Differential avidity determination of IgG directed towards the receptor‐binding domain (RBD) of SARS‐CoV‐2 wild‐type and its variants in one assay: Rational tool for the assessment of protective immunity

Abstract

The avidity (binding strength) of IgG directed towards the receptor‐binding domain (RBD) of spike protein has been recognized as a central marker in severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) serology. It seems to be linked to increased infection‐neutralization potential and therefore might indicate protective immunity. Using a prototype line assay based on the established recomLine SARS‐CoV‐2 assay, supplemented with RBD of the delta and the omicron variant, differential avidity determination of IgG directed towards RBD of wild‐type (WT) SARS‐CoV‐2 and distinct variants was possible within one assay. Our data confirm that natural SARS‐CoV‐2 infection or one vaccination step lead to low avidity IgG, whereas further vaccination steps gradually increase avidity to high values. High avidity is not reached by infection alone. After infection with WT SARS‐CoV‐2 or vaccination based on mRNA WT, the avidity of cross‐reacting IgG directed towards RBD of the delta variant only showed marginal differences compared to IgG directed towards RBD WT. In contrast, the avidity of IgG cross‐reacting with RBD of the omicron variant was always much lower than for IgG RBD WT, except after the third vaccination step. Therefore, parallel avidity testing of RBD WT and omicron seems to be mandatory for a significant assessment of protective immunity towards SARS‐CoV‐2.

The long term vaccine‐induced anti‐SARS‐CoV‐2 immune response is impaired in quantity and quality under TNFα blockade

“… 13 In line with these results, a recent publication has shown that three vaccinations with the wt S protein‐based vaccines are required to achieve at all highly avid antibodies against the Omicron VOC. 25 This decline of avidity several months after the vaccination in anti‐TNF‐α patients has not been previously reported.…”

Deep physico-chemical characterization of individual serum antibody responses against SARS-CoV-2 RBD using a dual titration microspot assay

“…Neutralization assays are considered good correlates of protection and they show correlations with serological measurements. The determination of Ab affinity has also been suggested to provide useful clinical information (51,52). Unfortunately, most of these assays generate distinct results in terms of units and comparability even after transformations.…”

Comparison of Kinetics of Antibody Avidity and IgG Subclasses’ Response in Patients with COVID-19 and Healthy Individuals Vaccinated with the BNT162B2 (Comirnaty, Pfizer/BioNTech) mRNA Vaccine

“…There are many reports on the kinetics between the IgG, IgA, and IgM antibodies and the S1 and N proteins of the SARS-CoV-2 virus, both in patients infected with COVID-19 and healthy vaccinated individuals. However, there are only limited reports concerning the levels of antibodies in particular IgG subclasses and the avidity of IgG, which is the functional strength with which an antibody binds to an antigen in serum samples obtained at different times after infection or vaccination [1,2]. This information constitutes an important qualitative characteristic of immunity after infections of SARS-CoV-2, and could provide insights into the efficacy of anti-COVID-19 immunization.…”