The potential significance of high avidity immunoglobulin G (IgG) for protective immunity towards SARS-CoV-2

BACKGROUND: Avidity is defined as the strength of binding between immunoglobulin G (IgG) and its specific target epitope. IgG of high avidity is established during affinity maturation. Failure to achieve high avidity IgG may result in a lack of protective immunity towards infection and disease. It is known that the interaction between SARS-CoV-2 spike protein and its cellular receptor is driven by high affinity. Therefore, it is predictable that protective antibodies towards SARS-CoV-2 should show high affinity/avidity. AVIDITY AFTER SARS-COV-2 INFECTION: Recent findings by several groups demonstrate that the serological response towards infection with SARS-CoV-2 and seasonal coronaviruses is characterized by incomplete avidity maturation, followed by a decline of the serological response. This response might facilitate reinfection, prevent herd immunity and potentially allow repeated cycles of infection. CONSEQUENCES FOR VACCINATION TOWARDS SARS-COV-2: Therefore, the sole focus on antibody titers reached after vaccination towards SARS-CoV-2 might not be sufficient to evaluate the degree of achieved protection. Rather, it is suggested to include avidity determination to optimize vaccination protocols and achieve high avidity IgG directed towards SARS-CoV-2 through vaccination. Avidity determination might also be useful to control for truly protective immunity towards SARS-CoV-2 in individual cases.