Bluetongue in the Mediterranean Basin: An Overview of Recent Hotspots and Advances in Vaccine Technologies

Bluetongue (BT) is a noncontagious, arthropod-borne viral disease of domestic and wild ruminants caused by bluetongue virus (BTV), an arbovirus of the Orbivirus genus within the Sedoreoviridae family. At least 36 serotypes have been identified globally; recurrent circulation of BTV-1, -4, and -8, along with the recent emergence of BTV-3 in northern Europe, underscores a persistent incursion risk for Mediterranean herds. Key drivers include climate-driven expansion of Culicoides vector niches, windborne dispersal, animal movements, and subclinical reservoirs in cattle and goats. As no specific treatment is currently available, control of bluetongue disease still relies largely on vaccination. Live-attenuated vaccines and inactivated vaccines have reduced incidence, but important limitations persist: risk of reversion and the possibility of reassortment for LAVs; requirement for multiple doses and limited cross-protection for inactivated products; and the absence of DIVA capability for both. As an alternative, next-generation platforms are under active evaluation. Subunit formulations, often VP2 combined with VP5 and/or NS1/NS2 virus-like particles (VLPs), and viral-vectored constructs demonstrate favorable safety, strong humoral and cellular responses, inherent or engineered DIVA compatibility, and potential for rapid updating against emergent serotypes. This review synthesizes recent bluetongue activity across the Mediterranean Basin and provides a critical assessment of both existing and emerging vaccine strategies, with a focus on recommending next-generation platforms that emphasize DIVA-compliant, multiserotype, and adaptable vaccination approaches, supported by integrated surveillance and vector control in the region.