Development of a plant-derived subunit vaccine candidate against hepatitisC virus

Hepatitis C virus (HCV) is a major cause of acute and chronic hepatitis wit h over 180 million cases worldwide. Vaccine development for HCV has been di fficult. Presently, the virus cannot be grown in tissue culture and there i s no vaccine or effective therapy against this virus. In this research, we describe the development of an experimental plant-derived subunit vaccine a gainst HCV. A tobamoviral vector was engineered to encode a consensus seque nce of hypervariable region 1 (HVR1), a potential neutralizing epitope of H CV, genetically fused to the C-terminal of the B subunit of cholera toxin ( CTB). This epitope was selected from among the amino acid sequences of HVR1 "mimotopes" previously derived by phage display technology. The nucleotide sequence encoding this epitope was designed utilizing optimal plant codons . This mimotope is capable of inducing cross-neutralizing antibodies agains t different variants of the virus. Plants infected with recombinant tobacco mosaic virus (TMV) engineered to express the HVR1/CTB chimeric protein, co ntained intact TMV particles and produced the HVR1 consensus peptide fused to the functionally active, pentameric B subunit of cholera toxin. Plant-de rived HVR1/CTB reacted with HVR1-specific monoclonal antibodies and immune sera from individuals infected with virus from four of the major genotypes of HCV. Intranasal immunization of mice with a crude plant extract containi ng the recombinant HVR1/CTB protein elicited both anti-CTB serum antibody a nd anti-HVR1 serum antibody which specifically bound to HCV virus-like part icles. Using plant-virus transient expression to produce this unique chimer ic antigen will facilitate the development and production of an experimenta l HCV vaccine. A plant-derived recombinant HCV vaccine can potentially redu ce expenses normally associated with production and delivery of conventiona l vaccines.