Microspheres-prime/rMVA-boost vaccination enhances humoral and cellular immune response in IFNAR(−/−) mice conferring protection against serotypes 1 and 4 of bluetongue virus

- The combination of microspheres and rMVA in the vaccination strategy improves cross-protection against BTV.
- The booster with rMVA-VP2/VP7/NS1 of animals primed with MS-VP2/VP7/NS1 enhances the ratio of IgG2a/IgG1.
- The booster with rMVA-VP2/VP7/NS1 of animals primed with MS-VP2/VP7/NS1 elicits an specific cytotoxic CD8+ T cell response.
- Peptide NS1-150 is identified as a CD8+ T cell epitope and an inducer of the cytotoxicity marker CD107a in CD8+ T cells.

Bluetongue virus (BTV) is the causative agent of bluetongue disease (BT), which affects domestic and wild ruminants. At the present, 27 different serotypes have been documented. Vaccination has been demonstrated as one of the most effective methods to avoid viral dissemination. To overcome the drawbacks associated with the use of inactivated and attenuated vaccines we engineered a new recombinant BTV vaccine candidate based on proteins VP2, VP7, and NS1 of BTV-4 that were incorporated into avian reovirus muNS-Mi microspheres (MS-VP2/VP7/NS1) and recombinant modified vaccinia virus Ankara (rMVA). The combination of these two antigen delivery systems in a heterologous prime-boost vaccination strategy generated significant levels of neutralizing antibodies in IFNAR(−/−) mice. Furthermore, this immunization strategy increased the ratio of IgG2a/IgG1 in sera, indicating an induction of a Th1 response, and elicited a CD8 T cell response. Immunized mice were protected against lethal challenges with the homologous serotype 4 and the heterologous serotype 1 of BTV. All these results support the strategy based on microspheres in combination with rMVAs as a promising multiserotype vaccine candidate against BTV.