A cocktail of human monoclonal antibodies broadly neutralizes North American rabies virus variants as a promising candidate for rabies post-exposure prophylaxis

Ejemel, MonirSmith, Todd GGreenberg, LaurenCarson, William CLowe, DavidYang, YongJackson, Felix RMorgan, Clint NMartin, Brock EKling, ChantalHutson, Christina LGallardo-Romero, NadiaEllison, James AMoore, SusanBuzby, AdamSullivan-Bolyai, JohnKlempner, Mark S.Wang, Yang2023-11-092023-11-092022-06-07Ejemel M, Smith TG, Greenberg L, Carson WC, Lowe D, Yang Y, Jackson FR, Morgan CN, Martin BE, Kling C, Hutson CL, Gallardo-Romero N, Ellison JA, Moore S, Buzby A, Sullivan-Bolyai J, Klempner M, Wang Y. A cocktail of human monoclonal antibodies broadly neutralizes North American rabies virus variants as a promising candidate for rabies post-exposure prophylaxis. Sci Rep. 2022 Jun 7;12(1):9403. doi: 10.1038/s41598-022-13527-0. PMID: 35672343; PMCID: PMC9174473.2045-232210.1038/s41598-022-13527-035672343https://hdl.handle.net/20.500.14038/52717Human rabies remains a globally significant public health problem. Replacement of polyclonal anti-rabies immunoglobulin (RIG), a passive component of rabies post-exposure prophylaxis (PEP), with a monoclonal antibody (MAb), would eliminate the cost and availability constraints associated with RIG. Our team has developed and licensed a human monoclonal antibody RAB1 (Rabishield©), as the replacement for RIG where canine rabies is enzootic. However, for the highly diverse rabies viruses of North America, a cocktail containing two or more MAbs targeting different antigenic sites of the rabies glycoprotein should be included to ensure neutralization of all variants of the virus. In this study, two MAb cocktails, R172 (RAB1-RAB2) and R173 (RAB1-CR57), were identified and evaluated against a broad range of rabies variants from North America. R173 was found to be the most potent cocktail, as it neutralized all the tested North American RABV isolates and demonstrated broad coverage of isolates from both terrestrial and bat species. R173 could be a promising candidate as an alternative or replacement for RIG PEP in North America.enOpen Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http:// creativecommons. org/ licenses/ by/4. 0/. © The Author(s) 2022Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/Drug discoveryImmunologyMedical researchNeurologyA cocktail of human monoclonal antibodies broadly neutralizes North American rabies virus variants as a promising candidate for rabies post-exposure prophylaxisJournal ArticleScientific reports