Ratio of HCV structural antigens in protein-based vaccine formulations is critical for functional immune response induction.
HCV (hepatitis C virus) infection is among the leading causes of chronic liver disease, but currently there is no vaccine available. Data have accumulated about the importance of targeting different HCV antigens in vaccine candidate preparations. Here, a surface response study to select the optimal ratio of recombinant HCV structural antigens in a vaccine preparation, capable of generating in vivo functional cellular immune response in mice, was performed. The immunogenicity of the selected HCV structural protein mixture (Co-E1-E2) in mice and African green monkeys, after five doses of immunization, was also demonstrated. Specific T-cell proliferative response against HCV structural antigens was induced in vaccinated mice. Moreover, on challenge with recombinant HCV VV (vaccinia virus), all mice controlled the viraemia and 80% were protected. On the other hand, monkeys immunized with Co-E1-E2 developed antibodies, specifically directed to region 412-438 of E2 protein, that include an epitope implicated in HCV neutralization, in addition to a specific proliferative response against HCV Core and E2 proteins. These results indicated that the optimal amount and ratio of HCV recombinant proteins should be taken into account to elicit a successful immune response against HCV and therefore have important implications for vaccine design.
Biomedical Research, Hepatitis C, Center for Genetic Engineering and Biotechnology, P.O. Box 6162, Havana 10600, Cuba. gillian.martinez@cigb.edu.cu
Gillian
G
Martínez-Donato
Alexis
A
Musacchio
Liz
L
Alvarez-Lajonchere
Nelson
N
Acosta-Rivero
Yalena
Y
Amador
Ivis
I
Guerra
Dilver
D
Peña
Angel
A
Pérez
Jorge
J
Castro
Pedro
P
Puentes
Yordanka
Y
Soria
Karelia
K
Cosme
Jorge
J
Sanchez
Santiago
S
Dueñas-Carrera
D000818:Animals; D002522:Chlorocebus aethiops; D005260:Female; D018937:Hepatitis C Antibodies / Q000097:blood; D018936:Hepatitis C Antigens / Q000276:immunology / Q000494:pharmacology; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000517:prevention & control; D006801:Humans; D007111:Immunity, Cellular; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D014758:Viral Core Proteins / Q000276:immunology* / Q000494:pharmacology; D014759:Viral Envelope Proteins / Q000276:immunology* / Q000494:pharmacology; D014761:Viral Hepatitis Vaccines / Q000276:immunology*
D018937:Hepatitis C Antibodies; D018936:Hepatitis C Antigens; D011994:Recombinant Proteins; D014758:Viral Core Proteins; D014759:Viral Envelope Proteins; D014761:Viral Hepatitis Vaccines; C069130:nucleocapsid protein, Hepatitis C virus; C091015:glycoprotein E2, Hepatitis C virus