Prophylactic Activity of Orally Administered FliD-Reactive Monoclonal SIgA Against Campylobacter Infection
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Issue Date
2020-06-09Author
Perruzza, Lisa
Jaconi, Stefano
Lombardo, Gloria
Pinna, Debora
Strati, Francesco
Morone, Diego
Seehusen, Frauke
Hu, Yue
Bajoria, Sakshi
Xiong, Jian
Kumru, Ozan S.
Joshi, Sangeeta B.
Volkin, David Bernard
Piantanida, Renato
Benigni, Fabio
Grassi, Fabio
Corti, Davide
Pizzuto, Matteo Samuele
Publisher
Frontiers Media
Type
Article
Article Version
Scholarly/refereed, publisher version
Rights
© 2020 Perruzza, Jaconi, Lombardo, Pinna, Strati, Morone, Seehusen, Hu, Bajoria, Xiong, Kumru, Joshi, Volkin, Piantanida, Benigni, Grassi, Corti and Pizzuto.
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Campylobacter infection is one of the most common causes of bacterial gastroenteritis worldwide and a major global health threat due to the rapid development of antibiotic resistance. Currently, there are no vaccines approved to prevent campylobacteriosis, and rehydration is the main form of therapy. Secretory immunoglobulin A (SIgA) is the main antibody class found in mucous secretions, including human milk, and serves as the first line of defense for the gastrointestinal epithelium against enteric pathogens. In this study, we describe the prophylactic activity of orally delivered recombinant SIgA generated from two human monoclonal antibodies (CAA1 and CCG4) isolated for their reactivity against the flagellar-capping protein FliD, which is essential for bacteria motility and highly conserved across Campylobacter species associated with severe enteritis. In an immunocompetent weaned mouse model, a single oral administration of FliD-reactive SIgA CAA1 or CCG4 at 2 h before infection significantly enhances Campylobacter clearance at early stages post-infection, reducing the levels of inflammation markers associated with epithelial damage and polymorphonuclear (PMN) cells infiltration in the cecum lamina propria. Our data indicate that the prophylactic activity of CAA1 and CCG4 is not only dependent on the specificity to FliD but also on the use of the SIgA format, as the immunoglobulin G (IgG) versions of the same antibodies did not confer a comparable protective effect. Our work emphasizes the potential of FliD as a target for the development of vaccines and supports the concept that orally administered FliD-reactive SIgA can be developed to prevent or mitigate the severity of Campylobacter infections as well as the development of post-infection syndromes.
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This work is licensed under a Creative Commons Attribution 4.0 International License.
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Citation
Perruzza, L., Jaconi, S., Lombardo, G., Pinna, D., Strati, F., Morone, D., Seehusen, F., Hu, Y., Bajoria, S., Xiong, J., Kumru, O. S., Joshi, S. B., Volkin, D. B., Piantanida, R., Benigni, F., Grassi, F., Corti, D., & Pizzuto, M. S. (2020). Prophylactic Activity of Orally Administered FliD-Reactive Monoclonal SIgA Against Campylobacter Infection. Frontiers in immunology, 11, 1011. https://doi.org/10.3389/fimmu.2020.01011
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