Pentavalent Disabled Infectious Single Animal (DISA)/DIVA Vaccine Provides Protection in Sheep and Cattle against Different Serotypes of Bluetongue Virus.

Piet A Van Rijn,Massimo Spedicato,Giovanni Savini,René G P Van Gennip,Mieke A Maris-Veldhuis

doi:10.3390/vaccines9101150

Abstract

Bluetongue (BT) is a midge-borne OIE-notifiable disease of ruminants caused by the bluetongue virus (BTV). There are at least 29 BTV serotypes as determined by serum neutralization tests and genetic analyses of genome segment 2 encoding serotype immunodominant VP2 protein. Large parts of the world are endemic for multiple serotypes. The most effective control measure of BT is vaccination. Conventionally live-attenuated and inactivated BT vaccines are available but have their specific pros and cons and are not DIVA compatible. The prototype Disabled Infectious Single Animal (DISA)/DIVA vaccine based on knockout of NS3/NS3a protein of live-attenuated BTV, shortly named DISA8, fulfills all criteria for modern veterinary vaccines of sheep. Recently, DISA8 with an internal in-frame deletion of 72 amino acid codons in NS3/NS3a showed a similar ideal vaccine profile in cattle. Here, the DISA/DIVA vaccine platform was applied for other serotypes, and pentavalent DISA/DIVA vaccine for “European” serotypes 1, 2, 3, 4, 8 was studied in sheep and cattle. Protection was demonstrated for two serotypes, and neutralization Ab titers indicate protection against other included serotypes. The DISA/DIVA vaccine platform is flexible in use and generates monovalent and multivalent DISA vaccines to combat specific field situations with respect to Bluetongue.

Highlights

Bluetongue (BT) is a severe notifiable midge-borne disease of domestic and wild ruminants caused by the bluetongue virus (BTV) [1]
The Disabled Infectious Single Animal (DISA)/DIVA vaccine platform was applied for different serotypes aiming for protection against multiple serotypes and eventually broad protection
All DISA vaccines contain the backbone of LAV strain BTV6/net08 with the in-frame 72-aa deletion in Seg-10 (NS3/NS3a) [47]

Summary

Introduction

Bluetongue (BT) is a severe notifiable midge-borne disease of domestic and wild ruminants caused by the bluetongue virus (BTV) [1]. Sheep species are the most susceptible among domestic livestock, while cattle are considered the main reservoir host for onward transmission of the virus to vectors. BT outbreaks lead to large economic losses related to diseased animals, production losses, and restrictions on trade and movements of ruminants from affected areas [4,5]. BTV is a distinct virus species within the genus Orbivirus of the family Reoviridae and is the prototype orbivirus [6]. The genus Orbivirus consists of at least 22 virus species of which midge-borne African horse sickness virus and enzootic hemorrhagic disease virus cause notifiable disease of equids and ruminants, respectively [1]. The virion consists of a multilayered nonenveloped particle containing a 10-segmented genome of double-stranded RNAs (Seg-1 to -10) encoding seven structural proteins VP1-7 and at least

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