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

tetano

Editor, Senior Moderator
Nat Commun


. 2021 Feb 15;12(1):1018.
doi: 10.1038/s41467-021-21336-8.
Discrete SARS-CoV-2 antibody titers track with functional humoral stability


Yannic C Bartsch[SUP] #[/SUP][SUP] 1 [/SUP], Stephanie Fischinger[SUP] #[/SUP][SUP] 1 2 [/SUP], Sameed M Siddiqui[SUP] #[/SUP][SUP] 3 4 [/SUP], Zhilin Chen[SUP] 1 [/SUP], Jingyou Yu[SUP] 1 5 [/SUP], Makda Gebre[SUP] 1 5 [/SUP], Caroline Atyeo[SUP] 1 [/SUP], Matthew J Gorman[SUP] 1 [/SUP], Alex Lee Zhu[SUP] 1 [/SUP], Jaewon Kang[SUP] 1 [/SUP], John S Burke[SUP] 1 [/SUP], Matthew Slein[SUP] 1 [/SUP], Matthew J Gluck[SUP] 6 7 [/SUP], Samuel Beger[SUP] 6 [/SUP], Yiyuan Hu[SUP] 6 [/SUP], Justin Rhee[SUP] 6 [/SUP], Eric Petersen[SUP] 6 [/SUP], Benjamin Mormann[SUP] 6 [/SUP], Michael de St Aubin[SUP] 8 [/SUP], Mohammad A Hasdianda[SUP] 9 [/SUP], Guruprasad Jambaulikar[SUP] 9 [/SUP], Edward W Boyer[SUP] 9 [/SUP], Pardis C Sabeti[SUP] 4 10 11 12 [/SUP], Dan H Barouch[SUP] 1 5 12 [/SUP], Boris D Julg[SUP] 1 [/SUP], Elon R Musk[SUP] 6 [/SUP], Anil S Menon[SUP] 13 [/SUP], Douglas A Lauffenburger[SUP] 14 [/SUP], Eric J Nilles[SUP] 15 [/SUP], Galit Alter[SUP] 16 17 [/SUP]



Affiliations

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.
 
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