Evolution of Humoral and Cellular Immunity Post-Breakthrough Coronavirus Disease 2019 in Vaccinated Patients With Hematologic Malignancy Receiving Tixagevimab-Cilgavimab

Hall, VG; Nguyen, THO; Allen, LF; Rowntree, LC; Kedzierski, L; Chua, BY; Lim, C; Saunders, NR; Klimevski, E; Tennakoon, GS; Seymour, JF; Wadhwa, V; Cain, N; Vo, KL; Nicholson, S; Karapanagiotidis, T; Williamson, DA; Thursky, KA; Spelman, T; Yong, MK; Slavin, MA; Kedzierska, K; Teh, BW

Author(s): Hall, VG; Nguyen, THO; Allen, LF; Rowntree, LC; Kedzierski, L; Chua, BY; Lim, C; Saunders, NR; Klimevski, E; Tennakoon, GS; Seymour, JF; Wadhwa, V; Cain, N; Vo, KL; Nicholson, S; Karapanagiotidis, T; Williamson, DA; Thursky, KA; Spelman, T; Yong, MK; Slavin, MA; Kedzierska, K; Teh, BW;
Details: Publication Year 2023-11,Volume 10,Issue #11,Page ofad550
Journal Title: Open Forum Infectious Diseases
Publication Type: Research article
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.
Keywords: Covid-19; breakthrough; hematologic malignancy; monoclonal antibody; vaccination
Department(s): Infectious Diseases; Clinical Haematology; Ambulatory Services; Health Services Research
Publisher's Version: https://doi.org/10.1093/ofid/ofad550
Open Access at Publisher's Site: https://doi.org/10.1093/ofid/ofad550
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2023-12-20 12:18:37

Last Modified: 2023-12-20 12:24:05