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Recombinant neutralizing secretory IgA antibodies for preventing mucosal acquisition and transmission of SARS-CoV-2.

Title: Recombinant neutralizing secretory IgA antibodies for preventing mucosal acquisition and transmission of SARS-CoV-2.
Authors: Göritzer, K; Groppelli, E; Grünwald-Gruber, C; Figl, R; Ni, F; Hu, H; Li, Y; Liu, Y; Hu, Q; Puligedda, RD; Jung, J-W; Strasser, R; Dessain, S; Ma, JK-C
Publisher Information: Elsevier
Publication Year: 2024
Collection: St George's University of London: Repository
Description: Passive delivery of antibodies to mucosal sites may be a valuable adjunct to COVID-19 vaccination to prevent infection, treat viral carriage, or block transmission. Neutralizing monoclonal IgG antibodies are already approved for systemic delivery, and several clinical trials have been reported for delivery to mucosal sites where SARS-CoV-2 resides and replicates in early infection. However, secretory IgA may be preferred because the polymeric complex is adapted for the harsh, unstable external mucosal environment. Here, we investigated the feasibility of producing neutralizing monoclonal IgA antibodies against SARS-CoV-2. We engineered two class-switched mAbs that express well as monomeric and secretory IgA (SIgA) variants with high antigen-binding affinities and increased stability in mucosal secretions compared to their IgG counterparts. SIgAs had stronger virus neutralization activities than IgG mAbs and were protective against SARS-CoV-2 infection in an in vivo murine model. Furthermore, SIgA1 can be aerosolized for topical delivery using a mesh nebulizer. Our findings provide a persuasive case for developing recombinant SIgAs for mucosal application as a new tool in the fight against COVID-19.
Document Type: article in journal/newspaper
File Description: application/pdf
Language: English
ISSN: 1525-0024
Relation: https://openaccess.sgul.ac.uk/id/eprint/116123/6/1-s2.0-S152500162400025X-main.pdf; https://openaccess.sgul.ac.uk/id/eprint/116123/11/1-s2.0-S152500162400025X-mmc1.pdf; Göritzer, K; Groppelli, E; Grünwald-Gruber, C; Figl, R; Ni, F; Hu, H; Li, Y; Liu, Y; Hu, Q; Puligedda, RD; et al. Göritzer, K; Groppelli, E; Grünwald-Gruber, C; Figl, R; Ni, F; Hu, H; Li, Y; Liu, Y; Hu, Q; Puligedda, RD; Jung, J-W; Strasser, R; Dessain, S; Ma, JK-C (2024) Recombinant neutralizing secretory IgA antibodies for preventing mucosal acquisition and transmission of SARS-CoV-2. Mol Ther, 32 (3). pp. 689-703. ISSN 1525-0024 https://doi.org/10.1016/j.ymthe.2024.01.025 SGUL Authors: Groppelli, Elisabetta Angela Ma, Julian
DOI: 10.1016/j.ymthe.2024.01.025
Availability: https://openaccess.sgul.ac.uk/id/eprint/116123/; https://doi.org/10.1016/j.ymthe.2024.01.025
Rights: cc_by_4
Accession Number: edsbas.52B22FB0
Database: BASE