Neutralizing antibodies and broad, functional T cell immune response following immunization with hepatitis C virus proteins-based vaccine formulation.
HCV is a worldwide health problem despite the recent advances in the development of more effective therapies. No preventive vaccine is available against this pathogen. However, non-sterilizing immunity has been demonstrated and supports the potential success of HCV vaccines. Induction of cross-neutralizing antibodies and T cell responses targeting several conserved epitopes, have been related to hepatitis C virus (HCV) clearance. Therefore, in this work, the immunogenicity of a preparation (MixprotHC) based on protein variants of HCV Core, E1, E2 and NS3 was evaluated in mice and monkeys. IgG from MixprotHC immunized mice and monkeys neutralized the infectivity of heterologous HCVcc. Moreover, strong CD4+ and CD8+ T cells proliferative and IFN-γ secretion responses were elicited against HCV proteins. Remarkably, immunization with MixprotHC induced control of viremia in a surrogate challenge model in mice. These results suggest that MixprotHC might constitute an effective immunogen against HCV in humans with potential for reducing the likelihood of immune escape and viral persistence.
Center for Genetic Engineering and Biotechnology (CIGB), Ave 31, P.O. Box 6162, Havana, 10 600, Cuba. Electronic address: gillian.martinez@cigb.edu.cu.
Gillian
G
Martinez-Donato
Center for Genetic Engineering and Biotechnology (CIGB), Ave 31, P.O. Box 6162, Havana, 10 600, Cuba.
Yalena
Y
Amador-Cañizares
Center for Genetic Engineering and Biotechnology (CIGB), Ave 31, P.O. Box 6162, Havana, 10 600, Cuba.
Liz
L
Alvarez-Lajonchere
Center for Genetic Engineering and Biotechnology (CIGB), Ave 31, P.O. Box 6162, Havana, 10 600, Cuba.
Ivis
I
Guerra
Center for Genetic Engineering and Biotechnology (CIGB), Ave 31, P.O. Box 6162, Havana, 10 600, Cuba.
Angel
A
Pérez
Institut de Biologie de Lille (UMR8161), CNRS, Universite de Lille I & II and Institut Pasteur de Lille, Lille, France.
Jean
J
Dubuisson
Institut de Biologie de Lille (UMR8161), CNRS, Universite de Lille I & II and Institut Pasteur de Lille, Lille, France.
Czeslaw
C
Wychowsk
Center for Genetic Engineering and Biotechnology (CIGB), Ave 31, P.O. Box 6162, Havana, 10 600, Cuba.
Alexis
A
Musacchio
Center for Genetic Engineering and Biotechnology (CIGB), Ave 31, P.O. Box 6162, Havana, 10 600, Cuba.
Daylen
D
Aguilar
Center for Genetic Engineering and Biotechnology (CIGB), Ave 31, P.O. Box 6162, Havana, 10 600, Cuba.
Santiago
S
Dueñas-Carrera
D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood*; D002522:Chlorocebus aethiops; D005260:Female; D006526:Hepatitis C / Q000517:prevention & control*; D018937:Hepatitis C Antibodies / Q000097:blood*; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013601:T-Lymphocytes / Q000276:immunology*; D014758:Viral Core Proteins / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology; D014761:Viral Hepatitis Vaccines / Q000276:immunology*; D017361:Viral Nonstructural Proteins / Q000276:immunology; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D057134:Antibodies, Neutralizing; D018937:Hepatitis C Antibodies; D007074:Immunoglobulin G; D007371:Interferon-gamma; 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
HCV; IFN-γ; Mice; Monkeys; Neutralizing antibody; T cell proliferation