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Herein, we explored the versatile and effective Tag\/Catcher-AP205 capsid VLP (cVLP) vaccine platform to address the urgent need for the development of an effective and safe vaccine against gonorrhea. The benefits of this clinically validated cVLP platform include its ability to facilitate unidirectional, high-density display of complex\/full-length antigens through an effective split-protein Tag\/Catcher conjugation system. To assess this modular approach for making cVLP vaccines, we used a conserved surface lipoprotein, SliC, that contributes to the\n                    <jats:italic>Neisseria gonorrhoeae<\/jats:italic>\n                    defense against human lysozyme, as a model antigen. This protein was genetically fused at the N- or C-terminus to the small peptide Tag enabling their conjugation to AP205 cVLP, displaying the complementary Catcher. We determined that SliC with the N-terminal SpyTag, N-SliC, retained lysozyme-blocking activity and could be displayed at high density on cVLPs without causing aggregation. In mice, the N-SliC-VLP vaccines, adjuvanted with AddaVax or CpG, induced significantly higher antibody titers compared to controls. In contrast, similar vaccine formulations containing monomeric SliC were non-immunogenic. Accordingly, sera from N-SliC-VLP-immunized mice also had significantly higher human complement-dependent serum bactericidal activity. Furthermore, the N-SliC-VLP vaccines administered subcutaneously with an intranasal boost elicited systemic and vaginal IgG and IgA, whereas subcutaneous delivery alone failed to induce vaginal IgA. The N-SliC-VLP with CpG (10 \u00b5g\/dose) induced the most significant increase in total serum IgG and IgG3 titers, vaginal IgG and IgA, and bactericidal antibodies.\n                  <\/jats:p>","DOI":"10.1128\/iai.00245-23","type":"journal-article","created":{"date-parts":[[2023,11,2]],"date-time":"2023-11-02T09:00:59Z","timestamp":1698915659000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":16,"title":["Development of a Tag\/Catcher-mediated capsid virus-like particle vaccine presenting the conserved\n                    <i>Neisseria gonorrhoeae<\/i>\n                    SliC antigen that blocks human lysozyme"],"prefix":"10.1128","volume":"91","author":[{"given":"Fabian G.","family":"Martinez","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, Oregon, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryszard A.","family":"Zielke","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, Oregon, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyrielle E.","family":"Fougeroux","sequence":"additional","affiliation":[{"name":"AdaptVac Aps, H\u00f8rsholm, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, Oregon, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam F.","family":"Sander","sequence":"additional","affiliation":[{"name":"AdaptVac Aps, H\u00f8rsholm, Denmark"},{"name":"Faculty of Health Science, University of Copenhagen, Copenhagen, Denmark"},{"name":"Institute for Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7977-2596","authenticated-orcid":false,"given":"Aleksandra E.","family":"Sikora","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, Oregon, USA"},{"name":"Vaccine and Gene Therapy Institute, Oregon Health &amp; Science University, Beaverton, Oregon, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_3_2","unstructured":"CDC. 2018. 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