Toxicology and biodistribution study of CIGB-230, a DNA vaccine against hepatitis C virus

Abstract

<jats:p> 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 μg of plasmid DNA mixed with 5 μg 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. </jats:p>

Evaluation of Drug Toxicity for DNA Vaccine Candidates Against Infectious Diseases: Hepatitis C as Experimental Model

“…In the case of CIGB-230, as previously described (Bacardí et al, 2009), no toxic effects were found after repeated intramuscular injection in Sprague-Dawley rats. The study was conformed by 6 groups: a non-treated group, a placebo one, a satellite group and three groups treated with 5, 15 and 50 times the planned therapeutic dose, respectively.…”

“…At the site of administration, most rats showed minimum focal infiltrate of lymphocytes and histiocytes. In the satellite group (VI), the reversion of this finding was observed, because it was present in only four of the animals (Bacardí et al, 2009). …”

“…The results suggest full hematopoietic functionality without evidences of alterations produced by the repeated administration of this vaccine candidate. An integral analysis of hemochemical determinations indicates that the repeated inoculation of CIGB-230 in rats does not cause toxic effects on kidneys and liver, which are main target organs given their participation in metabolic and excretion processes (Bacardí et al, 2009). Histopathological evaluation proved that the single or multiple administration of the product did not induce morphological alterations in the studied organs of rats, also showing full functional morphology in those from the immune system.…”

“…In the case of CIGB-230, the biodistribution study conducted demonstrated that after repeated intramuscular administration in mice, plasmid was readily detected in blood, as well as in all evaluated organs, except pancreas, as early as 1 h after inoculation (Bacardí et al, 2009). This wide organ distribution is consistent with the above mentioned results regardless of the animal model or the method and route of administration.…”

Biodistribution, persistence and lack of integration of a multigene HIV vaccine delivered by needle-free intradermal injection and electroporation

“…During the efforts to prove the safety of plasmid DNA, the biodistribution of plasmids has been studied in several animal species, and the results from published experiments all indicate that the plasmid is rapidly cleared from the body (Table 1 [1][2][3][4][5][6][7][8][9][10][11]). Directly after injection into skin or muscle, low levels of plasmids are transported via the blood stream and can therefore often be detected in various organs at early time points 0264-410X/$ -see front matter © 2010 Elsevier Ltd. All rights reserved.…”