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.
Highlights
Antibodies serve as biomarkers of infection, but if sustained can confer long-term immunity
Limited antibody waning was noted over the study period, but a discrete titer threshold was observed across the population that discriminated individuals who evolved neutralizing and Fc-effector functions, as well as T cell immunity
In this study we included 4300 volunteers all of whom were employees at Space Exploration Technologies Corp. (SpaceX) that were followed from April 2020, including SARS-CoV-2 receptor-binding domain (RBD) antibody testing, and detailed symptomatology
Summary
Antibodies serve as biomarkers of infection, but if sustained can confer long-term immunity. 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. Limited antibody waning was noted over the study period, but a discrete titer threshold was observed across the population that discriminated individuals who evolved neutralizing and Fc-effector functions, as well as T cell immunity. These data suggest that a threshold of protective immunity may exist among naturally infected individuals, related to the functional potential of the humoral (and cellular) immune response
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