Nucleocapsid-specific antibody function is associated with therapeutic benefit from Covid-19 Convalescent plasma therapy
Name
PIIS2666379122003706.pdf
Description
Published version
Size
3.9 MB
Format
Adobe PDF
Checksum (MD5)
4e9944c5608a8b2866a669adae60f779
Author(s)
Herman, Jonathan D
Wang, Chuangqi
Burke, John Stephen
Zur, Yonatan
Compere, Hacheming
Kang, Jaewon
Macvicar, Ryan
Taylor, Sabian
Shin, Sally
Frank, Ian
Date Issued
2022
Journal
Cell Reports Medicine
Publisher
Elsevier BV
Citation
Herman, Jonathan D, Wang, Chuangqi, Burke, John Stephen, Zur, Yonatan, Compere, Hacheming et al. 2022. "Nucleocapsid-specific antibody function is associated with therapeutic benefit from Covid-19 Convalescent plasma therapy." Cell Reports Medicine, 3 (11).
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/J.XCRM.2022.100811
