{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T22:07:27Z","timestamp":1768514847322,"version":"3.49.0"},"posted":{"date-parts":[[2024,9,26]]},"group-title":"Microbiology","reference-count":90,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,9,26]],"date-time":"2024-09-26T00:00:00Z","timestamp":1727308800000},"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":[[2024,9,26]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Lyme disease (LD) is the most common vector-borne disease in the northern hemisphere and is caused by the bacteria\n                  <jats:italic>Borrelia burgdorferi<\/jats:italic>\n                  sensu lato (also known as Lyme borreliae) with no effective prevention available. Lyme borreliae evade complement killing, a critical arm of host immune defense, by producing outer surface proteins that bind to a host complement inhibitor, factor H (FH). These outer surface proteins include CspA and CspZ, which bind to the 6\n                  <jats:sup>th<\/jats:sup>\n                  and 7\n                  <jats:sup>th<\/jats:sup>\n                  short consensus repeats of FH (SCR(6-7)), and the OspE family of proteins (OspE), which bind to the 19\n                  <jats:sup>th<\/jats:sup>\n                  and 20\n                  <jats:sup>th<\/jats:sup>\n                  SCR (SCR19-20). In this study, we produced two chimeric proteins, FH-Fc, containing the Fc region of immunoglobulin G (Fc) with SCR(6-7) or SCR(19-20). We found that both FH-Fc constructs killed\n                  <jats:italic>B. burgdorferi<\/jats:italic>\n                  in the presence of complement and reduced bacterial colonization and LD-associated joint inflammation\n                  <jats:italic>in vivo<\/jats:italic>\n                  . While SCR(6-7)-Fc displayed Lyme borreliae species-specific bacterial killing, SCR(19-20)-Fc versatilely eradicated all tested bacterial species\/strains. This correlated with SCR(6-7)-Fc binding to select variants of CspA and CspZ, but SCR(19-20)-Fc binding to all tested OspE variants. Overall, we demonstrated the concept of using FH-Fc constructs to kill Lyme borreliae and defined underlying mechanisms, highlighting the potential of FH-Fc as a pre-exposure prophylaxis against LD infection.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>AUTHOR SUMMARY<\/jats:title>\n                  <jats:p>\n                    Transmitted by ticks, Lyme disease (LD) is the most common vector-borne disease in North America and has experienced an expanded geographical range and increasing number of cases in recent years. No effective prevention is currently available. The causative agent of LD,\n                    <jats:italic>Borrelia burgdorferi<\/jats:italic>\n                    sensu lato (\n                    <jats:italic>Bb<\/jats:italic>\n                    sl), is a complex containing a variety of species. To escape from killing by complement, one of the mammalian host defense mechanisms,\n                    <jats:italic>Bb<\/jats:italic>\n                    sl produces outer surface proteins that bind to a complement inhibitor, factor H (FH). These FH-binding proteins (i.e., CspA, CspZ, and OspE) evade complement by recruiting FH to the bacterial surface. Here we produced two FH-Fc fusion proteins, which combine human immunoglobulin Fc with the human FH domains that bind to\n                    <jats:italic>Bb<\/jats:italic>\n                    sl FH-binding proteins. We found that FH-Fc constructs kill\n                    <jats:italic>Bb<\/jats:italic>\n                    sl\n                    <jats:italic>in vitro<\/jats:italic>\n                    and prevent colonization and LD manifestations in murine models, correlating with these FH-Fc constructs\u2019 ability to bind to CspA, CspZ, and OspE from respective\n                    <jats:italic>Bb<\/jats:italic>\n                    sl species. These results suggest the possibility of using FH-Fc as a prevention against LD.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2024.09.26.615144","type":"posted-content","created":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T00:20:11Z","timestamp":1727396411000},"source":"Crossref","is-referenced-by-count":0,"title":["Complement therapeutic Factor H-IgG proteins as pre-exposure prophylaxes against Lyme borreliae infections"],"prefix":"10.64898","author":[{"given":"Connor W.","family":"McKaig","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jill","family":"Malfetano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y","family":"Tran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiuli","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Utpal","family":"Pal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keith","family":"Wycoff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5240-2031","authenticated-orcid":false,"given":"Yi-Pin","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024100114150634000_2024.09.26.615144v1.1","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.3201\/eid2708.204763","article-title":"Comparison of Lyme Disease in the United States and Europe","volume":"27","year":"2021","journal-title":"Emerging infectious diseases"},{"key":"2024100114150634000_2024.09.26.615144v1.2","doi-asserted-by":"publisher","DOI":"10.3201\/eid2702.202731"},{"key":"2024100114150634000_2024.09.26.615144v1.3","doi-asserted-by":"crossref","first-page":"S11","DOI":"10.1093\/infdis\/jiae230","article-title":"Lyme Disease Surveillance and Epidemiology in the United States: A Historical Perspective","volume":"230","year":"2024","journal-title":"The Journal of infectious diseases"},{"key":"2024100114150634000_2024.09.26.615144v1.4","doi-asserted-by":"publisher","DOI":"10.7326\/AITC201605030"},{"key":"2024100114150634000_2024.09.26.615144v1.5","doi-asserted-by":"crossref","first-page":"16090","DOI":"10.1038\/nrdp.2016.90","article-title":"Lyme borreliosis","volume":"2","year":"2016","journal-title":"Nature reviews. 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