TY - JOUR
T1 - Primary Exposure to SARS-CoV-2 via Infection or Vaccination Determines Mucosal Antibody-Dependent ACE2 Binding Inhibition
AU - Fröberg, Janeri
AU - Koomen, Vera J.C.H.
AU - Van Der Gaast-De Jongh, Christa E.
AU - Philipsen, Ria
AU - Geurtsvankessel, Corine H.
AU - De Vries, Rory D.
AU - Baas, Marije C.
AU - Van Der Molen, Renate G.
AU - De Jonge, Marien I.
AU - Hilbrands, Luuk B.
AU - Huynen, Martijn A.
AU - Diavatopoulos, Dimitri A.
N1 - Publisher Copyright:
© 2023 The Author(s). Published by Oxford University Press on behalf of Infectious Diseases Society of America.
PY - 2024/1/15
Y1 - 2024/1/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85177203308&partnerID=8YFLogxK
U2 - 10.1093/infdis/jiad385
DO - 10.1093/infdis/jiad385
M3 - Article
C2 - 37675756
AN - SCOPUS:85177203308
SN - 0022-1899
VL - 229
SP - 137
EP - 146
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 1
ER -