Immunodominant extracellular loops of Treponema pallidum FadL outer membrane proteins elicit antibodies with opsonic and growth-inhibitory activities.

Autor: Delgado KN; Department of Medicine, UConn Health, Farmington, Connecticut, United States of America., Caimano MJ; Department of Medicine, UConn Health, Farmington, Connecticut, United States of America.; Department of Pediatrics, UConn Health, Farmington, Connecticut, United States of America.; Department of Molecular Biology and Biophysics, UConn Health, Farmington, Connecticut, United States of America.; Department of Research, Connecticut Children's Research Institute, Hartford, Connecticut, United States of America., Orbe IC; Department of Pediatrics, UConn Health, Farmington, Connecticut, United States of America., Vicente CF; Department of Pediatrics, UConn Health, Farmington, Connecticut, United States of America., La Vake CJ; Department of Pediatrics, UConn Health, Farmington, Connecticut, United States of America., Grassmann AA; Department of Medicine, UConn Health, Farmington, Connecticut, United States of America., Moody MA; Duke Human Vaccine Institute, Durham, North Carolina, United States of America.; Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, United States of America.; Department of Immunology, Duke University Medical Center, Durham, North Carolina, United States of America., Radolf JD; Department of Medicine, UConn Health, Farmington, Connecticut, United States of America.; Department of Pediatrics, UConn Health, Farmington, Connecticut, United States of America.; Department of Molecular Biology and Biophysics, UConn Health, Farmington, Connecticut, United States of America.; Department of Research, Connecticut Children's Research Institute, Hartford, Connecticut, United States of America.; Department of Immunology, UConn Health, Farmington, Connecticut, United States of America.; Department of Genetics and Genome Sciences, UConn Health, Farmington, Connecticut, United States of America., Hawley KL; Department of Medicine, UConn Health, Farmington, Connecticut, United States of America.; Department of Pediatrics, UConn Health, Farmington, Connecticut, United States of America.; Department of Research, Connecticut Children's Research Institute, Hartford, Connecticut, United States of America.; Department of Immunology, UConn Health, Farmington, Connecticut, United States of America.; Division of Infectious Diseases and Immunology, Connecticut Children's, Hartford, Connecticut, United States of America.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2024 Dec 23; Vol. 20 (12), pp. e1012443. Date of Electronic Publication: 2024 Dec 23.
DOI: 10.1371/journal.ppat.1012443
Abstrakt: The global resurgence of syphilis has created a potent stimulus for vaccine development. To identify potentially protective antibodies against Treponema pallidum (TPA), we used Pyrococcus furiosus thioredoxin (PfTrx) to display extracellular loops (ECLs) from three TPA outer membrane protein families (outer membrane factors for efflux pumps, eight-stranded β-barrels, and FadLs) to assess their reactivity with immune rabbit serum (IRS). We identified five immunodominant loops from the FadL orthologs TP0856, TP0858 and TP0865 by immunoblotting and ELISA. Rabbits and mice immunized with these five PfTrx constructs produced loop-specific antibodies that promoted opsonophagocytosis of TPA by rabbit peritoneal and murine bone marrow-derived macrophages at levels comparable to IRS and mouse syphilitic serum. Heat-inactivated IRS and loop-specific rabbit and mouse antisera also impaired viability, motility, and cellular attachment of spirochetes during in vitro cultivation. The results support the use of ECL-based vaccines and suggest that loop-specific antibodies promote spirochete clearance via Fc receptor-independent as well as Fc receptor-dependent mechanisms.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Delgado et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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