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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
Nature communications, 02/2021, Volume: 12, Issue: 1Journal Article
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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