Evolution of humoral and cellular immunity post-breakthrough coronavirus disease 2019 in vaccinated patients with hematologic malignancy receiving tixagevimab-cilgavimab

Victoria G Hall; Thi H O Nguyen; Lilith F Allen; Louise C Rowntree; Lukasz Kedzierski; Brendon Y Chua; Chhay Lim; Natalie R Saunders; Emily Klimevski; Gayani S Tennakoon; John F Seymour; Vikas Wadhwa; Natalie Cain; Kim L Vo; Suellen Nicholson; Theo Karapanagiotidis; Deborah A Williamson; Karin A Thursky; Timothy Spelman; Michelle K Yong; Monica A Slavin; Katherine Kedzierska; Benjamin W Teh

doi:10.1093/ofid/ofad550

Evolution of humoral and cellular immunity post-breakthrough coronavirus disease 2019 in vaccinated patients with hematologic malignancy receiving tixagevimab-cilgavimab

Victoria G Hall^*, Thi H O Nguyen, Lilith F Allen, Louise C Rowntree, Lukasz Kedzierski, Brendon Y Chua, Chhay Lim, Natalie R Saunders, Emily Klimevski, Gayani S Tennakoon, John F Seymour, Vikas Wadhwa, Natalie Cain, Kim L Vo, Suellen Nicholson, Theo Karapanagiotidis, Deborah A Williamson, Karin A Thursky, Timothy Spelman, Michelle K YongMonica A Slavin, Katherine Kedzierska, Benjamin W Teh^*

^*Corresponding author for this work

School of Medicine

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Article number	ofad550
Pages (from-to)	1-12
Number of pages	12
Journal	Open Forum Infectious Diseases
Volume	10
Issue number	11
Early online date	14 Nov 2023
DOIs	https://doi.org/10.1093/ofid/ofad550
Publication status	Published - Nov 2023

Keywords

Breakthrough
COVID-19
Hematologic malignancy
Monoclonal antibody
Vaccination

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Hall, V. G., Nguyen, T. H. O., Allen, L. F., Rowntree, L. C., Kedzierski, L., Chua, B. Y., Lim, C., Saunders, N. R., Klimevski, E., Tennakoon, G. S., Seymour, J. F., Wadhwa, V., Cain, N., Vo, K. L., Nicholson, S., Karapanagiotidis, T., Williamson, D. A., Thursky, K. A., Spelman, T., ... Teh, B. W. (2023). Evolution of humoral and cellular immunity post-breakthrough coronavirus disease 2019 in vaccinated patients with hematologic malignancy receiving tixagevimab-cilgavimab. Open Forum Infectious Diseases, 10(11), 1-12. Article ofad550. https://doi.org/10.1093/ofid/ofad550

@article{c999d745a4a94e07b9f7a507b0e5123d,

title = "Evolution of humoral and cellular immunity post-breakthrough coronavirus disease 2019 in vaccinated patients with hematologic malignancy receiving tixagevimab-cilgavimab",

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 = "Breakthrough, COVID-19, Hematologic malignancy, Monoclonal antibody, Vaccination",

author = "Hall, {Victoria G} and Nguyen, {Thi H O} and Allen, {Lilith F} and Rowntree, {Louise C} and Lukasz Kedzierski and Chua, {Brendon Y} and Chhay Lim and Saunders, {Natalie R} and Emily Klimevski and Tennakoon, {Gayani S} and Seymour, {John F} and Vikas Wadhwa and Natalie Cain and Vo, {Kim L} and Suellen Nicholson and Theo Karapanagiotidis and Williamson, {Deborah A} and Thursky, {Karin A} and Timothy Spelman and Yong, {Michelle K} and Slavin, {Monica A} and Katherine Kedzierska and Teh, {Benjamin W}",

