Recombinant retrovirus-derived virus-like particle-based vaccines induce hepatitis C virus-specific cellular and neutralizing immune responses in mice.
While the immunological correlates of hepatitis C virus (HCV)-specific immunity are not well understood, it is now admitted that an effective vaccine against HCV will need to induce both cellular and humoral immune responses and address viral heterogeneity to prevent immune escape. We developed a vaccine platform specifically aimed at inducing such responses against HCV antigens displayed by recombinant retrovirus-based virus-like particles (VLPs) made of Gag of murine leukemia virus. Both ex vivo produced VLPs and plasmid DNA encoding VLPs can be used as vaccines. Here, we report that immunizations with plasmid DNA forming VLPs pseudotyped with HCV E1 and E2 envelope glycoproteins (HCV-specific plasmo-retroVLPs) induce strong T-cell-mediated immune responses that can be optimized by using proper DNA delivery methods and/or genetic adjuvants. Additionally, multigenotype or multi-specific T-cell responses were observed after immunization with plasmids that encode VLPs pseudotyped with E1E2 derived from numerous viral genotypes and/or displaying NS3 antigen in capsid proteins. While homologous prime-boost immunizations with HCV-specific plasmo-retroVLPs or ex vivo produced VLPs induce a low level of specific antibody responses, optimal combination of plasmo-retroVLPs and VLPs was identified for inducing HCV-specific T-cell and B-cell responses as well as neutralizing antibodies. Altogether, these results have important meanings for the development of anti-HCV preventive vaccines and exemplify the flexibility and potential of our retrovirus-based platform in inducing broad cellular and humoral immune responses.
UPMC Univ. Paris 06, UMR7211, I³, F-75013 Paris, France.
Christophe
C
Huret
Delphine
D
Desjardins
Mathilde
M
Miyalou
Béatrice
B
Levacher
Martin
M
Amadoudji Zin
Olivia
O
Bonduelle
Béhazine
B
Combadière
Charlotte
C
Dalba
David
D
Klatzmann
Bertrand
B
Bellier
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D005260:Female; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D018937:Hepatitis C Antibodies / Q000097:blood*; D009052:Leukemia Virus, Murine / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D010957:Plasmids; D013601:T-Lymphocytes / Q000276:immunology*; D014161:Transduction, Genetic; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014761:Viral Hepatitis Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
D018937:Hepatitis C Antibodies; D014614:Vaccines, Synthetic; D058425:Vaccines, Virus-Like Particle; D014761:Viral Hepatitis Vaccines