Primary Exposure to SARS-CoV-2 via Infection or Vaccination Determines Mucosal Antibody-Dependent ACE2 Binding Inhibition

Author:

Fröberg Janeri12ORCID,Koomen Vera J C H123ORCID,van der Gaast-de Jongh Christa E1,Philipsen Ria4,GeurtsvanKessel Corine H5,de Vries Rory D5,Baas Marije C3,van der Molen Renate G1,de Jonge Marien I12ORCID,Hilbrands Luuk B3ORCID,Huynen Martijn A6ORCID,Diavatopoulos Dimitri A12ORCID

Affiliation:

1. Department of Laboratory Medicine, Laboratory of Medical Immunology, Radboud University Medical Center, Nijmegen

2. Radboudumc Center for Infectious Diseases, Radboud University Medical Center , Nijmegen

3. Department of Nephrology, Radboud University Medical Center , Nijmegen

4. Radboud Technology Center Clinical Studies , Radboud University Medical Center, Nijmegen

5. Department of Viroscience, Erasmus Medical Center , Rotterdam

6. Department of Medical BioSciences, Radboud University Medical Center , Nijmegen, The Netherlands

Abstract

Abstract Background Mucosal antibodies play a critical role in preventing SARS-CoV-2 infections or reinfections by blocking the interaction of the receptor-binding domain (RBD) with the angiotensin-converting enzyme 2 (ACE2) receptor on the cell surface. In this study, we investigated the difference between the mucosal antibody response after primary infection and vaccination. Methods We assessed longitudinal changes in the quantity and capacity of nasal antibodies to neutralize the interaction of RBD with the ACE2 receptor using the spike protein and RBD from ancestral SARS-CoV-2 (Wuhan-Hu-1), as well as the RBD from the Delta and Omicron variants. Results Significantly higher mucosal IgA concentrations were detected postinfection vs postvaccination, while vaccination induced higher IgG concentrations. However, ACE2-inhibiting activity did not differ between the cohorts. Regarding whether IgA or IgG drove ACE2 inhibition, infection-induced binding inhibition was driven by both isotypes, while postvaccination binding inhibition was mainly driven by IgG. Conclusions 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 response quantity, postinfection and postvaccination ACE2 binding inhibition capacity did not differ.

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Immunology and Allergy

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