title: Immunization With a Subunit Hepatitis C Virus Vaccine Elicits Pan-Genotypic Neutralizing Antibodies and Intrahepatic T-Cell Responses in Nonhuman Primates.
abstract: The global control of hepatitis C virus (HCV) infection remains a great burden, owing to the high prices and potential drug resistance of the new direct-acting antivirals (DAAs), as well as the risk of reinfection in DAA-cured patients. Thus, a prophylactic vaccine for HCV is of great importance. We previously reported that a single recombinant soluble E2 (sE2) vaccine produced in insect cells was able to induce broadly neutralizing antibodies (NAbs) and prevent HCV infection in mice. Here the sE2 vaccine was evaluated in non-human primates.
  
  
  
  Rhesus macaques were immunized with sE2 vaccine in combination with different adjuvants. Vaccine-induced NAbs in antisera were tested for neutralization activities against a panel of cell culture-derived HCV (HCVcc), while T-cell responses were evaluated in splenocytes, peripheral blood mononuclear cells, and hepatic lymphocytes.
  
  
  
  sE2 is able to elicit NAbs against HCVcc harboring structural proteins from multiple HCV genotypes in rhesus macaques. Moreover, sE2-immunized macaques developed systemic and intrahepatic memory T cells specific for E2. A significant correlation between the sE2-specific immunoglobulin G titers and neutralization spectrum was observed, highlighting the essential role of sE2 immunogenicity on achieving broad NAbs.
  
  
  
  sE2 is a promising HCV vaccine candidate that warrants further preclinical and clinical development.
authors.affiliation: Unit of Vaccinology and Antiviral Strategies.|Unit of Viral Hepatitis, CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai.
authors.forename: Dapeng
authors.initials: D
authors.lastname: Li
authors.affiliation: Unit of Vaccinology and Antiviral Strategies.|Unit of Viral Hepatitis, CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Molecular Biology, Princeton University, New Jersey.
authors.forename: Markus
authors.initials: M
authors.lastname: von Schaewen
authors.affiliation: Unit of Viral Hepatitis, CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai.
authors.forename: Wanyin
authors.initials: W
authors.lastname: Tao
authors.affiliation: Unit of Vaccinology and Antiviral Strategies.
authors.forename: Yunfang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Molecular Biology, Princeton University, New Jersey.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Heller
authors.affiliation: Department of Molecular Biology, Princeton University, New Jersey.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Hrebikova
authors.affiliation: Unit of Vaccinology and Antiviral Strategies.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Deng
authors.affiliation: Key Laboratory of Primate Neurobiology, Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai.|Suzhou Nonhuman Primate Facility, Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Suzhou, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Department of Molecular Biology, Princeton University, New Jersey.
authors.forename: Alexander
authors.initials: A
authors.lastname: Ploss
authors.affiliation: Unit of Viral Hepatitis, CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Unit of Vaccinology and Antiviral Strategies.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Huang
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D006526:Hepatitis C / Q000517:prevention & control / Q000821:virology; D018937:Hepatitis C Antibodies / Q000097:blood*; D006801:Humans; D007114:Immunization; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008099:Liver / Q000276:immunology / Q000821:virology; D008253:Macaca mulatta; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology*; D014761:Viral Hepatitis Vaccines / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D018937:Hepatitis C Antibodies; D014761:Viral Hepatitis Vaccines
keywords: Hepatitis C virus; neutralizing antibodies; nonhuman primates; vaccine