SARS-CoV-2 Variants Omicron BA.4/5 and XBB.1.5 Significantly Escape T Cell Recognition in Solid-organ Transplant Recipients Vaccinated Against the Ancestral Strain.

Autor: Halvorson T; Department of Medicine, University of British Columbia, Vancouver, BC, Canada.; Department of Surgery, University of British Columbia, Vancouver, BC, Canada.; BC Children's Hospital Research Institute, Vancouver, BC, Canada., Ivison S; Department of Surgery, University of British Columbia, Vancouver, BC, Canada.; BC Children's Hospital Research Institute, Vancouver, BC, Canada., Huang Q; Department of Surgery, University of British Columbia, Vancouver, BC, Canada.; BC Children's Hospital Research Institute, Vancouver, BC, Canada., Ladua G; Department of Medicine, University of British Columbia, Vancouver, BC, Canada.; Infection and Immunity Research Centre, Vancouver Coastal Health Research Institute, Vancouver, BC, Canada., Yotis DM; Canadian Donation and Transplantation Research Program, Edmonton, AB, Canada., Mannar D; Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada., Subramaniam S; Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada., Ferreira VH; Ajmera Transplant Centre, University Health Network, Toronto, ON, Canada., Kumar D; Ajmera Transplant Centre, University Health Network, Toronto, ON, Canada., Belga S; Department of Medicine, University of British Columbia, Vancouver, BC, Canada.; Infection and Immunity Research Centre, Vancouver Coastal Health Research Institute, Vancouver, BC, Canada., Levings MK; Department of Surgery, University of British Columbia, Vancouver, BC, Canada.; BC Children's Hospital Research Institute, Vancouver, BC, Canada.; School of Biomedical Engineering, University of British Columbia, Vancouver, BC, Canada.
Jazyk: angličtina
Zdroj: Transplantation [Transplantation] 2024 Apr 01; Vol. 108 (4), pp. e49-e62. Date of Electronic Publication: 2023 Nov 28.
DOI: 10.1097/TP.0000000000004873
Abstrakt: Background: Immune-suppressed solid-organ transplant recipients (SOTRs) display impaired humoral responses to COVID-19 vaccination, but T cell responses are incompletely understood. SARS-CoV-2 variants Omicron BA.4/5 (BA.4/5) and XBB.1.5 escape neutralization by antibodies induced by vaccination or infection with earlier strains, but T cell recognition of these lineages in SOTRs is unclear.
Methods: We characterized Spike-specific T cell responses to ancestral SARS-CoV-2 and BA.4/5 peptides in 42 kidney, liver, and lung transplant recipients throughout a 3- or 4-dose ancestral Spike mRNA vaccination schedule. As the XBB.1.5 variant emerged during the study, we tested vaccine-induced T cell responses in 10 additional participants using recombinant XBB.1.5 Spike protein. Using an optimized activation-induced marker assay, we quantified circulating Spike-specific CD4 + and CD8 +  T cells based on antigen-stimulated expression of CD134, CD69, CD25, CD137, and/or CD107a.
Results: Vaccination strongly induced SARS-CoV-2-specific T cells, including BA.4/5- and XBB.1.5-reactive T cells, which remained detectable over time and further increased following a fourth dose. However, responses to BA.4/5 (1.34- to 1.67-fold lower) XBB.1.5 (2.0- to 18-fold lower) were significantly reduced in magnitude compared with ancestral strain responses. CD4 + responses correlated with anti-receptor-binding domain antibodies and predicted subsequent antibody responses in seronegative individuals. Lung transplant recipients receiving prednisone and older adults displayed weaker responses.
Conclusions: Ancestral strain vaccination stimulates BA.4/5 and XBB.1.5-cross-reactive T cells in SOTRs, but at lower magnitudes. Antigen-specific T cells can predict future antibody responses. Our data support monitoring both humoral and cellular immunity in SOTRs to track COVID-19 vaccine immunogenicity against emerging variants.
(Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: