B-Cell Epitope Mapping of TprC and TprD Variants of Treponema pallidum Subspecies Informs Vaccine Development for Human Treponematoses
Several recent studies have focused on the identification, functional analysis, and structural characterization of outer membrane proteins (OMPs) of Treponema pallidum (Tp). The Tp species encompasses the highly related pallidum, pertenue, and endemicum subspecies of this pathogen, known to be the c...
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Frontiers Media S.A.
2022-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.862491/full |
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| author | Barbara Molini Mark C. Fernandez Charmie Godornes Anastassia Vorobieva Anastassia Vorobieva Sheila A. Lukehart Sheila A. Lukehart Lorenzo Giacani Lorenzo Giacani |
| author_facet | Barbara Molini Mark C. Fernandez Charmie Godornes Anastassia Vorobieva Anastassia Vorobieva Sheila A. Lukehart Sheila A. Lukehart Lorenzo Giacani Lorenzo Giacani |
| author_sort | Barbara Molini |
| collection | DOAJ |
| description | Several recent studies have focused on the identification, functional analysis, and structural characterization of outer membrane proteins (OMPs) of Treponema pallidum (Tp). The Tp species encompasses the highly related pallidum, pertenue, and endemicum subspecies of this pathogen, known to be the causative agents of syphilis, yaws, and bejel, respectively. These studies highlighted the importance of identifying surface-exposed OMP regions and the identification of B-cell epitopes that could be protective and used in vaccine development efforts. We previously reported that the TprC and TprD OMPs of Tp are predicted to contain external loops scattered throughout the entire length of the proteins, several of which show a low degree of sequence variability among strains and subspecies. In this study, these models were corroborated using AlphaFold2, a state-of-the-art protein structure modeling software. Here, we identified B-cell epitopes across the full-length TprC and TprD variants using the Geysan pepscan mapping approach with antisera from rabbits infected with syphilis, yaws, and bejel strains and from animals immunized with refolded recombinant TprC proteins from three syphilis strains. Our results show that the humoral response is primarily directed to sequences predicted to be on surface-exposed loops of TprC and TprD proteins, and that the magnitude of the humoral response to individual epitopes differs among animals infected with various syphilis strains and Tp subspecies. Rather than exhibiting strain-specificity, antisera showed various degrees of cross-reactivity with variant sequences from other strains. The data support the further exploration of TprC and TprD as vaccine candidates. |
| first_indexed | 2024-12-23T04:52:30Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-23T04:52:30Z |
| publishDate | 2022-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-27f456d282b546e9908ea8ee2226ec2f2022-12-21T17:59:25ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-03-011310.3389/fimmu.2022.862491862491B-Cell Epitope Mapping of TprC and TprD Variants of Treponema pallidum Subspecies Informs Vaccine Development for Human TreponematosesBarbara Molini0Mark C. Fernandez1Charmie Godornes2Anastassia Vorobieva3Anastassia Vorobieva4Sheila A. Lukehart5Sheila A. Lukehart6Lorenzo Giacani7Lorenzo Giacani8Department of Medicine, University of Washington, Seattle, WA, United StatesDepartment of Medicine, University of Washington, Seattle, WA, United StatesDepartment of Medicine, University of Washington, Seattle, WA, United StatesVIB-VUB Center for Structural Biology, VIB, Brussels, BelgiumStructural Biology Brussels, Vrije Universiteit Brussel, Brussels, BelgiumDepartment of Medicine, University of Washington, Seattle, WA, United StatesDepartment of Global Health, University of Washington, Seattle, WA, United StatesDepartment of Medicine, University of Washington, Seattle, WA, United StatesDepartment of Global Health, University of Washington, Seattle, WA, United StatesSeveral recent studies have focused on the identification, functional analysis, and structural characterization of outer membrane proteins (OMPs) of Treponema pallidum (Tp). The Tp species encompasses the highly related pallidum, pertenue, and endemicum subspecies of this pathogen, known to be the causative agents of syphilis, yaws, and bejel, respectively. These studies highlighted the importance of identifying surface-exposed OMP regions and the identification of B-cell epitopes that could be protective and used in vaccine development efforts. We previously reported that the TprC and TprD OMPs of Tp are predicted to contain external loops scattered throughout the entire length of the proteins, several of which show a low degree of sequence variability among strains and subspecies. In this study, these models were corroborated using AlphaFold2, a state-of-the-art protein structure modeling software. Here, we identified B-cell epitopes across the full-length TprC and TprD variants using the Geysan pepscan mapping approach with antisera from rabbits infected with syphilis, yaws, and bejel strains and from animals immunized with refolded recombinant TprC proteins from three syphilis strains. Our results show that the humoral response is primarily directed to sequences predicted to be on surface-exposed loops of TprC and TprD proteins, and that the magnitude of the humoral response to individual epitopes differs among animals infected with various syphilis strains and Tp subspecies. Rather than exhibiting strain-specificity, antisera showed various degrees of cross-reactivity with variant sequences from other strains. The data support the further exploration of TprC and TprD as vaccine candidates.https://www.frontiersin.org/articles/10.3389/fimmu.2022.862491/fullTreponema pallidumsyphilisTpr proteinsB-cell epitope mappingvaccine development |
| spellingShingle | Barbara Molini Mark C. Fernandez Charmie Godornes Anastassia Vorobieva Anastassia Vorobieva Sheila A. Lukehart Sheila A. Lukehart Lorenzo Giacani Lorenzo Giacani B-Cell Epitope Mapping of TprC and TprD Variants of Treponema pallidum Subspecies Informs Vaccine Development for Human Treponematoses Frontiers in Immunology Treponema pallidum syphilis Tpr proteins B-cell epitope mapping vaccine development |
| title | B-Cell Epitope Mapping of TprC and TprD Variants of Treponema pallidum Subspecies Informs Vaccine Development for Human Treponematoses |
| title_full | B-Cell Epitope Mapping of TprC and TprD Variants of Treponema pallidum Subspecies Informs Vaccine Development for Human Treponematoses |
| title_fullStr | B-Cell Epitope Mapping of TprC and TprD Variants of Treponema pallidum Subspecies Informs Vaccine Development for Human Treponematoses |
| title_full_unstemmed | B-Cell Epitope Mapping of TprC and TprD Variants of Treponema pallidum Subspecies Informs Vaccine Development for Human Treponematoses |
| title_short | B-Cell Epitope Mapping of TprC and TprD Variants of Treponema pallidum Subspecies Informs Vaccine Development for Human Treponematoses |
| title_sort | b cell epitope mapping of tprc and tprd variants of treponema pallidum subspecies informs vaccine development for human treponematoses |
| topic | Treponema pallidum syphilis Tpr proteins B-cell epitope mapping vaccine development |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.862491/full |
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