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

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Cell Rep Med


. 2022 Oct 24;100811.
doi: 10.1016/j.xcrm.2022.100811. Online ahead of print.
Nucleocapsid-specific antibody function is associated with therapeutic benefits from COVID-19 convalescent plasma therapy


Jonathan D Herman ¹ , Chuangqi Wang ² , John Stephen Burke ³ , Yonatan Zur ³ , Hacheming Compere ³ , Jaewon Kang ³ , Ryan Macvicar ³ , Sabian Taylor ³ , Sally Shin ³ , Ian Frank ⁴ , Don Siegel ⁵ , Pablo Tebas ⁴ , Grace H Choi ⁶ , Pamela A Shaw ⁷ , Hyunah Yoon ⁸ , Liise-Anne Pirofski ⁹ , Boris D Julg ³ , Katharine J Bar ¹⁰ , Douglas Lauffenburger ¹¹ , Galit Alter ¹²



Affiliations

• PMID: 36351430
• DOI: 10.1016/j.xcrm.2022.100811

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.