Coupling enterotoxigenic Escherichia coli heat-stable peptide toxin with 8-arm PEG enhances immunogenicity.

Autor: Zegeye ED; Marine Biotechnology, NORCE Norwegian Research Centre, Bergen, Norway.; Department of Paraclinical Sciences, Faculty of Veterinary Medicine, Norwegian University of Life Sciences (NMBU), Ås, Norway., Chaukimath P; Department of Developmental Biology and Genetics, Indian Institute of Science, Bengaluru, India., Diaz Y; Marine Biotechnology, NORCE Norwegian Research Centre, Bergen, Norway., Visweswariah SS; Department of Developmental Biology and Genetics, Indian Institute of Science, Bengaluru, India., Puntervoll P; Marine Biotechnology, NORCE Norwegian Research Centre, Bergen, Norway.
Jazyk: angličtina
Zdroj: Journal of peptide science : an official publication of the European Peptide Society [J Pept Sci] 2025 Jan; Vol. 31 (1), pp. e3647. Date of Electronic Publication: 2024 Aug 01.
DOI: 10.1002/psc.3647
Abstrakt: Enterotoxigenic Escherichia coli (ETEC) strains, which produce the heat-stable enterotoxin (ST) either alone or in combination with the heat-labile enterotoxin, contribute to the bulk of the burden of child diarrheal disease in resource-limited countries and are associated with mortality. Developing an effective vaccine targeting ST presents challenges due to its potent enterotoxicity, non-immunogenicity, and the risk of autoimmune reaction stemming from its structural similarity to the human endogenous ligands, guanylin, and uroguanylin. This study aimed to assess a novel synthetic vaccine carrier platform employing a single chemical coupling step for making human ST (STh) immunogenic. Specifically, the method involved cross-linking STh to an 8-arm N-hydroxysuccinimide (NHS) ester-activated PEG cross-linker. A conjugate of STh with 8-arm structure was prepared, and its formation was confirmed through immunoblotting analysis. The impact of conjugation on STh epitopes was assessed using ELISAs with polyclonal and monoclonal antibodies targeting various epitopes of STh. Immunization of mice with the conjugate induced the production of anti-STh antibodies, exhibiting neutralizing activity against STh.
(© 2024 The Author(s). Journal of Peptide Science published by European Peptide Society and John Wiley & Sons Ltd.)
Databáze: MEDLINE