Abstract
Bluetongue virus (BTV) belongs to the genus Orbivirus within the family Reoviridae. The development of vector-based vaccines expressing conserved protective antigens results in increased immune activation and could reduce the number of multiserotype vaccinations required, therefore providing a cost-effective product. Recent recombinant DNA technology has allowed the development of novel strategies to develop marker and safe vaccines against BTV. We have now engineered naked DNAs and recombinant modified vaccinia virus Ankara (rMVA) expressing VP2, VP7 and NS1 proteins from BTV-4. IFNAR(−/−) mice inoculated with DNA/rMVA-VP2,-VP7-NS1 in an heterologous prime boost vaccination strategy generated significant levels of antibodies specific of VP2, VP7, and NS1, including those with neutralizing activity against BTV-4. In addition, vaccination stimulated specific CD8+ T cell responses against these three BTV proteins. Importantly, the vaccine combination expressing NS1, VP2 and VP7 proteins of BTV-4, elicited sterile protection against a lethal dose of homologous BTV-4 infection. Remarkably, the vaccine induced cross-protection against lethal doses of heterologous BTV-8 and BTV-1 suggesting that the DNA/rMVA-VP2,-VP7,-NS1 marker vaccine is a promising multiserotype vaccine against BTV.
Highlights
Bluetongue (BT) is a non-contagious, insect-transmitted disease of wild and domestic ruminants that is caused by bluetongue virus (BTV)
These data confirm the efficient expression of the proteins from BTV-4 cloned in the DNA and MVA vaccine vectors used for immunization of IFNAR(2/2) mice
N immunization mice were intravenously inoculated with 100 PFUs of BTV-8 (&) or BTV-1 ( ). (A) Survival rates of immunized and nonimmunized IFNAR(2/2) mice after inoculation with BTV-8 or BTV-1
Summary
Bluetongue (BT) is a non-contagious, insect-transmitted disease of wild and domestic ruminants that is caused by bluetongue virus (BTV). BTV infection of ruminants occurs throughout much of the tropical and recently the temperate climate regions of the world, coincident with the distribution of specific species of Culicoides biting midges that are the biological vectors of the virus [1,2]. Live attenuated vaccines are available for different serotypes of BTV. These cell culture adapted viruses, which can replicate in the vaccinated host, generate significant viremia and neutralizing antibodies, with long-lasting and serotype-specific protection in the recovered animal. Despite their relatively crude nature, inactivated BTV-8 and BTV-1 vaccines are being used in Europe and they have been effective in preventing further outbreaks of both serotypes
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