Monoclonal antibodies for rabies post-exposure prophylaxis: A paradigm shift in passive immunization

SUMMARYRabies is one of the most important zoonotic infections worldwide. The burden of the disease continues to be significant in countries in the Middle East where the most important vector is stray dogs. Control efforts are hindered by lack of awareness and incomplete post-exposure prophylaxis. The aim of this article is to re-assess the situation of rabies in Lebanon and compare it to other Middle Eastern countries. Eight cases of rabies and 5280 incidents of animal bites to humans were reported to the Lebanese Ministry of Public Health between 2001 and 2012. Dogs were the only vector of infection and were responsible for most reported animal bites to humans. An average of 3·2 doses of vaccine per bite was administered as post-exposure prophylaxis. The status of human and canine rabies control, the risks associated with children's behaviour and the hazards of secondary wild reservoirs are discussed. Our data illustrates the importance of prevention through vector control, public awareness and education, and timely administration of active and passive immunization, as well as the significance of regional cooperation and monitoring the circulation of viral variants in wild animals.

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

10.20944/preprints202102.0075.v1 ◽

2021 ◽

Author(s):

Dawn Weir ◽

Si'Ana Coggins ◽

Bang Vu ◽

Jessica Coertse ◽

Lianying Yan ◽

...

Keyword(s):

Monoclonal Antibodies ◽

G Protein ◽

Passive Immunization ◽

Diagnostic Tools ◽

Post Exposure Prophylaxis ◽

Human Monoclonal Antibodies ◽

Isolation And Characterization ◽

Glycoprotein G ◽

Exposure Prophylaxis ◽

Australian Bat Lyssavirus

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, ad-ministration 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 0.19-3.12 µg/mL and 0.39-6.25 µg/mL respectively. A6 and F11 recognize overlapping epitopes in the lyssavirus G protein, ef-fectively neutralizing phylogroup 1 lyssaviruses, while having little effect on phylogroup 2 and non-grouped diverse lyssaviruses. These results suggest A6 and F11 could be effective therapeutic and diagnostic tools for phylogroup 1 lyssavirus infections.

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