{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T07:19:51Z","timestamp":1776842391450,"version":"3.51.2"},"posted":{"date-parts":[[2024,10,28]]},"group-title":"Immunology","reference-count":80,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T00:00:00Z","timestamp":1730073600000},"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":[[2024,10,28]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  The quality of protective immunity plays a critical role in modulating vaccine efficacy, with native antigens often not able to trigger sufficiently strong immune responses for pathogen killing. This warrants creation of structure-based vaccine design, leveraging high-resolution antigen structures for mutagenesis to improve protein stability and efficient immunization strategies. Here, we investigated the mechanisms underlying structure-based vaccine design using CspZ-YA, a vaccine antigen from\n                  <jats:italic>Borrelia burgdorferi<\/jats:italic>\n                  , the bacteria causing Lyme disease (LD), the most common vector-borne disease in the Northern Hemisphere. Compared to wild-type CspZ-YA, we found CspZ-YA\n                  <jats:sub>I183Y<\/jats:sub>\n                  and CspZ-YA\n                  <jats:sub>C187S<\/jats:sub>\n                  required lower immunization frequency to protect mice from LD-associated manifestations and bacterial colonization. We observed indistinguishable human and mouse antigenicity between wild-type and mutant CspZ-YA proteins after native infection or active immunization. This supports our newly generated, high-resolution structures of CspZ-YA\n                  <jats:sub>I183Y<\/jats:sub>\n                  and CspZ-YA\n                  <jats:sub>C187S<\/jats:sub>\n                  , showing no altered surface epitopes after mutagenesis. However, CspZ-YA\n                  <jats:sub>I183Y<\/jats:sub>\n                  and CspZ-YA\n                  <jats:sub>C187S<\/jats:sub>\n                  favored the interactions between helices H and I, consistent with their elevated thermostability. Such findings are further strengthened by increasing ability of protective CspZ-YA monoclonal antibodies in binding to CspZ-YA at a physiological temperature (37\u00b0C). Overall, this study demonstrated enhanced intramolecular interactions improved long-term stability of antigens while maintaining protective epitopes, providing a mechanism for structure-based vaccine design. These findings can ultimately be extended to other vaccine antigens against newly emerging pathogens for the improvement of protective immunity.\n                <\/jats:p>","DOI":"10.1101\/2024.10.23.619738","type":"posted-content","created":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T22:25:15Z","timestamp":1730154315000},"source":"Crossref","is-referenced-by-count":1,"title":["Mechanistic insights into structure-based design of a Lyme disease subunit vaccine"],"prefix":"10.64898","author":[{"given":"Kalvis","family":"Brangulis","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jill","family":"Malfetano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashley L.","family":"Marcinkiewicz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Lin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jungsoon","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuyun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiuli","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulrich","family":"Strych","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria-Elena","family":"Bottazzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Utpal","family":"Pal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ching-Lin","family":"Hsieh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Hsiang","family":"Chen","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":"2024103013550524000_2024.10.23.619738v1.1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.14.4.872-908.2001"},{"key":"2024103013550524000_2024.10.23.619738v1.2","doi-asserted-by":"publisher","DOI":"10.1517\/14740338.2016.1167869"},{"issue":"2 Suppl Vaccines","key":"2024103013550524000_2024.10.23.619738v1.3","first-page":"S61","article-title":"Addressing immunization barriers, benefits, and risks","volume":"56","year":"2007","journal-title":"J Fam Pract"},{"key":"2024103013550524000_2024.10.23.619738v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/nrd818"},{"key":"2024103013550524000_2024.10.23.619738v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-021-00417-1"},{"key":"2024103013550524000_2024.10.23.619738v1.6","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-121217-094234"},{"key":"2024103013550524000_2024.10.23.619738v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2022.102209"},{"key":"2024103013550524000_2024.10.23.619738v1.8","doi-asserted-by":"publisher","DOI":"10.1126\/science.abd0826"},{"key":"2024103013550524000_2024.10.23.619738v1.9","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-45404-x"},{"key":"2024103013550524000_2024.10.23.619738v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109929"},{"key":"2024103013550524000_2024.10.23.619738v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2022.102385"},{"key":"2024103013550524000_2024.10.23.619738v1.12","doi-asserted-by":"publisher","DOI":"10.3201\/eid2702.202731"},{"key":"2024103013550524000_2024.10.23.619738v1.13","doi-asserted-by":"publisher","DOI":"10.3201\/eid2702.202728"},{"key":"2024103013550524000_2024.10.23.619738v1.14","doi-asserted-by":"publisher","DOI":"10.7326\/AITC201605030"},{"key":"2024103013550524000_2024.10.23.619738v1.15","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.90"},{"key":"2024103013550524000_2024.10.23.619738v1.16","doi-asserted-by":"publisher","DOI":"10.21775\/cimb.042.333"},{"key":"2024103013550524000_2024.10.23.619738v1.17","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciz872"},{"key":"2024103013550524000_2024.10.23.619738v1.18","doi-asserted-by":"publisher","DOI":"10.1038\/s41541-022-00429-5"},{"key":"2024103013550524000_2024.10.23.619738v1.19","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(23)00210-4"},{"key":"2024103013550524000_2024.10.23.619738v1.20","unstructured":"Valneva and Pfizer Report Positive Pediatric and Adolescent Phase 2 Booster Results for Lyme Disease Vaccine Candidate 2023 [September 7, 2023]. 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