Transplacental transmission of BTV-8 in sheep: BTV viraemia, antibody responses and vaccine efficacy in lambs infected in utero.

Bluetongue virus (BTV) is an insect vector transmitted virus which causes an economically important disease in ruminants. BTV infection during pregnancy can result in infection of the foetus, which may lead to the birth of persistently infected or immunotolerant offspring. Since persistently infected animals continuously produce large amounts of virus they could be a source of infection for the insect vector. This could significantly influence the epidemiology of the virus and hence might require additional measures to control a BTV outbreak. Therefore, we investigated the potential of BTV-8 to induce persistent infection or immunotolerance in lambs in an experimental setting. Infection of eighteen 70-75 days pregnant ewes with wild type BTV-8 led to the birth of 25 out of 44 BTV RNA positive lambs (foetal infected, FI). All 23 FI lambs born alive also had anti BTV antibodies at birth; infectious virus could be recovered from 5 out of 25 FI lambs. Viral RNA loads decreased rapidly after birth; 19 out of 20 FI lambs that remained in the experiment until week 14 after birth, were RNA negative at that time. Since persistence of BTV-8 infection could not be demonstrated, we investigated whether foetal infection had an effect on protection against a field virus infection and on efficacy of vaccination. To this end, 5 FI lambs and 5 foetal non-infected (FNI) lambs were vaccinated with the inactivated Bovilis(®) BTV-8 vaccine, five months after birth. Three weeks after the vaccination, all lambs were infected with wild type BTV-8. The foetal infection did not interfere with vaccination efficacy. In contrast, foetal BTV-8 infection induced an immune response which afforded protection against BTV challenge comparable to the level of protection induced by vaccination.

Scaling from challenge experiments to the field: Quantifying the impact of vaccination on the transmission of bluetongue virus serotype 8.

Bluetongue (BT) is an economically important disease of ruminants caused by bluetongue virus (BTV) and transmitted by Culicoides biting midges. The most practical and effective way to protect susceptible animals against BTV is by vaccination. Data from challenge studies in calves and sheep conducted by Intervet International b.v., in particular, presence of viral RNA in the blood of challenged animals, were used to estimate vaccine efficacy. The results of the challenge studies for calves indicated that vaccination is likely to reduce the basic reproduction number (R(0)) for BTV in cattle to below one (i.e. prevent major outbreaks within a holding) and that this reduction is robust to uncertainty in the model parameters. Sensitivity analysis showed that the whether or not vaccination is predicted to reduce R(0) to below one depended on the following assumptions: (i) whether "doubtful" results from the challenge studies are treated as negative or positive; (ii) whether or not the probability of transmission from host to vector is reduced by vaccination; and (iii) whether the extrinsic incubation period follows a realistic gamma distribution or the more commonly used exponential distribution. For sheep, all but one of the vaccinated animals were protected and, consequently, vaccination will consistently reduce R(0) in sheep to below one. Using a stochastic spatial model for the spread of BTV in Great Britain (GB), vaccination was predicted to reduce both the incidence of disease and spatial spread in simulated BTV outbreaks in GB, in both reactive vaccination strategies and when an incursion occurred into a previously vaccinated population.

Effect of vaccination with an inactivated vaccine on transplacental transmission of BTV-8 in mid term pregnant ewes and heifers.

The effect of vaccination with a commercial inactivated Bluetongue virus serotype 8 (BTV-8) vaccine on the ability of BTV-8 to cross the ruminant placenta was investigated in two experiments. Ten pregnant ewes (Experiment 1) or heifers (Experiment 2) were vaccinated according to the manufacturer's instructions. Three weeks after the completion of the vaccination schedule, all vaccinated animals were infected with BTV-8 together with ten non-vaccinated pregnant animals that served as challenged controls. Four additional pregnant animals received a mock challenge at the same time point. Three weeks after the challenge, the foetuses were collected. In the sheep experiment, the lambs of the vaccinated ewes and the mock infected ewes were negative in the virus isolation, whereas BTV-8 could be isolated from 11/23 lambs of 6/10 ewes in the BTV-8 challenged control group. The incidence and severity of BTV associated lesions, such as haemorrhages, meningitis/encephalitis and necrosis in the placentomes was significantly higher in the BTV-8 challenged control group. The rate of transplacental transmission was less in the cattle experiment: BTV-8 could be detected in 2/10 calves in the BTV-8 challenged control group. All other calves were negative. Vaccination clearly reduced transplacental transmission of BTV-8 in the sheep experiment, whereas in the cattle experiment, the incidence of transmission was too low to demonstrate a significant reduction of transmission by vaccination. However, the vaccine very effectively blocked viraemia, which suggests that the vaccine might prevent transmission in cattle as well. Transplacental transmission of BTV has serious economical consequences, due to the loss of progeny to the livestock industry. Vaccination can be an important aid in the reduction of these economic losses.