Primary exposure to SARS-CoV-2 via infection or vaccination determines mucosal antibody-dependent ACE2 binding inhibition.

Publication date: Sep 07, 2023

Mucosal antibodies play a critical role in preventing SARS-CoV-2 (re)infections by blocking the interaction of receptor binding domain (RBD) with angiotensin converting enzyme 2 receptor (ACE2) on the cell surface. In this study, we investigated the difference between the mucosal antibody response after primary infection or vaccination. We assessed longitudinal changes in the quantity and capacity of nasal antibodies to neutralize the interaction of RBD with the ACE2 receptor using Spike protein and RBD from ancestral SARS-CoV-2 (Wuhan-Hu-1), as well as RBD from the Delta and Omicron variant. Significantly higher mucosal IgA concentrations were detected post-infection compared to post-vaccination, while vaccination induced higher IgG concentrations. However, ACE2 inhibiting activity did not differ between the cohorts. When investigating if IgA or IgG drove the ACE2 inhibition, infection-induced binding inhibition was driven by both isotypes, while post-vaccination binding inhibition was mainly driven by IgG. Our study provides new insights into the relationship between antibody isotypes and neutralization by using a sensitive and high-throughput ACE2 binding inhibition assay. Key differences are highlighted between vaccination and infection at the mucosal level, showing that despite differences in the quantity of the response, post-infection and post-vaccination ACE2 binding inhibition capacity did not differ.

Concepts Keywords
Antibodies ACE2 inhibition
Mucosal infection
Throughput local immune response
Vaccination mucosal antibodies
Wuhan neutralizing antibodies


Type Source Name
disease MESH infection
disease VO vaccination
drug DRUGBANK Angiotensin II
disease IDO primary infection
disease IDO assay
disease IDO immune response

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