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In some instances, the prevalence of antibiotic-resistant pathogens is rising, which exacerbates the challenge. STIs cause severe complications, including infertility, ectopic pregnancies, pre-term births, and heightened risks of HIV acquisition. These outcomes underscore the need for innovative therapeutic and prophylactic strategies. In this review, we provide a comprehensive analysis of the current state of biologic drug development targeting key STIs, focusing on\n                    <jats:italic toggle=\"yes\">Chlamydia trachomatis<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">Neisseria gonorrhoeae<\/jats:italic>\n                    , herpes simplex virus type 2 (HSV-2), and\n                    <jats:italic toggle=\"yes\">Treponema pallidum<\/jats:italic>\n                    . We examine the complexity of host\u2013pathogen interactions that inform biologic drug design, such as multiple mechanisms of infection, immune evasion strategies, and pathogenic latency. We also explore the role of mucosal immunity, highlighting advances in resident memory T cells and cytokine-driven responses that guide therapeutic targeting, concentrating on\n                    <jats:italic toggle=\"yes\">Chlamydia trachomatis<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">Neisseria gonorrhoeae<\/jats:italic>\n                    , where recent advances in vaccine development appear promising. We conduct a comprehensive survey of platforms, including vaccines, and explore modalities such as monoclonal antibodies and protein therapeutics. Additionally, we examine emerging technologies like nucleic acid-based therapies, microbiome modulation, and phage-based interventions, highlighting their potential against challenging pathogens like HSV-2 and\n                    <jats:italic toggle=\"yes\">Treponema pallidum<\/jats:italic>\n                    . By examining these established and emerging approaches, this review prioritizes critical opportunities for innovation in biologic therapeutics, addressing unmet needs in STI management. It advocates for integrated strategies leveraging antigenic conservation, host immunity modulation, and novel delivery platforms to achieve durable prophylaxis and effective treatment for high-burden infections globally.\n                  <\/jats:p>","DOI":"10.1128\/cmr.00107-24","type":"journal-article","created":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T09:00:47Z","timestamp":1748509247000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":10,"title":["Biologic drug development for treatment and prevention of sexually transmitted infections"],"prefix":"10.1128","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6042-598X","authenticated-orcid":true,"given":"Davinder S.","family":"Gill","sequence":"first","affiliation":[{"name":"StiRx Inc","place":["Mansfield, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0058-9532","authenticated-orcid":true,"given":"Sanjay","family":"Ram","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0464eyp60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, Division of Infectious Diseases and Immunology, University of Massachusetts Chan Medical School","place":["Worcester, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A.","family":"Rice","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0464eyp60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Medicine, Division of Infectious Diseases and Immunology, University of Massachusetts Chan Medical School","place":["Worcester, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(17)30310-9"},{"key":"e_1_3_3_3_2","unstructured":"Centers for Disease Control and Prevention. 2023. 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