Kinetics of the SARS-CoV-2 Antibody Avidity Response Following Infection and Vaccination

Abstract

Serological assays capable of measuring antibody responses induced by previous infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been critical tools in the response to the COVID-19 pandemic. In this study, we use bead-based multiplex assays to measure IgG and IgA antibodies and IgG avidity to five SARS-CoV-2 antigens (Spike (S), receptor-binding domain (RBD), Nucleocapsid (N), S subunit 2, and Membrane-Envelope fusion (ME)). These assays were performed in several cohorts of healthcare workers and nursing home residents, who were followed for up to eleven months after SARS-CoV-2 infection or up to six months after vaccination. Our results show distinct kinetic patterns of antibody quantity (IgG and IgA) and avidity. While IgG and IgA antibody levels waned over time, with IgA antibody levels waning more rapidly, avidity increased with time after infection or vaccination. These contrasting kinetic patterns allow for the estimation of time since previous SARS-CoV-2 infection. Including avidity measurements in addition to antibody levels in a classification algorithm for estimating time since infection led to a substantial improvement in accuracy, from 62% to 78%. The inclusion of antibody avidity in panels of serological assays can yield valuable information for improving serosurveillance during SARS-CoV-2 epidemics.

Low antibody levels associated with significantly increased rate of SARS‐CoV‐2 infection in a highly vaccinated population from the US National Basketball Association

“…Vaccine‐induced antibody levels wane over time, but earlier studies 28–30 assessed a relatively short window—generally up to 4 months postvaccination. Since then, additional research 31–37 confirmed that antibody titers continue to decrease up to 12 months after SARS‐CoV‐2 vaccination and observed reduced neutralization activity to emerging variants including Delta and Omicron. Although antibody levels in this study were measured at only one time‐point, results are consistent with this prior research, 31–34 as unboosted individuals for whom more time had passed between receipt of their primary vaccine and serologic testing (≥7 months) tended to have lower antibody levels than those vaccinated within 4 months of testing.…”

Low Antibody Titers Demonstrate Significantly Increased Rate of SARS-CoV-2 Infection in a Highly Vaccinated Population from the National Basketball Association

“…Vaccine-induced antibody levels wane over time, but earlier studies [28][29][30] assessed a relatively short window-generally up to 4 months post-vaccination. Since then, additional research [31][32][33][34] confirmed that antibody titers continue to decrease up to 6 months after SARS-CoV-2 vaccination and observed reduced neutralization activity to emerging variants including Delta and Omicron. Consistent with this prior research, the analyses in this study demonstrate that in a cohort of vaccinated individuals, titers decrease over time, as individuals who were vaccinated at least seven months prior to serologic testing tended to have substantially lower titers than those vaccinated within four months of testing.…”

Retained avidity despite reduced cross-binding and cross-neutralizing antibody levels to Omicron after SARS-COV-2 wild-type infection or mRNA double vaccination

“…Antibody avidity refers to the binding strength to the target antigen and is a crucial feature of functionality. Although both binding and neutralizing antibodies have been described to wane over time (13)(14)(15)(16)(17)(18)(19), avidity has been shown to increase with the duration after contact through B cell maturation at germinal centers (14)(15)(16), thereby possibly offsetting the waning effect to an extent.…”