title: Immunization with a recombinant fowlpox virus expressing a hepatitis C virus core-E1 polyprotein variant, protects mice and African green monkeys (Chlorocebus aethiops sabaeus) against challenge with a surrogate vaccinia virus.
abstract: HCV (hepatitis C virus) is a worldwide health problem nowadays. No preventive vaccine is available against this pathogen, and therapeutic treatments currently in use have important drawbacks, including limited efficacy. In the present work a recombinant fowlpox virus, FPCoE1, expressing a truncated HCV core-E1 polyprotein, was generated. FPCoE1 virus generally failed to elicit a humoral immune response against HCV antigens in BALB/c mice. By contrast, mice inoculated with FPCoE1 elicited a positive interferon-gamma secretion response against HCV core in ex-vivo ELISPOT (enzyme-linked immunospot) assays. Remarkably, mice inoculated with FPCoE1 significantly controlled viraemia in a surrogate challenge model with vvRE, a recombinant vaccinia virus expressing HCV structural antigens. In fact, 40% of the mice had no detectable levels of vvRE in their ovaries. Administration of FPCoE1 in vervet monkeys [Chlorocebus (formerly Cercophitecus) aethiops sabaeus] induced lymphoproliferative response against HCV core and E1 proteins in 50% of immunized animals. Monkeys immunized with FPCoE1 had no detectable levels of vvRE in their blood, whereas monkeys inoculated with FP9, the negative control virus, had detectable levels of vvRE in blood up to 7 days after challenge. In conclusion, recombinant fowlpox virus FPCoE1 is able to induce an anti-HCV immune response in mice and monkeys. This ability could be rationally employed to develop effective strategies against HCV infection by using FPCoE1 in combination with other vaccine candidates or antiviral treatments.
authors.affiliation: HCV Department, Vaccine Division, Centro de Ingeniería Genética y Biotecnología, Ave 31, 58 and 190, Playa, PO Box 6162, Havana, Cuba. liz.lajonchere@cigb.edu.cu
authors.forename: Liz
authors.initials: L
authors.lastname: Alvarez-Lajonchere
authors.forename: Yalena
authors.initials: Y
authors.lastname: Amador-Cañizares
authors.forename: Roberto
authors.initials: R
authors.lastname: Frías
authors.forename: Yoamel
authors.initials: Y
authors.lastname: Milian
authors.forename: Alexis
authors.initials: A
authors.lastname: Musacchio
authors.forename: Ivis
authors.initials: I
authors.lastname: Guerra
authors.forename: Nelson
authors.initials: N
authors.lastname: Acosta-Rivero
authors.forename: Gillian
authors.initials: G
authors.lastname: Martínez
authors.forename: Jorge
authors.initials: J
authors.lastname: Castro
authors.forename: Pedro
authors.initials: P
authors.lastname: Puentes
authors.forename: Karelia
authors.initials: K
authors.lastname: Cosme
authors.forename: Santiago
authors.initials: S
authors.lastname: Dueñas-Carrera
mesh_terms: D000818:Animals; D002522:Chlorocebus aethiops / Q000276:immunology* / Q000821:virology; D004279:DNA, Viral / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005587:Fowlpox virus / Q000235:genetics* / Q000276:immunology; D006526:Hepatitis C / Q000276:immunology* / Q000517:prevention & control; D007114:Immunization; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics / Q000276:immunology*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D004279:DNA, Viral; C087035:E1 protein, Hepatitis C virus; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins