Hamers C. – Galleau S. - Blanchet M. – Chery R. – Razanajaona-Doll D. –Duboeuf M. - Besancon L. – Goutebroze S. - Hudelet P. / Merial S.A.S. – 69007 Lyon, France

1. EFFICACY OF BTVPUR ALSAP® 1-8, AN INACTIVATED
BIVALENT BTV-1 / BTV-8 VACCINE, AGAINST A
BTV-1 OR BTV-8 VIRULENT CHALLENGE IN SHEEP
Hamers C. – Galleau S. - Blanchet M. – Chery R. – Razanajaona-Doll D. –
Duboeuf M. - Besancon L. – Goutebroze S. - Hudelet P.
Merial S.A.S. Lyon - France
Introduction
Since 2006, Bluetongue Virus serotype 8 (BTV-8) has spread throughout Europe, causing severe disease and heavy financial losses. Almost
simultaneously, BTV-1, another devastating BTV serotype appeared in Southern Europe and progressed rapidly North. To date, several regions of the
Iberic Peninsula and of France are simultaneously affected with BTV-1 and BTV-8.
Vaccination campaigns have been demonstrated effective at controlling the disease and even in some case at eradicating BTV, provided that the vaccine
was able to completely prevent viraemia and when vaccination coverage was high.
As there is little cross-protection between BTV serotypes, the availability of efficacious multivalent BTV vaccines, covering all serotypes circulating in one
region, represents a significant improvement of convenience, as compared to monovalent vaccines, by reducing the number of vaccination/handling of
animals. High convenience is a key element to achieve high a vaccination coverage and thus increase the likelihood of eradicating BTV.
Here, we describe the clinical and virological evaluation of an inactivated vaccine containing purified BTV serotypes 1 and 8. Vaccination / challenge
experiments were conducted to determine the level of protection induced by the vaccine in sheep.
Material & Methods Clinical Scores
8
Vaccine : BTV-1/BTV-8 bivalent inactivated, purified vaccine two
7
injections, 3 weeks apart (1mL sub-cutaneous). G1 (Vac cinates/Chall BTV-8)
Mean daily clinical score .
G2 (Controls/Chall BTV-8)
6
Animals : 3-4 months-old Lacaune lambs randomly allocated to 4 groups G3 (Vac cinates/Chall BTV-1)
of 5 (vaccinates) to 6 (controls) lambs. 5 G4 (Controls/Chall BTV-1)
Treatment Challenge 4
G1 : vaccinated (D0+D21) BTV-8 challenged (D42)
3
G2 : controls BTV-8 challenged (D42)
G3 : vaccinated (D0+D21) BTV-1 challenged (D44) 2
G4 : controls BTV-1 challenged (D44)
1
Challenges : performed intradermally with virulent BTV strains, differing 0
from the vaccine strains 5 6 7 8 9 10 11 12 13 14
Days after c hallenge
groups G1 & G2 : BTV-8 (Belgium), groups G3 & G4 : BTV-1 (Portugal).
Monitoring : All animals were monitored daily from 5 to 14 days after
Viraemia
challenge for rectal temperature and clinical signs, and were blood 9.0
sampled to assess viraemia (quantitative RT-PCR).
Mean viraemia (log10 RNA copies / mL blood) .
Serum sampling occurred on D0, D14, D21, D42 (or D44) & D56 (or D58) 8.0
for antibody titrations (Virus Neutralization Tests).
7.0
Results 6.0
G1 (Vac cinates/Chall BTV-8)
Hyperthermia
5.0 G2 (Controls/Chall BTV-8)
G3 (Vac cinates/Chall BTV-1)
42.0 4.0 G4 (Controls/Chall BTV-1)
G1 (Vaccinates/Chall BTV-8) Limit of Detection
41.5 G2 (Controls/Chall BTV-8) 3.0
G3 (Vaccinates/Chall BTV-1)
Mean rectal temperature (°C)
41.0 G4 (Controls/Chall BTV-1) 2.0
0 2 4 6 8 10 12 14
BTV-8 or BTV-1 Days after challenge
40.5 challenge
40.0 BTV neutralizing antibodies
BTV-1 VN titers BTV-8 VN titers
39.5 3.5
3.5
3.0
3.0 G1 (Vacc inates/Chall BTV-8)
BTV-8 SN titre (log10 PD50/mL) .
G1 (Vaccinates/Chall BTV-8)
BTV-1 SN titre (log10 PD50/mL) .
39.0 G2 (Controls/Chall BTV-8) 2.5
G2 (Controls/Chall BTV-8)
2.5 BTV-8 or BTV-1 BTV-8 or BTV-1
challenge G3 (Vacc inates/Chall BTV-1) challenge
G3 (Vaccinates/Chall BTV-1)
2.0 2.0 G4 (Controls/Chall BTV-1)
G4 (Controls/Chall BTV-1)
38.5
1.5 Vaccine injection 1.5 Vaccine injection
0 2 4 6 8 10 12 14
1.0 1.0
Days after challenge
BTV-8 or BTV-1
0.5 0.5
challenge
0.0 0.0
0 10 20 30 40 50 60 0 10 20 30 40 50 60
Day of protocol Day of protoc ol
Conclusions
Vaccine injection Vaccine injection
In the present study, vaccination with the tested vaccine : i) induced production of serotype specific neutralizing antibodies; ii) provided strong,
significant clinical protection against challenge; and iii) resulted in a complete prevention of viraemia.
These results show that BTVPUR ALSAP® 1-8 may be used for bluetongue disease prevention (clinical protection) and for epidemiological control
of BTV (virological protection).
® : BTVPUR ALSAP is a registered trademark of Merial in the European Union and Elsewhere.
This product can be used ONLY under governmental direction.