Weir, Dawn L.Coggins, Si Ana A.Vu, Bang K.Coertse, JessicaYan, LianyingSmith, Ina L.Laing, Eric D.Markotter, WandaBroder, Christopher C.Schaefer, Brian C.2022-09-072022-09-072021-03-01Weir, D.L.; Coggins, S.A.; Vu, B.K.; Coertse, J.; Yan, L.; Smith, I.L.; Laing, E.D.; Markotter, W.; Broder, C.C.; Schaefer, B.C. Isolation and Characterization of Cross-Reactive Human Monoclonal Antibodies That Potently Neutralize Australian Bat Lyssavirus Variants and Other Phylogroup 1 Lyssaviruses. Viruses 2021, 13, 391. https://doi.org/10.3390/v13030391.1999-4915 (online)10.3390/v13030391https://repository.up.ac.za/handle/2263/87110: Australian bat lyssavirus (ABLV) is a rhabdovirus that circulates in four species of pteropid bats (ABLVp) and the yellow-bellied sheath-tailed bat (ABLVs) in mainland Australia. In the three confirmed human cases of ABLV, rabies illness preceded fatality. As with rabies virus (RABV), postexposure prophylaxis (PEP) for potential ABLV infections consists of wound cleansing, administration of the rabies vaccine and injection of rabies immunoglobulin (RIG) proximal to the wound. Despite the efficacy of PEP, the inaccessibility of human RIG (HRIG) in the developing world and the high immunogenicity of equine RIG (ERIG) has led to consideration of human monoclonal antibodies (hmAbs) as a passive immunization option that offers enhanced safety and specificity. Using a recombinant vesicular stomatitis virus (rVSV) expressing the glycoprotein (G) protein of ABLVs and phage display, we identified two hmAbs, A6 and F11, which completely neutralize ABLVs/ABLVp, and RABV at concentrations ranging from 0.39 and 6.25 µg/mL and 0.19 and 0.39 µg/mL respectively. A6 and F11 recognize overlapping epitopes in the lyssavirus G protein, effectively neutralizing phylogroup 1 lyssaviruses, while having little effect on phylogroup 2 and non-grouped diverse lyssaviruses. These results suggest that A6 and F11 could be effective therapeutic and diagnostic tools for phylogroup 1 lyssavirus infections.en© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).Monoclonal antibodiesLyssavirusesNeutralizationGlycoproteinRabiesPhage displayBatsAustralian bat lyssavirus (ABLV)AustraliaPteropid batsFruit batsYellow-bellied sheath-tailed bat (Saccolaimus flaviventris)Rabies lyssavirus (RABV)Postexposure prophylaxis (PEP)Rabies immunoglobulin (RIG)Human monoclonal antibodies (hmAbs)Article