Characterisation of a new chimeric marker vaccine candidate with a mutated antigenic E2-epitope

Ilona Reimann , Klaus Depner , Katrin Utke , Immanuel Leifer , Elke Lange , Martin Beer

A new chimeric pestivirus “CP7_E1E2alf_TLA”, based on the infectious cDNA of bovine viral diarrhea virus (BVDV) strain CP7, was constructed. The substitution of BVDV E1 and E2 with the respective proteins of classical swine fever (CSF) strain Alfort 187 allows an optimal heterodimerization of E1 and E2 in the chimeric virus, which is beneficial for efficient and authentic virus assembly and growth. In addition, for implementation of E2-based marker diagnostics, the previously described antigenic CSFV-specific TAVSPTTLR-epitope was exchanged with the corresponding E2-epitope of BVDV strain CP7. Recombinant virus CP7_E1E2alf_TLA displayed a growth defect, and was not reacting with monoclonal antibodies used in commercial E2 antibody blocking ELISAs. Therefore, efficacy as well as marker properties of CP7_E1E2alf_TLA were investigated in an animal experiment with both a high dose and a low dose vaccine preparation. All CP7_E1E2alf_TLA-vaccinated animals seroconverted until day 14 post challenge infection with neutralizing antibodies. Furthermore, at the day of challenge infection CP7_E1E2alf_TLA-immunised animals showed distinct lower ELISA-values in a commercial CSFV-E2-antibody test in comparison to the C-strain vaccinated controls. However, E2-ELISA reactivity as well as neutralizing titres were directly connected to the dosage used for vaccination, and only the low dose group had E2-ELISA values below threshold until challenge infection. Following challenge infection with highly virulent CSFV-strain Koslov, all vaccinees were protected, however, short-term fever episodes and very limited CSFV-genome detection with very low copy numbers could be observed. In conclusion, manipulation of the TAVSPTTLR-epitope within the tested chimeric virus resulted in an slightly reduced efficacy, but the E2-marker properties unexpectedly did not allow a clear differentiation of infected from vaccinated animals in some cases.

Mots clés: Pestivirus; classical swine fever; marker vaccine; DIVA; chimeric construct

Ilona Reimann, Klaus Depner, Katrin Utke, Immanuel Leifer, Elke Lange, et al.. Characterisation of a new chimeric marker vaccine candidate with a mutated antigenic E2-epitope. Veterinary Microbiology, 2010, 142 (1-2), pp.45. ⟨10.1016/j.vetmic.2009.09.042⟩. ⟨hal-00578399⟩