Abstract
Bluetongue virus (BTV) can infect most species of domestic and wild ruminants causing substantial morbidity and mortality and, consequently, high economic losses. In 2006, an epizootic of BTV serotype 8 (BTV-8) started in northern Europe that caused significant disease in cattle and sheep before comprehensive vaccination was introduced two years later. Here, we evaluate the potential of equine herpesvirus type 1 (EHV-1), an alphaherpesvirus, as a novel vectored DIVA (differentiating infected from vaccinated animals) vaccine expressing VP2 of BTV-8 alone or in combination with VP5. The EHV-1 recombinant viruses stably expressed the transgenes and grew with kinetics that were identical to those of parental virus in vitro. After immunization of mice, a BTV-8-specific neutralizing antibody response was elicited. In a challenge experiment using a lethal dose of BTV-8, 100% of interferon-receptor-deficient (IFNAR−/−) mice vaccinated with the recombinant EHV-1 carrying both VP2 and VP5, but not VP2 alone, survived. VP7 was not included in the vectored vaccines and was successfully used as a DIVA marker. In summary, we show that EHV-1 expressing BTV-8 VP2 and VP5 is capable of eliciting a protective immune response that is distinguishable from that after infection and as such may be an alternative for BTV vaccination strategies in which DIVA compatibility is of importance.
Highlights
Bluetongue virus (BTV), the prototype of the genus Orbivirus within the family Reoviridae, is the causative agent of bluetongue disease in many species of domestic ruminants, especially sheep
We describe the construction and evaluation of two EHV1 RacH-based recombinant vaccines against BTV serotype 8 (BTV-8) expressing the immunodominant outer capsid protein VP2 alone or in combination with VP5. We show that both recombinant equine herpesvirus type 1 (EHV-1) mutants stably express the transgenes and induce a BTV-8-specific neutralizing antibody response
VP2 and VP5 were separated by the internal ribosome entry site (IRES) sequence such that the two genes could be co-expressed as a single transcriptional unit under the control of the common upstream HCMV IE promoter
Summary
Bluetongue virus (BTV), the prototype of the genus Orbivirus within the family Reoviridae, is the causative agent of bluetongue disease in many species of domestic ruminants, especially sheep. The virus is highly infectious but not contagious; it is transmitted to ruminants by biting midges belonging to the genus Culicoides [1]. VP2 and VP5 are the major structural proteins forming the outer capsid of the virus particle. VP2 is the main determinant of BTV serotype and is responsible for receptor binding, hemagglutination, and induction of serotype-specific neutralizing antibodies, while VP5 influences virus neutralization through its conformational interaction with VP2 [3,4]. VP7 and VP3 are the major core proteins and play important roles with respect to the structural integrity of virions [3]. 26 distinct serotypes of BTV (BTV-1 to -26) are recognized, between which there is only little cross-protection, a fact that complicates vaccination strategies [3,5,6]
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