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

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.
Monir Ejemel # 1 Todd G Smith # 2 Lauren Greenberg 3 William C Carson 3 David Lowe 3 Yong Yang 3 Felix R Jackson 3 Clint N Morgan 3 Brock E Martin 3 Chantal Kling 3 Christina L Hutson 3 Nadia Gallardo-Romero 3 James A Ellison 3 Susan Moore 4 5 Adam Buzby 1 6 John Sullivan-Bolyai 1 Mark Klempner 1 Yang Wang 7
Affiliations

Affiliations

  • 1 MassBiologics of the University of Massachusetts Chan Medical School, 460 Walk Hill, Boston, MA, 02126, USA.
  • 2 Poxvirus and Rabies Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Atlanta, GA, 30329, USA. tgsmith1@cdc.gov.
  • 3 Poxvirus and Rabies Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, 1600 Clifton Road NE, Atlanta, GA, 30329, USA.
  • 4 Veterinary Diagnostic Laboratory, Rabies Laboratory, Kansas State University, Manhattan, KS, 66502, USA.
  • 5 Veterinary Medical Diagnostic Laboratory, University of Missouri, Columbia, MO, 65211, USA.
  • 6 Apellis Pharmaceuticals, Waltham, MA, USA.
  • 7 MassBiologics of the University of Massachusetts Chan Medical School, 460 Walk Hill, Boston, MA, 02126, USA. yang.wang@umassmed.edu.
  • # Contributed equally.
Abstract

Human 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.

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