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Discrete SARS-CoV-2 antibody titers track with functional humoral stability #MMPMID33589636
Bartsch YC; Fischinger S; Siddiqui SM; Chen Z; Yu J; Gebre M; Atyeo C; Gorman MJ; Zhu AL; Kang J; Burke JS; Slein M; Gluck MJ; Beger S; Hu Y; Rhee J; Petersen E; Mormann B; Aubin MS; Hasdianda MA; Jambaulikar G; Boyer EW; Sabeti PC; Barouch DH; Julg BD; Musk ER; Menon AS; Lauffenburger DA; Nilles EJ; Alter G
Nat Commun 2021[Feb]; 12 (1): 1018 PMID33589636show ga
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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Nat+Commun 2021 ; 12 (1): 1018
