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Trop. Med. Infect. Dis. 2017, 2(3), 37; https://doi.org/10.3390/tropicalmed2030037

Pathogenicity and Immunogenicity of Recombinant Rabies Viruses Expressing the Lagos Bat Virus Matrix and Glycoprotein: Perspectives for a Pan-Lyssavirus Vaccine

1
Centre for Emerging and Zoonotic Diseases, National Institute for Communicable Diseases, National Health Laboratory Service, Sandringham 2193, South Africa
2
Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA 19107, USA
3
Department of Microbiology and Plant Pathology, Faculty of Natural and Agricultural Sciences, University of Pretoria, Pretoria 0001, South Africa
4
Centre for Viral Zoonoses, Department of Medical Virology, Faculty of Health Sciences, University of Pretoria, Pretoria 0001, South Africa
*
Author to whom correspondence should be addressed.
Received: 30 June 2017 / Revised: 31 July 2017 / Accepted: 4 August 2017 / Published: 9 August 2017
(This article belongs to the Special Issue Rabies Symptoms, Diagnosis, Prophylaxis and Treatment)
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Abstract

Lagos bat virus (LBV) is a phylogroup II lyssavirus exclusively found in Africa. Previous studies indicated that this virus is lethal to mice after intracranial and intramuscular inoculation. The antigenic composition of LBV differs substantially from that of rabies virus (RABV) and current rabies vaccines do not provide cross protection against phylogroup II lyssaviruses. To investigate the potential role of the LBV matrix protein (M) and glycoprotein (G) in pathogenesis, reverse genetics technology was used to construct recombinant viruses. The genes encoding the glycoprotein, or the matrix and glycoprotein of the attenuated RABV strain SPBN, were replaced with those of LBV resulting in SPBN-LBVG and SPBN-LBVM-LBVG, respectively. To evaluate the immunogenicity of the LBV G, the recombinant RABV SPBNGAS-LBVG-GAS was constructed with the LBV G inserted between two mutated RABV G genes (termed GAS). All the recombinant viruses were lethal to mice after intracranial (i.c.) inoculation although the pathogenicity of SPBNGAS-LBVG-GAS was lower compared to the other recombinant viruses. Following intramuscular (i.m.) inoculation, only SPBN-LBVM-LBVG was lethal to mice, indicating that both the M and G of LBV play a role in the pathogenesis. Most interestingly, serum collected from mice that were inoculated i.m. with SPBNGAS-LBVG-GAS neutralized phylogroup I and II lyssaviruses including RABV, Duvenhage virus (DUVV), LBV, and Mokola virus (MOKV), indicating that this recombinant virus has potential to be developed as a pan-lyssavirus vaccine. View Full-Text
Keywords: rabies; vaccines; Africa; lyssavirus; pathogenesis; recombinant viruses rabies; vaccines; Africa; lyssavirus; pathogenesis; recombinant viruses
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Kgaladi, J.; Faber, M.; Dietzschold, B.; Nel, L.H.; Markotter, W. Pathogenicity and Immunogenicity of Recombinant Rabies Viruses Expressing the Lagos Bat Virus Matrix and Glycoprotein: Perspectives for a Pan-Lyssavirus Vaccine. Trop. Med. Infect. Dis. 2017, 2, 37.

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