SARS-CoV-2 Monoclonal Antibody Treatment Followed by Vaccination Shifts Human Memory B-Cell Epitope Recognition, Suggesting Antibody Feedback

被引：3

作者：

Bloom, Nathaniel ^{[1
]}

Ramirez, Sydney, I ^{[1
,2
]}

Cohn, Hallie ^{[3
,4
]}

Parikh, Urvi M. ^{[5
]}

Heaps, Amy ^{[5
]}

Sieg, Scott F. ^{[6
]}

Greninger, Alex ^{[7
]}

Ritz, Justin ^{[8
]}

Moser, Carlee ^{[8
]}

Eron, Joseph J. ^{[9
]}

Bajic, Goran ^{[3
]}

Currier, Judith S. ^{[10
]}

Klekotka, Paul ^{[11
]}

Wohl, David A. ^{[9
]}

Daar, Eric S. ^{[12
]}

Li, Jonathan ^{[13
]}

Hughes, Michael D. ^{[8
]}

Chew, Kara W. ^{[10
]}

Smith, Davey M. ^{[2
]}

Crotty, Shane ^{[1
,2
]}

Coelho, Camila H. ^{[3
,4
,14
]}

机构：

[1] La Jolla Inst Immunol, Ctr Vaccine Innovat, 9420 Athena Circle, La Jolla, CA 92037 USA

[2] Univ Calif San Diego, Dept Med, Div Infect Dis & Global Publ Hlth, La Jolla, CA USA

[3] Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY USA

[4] Icahn Sch Med Mt Sinai, Ctr Vaccine Res & Pandem Preparedness, New York, NY USA

[5] Univ Pittsburgh, Sch Med, Div Infect Dis, Dept Med, Pittsburgh, PA USA

[6] Case Western Reserve Sch Med, Dept Med, Div Infect Dis & HIV Med, Cleveland, OH USA

[7] Univ Washington, Dept Med, Seattle, WA USA

[8] Harvard TH Chan Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA USA

[9] Univ North Carolina Chapel Hill, Sch Med, Dept Med, Chapel Hill, NC USA

[10] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Infect Dis, Los Angeles, CA USA

[11] Eli Lilly & Co, San Diego, CA USA

[12] Harbor UCLA Med Ctr, Lundquist Inst, Torrance, CA USA

[13] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Boston, MA USA

[14] Icahn Sch Med Mt Sinai, Precis Immunol Inst, New York, NY USA

来源：

JOURNAL OF INFECTIOUS DISEASES | 2024年 / 230卷 / 05期

基金：

美国国家卫生研究院;

关键词：

COVID-19; mAb therapy; bamlanivimab; SARS-CoV-2; memory B cells; RECEPTOR-BINDING DOMAIN; MUTATIONS; ESCAPE; RESPONSES; COCKTAIL; IMMUNITY;

D O I：

10.1093/infdis/jiae371

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Therapeutic monoclonal antibodies (mAbs) have been studied in humans, but the impact on immune memory of mAb treatment during an ongoing infection remains unclear. We evaluated the effect of infusion of the anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD) mAb bamlanivimab on memory B cells (MBCs) in SARS-CoV-2-infected individuals. Bamlanivimab treatment skewed the repertoire of MBCs targeting spike toward non-RBD epitopes. Furthermore, the relative affinity of RBD MBCs was weaker in mAb-treated individuals compared to placebo-treated individuals over time. Subsequently, after mRNA coronavirus disease 2019 vaccination, MBC differences persisted and mapped to a specific reduction in recognition of the class II RBD site, the same RBD epitope recognized by bamlanivimab. These findings indicate a substantial role of antibody feedback in regulating MBC responses to infection, and single mAb administration can continue to impact MBC responses to additional antigen exposures months later. We report for the first time the effect of monoclonal antibody (mAb) treatment on SARS-CoV-2-specific human memory B cells of SARS-CoV-2-infected humans receiving, or not receiving, mRNA immunization. Our data show that mAb treatment alters later immune memory responses to vaccination.

引用

页码：1187 / 1196

页数：10

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