{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T19:27:19Z","timestamp":1783711639397,"version":"3.55.0"},"reference-count":60,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2023,11,25]],"date-time":"2023-11-25T00:00:00Z","timestamp":1700870400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Military Infectious Diseases Research Program (MIDRP)","award":["MI210160"],"award-info":[{"award-number":["MI210160"]}]},{"name":"M.T. Campagna","award":["MI210160"],"award-info":[{"award-number":["MI210160"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Orientia tsutsugamushi is the causative pathogen of scrub typhus, an acute febrile disease prevalent in the Asia\u2013Pacific region that is spread to people through chigger bites. Despite the emerging threat, there is no currently available vaccine against O. tsutsugamushi. Here, we developed dual-antigen subunit vaccine nanoparticles using recombinant 47 kD and 56 kD proteins, which are immunogenic outer membrane antigens of O. tsutsugamushi. The biocompatible protein vaccine nanoparticles were formed via desolvation of r56 or r47E antigens with acetone, coating with an additional layer of the 56 kD protein, and stabilization with reducible homobifunctional DTSSP and heterobifunctional SDAD crosslinkers. The dual-antigen subunit vaccine nanoparticles significantly improved antigen-specific antibody responses in vaccinated mice. Most importantly, the dual-antigen nanoparticles coated with an additional layer of the 56 kD protein were markedly more immunogenic than soluble antigens or single-antigen nanoparticles in the context of cellular immune responses. Given the significance of cellular immune responses for protection against O. tsutsugamushi, these results demonstrate the potent immunogenicity of dual-layered antigen nanoparticles and their potential as a promising strategy for developing vaccines against scrub typhus.<\/jats:p>","DOI":"10.3390\/pathogens12121390","type":"journal-article","created":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T03:32:03Z","timestamp":1701055923000},"page":"1390","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Dual-Antigen Subunit Vaccine Nanoparticles for Scrub Typhus"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2718-0852","authenticated-orcid":false,"given":"Jaeyoung","family":"Park","sequence":"first","affiliation":[{"name":"School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, 950 Atlantic Dr. NW, Atlanta, GA 30332, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiwen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Henry Jackson Foundation for the Advancement of Military Medicine, 6720A Rockledge Dr, Bethesda, MD 20817, USA"},{"name":"Naval Medical Research Center, 503 Robert Grant Ave., Silver Spring, MD 20910, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatyana","family":"Belinskaya","sequence":"additional","affiliation":[{"name":"Henry Jackson Foundation for the Advancement of Military Medicine, 6720A Rockledge Dr, Bethesda, MD 20817, USA"},{"name":"Naval Medical Research Center, 503 Robert Grant Ave., Silver Spring, MD 20910, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra N.","family":"Tsoras","sequence":"additional","affiliation":[{"name":"School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, 950 Atlantic Dr. NW, Atlanta, GA 30332, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-Chung","family":"Chao","sequence":"additional","affiliation":[{"name":"Naval Medical Research Center, 503 Robert Grant Ave., Silver Spring, MD 20910, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Jiang","sequence":"additional","affiliation":[{"name":"Henry Jackson Foundation for the Advancement of Military Medicine, 6720A Rockledge Dr, Bethesda, MD 20817, USA"},{"name":"Naval Medical Research Center, 503 Robert Grant Ave., Silver Spring, MD 20910, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A.","family":"Champion","sequence":"additional","affiliation":[{"name":"School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, 950 Atlantic Dr. NW, Atlanta, GA 30332, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Jiang, J., and Richards, A.L. 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