Abstract
Bovine viral diarrhoea virus (BVDV) is an important pathogen that causes infectious disease of cattle worldwide and results in significant economic losses. Vaccination has long been used as a tool for control of BVDV but inadequacies of existing vaccines have hampered eradication efforts. Attempts to develop sub-unit vaccines have focused on the structural envelope protein E2, which is a dominant target of neutralising antibodies and as well as CD4 T cell responses. This study aimed to rationally address the development of more efficacious vaccines by characterising the kinetics and specificity of T cell responses to a BVDV type 1 peptide library in calves rendered immune to BVDV following recovery from experimental infection. Upon identification of E2 and NS3 as the dominant targets of CD4 T cell responses, we assessed whether T cells induced by one virus genotype were capable of responding to a heterologous virus genotype and to identified E2 and NS3 as targets of genotype-specific and genotype transcending responses, respectively. This finding strengthened the argument for inclusion of both antigens in a subunit vaccine formulation. A nanoparticulate formulation of E2 and NS3 adjuvanted with poly(I:C) was shown to induce protective responses comparable to a commercial available BVDV vaccine in a vaccination and challenge experiment. It is hoped that the data generated will have implications for the design of improved vaccines against BVD.