Nucleocapsid-specific antibody function is associated with therapeutic benefits from COVID-19 convalescent plasma therapy

Jonathan D Herman; Chuangqi Wang; John Stephen Burke; Yonatan Zur; Hacheming Compere; Jaewon Kang; Ryan Macvicar; Sabian Taylor; Sally Shin; Ian Frank; Don Siegel; Pablo Tebas; Grace H Choi; Pamela A Shaw; Hyunah Yoon; Liise-Anne Pirofski; Boris D Julg; Katharine J Bar; Douglas Lauffenburger; Galit Alter

doi:10.1016/j.xcrm.2022.100811

Nucleocapsid-specific antibody function is associated with therapeutic benefits from COVID-19 convalescent plasma therapy

Cell Rep Med. 2022 Nov 15;3(11):100811. doi: 10.1016/j.xcrm.2022.100811. Epub 2022 Oct 24.

Authors

Jonathan D Herman¹, Chuangqi Wang², John Stephen Burke³, Yonatan Zur³, Hacheming Compere³, Jaewon Kang³, Ryan Macvicar³, Sabian Taylor³, Sally Shin³, Ian Frank⁴, Don Siegel⁵, Pablo Tebas⁴, Grace H Choi⁶, Pamela A Shaw⁷, Hyunah Yoon⁸, Liise-Anne Pirofski⁹, Boris D Julg³, Katharine J Bar¹⁰, Douglas Lauffenburger¹¹, Galit Alter¹²

Affiliations

¹ Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA; Division of Infectious Disease, Brigham and Women's Hospital, Boston, MA, USA.
² Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA.
³ Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA.
⁴ Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁵ Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, USA.
⁶ Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Philadelphia, PA, USA.
⁷ Biostatistics Unit, Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA.
⁸ Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, USA.
⁹ Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, USA; Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA.
¹⁰ Department of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: bark@pennmedicine.upenn.edu.
¹¹ Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, USA. Electronic address: lauffen@mit.edu.
¹² Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA, USA. Electronic address: galter@mgh.harvard.edu.

Abstract

Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP), a passive polyclonal antibody therapeutic agent, has had mixed clinical results. Although antibody neutralization is the predominant approach to benchmarking CCP efficacy, CCP may also influence the evolution of the endogenous antibody response. Using systems serology to comprehensively profile severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) functional antibodies of hospitalized people with COVID-19 enrolled in a randomized controlled trial of CCP (ClinicalTrials.gov: NCT04397757), we find that the clinical benefits of CCP are associated with a shift toward reduced inflammatory Spike (S) responses and enhanced nucleocapsid (N) humoral responses. We find that CCP has the greatest clinical benefit in participants with low pre-existing anti-SARS-CoV-2 antibody function and that CCP-induced immunomodulatory Fc glycan profiles and N immunodominant profiles persist for at least 2 months. We highlight a potential mechanism of action of CCP associated with durable immunomodulation, outline optimal patient characteristics for CCP treatment, and provide guidance for development of a different class of COVID-19 hyperinflammation-targeting antibody therapeutic agents.

Keywords: COVID immunomodulation; COVID-19; Fc effector functions; SARS-CoV-2; antibody Fc glycosylation; convalescent plasma; functional antibodies; immunodominance shift; nucleocapsid; systems serology.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Antibodies, Viral / therapeutic use
COVID-19 Serotherapy
COVID-19* / therapy
Humans
Immunization, Passive / methods
Nucleocapsid
SARS-CoV-2

Nucleocapsid-specific antibody function is associated with therapeutic benefits from COVID-19 convalescent plasma therapy

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