Use of conventional or replicating nucleic acid-based vaccines and recombinant Semliki forest virus-derived particles for the induction of immune responses against hepatitis C virus core and E2 antigens.
Replicating and nonreplicating nucleic acid-based vaccines as well as Semliki Forest-recombinant Viruses (rSFVs) were evaluated for the development of a vaccine against hepatitis C virus (HCV). Replicating SFV-DNA vaccines (pSFV) and rSFVs expressing HCV core or E2 antigens were compared with classical CMV-driven plasmids (pCMV) in single or bimodal vaccine protocols. In vitro experiments indicated that all vaccine vectors produced the HCV antigens but to different levels depending on the antigen expressed. Both replicating and nonreplicating core-expressing plasmids induced, upon injection in mice, specific comparable CTL responses ranging from 10 to 50% lysis (E:T ratio 100:1). Comparison of different injection modes (intramuscular versus intraepidermal) and the use of descalating doses of DNA (1-100 microgram) did not show an increased efficacy of the core-SFV plasmid compared with the CMV-driven one. Surprisingly, rSFVs yielded either no detectable anticore CTL or very low anti-E2 antibody titers following either single or bimodal administration together with CMV-expressing counterparts. Prime-boost experiments revealed, in all cases, the superiority of DNA-based only vaccines. The anti-E2 antibody response was evaluated using three different assays which indicated that all generated anti-E2 antibodies were targeted at similar determinants. This study emphasizes the potential of DNA-based vaccines for induction of anti-HCV immune responses and reveals an unexpected and limited benefit of SFV-based vaccinal approaches in the case of HCV core and E2.
Vidalin
O
O
INSERM U271-151, Cours Albert Thomas, 69424 Lyon Cedex 03, France.
Fournillier
A
A
Renard
N
N
Chen
M
M
Depla
E
E
Boucreux
D
D
Brinster
C
C
Baumert
T
T
Nakano
I
I
Fukuda
Y
Y
Liljeström
P
P
Trépo
C
C
Inchauspé
G
G
D000818:Animals; D004279:DNA, Viral / Q000096:biosynthesis; D015195:Drug Design; D005260:Female; D016174:Hepacivirus / Q000276:immunology*; D006510:Hepatitis B Antibodies / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D012672:Semliki forest virus / Q000235:genetics*; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D014758:Viral Core Proteins / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*; D014761:Viral Hepatitis Vaccines / Q000276:immunology*
D004279:DNA, Viral; D006510:Hepatitis B Antibodies; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D014758:Viral Core Proteins; D014759:Viral Envelope Proteins; D014761:Viral Hepatitis Vaccines; C069130:nucleocapsid protein, Hepatitis C virus; C091015:glycoprotein E2, Hepatitis C virus