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Discrete SARS-CoV-2 antibody titers track with functional humoral stability

Author(s)
Bartsch, Yannic C.; Fischinger, Stephanie; Siddiqui, Sameed M.; Chen, Zhilin; Yu, Jingyou; Gebre, Makda; Atyeo, Caroline; Gorman, Matthew J.; Zhu, Alex Lee; Kang, Jaewon; Burke, John S.; Slein, Matthew; Gluck, Matthew J.; Beger, Samuel; Hu, Yiyuan; Rhee, Justin; Petersen, Eric; Mormann, Benjamin; Aubin, Michael de St; Hasdianda, Mohammad A.; Jambaulikar, Guruprasad; Boyer, Edward W.; Sabeti, Pardis C.; Barouch, Dan H.; Julg, Boris D.; Musk, Elon R.; Menon, Anil S.; Lauffenburger, Douglas A; Nilles, Eric J.; Alter, Galit; ... Show more Show less
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Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/
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Abstract
Antibodies serve as biomarkers of infection, but if sustained can confer long-term immunity. Yet, for most clinically approved vaccines, binding antibody titers only serve as a surrogate of protection. Instead, the ability of vaccine induced antibodies to neutralize or mediate Fc-effector functions is mechanistically linked to protection. While evidence has begun to point to persisting antibody responses among SARS-CoV-2 infected individuals, cases of re-infection have begun to emerge, calling the protective nature of humoral immunity against this highly infectious pathogen into question. Using a community-based surveillance study, we aimed to define the relationship between titers and functional antibody activity to SARS-CoV-2 over time. Here we report significant heterogeneity, but limited decay, across antibody titers amongst 120 identified seroconverters, most of whom had asymptomatic infection. Notably, neutralization, Fc-function, and SARS-CoV-2 specific T cell responses were only observed in subjects that elicited RBD-specific antibody titers above a threshold. The findings point to a switch-like relationship between observed antibody titer and function, where a distinct threshold of activity—defined by the level of antibodies—is required to elicit vigorous humoral and cellular response. This response activity level may be essential for durable protection, potentially explaining why re-infections occur with SARS-CoV-2 and other common coronaviruses.
Date issued
2021-02
URI
https://hdl.handle.net/1721.1/129807
Department
Massachusetts Institute of Technology. Department of Biological Engineering
Journal
Nature Communications
Publisher
Springer Science and Business Media LLC
Citation
Bartsch, Yannic C. et al. "Discrete SARS-CoV-2 antibody titers track with functional humoral stability." Nature Communications 12, 1 (February 2021): 1018 © 2021 The Author(s)
Version: Final published version
ISSN
2041-1723

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