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

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.

A New Look at Vaccine Strategies Against PPRV Focused on Adenoviral Candidates

“…These viruses have a broad spectrum of infectivity but their replication is limited in mammalian host cells, thus, raising their safety profile when used as a recombinant vector in mammals. Dual injection of NDV expressing PPRV-H induced a similar degree of protection against challenge as vaccination with the conventional Nigeria 75/1 vaccine ( 44 ), indicating that NDV-based vector could be useful for PPRV control.…”

“…The H and F glycoproteins are the principal targets of neutralizing antibodies of the humoral immune response. These two glycoproteins have been considered the best to include in vaccine candidates and their genes have been cloned and expressed in several recombinant, replication-defective viral vectors: (i) Poxviruses ( 39 , 40 ), (ii), Bovine-Herpes viruses ( 43 ), (iii) Newcastle disease virus ( 44 ), and (iv) Adenoviruses ( 33 , 34 , 36 , 37 , 68 ).…”

“…Recently a recombinant Newcastle disease virus expressing PPRV H protein was shown to induce protective immunity against virulent PPRV challenge in goats ( 44 ). NDV is a Paramyxovirus that produces diseases in poultry, but attenuated strains are used as vaccine.…”

“…Currently, several laboratories are working on different approaches, aimed at overcoming the aforementioned weak points of current vaccines, by developing a new generation of vaccines against PPRV. These alternative approaches include inactivated vaccines, DNA vaccines ( 19 , 20 ), recombinant subunit vaccines ( 21 – 23 ), virus-like-particles (VLPs) vaccines ( 24 – 27 ), reverse-genetic vaccines ( 28 – 30 ), and vectored vaccines ( 31 – 44 ) ( Figure 1 ).…”

Progress towards Eradication of Peste des Petits Ruminants through Vaccination

“…From 2014 to 2017, Liu et al generated a variety of PPRV virus-like particles (VLPs) by expressing different PPRV proteins [47][48][49]. Other recombinant vaccines using Capripoxvirus [50][51][52][53], Adenovirus [54][55][56][57][58], Vaccinia virus [59,60], Newcastle disease virus [61], or PPR [62,63] as vectors have been reported. To date, all of these recombinant vaccines do not provide the ability to differentiate wild type virus infection from vaccinal immunity and currently remain at an experimental stage.…”