VP2, VP7, and NS1 proteins of bluetongue virus targeted in avian reovirus muNS-Mi microspheres elicit a protective immune response in IFNAR(−/−) mice

Vaccination is critical for controlling the spread of bluetongue virus (BTV). The inactivated BTV vaccines that are now being used in Europe are effective in preventing outbreaks of BTV but secondary effects associated to repetitive inoculation of aluminum-containing adjuvants and the need to develop safer, cross-reactive, and more efficacious vaccines with differential diagnostic capability have re-stimulated the interest in developing improved vaccination strategies against BTV. We have engineered a subunit BTV vaccine candidate based on proteins VP2, VP7, and NS1 of BTV-4 incorporated into avian reovirus (ARV) muNS-Mi microspheres (MS-VP2/MS-VP7/MS-NS1). IFNAR(−/−) mice immunized with MS-VP2/MS-VP7/MS-NS1 without adjuvant generated significant levels of neutralizing antibodies specific to BTV-4. In addition, vaccination stimulated specific T cell responses, predominantly CD4+, against the virus. Immunized mice were fully protected against a homologous challenge with a lethal dose of BTV-4 and partially cross-protected against a heterologous challenge with a lethal dose of BTV-1. These results support MS-VP2/MS-VP7/MS-NS1 as a promising subunit vaccine candidate against multiple serotypes of BTV as well as the use of microspheres as an alternative delivery method with potent intrinsic adjuvant activity.