DNA vaccination for the induction of immune responses against hepatitis C virus proteins.
Recent analysis of clinical and experimental cases of hepatitis C virus (HCV) infection suggest the possible role of the viral nucléocapsid (C), the nonstructural protein 3 (NS3) and the envelope glycoproteins E1 and/or E2 in the mounting of immune responses capable to control infection (Botarelli et al., Gastroenterology, 1993, 104, 580-587; Choo et al., Proc. Natl Acad. Sci. USA, 1994, 91, 1294-1298). We have used DNA-based immunization to study the immune responses that can be induced by injecting DNA-derived immunogens encoding C and E2 sequences. Comparative analysis were performed in mice using expression plasmids containing full-length or partial gene sequences cloned in fusion with the hepatitis B virus surface antigen (HBV-HCV chimeras). The results obtained indicate that: (1) anti-C and anti-E2 antibodies can be induced with all constructs including the HBV-HCV chimeras; (2) titers range from 1:100 to 1:100000 depending on the antigen and nucleotide sequence context; (3) all HCV DNA immunogens are associated with a predominant Th1 response; (4) CTL can be detected against both HCV and HBV determinants.
Inchauspé
G
G
INSERM U271, Lyon, France.
Major
M E
ME
Nakano
I
I
Vitvitski
L
L
Trépo
C
C
D000818:Animals; D002478:Cells, Cultured; D019084:Fluorescent Antibody Technique, Indirect; D016174:Hepacivirus / Q000235:genetics* / Q000276:immunology; D018937:Hepatitis C Antibodies / Q000096:biosynthesis; D018936:Hepatitis C Antigens / Q000235:genetics / Q000276:immunology*; D007111:Immunity, Cellular; D051379:Mice; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology*; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology; D014761:Viral Hepatitis Vaccines / Q000235:genetics / Q000276:immunology*; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D018937:Hepatitis C Antibodies; D018936:Hepatitis C Antigens; D019444:Vaccines, DNA; D014758:Viral Core Proteins; D014759:Viral Envelope Proteins; D014761:Viral Hepatitis Vaccines; D017361:Viral Nonstructural Proteins; C087035:E1 protein, Hepatitis C virus; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C069130:nucleocapsid protein, Hepatitis C virus; C091015:glycoprotein E2, Hepatitis C virus