note = "Funding: This project has received funding from a VC2 Research Grant (V. G. H.). V. G. H. is supported by a National Health and Medical Research Council (NHMRC) postgraduate PhD scholarship (award number 2014210). D. A. W. is funded by an NHMRC Investigator Grant (grant number APP1174555). B. W. T. is supported by the Australian government Medical Research Future Fund (MRFF) Investigator Fellowship (EL-2, award number 1195894). This work was supported by the NHMRC Leadership Investigator Grant to K. K. (grant number 1173871); an NHMRC Emerging Leadership Level 1 Investigator Grant to T. H. O. N. (grant number 1194036); and MRFF Award (award number 2016062) to K. K., T. H. O. N., L. C. R., and B. W. T.",

year = "2023",

month = nov,

doi = "10.1093/ofid/ofad550",

language = "English",

volume = "10",

pages = "1--12",

journal = "Open Forum Infectious Diseases",

issn = "2328-8957",

publisher = "Oxford University Press",

number = "11",

}

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 2023, 'Evolution of humoral and cellular immunity post-breakthrough coronavirus disease 2019 in vaccinated patients with hematologic malignancy receiving tixagevimab-cilgavimab', Open Forum Infectious Diseases, vol. 10, no. 11, ofad550, pp. 1-12. https://doi.org/10.1093/ofid/ofad550

Evolution of humoral and cellular immunity post-breakthrough coronavirus disease 2019 in vaccinated patients with hematologic malignancy receiving tixagevimab-cilgavimab. / Hall, Victoria G; Nguyen, Thi H O; Allen, Lilith F et al.
In: Open Forum Infectious Diseases, Vol. 10, No. 11, ofad550, 11.2023, p. 1-12.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Evolution of humoral and cellular immunity post-breakthrough coronavirus disease 2019 in vaccinated patients with hematologic malignancy receiving tixagevimab-cilgavimab

AU - Hall, Victoria G

AU - Nguyen, Thi H O

AU - Allen, Lilith F

AU - Rowntree, Louise C

AU - Kedzierski, Lukasz

AU - Chua, Brendon Y

AU - Lim, Chhay

AU - Saunders, Natalie R

AU - Klimevski, Emily

AU - Tennakoon, Gayani S

AU - Seymour, John F

AU - Wadhwa, Vikas

AU - Cain, Natalie

AU - Vo, Kim L

AU - Nicholson, Suellen

AU - Karapanagiotidis, Theo

AU - Williamson, Deborah A

AU - Thursky, Karin A

AU - Spelman, Timothy

AU - Yong, Michelle K

AU - Slavin, Monica A

AU - Kedzierska, Katherine

AU - Teh, Benjamin W

N1 - Funding: This project has received funding from a VC2 Research Grant (V. G. H.). V. G. H. is supported by a National Health and Medical Research Council (NHMRC) postgraduate PhD scholarship (award number 2014210). D. A. W. is funded by an NHMRC Investigator Grant (grant number APP1174555). B. W. T. is supported by the Australian government Medical Research Future Fund (MRFF) Investigator Fellowship (EL-2, award number 1195894). This work was supported by the NHMRC Leadership Investigator Grant to K. K. (grant number 1173871); an NHMRC Emerging Leadership Level 1 Investigator Grant to T. H. O. N. (grant number 1194036); and MRFF Award (award number 2016062) to K. K., T. H. O. N., L. C. R., and B. W. T.

PY - 2023/11

Y1 - 2023/11

N2 - 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.

AB - 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.

KW - Breakthrough

KW - COVID-19

KW - Hematologic malignancy

KW - Monoclonal antibody

KW - Vaccination

U2 - 10.1093/ofid/ofad550

DO - 10.1093/ofid/ofad550

M3 - Article

C2 - 38023562

SN - 2328-8957

VL - 10

SP - 1

EP - 12

JO - Open Forum Infectious Diseases

JF - Open Forum Infectious Diseases

IS - 11

M1 - ofad550

ER -

Evolution of humoral and cellular immunity post-breakthrough coronavirus disease 2019 in vaccinated patients with hematologic malignancy receiving tixagevimab-cilgavimab

Abstract

Keywords

UN SDGs

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