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While anti\u2010sperm IgM is responsible for infertility in many women, stability and bioprocessing challenges with IgM make them ill\u2010suited for non\u2010hormonal contraception. Similarly, IgG lacks sufficient sperm agglutination potencies. To overcome these shortcomings, a novel, multivalent mAb platform is developed, based on fusing the Laminin 511 heterotrimerization domains to Fabs and IgG1\u2010Fc, allowing for tuning of Fab valency (from 2\u201312) with molecular specificity. \u2018LamH10\u2019, the most potent mAb among the panel of polyvalent antibodies against CD52g on human sperm, comprises 10 Fabs per molecule, and achieves nanomolar potencies at physiological temperatures and retains stability in the acidic environment of human cervicovaginal mucus. In sheep, LamH10 reduced progressively motile sperm in the vagina by &gt;99% within 2 min at just 33 \u00b5g per sheep. LamH10 utilizes the same conventional bioprocessing as IgGs, and can be formulated into rapidly dissolving tablets for on\u2010demand contraception, achieving 100% sperm agglutination within minutes of vaginal dosing. The laminin\u2010IgG hybrid platform not only forms the basis of the most potent biologic for nonhormonal contraception to date, but also represents a promising platform for multivalent mAbs for other applications.<\/jats:p>","DOI":"10.1002\/advs.202506272","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T10:26:49Z","timestamp":1753266409000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Engineering Decavalent, Sperm\u2010Binding Laminin\u2010IgG Hybrid Antibodies for Potent Non\u2010Hormonal Contraception"],"prefix":"10.1002","volume":"12","author":[{"given":"Alison","family":"Schaefer","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering University of North Carolina \u2013 Chapel Hill  Morrisville NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keiichiro","family":"Kushiro","sequence":"additional","affiliation":[{"name":"Mucommune LLC  Morrisville NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bhawana","family":"Shrestha","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology University of North Carolina \u2013 Chapel Hill  Morrisville NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Zhu","sequence":"additional","affiliation":[{"name":"University of Texas Medical Branch at Galveston  Galveston TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alysha","family":"Panjwani","sequence":"additional","affiliation":[{"name":"University of Texas Medical Branch at Galveston  Galveston TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauren","family":"Dawson","sequence":"additional","affiliation":[{"name":"University of Texas Medical Branch at Galveston  Galveston TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haley","family":"Flowers","sequence":"additional","affiliation":[{"name":"University of Texas Medical Branch at Galveston  Galveston TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen L.","family":"Vincent","sequence":"additional","affiliation":[{"name":"University of Texas Medical Branch at Galveston  Galveston TX USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4721-528X","authenticated-orcid":false,"given":"Samuel K.","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of North Carolina \u2013 Chapel Hill  Morrisville NC USA"},{"name":"Mucommune LLC  Morrisville NC USA"},{"name":"Department of Immunology and Microbiology University of North Carolina \u2013 Chapel Hill  Morrisville NC USA"},{"name":"Division of Pharmacoengineering and Molecular Pharmaceutics Eshelman School of Pharmacy University of North Carolina \u2013 Chapel Hill  Morrisville NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,7,23]]},"reference":[{"key":"e_1_2_8_1_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2022.19097"},{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1363\/4309411"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMsa1506575"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1363\/3809006"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/13625180410001715681"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.contraception.2009.01.019"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12978-018-0561-0"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1177\/2042098614548857"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003081-198109000-00016"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12978-016-0153-9"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.contraception.2017.05.012"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjsrh-2018-200296"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)11079-8"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/00042560-199804010-00006"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007435-199107000-00010"},{"key":"e_1_2_8_16_1","first-page":"1","volume":"10","author":"Brazdova A.","year":"2016","journal-title":"Int. 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