Toxicology and biodistribution study of CIGB-230, a DNA vaccine against hepatitis C virus.
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.
Bacardí
Dania
D
Center for Genetic Engineering and Biotechnology, 31st Avenue 158/190, Cubanacán, Playa, Havana, Cuba. dania.bacardi@cigb.edu.cu
Amador-Cañizares
Yalena
Y
Cosme
Karelia
K
Urquiza
Dioslaida
D
Suárez
José
J
Marante
Jeny
J
Viña
Ariel
A
Vázquez
Ariel
A
Concepción
Joel
J
Pupo
Maylín
M
Aldana
Lizet
L
Soria
Yordanka
Y
Romero
Juan
J
Madrigal
Roberto
R
Martínez
Leticia
L
Hernández
Lourdes
L
González
Idania
I
Dueñas-Carrera
Santiago
S
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*
D018963:Hepatitis Antigens; D019444:Vaccines, DNA; D014758:Viral Core Proteins; D014761:Viral Hepatitis Vaccines