Immunization with a DNA vaccine candidate in chronic hepatitis C patients is safe, well tolerated and does not impair immune response induction after anti-hepatitis B vaccination.
BACKGROUND
In the present study, we evaluated the safety of CIGB-230, a novel vaccine candidate based on the mixture of a plasmid for DNA immunization, expressing hepatitis C virus (HCV) structural antigens, with a recombinant HCV Core protein.


METHODS
Fifteen HCV chronically-infected volunteers with detectable levels of HCV RNA genotype 1b, who were nonresponders to previous treatment with interferon plus ribavirin, were intramuscularly injected with CIGB-230 on weeks 0, 4, 8, 12, 16 and 20. Individuals were also immunized at weeks 28, 32 and 36 with a recombinant vaccine against hepatitis B. Adverse events were recorded and analyzed. Blood samples were taken every 4 weeks up to month 12 for hematological, biochemical, virological and immunological analysis.


RESULTS
All patients completed the treatment with CIGB-230. Adverse events were only slight (83.6%) or moderate (16.4%). No significant differences in hematological and biochemical parameters, including serum aminotransferases, were detected between the baseline and post-treatment state. Induction of a CD4+ T lymphocyte response against a particular region in HCV E1, spanning amino acids 230-312 in HCV polyprotein, was detected in 42.8% of patients during treatment with CIGB-230. The ability of T cells to proliferate in response to mitogenic stimulation was not weakened. Most individuals (78.6%) were seroprotected after anti-hepatitis B vaccination and 42.8% were hyper-responders (antibody titers > 100 UI/ml). No anti-mitochondrial, anti-nuclear and anti-extractable nuclear antigen antibodies were generated during immunization with CIGB-230.


CONCLUSIONS
Vaccination with CIGB-230 in HCV chronically-infected individuals was safe, well tolerated and did not impair the ability to respond to non-HCV antigens.
Instituto Nacional de Gastroenterología, Havana City, Cuba.
Marlen
M
Castellanos
Zurina
Z
Cinza
Zaily
Z
Dorta
Gloria
G
Veliz
Héctor
H
Vega
Irma
I
Lorenzo
Sergio
S
Ojeda
Santiago
S
Dueñas-Carrera
Liz
L
Alvarez-Lajonchere
Gillian
G
Martínez
Elena
E
Ferrer
Miladys
M
Limonta
Marbelis
M
Linares
Odalis
O
Ruiz
Boris
B
Acevedo
Dinorah
D
Torres
Gabriel
G
Márquez
Luis
L
Herrera
Enrique
E
Arús
D000328:Adult; D000974:Antibodies, Antinuclear / Q000276:immunology; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D000939:Epitopes / Q000276:immunology; D005260:Female; D006509:Hepatitis B / Q000276:immunology / Q000517:prevention & control*; D006510:Hepatitis B Antibodies / Q000276:immunology; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007109:Immunity / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D008934:Mitogens / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D014611:Vaccination / Q000009:adverse effects*; D019444:Vaccines, DNA / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology
D000974:Antibodies, Antinuclear; C087035:E1 protein, Hepatitis C virus; D000939:Epitopes; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D008934:Mitogens; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins