Immunization with a Subunit Hepatitis C Virus Vaccine Elicits Pan-Genotypic Neutralizing Antibodies and Intrahepatic T-Cell Responses in Nonhuman Primates

Dapeng Li, Xuesong Wang, Markus Von Schaewen, Wanyin Tao, Yunfang Zhang, Brigitte Heller, Gabriela Hrebikova, Qiang Deng, Qiang Sun, Alexander Ploss, Jin Zhong, Zhong Huang

Research output: Contribution to journalArticle

12 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1824-1831
Number of pages8
JournalJournal of Infectious Diseases
Volume215
Issue number12
DOIs
StatePublished - Jun 15 2017

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Infectious Diseases

Keywords

  • Hepatitis C virus
  • neutralizing antibodies
  • nonhuman primates
  • vaccine

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    Li, D., Wang, X., Von Schaewen, M., Tao, W., Zhang, Y., Heller, B., Hrebikova, G., Deng, Q., Sun, Q., Ploss, A., Zhong, J., & Huang, Z. (2017). Immunization with a Subunit Hepatitis C Virus Vaccine Elicits Pan-Genotypic Neutralizing Antibodies and Intrahepatic T-Cell Responses in Nonhuman Primates. Journal of Infectious Diseases, 215(12), 1824-1831. https://doi.org/10.1093/infdis/jix180