title: Toxicology and biodistribution study of CIGB-230, a DNA vaccine against hepatitis C virus.
abstract: CIGB-230, a mixture of a DNA plasmid expressing hepatitis C virus (HCV) structural antigens and a HCV recombinant capsid protein, has demonstrated to elicit strong immune responses in animals. The present study evaluated the plasmid biodistribution after the administration of CIGB-230 in mice, as well as toxicity of this vaccine candidate in rats. In the biodistribution study, mice received single or repeated intramuscular injections of CIGB-230, 50 microg of plasmid DNA mixed with 5 microg of Co.120 protein. Plasmid presence was assessed in ovaries, kidney, liver, pancreas, mesenteric ganglion, blood, and muscle of the injection site by a qualitative polymerase chain reaction. The toxicology evaluation included treatment groups receiving doses 5, 15, or 50 times higher, according to the body weight, than the expected therapeutic clinical dose. During the first hour after repeated inoculation, a promiscuous distribution was observed. However, 3 months later, plasmid could not be detected in any tissue. There was an absence of detectable adverse effects on key toxicology parameters and no damage evidenced in inspected organs and tissues. These results indicate that CIGB-230 is nontoxic at local and systemic levels and no concerns about persistence are observed, which support clinical testing of this vaccine candidate against HCV.
authors.affiliation: Center for Genetic Engineering and Biotechnology, 31st Avenue 158/190, Cubanacán, Playa, Havana, Cuba. dania.bacardi@cigb.edu.cu
authors.forename: Dania
authors.initials: D
authors.lastname: Bacardí
authors.forename: Yalena
authors.initials: Y
authors.lastname: Amador-Cañizares
authors.forename: Karelia
authors.initials: K
authors.lastname: Cosme
authors.forename: Dioslaida
authors.initials: D
authors.lastname: Urquiza
authors.forename: José
authors.initials: J
authors.lastname: Suárez
authors.forename: Jeny
authors.initials: J
authors.lastname: Marante
authors.forename: Ariel
authors.initials: A
authors.lastname: Viña
authors.forename: Ariel
authors.initials: A
authors.lastname: Vázquez
authors.forename: Joel
authors.initials: J
authors.lastname: Concepción
authors.forename: Maylín
authors.initials: M
authors.lastname: Pupo
authors.forename: Lizet
authors.initials: L
authors.lastname: Aldana
authors.forename: Yordanka
authors.initials: Y
authors.lastname: Soria
authors.forename: Juan
authors.initials: J
authors.lastname: Romero
authors.forename: Roberto
authors.initials: R
authors.lastname: Madrigal
authors.forename: Leticia
authors.initials: L
authors.lastname: Martínez
authors.forename: Lourdes
authors.initials: L
authors.lastname: Hernández
authors.forename: Idania
authors.initials: I
authors.lastname: González
authors.forename: Santiago
authors.initials: S
authors.lastname: Dueñas-Carrera
mesh_terms: D000818:Animals; D005260:Female; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D018963:Hepatitis Antigens / Q000235:genetics / Q000276:immunology; D006526:Hepatitis C / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D018675:Toxicity Tests; D019444:Vaccines, DNA / Q000493:pharmacokinetics* / Q000633:toxicity*; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology; D014761:Viral Hepatitis Vaccines / Q000493:pharmacokinetics* / Q000633:toxicity*
chemical_list: D018963:Hepatitis Antigens; D019444:Vaccines, DNA; D014758:Viral Core Proteins; D014761:Viral Hepatitis Vaccines