期刊
NATURE COMMUNICATIONS
卷 12, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-21336-8
关键词
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资金
- Ragon Institute of MGH, MIT, and Harvard
- Massachusetts Consortium on Pathogen Readiness (MassCPR)
- NIH [3R37AI080289-11S1, R01AI146785, U19AI42790-01, U19AI135995-02, 1U01CA260476 - 01, CIVIC75N93019C00052]
- Gates Foundation Global Health Vaccine Accelerator Platform [OPP1146996, INV-001650]
- Musk Foundation
- Translational Research Institute for Space Health through NASA Cooperative Agreement [NNX16AO69A]
- National Institute for Allergy and Infectious Disease [U19 AI135995]
- US Food and Drug Administration [HHSF223201810172C]
The study reveals significant heterogeneity in antibody responses following SARS-CoV-2 infection, with limited decay of antibody titers over time. Observing neutralization, Fc-function, and SARS-CoV-2 specific T cell responses requires reaching a certain threshold of receptor-binding domain (RBD)-specific antibody titers, indicating a switch-like relationship between antibody titer and function.
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. The extent of antibody protection against SARS-CoV-2 remains unclear. Here, using a cohort of 120 seroconverted individuals, the authors longitudinally characterize neutralization, Fc-function, and SARS-CoV-2 specific T cell responses, which they show to be prominent only in those subjects that elicited receptor-binding domain (RBD)-specific antibody titers above a certain threshold, suggesting that development of T cell responses to be related to anti-RBD Ab production.
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