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. 2018 Mar 15;10(3):130.
doi: 10.3390/v10030130.

Utilisation of Chimeric Lyssaviruses to Assess Vaccine Protection Against Highly Divergent Lyssaviruses

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Free PMC article

Utilisation of Chimeric Lyssaviruses to Assess Vaccine Protection Against Highly Divergent Lyssaviruses

Jennifer S Evans et al. Viruses. .
Free PMC article

Abstract

Lyssaviruses constitute a diverse range of viruses with the ability to cause fatal encephalitis known as rabies. Existing human rabies vaccines and post exposure prophylaxes (PEP) are based on inactivated preparations of, and neutralising antibody preparations directed against, classical rabies viruses, respectively. Whilst these prophylaxes are highly efficient at neutralising and preventing a productive infection with rabies virus, their ability to neutralise other lyssaviruses is thought to be limited. The remaining 15 virus species within the lyssavirus genus have been divided into at least three phylogroups that generally predict vaccine protection. Existing rabies vaccines afford protection against phylogroup I viruses but offer little to no protection against phylogroup II and III viruses. As such, work involving sharps with phylogroup II and III must be considered of high risk as no PEP is thought to have any effect on the prevention of a productive infection with these lyssaviruses. Whilst rabies virus itself has been characterised in a number of different animal models, data on the remaining lyssaviruses are scarce. As the lyssavirus glycoprotein is considered to be the sole target of neutralising antibodies we generated a vaccine strain of rabies using reverse genetics expressing highly divergent glycoproteins of West Caucasian Bat lyssavirus and Ikoma lyssavirus. Using these recombinants, we propose that recombinant vaccine strain derived lyssaviruses containing heterologous glycoproteins may be a suitable surrogate for wildtype viruses when assessing vaccine protection for the lyssaviruses.

Keywords: antigenic; chimera; lyssavirus; neutralizing antibody; rabies; vaccine.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Growth kinetics of recombinant lyssaviruses in vitro. Multiple step growth curves of each virus starting from MOI 0.01.
Figure 2
Figure 2
Survival curve of mice challenged IC. (a) The survival curve of mock vaccinated mice (n = 5 per virus). (b) The survival curve of mice vaccinated with VeroRAB and challenged with cSN, cSN-WCBV-G, or cSN-IKOV-G (n = 10/virus). Each mouse was challenged with 100 ffu/30 μL of virus via the intracranial route. Mice were observed for 28 days but results only shown up to day 12 for clarity as after this point no further mice developed clinical disease.
Figure 3
Figure 3
Survival curve of mice challenged peripherally. Each mouse was challenged with 1000 ffu/50 μL of either cSN, cSN-WCBV-G, or cSN-IKOV-G via the foot pad. (n = 5/virus). Mice were observed for 28 days. Results are shown up to day 12 after which no further mice developed clinical disease.

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