Isolation and Characterization of Cross-Reactive Human Monoclonal Antibodies That Potently Neutralize Australian Bat Lyssavirus Variants and Other Phylogroup 1 Lyssaviruses.

Dawn L Weir,Jessica Coertse,Bang K Vu,Brian C Schaefer,Ina L Smith,Si’Ana A Coggins,Wanda Markotter,Christopher C Broder,Eric D Laing,Lianying Yan

doi:10.3390/v13030391

Abstract

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), post-exposure 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.

Highlights

Australian bat lyssavirus (ABLV) was first isolated in 1996 from a grounded black flying fox (Pteropus alecto) found near Ballina, Australia [1]
We previously reported the isolation of potent henipavirus-neutralizing human monoclonal antibodies (hmAbs) m102 through the screening of a large naïve human Fab library against the soluble Hendra virus (HeV) G
We used the same phage library, which contains over 1010 phage-displayed human Fabs, to identify Fabs that are specific for ABLVs glycoprotein (ABLVs G)

Summary

Introduction

Australian bat lyssavirus (ABLV) was first isolated in 1996 from a grounded black flying fox (Pteropus alecto) found near Ballina, Australia [1]. ABLV has been isolated from all four mainland species of flying foxes (Pteropodidae family) as well as the yellow-bellied sheath-tailed bat (Saccolaimus flaviventris), with two genetically distinct lineages circulating in frugivorous (genus Pteropus, ABLVp) [2] and insectivorous Saccolaimus, ABLVs) [3] Australian bat populations. There have been three documented human ABLV cases [7,8,9,10], all of which manifested as fatal acute encephalitis that presented after variable periods of incubation following the exposure event (5 weeks to 2 years) (reviewed in [11]). In addition to the documented human infections, ABLV was isolated from two fatal horse infections in Australia in 2013 [12]

Methods

Results

Conclusion