{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T22:03:21Z","timestamp":1768514601849,"version":"3.49.0"},"posted":{"date-parts":[[2024,7,30]]},"group-title":"Immunology","reference-count":96,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T00:00:00Z","timestamp":1722297600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,7,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  The global resurgence of syphilis has created a potent stimulus for vaccine development. To identify potentially protective antibodies (Abs) against\n                  <jats:italic>Treponema pallidum<\/jats:italic>\n                  (\n                  <jats:italic>TPA<\/jats:italic>\n                  ), we used\n                  <jats:italic>Pyrococcus furiosus<\/jats:italic>\n                  thioredoxin (\n                  <jats:italic>Pf<\/jats:italic>\n                  Trx) to display extracellular loops (ECLs) from three\n                  <jats:italic>TPA<\/jats:italic>\n                  outer membrane protein families (outer membrane factors for efflux pumps, eight-stranded \u03b2-barrels, and FadLs) to assess their reactivity with immune rabbit serum (IRS). Five ECLs from the FadL orthologs TP0856, TP0858 and TP0865 were immunodominant. Rabbits and mice immunized with these five\n                  <jats:italic>Pf<\/jats:italic>\n                  Trx constructs produced ECL-specific Abs that promoted opsonophagocytosis of\n                  <jats:italic>TPA<\/jats:italic>\n                  by rabbit peritoneal and murine bone marrow-derived macrophages at levels comparable to IRS and mouse syphilitic serum. ECL-specific rabbit and mouse Abs also impaired viability, motility, and cellular attachment of spirochetes during\n                  <jats:italic>in vitro<\/jats:italic>\n                  cultivation. The results support the use of ECL-based vaccines and suggest that ECL-specific Abs promote spirochete clearance via Fc receptor-independent as well as Fc receptor-dependent mechanisms.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Author Summary<\/jats:title>\n                  <jats:p>\n                    The resurgence of syphilis emphasizes the critical need for vaccine development against\n                    <jats:italic>Treponema pallidum<\/jats:italic>\n                    (\n                    <jats:italic>TPA<\/jats:italic>\n                    ). Research utilizing immune rabbit serum (IRS) suggests that an effective syphilis vaccine should induce \u201cfunctional\u201d antibodies (Abs) capable of enhancing the opsonophagocytosis of treponemes by activated macrophages. Structural models of\n                    <jats:italic>TPA<\/jats:italic>\n                    outer membrane proteins (OMPs), specifically the extracellular loops (ECLs), guided the identification of potential vaccine candidates. Antigenic analysis with IRS of individual ECLs from three\n                    <jats:italic>TPA<\/jats:italic>\n                    OMP families scaffolded onto\n                    <jats:italic>Pyrococcus furiosus<\/jats:italic>\n                    thioredoxin (\n                    <jats:italic>Pf<\/jats:italic>\n                    Trx) revealed five FadL antigenic ECLs. Immunization with immunodominant ECL antigens elicited robust ECL-specific Abs, demonstrating functional opsonic activity in the opsonophagocytosis assays. Furthermore, these Abs effectively inhibited the growth inhibition of\n                    <jats:italic>in vitro<\/jats:italic>\n                    -cultivated\n                    <jats:italic>TPA<\/jats:italic>\n                    in both rabbit and mouse models. Our findings underscore the value of antigenic analysis in identifying promising\n                    <jats:italic>TPA<\/jats:italic>\n                    OMP ECL vaccine targets and highlight the multifaceted protective capacity of ECL Abs against\n                    <jats:italic>TPA<\/jats:italic>\n                    . This approach also extends to identifying potential OMP vaccinogens in other bacterial pathogens, offering valuable insights for broader vaccine development strategies.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2024.07.30.605823","type":"posted-content","created":{"date-parts":[[2024,7,31]],"date-time":"2024-07-31T00:20:21Z","timestamp":1722385221000},"source":"Crossref","is-referenced-by-count":0,"title":["Immunodominant extracellular loops of\n                  <i>Treponema pallidum<\/i>\n                  FadL outer membrane proteins elicit antibodies with opsonic and growth-inhibitory activities"],"prefix":"10.64898","author":[{"given":"Kristina N.","family":"Delgado","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melissa J.","family":"Caimano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isabel C.","family":"Orbe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Crystal F.","family":"Vicente","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carson J.","family":"La Vake","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9 A.","family":"Grassmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. 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