학술논문
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
Document Type
Academic Journal
Author
Halvorson, Torin; Ivison, Sabine; Huang, Qing; Ladua, Gale; Yotis, Demitra M.; Mannar, Dhiraj; Subramaniam, Sriram; Ferreira, Victor H.; Kumar, Deepali; Belga, Sara; Levings, Megan K.; Delisle, Jean-Sébastien; Hosseini-Moghaddam, Sasan; Cardinal, Héloïse; Dieudé, Mélanie; Racine, Normand; Top, Karina; DeSerres, Gaston; West, Lori; Cloutier, Marc; Bazin, Renée; Lemieux, Christopher; De Serres, Sacha; Humar, Atul; Shalhoub, Sarah; Kabbani, Dima; Hébert, Marie-Josée; Gongal, Patricia; Stephens, Kristian; Turgeon, Julie; Khrifi, Zineb; Samson, France; Desjardins, Maryse; Brown, Hélène; Doiron, Johanne; Baker, Cadence; Toth, Taylor; Luke, Grant; Pinzon, Natalia; Hall, Victoria G.; Robertson, Kimberly; Mangan, Heather
Source
Transplantation. Apr 01, 2024 108(4):e49-e62
Subject
Language
English
ISSN
0041-1337
Abstract
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.