The serological response to SARS corona virus-2 is characterized by frequent incomplete maturation of functional affinity (avidity)

Abstract The humoral immune systems controls viral infections through recognition of critical viral target structures, selective proliferation stimulation of IgM-presenting B cells, class switch to IgG-generating B cells and subsequent affinity maturation of IgG. Affinity maturation is achieved through proliferation, hypermutation and clonal selection of IgG-generating B cells (1-4). The establishment of high affinity IgG is essential for sustained protective antiviral effects (5-10). While analyzing the maturation of functional affinity (avidity) of IgG towards SARS CoV-2 nucleoprotein, surface protein and its receptor-binding domain, we realized that avidity maturation was frequently not completed after infection. This finding gives insight into the biological strategy of SARS CoV-2 and is important for serodiagnosis. Incomplete avidity maturation might explain the observed decline of the humoral response (11-14), allow for secondary SARS CoV-2 infections and prevent the establishment of herd immunity. Therefore, future immunization strategies should achieve the goal to induce neutralizing IgG of high avidity.