RESUMO
Virus neutralizing antibody (vnAb) titers are the strongest laboratory correlate of protection from SARS-CoV-2. Providing individuals with real-time measures of their vnAb titers is predicted to improve their ability to make personal wellness decisions. Yet, widespread commercial testing of SARS-CoV-2 vnAbs does not currently occur. Here, we examined whether knowing their vnAb titer impacted wellness decision-making among individuals. To this end, starting on January 1, 2021, we offered all employees from two companies free IMMUNO-COV testing and conducted a survey to assess their behaviors and decisions regarding booster vaccination. IMMUNO-COV is a clinically validated, surrogate virus assay that quantitates serum titers of SARS-CoV-2 vnAbs. To help participants gauge their level of protection based on their vnAb titer, we calibrated IMMUNO-COV titers to the World Health Organization (WHO) International Standard (IU/mL), making them comparable to published reports of correlates of protection, and we fit historical IMMUNO-COV vnAb titer values into predictive models of immune protection from COVID-19. As expected, data for the 56 program participants showed variability in vnAb titers post vaccination, rates vnAb decay, and fold-increases in vnAb titers after booster vaccination. Based on the participant survey, the majority (66%) of participants indicated that knowing their vnAb titer impacted their social behaviors and/or their decision on the timing of a booster vaccination. Several participants indicated that knowing their vnAb titer contributed to their peace of mind regarding their high level of protection from COVID-19. Together, these data demonstrate that regular determination of SARS-CoV-2 neutralizing antibody titers can significantly impact decisions regarding social interactions and timing of booster vaccinations.
RESUMO
Neutralizing antibodies are key determinants of protection from future infection, yet well-validated high-throughput assays for measuring titers of SARS-CoV-2-neutralizing antibodies are not generally available. Here we describe the development and validation of IMMUNO-COV v2.0 a scalable surrogate virus assay, which titrates antibodies that block infection of Vero-ACE2 cells by a luciferase-encoding vesicular stomatitis virus displaying SARS-CoV-2 spike glycoproteins (VSV-SARS2-Fluc). Antibody titers, calculated using a standard curve consisting of stepped concentrations of SARS-CoV-2 spike monoclonal antibody, correlated closely (p < 0.0001) with titers obtained from a gold-standard PRNT50% assay performed using a clinical isolate of SARS-CoV-2. IMMUNO-COV v2.0 was comprehensively validated using data acquired from 242 assay runs performed over seven days by five analysts, utilizing two separate virus lots, and 176 blood samples. Assay performance was acceptable for clinical use in human serum and plasma based on parameters including linearity, dynamic range, limit of blank and limit of detection, dilutional linearity and parallelism, precision, clinical agreement, matrix equivalence, clinical specificity and sensitivity, and robustness. Sufficient VSV-SARS2-Fluc virus reagent has been banked to test 5 million clinical samples. Notably, a significant drop in IMMUNO-COV v2.0 neutralizing antibody titers was observed over a six-month period in people recovered from SARS-CoV-2 infection. Together, our results demonstrate the feasibility and utility of IMMUNO-COV v2.0 for measuring SARS-CoV-2-neutralizing antibodies in vaccinated individuals and those recovering from natural infections. Such monitoring can be used to better understand what levels of neutralizing antibodies are required for protection from SARS-CoV-2, and what booster dosing schedules are needed to sustain vaccine-induced immunity.