/1999/xlink">ClinicalTrials.gov</uri>) to longitudinally monitor the transfer of SARS-CoV-2-specific antiviral immunity from HCT donors, who were either vaccinated or had a history of COVID-19, to their recipients <italic>via</italic> T-cell replete graft. Levels, function, and quality of SARS-CoV-2-specific immune responses were longitudinally analyzed up to 6 months post-HCT in 14 matched unrelated donor/recipients and four haploidentical donor/recipient pairs. A markedly skewed donor-derived SARS-CoV-2 CD4 T-cell response was measurable in 15 (83%) recipients. It showed a polarized Th1 functional profile, with the prevalence of central memory phenotype subsets. SARS-CoV-2-specific IFN-γ was detectable throughout the observation period, including early post-transplant (day +30). Functionally experienced SARS-CoV-2 Th1-type T cells promptly expanded in two recipients at the time of post-HCT vaccination and in two others who were infected and survived post-transplant COVID-19 infection. Our data suggest that donor-derived SARS-CoV-2 T-cell responses are functional in immunosuppressed recipients and may play a critical role in post-HCT vaccine response and protection from the fatal disease.</p><sec><title>Clinical trial registration</title><p>clinicaltrials.gov, identifier NCT04666025.</p></sec>