학술논문
Evolution of Humoral and Cellular Immunity Post–Breakthrough Coronavirus Disease 2019 in Vaccinated Patients With Hematologic Malignancy Receiving Tixagevimab-Cilgavimab.
Document Type
Article
Author
Hall, Victoria G; Nguyen, Thi H O; Allen, Lilith F; Rowntree, Louise C; Kedzierski, Lukasz; Chua, Brendon Y; Lim, Chhay; Saunders, Natalie R; Klimevski, Emily; Tennakoon, Gayani S; Seymour, John F; Wadhwa, Vikas; Cain, Natalie; Vo, Kim L; Nicholson, Suellen; Karapanagiotidis, Theo; Williamson, Deborah A; Thursky, Karin A; Spelman, Timothy; Yong, Michelle K
Source
Subject
*COVID-19
*CELLULAR immunity
*CELLULAR evolution
*HEMATOLOGIC malignancies
*SARS-CoV-2 Omicron variant
*CORONAVIRUS diseases
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Language
ISSN
2328-8957
Abstract
Background In-depth immunogenicity studies of tixagevimab-cilgavimab (T-C) are lacking, including following breakthrough coronavirus disease 2019 (COVID-19) in vaccinated patients with hematologic malignancy (HM) receiving T-C as pre-exposure prophylaxis. Methods We performed a prospective, observational cohort study and detailed immunological analyses of 93 patients with HM who received T-C from May 2022, with and without breakthrough infection, during a follow-up period of 6 months and dominant Omicron BA.5 variant. Results In 93 patients who received T-C, there was an increase in Omicron BA.4/5 receptor-binding domain (RBD) immunoglobulin G (IgG) antibody titers that persisted for 6 months and was equivalent to 3-dose-vaccinated uninfected healthy controls at 1 month postinjection. Omicron BA.4/5 neutralizing antibody was lower in patients receiving B-cell–depleting therapy within 12 months despite receipt of T-C. COVID-19 vaccination during T-C treatment did not incrementally improve RBD or neutralizing antibody levels. In 16 patients with predominantly mild breakthrough infection, no change in serum neutralization of Omicron BA.4/5 postinfection was detected. Activation-induced marker assay revealed an increase in CD4+ (but not CD8+) T cells post infection, comparable to previously infected healthy controls. Conclusions Our study provides proof-of-principle for a pre-exposure prophylaxis strategy and highlights the importance of humoral and cellular immunity post–breakthrough COVID-19 in vaccinated patients with HM. [ABSTRACT FROM AUTHOR]