efficacy of btvpur alsap® 1-8, an inactivated bivalent btv-1 / btv-8 vaccine, against a btv-1 or...
DESCRIPTION
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, FranceTRANSCRIPT
EFFICACY OF BTVPUR ALSAP® 1-8, AN INACTIVATED BIVALENT BTV-1 / BTV-8 VACCINE, AGAINST A
BTV-1 OR BTV-8 VIRULENT CHALLENGE IN SHEEPHamers C. – Galleau S. - Blanchet M. – Chery R. – Razanajaona-Doll D. –
Duboeuf M. - Besancon L. – Goutebroze S. - Hudelet P.
Merial S.A.S. Lyon - France
IntroductionSince 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.
Clinical Scores
Viraemia
BTV neutralizing antibodies
BTV-1 VN titers BTV-8 VN titers
® : BTVPUR ALSAP is a registered trademark of Merial in the European Union and Elsewhere.
This product can be used ONLY under governmental direction.
Material & Methods
Vaccine : BTV-1/BTV-8 bivalent inactivated, purified vaccine two injections, 3 weeks apart (1mL sub-cutaneous).
Animals : 3-4 months-old Lacaune lambs randomly allocated to 4 groups of 5 (vaccinates) to 6 (controls) lambs.
Treatment Challenge
G1 : vaccinated (D0+D21) BTV-8 challenged (D42)
G2 : controls BTV-8 challenged (D42)
G3 : vaccinated (D0+D21) BTV-1 challenged (D44)
G4 : controls BTV-1 challenged (D44)
Challenges : performed intradermally with virulent BTV strains, differing from the vaccine strains
groups G1 & G2 : BTV-8 (Belgium), groups G3 & G4 : BTV-1 (Portugal).
Monitoring : All animals were monitored daily from 5 to 14 days after challenge for rectal temperature and clinical signs, and were blood sampled to assess viraemia (quantitative RT-PCR).
Serum sampling occurred on D0, D14, D21, D42 (or D44) & D56 (or D58) for antibody titrations (Virus Neutralization Tests).
ResultsHyperthermia
38.5
39.0
39.5
40.0
40.5
41.0
41.5
42.0
0 2 4 6 8 10 12 14
Days after challenge
Mean r
ect
al te
mpera
ture
(°C
)
G1 (Vaccinates/Chall BTV-8)
G2 (Controls/Chall BTV-8)
G3 (Vaccinates/Chall BTV-1)G4 (Controls/Chall BTV-1)
BTV-8 or BTV-1 challenge
0
1
2
3
4
5
6
7
8
5 6 7 8 9 10 11 12 13 14Days after challenge
Mean d
aily c
linic
al sc
ore
.
G1 (Vaccinates/Chall BTV-8)
G2 (Controls/Chall BTV-8)
G3 (Vaccinates/Chall BTV-1)
G4 (Controls/Chall BTV-1)
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
0 10 20 30 40 50 60Day of protocol
BTV-1
SN
titre
(lo
g10 P
D50/m
L) . G1 (Vaccinates/Chall BTV-8)
G2 (Controls/Chall BTV-8)
G3 (Vaccinates/Chall BTV-1)
G4 (Controls/Chall BTV-1)
Vaccine injection
Vaccine injection
BTV-8 or BTV-1 challenge
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
0 10 20 30 40 50 60Day of protocol
BTV-8
SN
titre
(lo
g10 P
D50/m
L) . G1 (Vaccinates/Chall BTV-8)
G2 (Controls/Chall BTV-8)
G3 (Vaccinates/Chall BTV-1)
G4 (Controls/Chall BTV-1)
Vaccine injection
Vaccine injection
BTV-8 or BTV-1 challenge
ConclusionsIn 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).
2.0
3.0
4.0
5.0
6.0
7.0
8.0
9.0
0 2 4 6 8 10 12 14Days after challenge
Mea
n v
irae
mia
(lo
g10 R
NA c
opie
s /
mL
blo
od)
.
G1 (Vaccinates/Chall BTV-8)
G2 (Controls/Chall BTV-8)
G3 (Vaccinates/Chall BTV-1)
G4 (Controls/Chall BTV-1)
BTV-8 or BTV-1 challenge
Limit of Detection