An Equine Herpesvirus Type 1 (EHV-1) Expressing VP2 and VP5 of Serotype 8 Bluetongue Virus (BTV-8) Induces Protection in a Murine Infection Model

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.

Intramuscular Immunization of Mice with the Live-Attenuated Herpes Simplex Virus 1 Vaccine Strain VC2 Expressing Equine Herpesvirus 1 (EHV-1) Glycoprotein D Generates Anti-EHV-1 Immune Responses in Mice

“…The mouse model of EHV-1 infection has been used to investigate the vaccine potentials of various EHV-1 immunogens, the effects of antiviral agents on EHV-1 infection, and the pathogenicities of EHV-1 strain variants and deletion or insertional mutants (16)(17)(18). The lung histopathology in EHV-1-infected mice is similar to that in infected horses and is characterized by an acute necrotizing alveolitis and bronchiolitis and eosinophilic intranuclear inclusion bodies in bronchiolar epithelial cells (19,20).…”

DNA vaccine prime and recombinant FPV vaccine boost: an important candidate immunization strategy to control bluetongue virus type 1

“…In certain studies, VP2 alone sufficiently induces a protective immune response in vaccinated animals (Kochinger et al 2014;Top et al 2012). However, in other studies, vaccination with VP2 and VP5 or co-expressed proteins (VP2+VP5) enhanced the protective immune response, whereas VP2 alone was not effective (Franceschi et al 2011;Lobato et al 1997;Ma et al 2012;Roy et al 1990). …”

“…Additionally, recombinant DNA vaccines and modified vaccinia Ankara viruses encoding different BTV proteins each elicited sterile protection against a lethal dose of homologous or partially heterologous BTV infection in a mouse model system (Calvo-Pinilla et al 2009Jabbar et al 2013). Furthermore, a study with recombinant equine herpesvirus type 1 (EHV-1) vaccine expressing VP2 alone or VP2 in combination with VP5 demonstrated that VP2 alone was unable to protect mice against a BTV challenge; however, substantial protection was observed when VP2 and VP5 were used in combination (Ma et al 2012).…”

Current and next-generation bluetongue vaccines: Requirements, strategies, and prospects for different field situations

“…Booster vaccination with 10 6 PFU induced partial protection against virulent BTV in IFNAR(À/À) mice (Franceschi et al, 2011). Two immunizations of IFNAR(À/À) mice with 10 6 PFU of Equine herpes virus expressing both VP2 and VP5 with a 3 weeks interval protected against mortality at 3 weeks post-booster vaccination but mild clinical signs were still observed (Ma et al, 2012).…”