Pathogenicity and immunogenicity of recombinant rabies viruses expressing the Lagos bat virus matrix and glycoprotein : perspectives for a pan-lyssavirus vaccine
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Date
Authors
Kgaladi, Joe
Faber, Milosz
Dietzschold, Bernhard
Nel, Louis Hendrik
Markotter, Wanda
Journal Title
Journal ISSN
Volume Title
Publisher
MDPI Publishing
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.
Description
Keywords
Vaccines, Africa, Lyssavirus, Pathogenesis, Recombinant viruses, Lagos bat virus (LBV), Rabies virus (RABV)
Sustainable Development Goals
Citation
Kgaladi, J., Faber, M., Dietzschold, B. et al. 2017, 'Pathogenicity and immunogenicity of recombinant rabies viruses expressing the Lagos bat virus matrix and glycoprotein : perspectives for a pan-lyssavirus vaccine', Tropical Medicine and Infectious Disease, vol. 2, no. 37, pp. 1-5.