A Novel Recombinant Newcastle Disease Virus Vectored DIVA Vaccine against Peste des Petits Ruminants in Goats.

Magdalena Murr,Bernd Hoffmann,Thomas C Mettenleiter,Angela Römer-Oberdörfer,Christian Grund

doi:10.3390/vaccines8020205

Magdalena Murr, Bernd Hoffmann + Show 3 more

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https://doi.org/10.3390/vaccines8020205

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Journal: Vaccines	Publication Date: Apr 28, 2020
Citations: 11	License type: CC BY 4.0

Affiliation: Friedrich-Loeffler-Institut

Abstract

Peste des petits ruminants virus (PPRV, species: small ruminant morbillivirus) is the causative agent of the eponymous notifiable disease, the peste des petits ruminants (PPR) in wild and domestic sheep and goats. Mortality rates vary between 50% and 100%, causing significant losses of estimated 1.5 to 2 billion US Dollars per year. Live-attenuated PPRV vaccine strains are used in the field for disease prevention, but the application of a more thermostable vaccine enabling differentiation between infected and vaccinated animals (DIVA) would be highly desirable to achieve the goal of global disease eradication. We generated a recombinant Newcastle disease virus (rNDV) based on the live-attenuated NDV Clone 30 that expresses the surface protein hemagglutinin (H) of PPRV strain Kurdistan/11 (rNDV_HKur). In vitro analyses confirmed transgene expression as well as virus replication in avian, caprine, and ovine cells. Two consecutive subcutaneous vaccinations of German domestic goats with rNDV_HKur prevented clinical signs and hematogenic dissemination after an intranasal challenge with virulent PPRV Kurdistan/11. Virus shedding by different routes was reduced to a similar extent as after vaccination with the live-attenuated PPRV strain Nigeria 75/1. Goats that were either not vaccinated or inoculated with parental rNDV were used as controls. In summary, we demonstrate in a proof-of-concept study that an NDV vectored vaccine can protect against PPR. Furthermore, it provides DIVA-applicability and a high thermal tolerance.

Highlights

Peste des petits ruminants virus (PPRV, species: small ruminant morbillivirus) belongs to the familyParamyxoviridae within the order Mononegavirales, which includes viruses with a single stranded, negative-sense, non-segmented RNA genome [1,2]
Newcastle disease virus (NDV) strain Clone 30 with appropriate gene start, gene end and non-coding sequences derived from the NDV HN gene (Figure 1)
It was assumed that replication of NDV in mammals is locally restricted to the site of inoculation, which is supported by our findings since NDV RNA could not be found in the blood or nasal swabs after immunization [77]

Summary

Introduction

Peste des petits ruminants virus (PPRV, species: small ruminant morbillivirus) belongs to the familyParamyxoviridae within the order Mononegavirales, which includes viruses with a single stranded, negative-sense, non-segmented RNA genome [1,2]. Peste des petits ruminants virus (PPRV, species: small ruminant morbillivirus) belongs to the family. The genome comprises about 15.9 kilobases (kb) and encodes viral proteins in the order 30 - nucleoprotein (N), phosphoprotein (P), matrix protein (M), fusion protein (F), hemagglutinin (H), RNA-dependent RNA-polymerase or large protein (L) -5’ [3,4,5]. It is the causative agent of peste des petits ruminants (PPR), a notifiable, highly contagious transboundary disease in wild and domestic small ruminants such as sheep and goats. It has spread across northern and sub-Saharan Africa into

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