SAFETY OF BIVALENT BTVPUR ALSAP® VACCINE IN YOUNG LAMBS

Galleau S.1 - Hamers C.1 – Hudelet P. 1 – Montange C.1 – Duboeuf M.1 –Goutebroze S.1

1 Merial S.A.S. – 69007 Lyon, France

®BTVPUR ALSAP is a registered trademark of Merial.

Bluetongue (BT) outbreaks have seriously affected the cattle and sheep industries in Europe. Since 2008, large-scale vaccination programmes using inactivated vaccines have been conducted in Europe to control BTV infections, notably against BTV-8. Inclusion of young animals in the vaccination programme is not only essential for the success of a BTV control strategy but also to ensure safe animal movements. Consequently, safety of a vaccine to be used in young animals is of great importance for farmer’s acceptance of the vaccination strategy.

Introduction

Material & methodStudy design

Twenty BTV sero-negative lambs, aged between 29 and 36 days, were randomly allocated to 2 groups of 10 animals each, on the basis of their body weight:

Vaccinates: vaccinated with a bivalent BTV-1/BTV-8 inactivated and overformulated vaccine by SC route on D0 (double dose of 2 mL), D14 and D29 (repeated single dose of 1 mL). Each vaccination was performed at separate injection sites: behind the right and left elbow (thoracic glabrous area) on D0 and D14 respectively and in the right inguinal region on D29.

Controls: injected with placebo (physiological saline) in the same conditions as for vaccinates

Monitoring

- Individual clinical examination and recording of rectal temperature for 4 days following each injection.

- Monitoring of local reactions until D49 with subsequent necropsy and histological analysis of the injection sites.

- Recording of body weight gain.

ResultsClinical monitoring

No treatment-related general reactions were recorded.

39.0

39.5

40.0

40.5

-1 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18

Mean

recta

l te

mp

era

ture

(°C

)

Vaccinates

Controls

D-1 D0 D1 D2 D3 D4 D13 D14 D15 D16 D17 D18 D28 D29 D30 D31 D32 D33

p=0.150, Student t test

*p=0.024, Mann Whitney W test

*p=0.015, Mann Whitney W test

Figure 1: Evolution of mean rectal temperature following each injection

ConclusionThe administration of an overdose and repeated administration of one dose of the overformulated bivalent BTV-1/BTV-8 vaccine was demonstrated to be safe in one-month-old lambs and does not impact the daily weight gain. The use of commercial BTVPUR ALSAP can thus be considered safe in young sheep.

The mean maximal temperature increase was +0.9°C, following the second injection. Globally, the temperature increase remained moderate and transient.

The present study assessed the safety of an overdosed BTV-1/8 bivalent vaccine of the BTVPUR ALSAP range administered to young lambs.

Local reactions

Only limited to moderate swelling reactions were observed at theinjection sites, particularly after the 2nd and 3rd injections likely due to increased inflammation in already primed animals. They had disappeared or were of very limited size on D49. Longer persistence was observed at the D29 injection sites due to the uncommon localization in the inguinal region.At histology, the modification corresponded to a classical local foreign-body-like lesion of very limited size (encysted necrotic material surrounding by fibro-inflammatory and macrophagic reaction) located in the subcutaneous tissue.

Figure 3: Distribution of individual body weights measured in vaccinates

and controls on D-1 and D49

Box-and-Whisker Plot

Body

wei

ght

(kg)

Vaccinates Controls Vaccinates Controls9

13

17

21

25

29

33

D-1 D49

Body weights

There was no impact of the vaccinations on the body weight gain.

Table I. Relative Average Daily Weight Gain (% / day) per group

Group Mean ± Sd Statistical comparison

Vaccinates 2.3 ± 0.2p=0.785

(Sudent t test)Controls 2.4 ± 0.3

Figure 2: Evolution of average local reactions size in vaccinates after each injection

0

1

2

3

4

5

6

7

0 10 20 30 40 50

Day of observation

Mean

su

rface

of

loca

l re

act

ion

(cm

2)

1st injection site (2 mL on D0)

2nd injection site (1 mL on D14)

3rd injection site (1 mL on D29)