EVA CALVO-PINILLA, CISA-CSIC

Luis Jiménez-Cabello, Sergio Utrilla-Trigo, Alejandro Carra-Valenzuela, Iván Belinchón, Iván Mazuecos, Javier Ortego, Eva Calvo-Pinilla. AFFILITION OF ALL AUTHORS: CISA-CSIC (MADRID, SPAIN)

Vaccines

Bluetongue (BT) is an important arthropod-borne livestock disease caused by Bluetongue virus (BTV) that circulates as multiple, serologically distinct types. BTV is partially controlled through inactivated vaccination approaches. However, conventional vaccines lead to serotype-specific protection and additional drawbacks. Non-structural viral proteins NS1 and NS2 are highly conserved among all described BTV serotypes, while VP2 is the most variable protein and the main inducer of neutralizing antibodies (NAbs). In this work, we have engineered a recombinant MVA co-expressing the protein NS1 and the N-terminal end of protein NS2 along with protein VP2 of BTV-4. We observed that this vaccine candidate confers full protection against a homologous serotype in the BTV-susceptible IFNAR (-/-) mouse model and sheep, a natural host of the disease. We also confirmed the capability of this vaccine candidate to elicit heterologous protection in mice, mainly through the induction of specific cellular immune responses.
In further experiments, we evaluated the multiserotype protective capacity of this vaccine candidate in sheep. After prime-boost immunization with MVA-VP2-NS1-2A-NS2-Nt and challenge with the heterologous BTV-8, we observed a significant blockade of viral replication and partial attenuation of the pathology induced by BTV infection. Unsurprisingly, MVA-VP2-NS1-2A-NS2-Nt immunization induced homologous but not heterologous NAbs. Importantly, we noticed the induction of potent CD8+ T cell immune responses specific of NS1 and NS2-Nt proteins of BTV, which mediate the high degree of protection against BTV-8 in sheep.