Immunodominant extracellular loops of Treponema pallidum FadL outer membrane proteins elicit antibodies with opsonic and growth-inhibitory activities.
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 familie...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2024-12-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1012443 |
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| author | Kristina N Delgado Melissa J Caimano Isabel C Orbe Crystal F Vicente Carson J La Vake André A Grassmann M Anthony Moody Justin D Radolf Kelly L Hawley |
| author_facet | Kristina N Delgado Melissa J Caimano Isabel C Orbe Crystal F Vicente Carson J La Vake André A Grassmann M Anthony Moody Justin D Radolf Kelly L Hawley |
| author_sort | Kristina N Delgado |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-0cf0caae360a40b0b38e6d4f5c7ea63c |
| institution | Kabale University |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-0cf0caae360a40b0b38e6d4f5c7ea63c2025-02-05T05:30:54ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742024-12-012012e101244310.1371/journal.ppat.1012443Immunodominant extracellular loops of Treponema pallidum FadL outer membrane proteins elicit antibodies with opsonic and growth-inhibitory activities.Kristina N DelgadoMelissa J CaimanoIsabel C OrbeCrystal F VicenteCarson J La VakeAndré A GrassmannM Anthony MoodyJustin D RadolfKelly L HawleyThe 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.https://doi.org/10.1371/journal.ppat.1012443 |
| spellingShingle | Kristina N Delgado Melissa J Caimano Isabel C Orbe Crystal F Vicente Carson J La Vake André A Grassmann M Anthony Moody Justin D Radolf Kelly L Hawley Immunodominant extracellular loops of Treponema pallidum FadL outer membrane proteins elicit antibodies with opsonic and growth-inhibitory activities. PLoS Pathogens |
| title | Immunodominant extracellular loops of Treponema pallidum FadL outer membrane proteins elicit antibodies with opsonic and growth-inhibitory activities. |
| title_full | Immunodominant extracellular loops of Treponema pallidum FadL outer membrane proteins elicit antibodies with opsonic and growth-inhibitory activities. |
| title_fullStr | Immunodominant extracellular loops of Treponema pallidum FadL outer membrane proteins elicit antibodies with opsonic and growth-inhibitory activities. |
| title_full_unstemmed | Immunodominant extracellular loops of Treponema pallidum FadL outer membrane proteins elicit antibodies with opsonic and growth-inhibitory activities. |
| title_short | Immunodominant extracellular loops of Treponema pallidum FadL outer membrane proteins elicit antibodies with opsonic and growth-inhibitory activities. |
| title_sort | immunodominant extracellular loops of treponema pallidum fadl outer membrane proteins elicit antibodies with opsonic and growth inhibitory activities |
| url | https://doi.org/10.1371/journal.ppat.1012443 |
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