Novel bluetongue vaccine platform- NS3/NS3a knockout virus as Disabled Infectious Single Animal (DISA) vaccine

Promovendus Femke Feenstra
Promotor prof.dr. RJM (Rob) Moormann PhD
prof.dr. PA (Piet) van Rijn
Organisatie Wageningen University, Wageningen Bioveterinary Research

di 19 januari 2016 16:15

Locatie University Utrecht

Promising novel bluetongue vaccine platform

PhD candidate Femke Feenstra has developed, together with researchers from Central Veterinary Institute (CVI), part of Wageningen UR, a novel bluetongue vaccine named DISA vaccine (Disabled Infectious Single Animal vaccine). She will defend her thesis entitled Novel bluetongue vaccine platform - NS3/NS3a knockout virus as Disabled Infectious Single Animal (DISA) vaccine” on January 19, 2016 in Utrecht. This novel vaccine is based on an altered live-attenuated bluetongue virus which does not give any local side effects nor clinical signs or fever, does not spread and raises full protection against bluetongue. The changed live-attenuated bluetongue virus cannot revert to its original form; it can be adapted to suit other bluetongue serotypes.

Bluetongue (BT) is a severe disease of ruminants caused by bluetongue virus (BTV) which is transmitted by bites of Culicoides midges. Bluetongue in north-western Europe was first reported by the Netherlands in 2006. This outbreak caused huge economic losses in whole north-western Europe. The epidemic has stopped through massive vaccination programmes. In 2015, no vaccination was no longer in place, but the same virus has been detected again in France in the summer of 2015.

Prevention of BT infections by midges is almost impossible without vaccination. Therefore, vaccination is the best method to control bluetongue. Currently, there are two types of vaccines of which one is licensed in the Netherlands. This vaccine is inactivated BTV and is consequently completely safe, but it requires several vaccinations for full protection. A drawback of both types of vaccines is that infected animals, causing a risk for onward virus transmission, cannot be differentiated from vaccinated animals.

The novel vaccine is based on BTV lacking one virus protein. This protein harbours several important viral functions, but is not required for production of this vaccine virus. Vaccine virus without this protein causes no disease and no virus release in the blood. In addition, vaccine virus is not multiplying in midges. Thus, spread of vaccine virus through midges is blocked on uptake and dissemination (DISA) by lack of one virus protein.

Vaccination of sheep with this novel DISA vaccine raises complete protection against bluetongue and after infection, BTV replication is completely blocked. By this, onward transmission of BTV by midges cannot occur. Of course, the missing protein in DISA vaccine is present after BTV infection of naïve animals; therefore these infected animals can be differentiated from vaccinated animals with a recently developed assay (DIVA). 

This novel, very promising DISA vaccine is safe and effective, and could be used as alternative for the current BT vaccine after registration/licensing. The DISA-vaccine platform is now also adapted for other BTV serotypes circulating in South Europe for many serotypes by exchange of VP2.

Situation Bluetongue restricted zones December 2015 (source: OIE)