Dapeng Li1,2, Xuesong Wang1,2, Markus von Schaewen3, Wanyin Tao2, Yunfang Zhang1, Brigitte Heller3, Gabriela Hrebikova3, Qiang Deng1, Qiang Sun4,5, Alexander Ploss3, Jin Zhong2, Zhong Huang1. 1. Unit of Vaccinology and Antiviral Strategies. 2. Unit of Viral Hepatitis, CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai. 3. Department of Molecular Biology, Princeton University, New Jersey. 4. Key Laboratory of Primate Neurobiology, Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai. 5. Suzhou Nonhuman Primate Facility, Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Suzhou, China.
Abstract
Background: 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. Methods: 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. Results: 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. Conclusions: sE2 is a promising HCV vaccine candidate that warrants further preclinical and clinical development.
Background: 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. Methods: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. Results: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. Conclusions: sE2 is a promising HCV vaccine candidate that warrants further preclinical and clinical development.
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