Altered glycosylation patterns increase immunogenicity of a subunit hepatitis C virus vaccine, inducing neutralizing antibodies which confer protection in mice

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

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Hepatitis C virus (HCV) infection is a global health problem for which no vaccine is available. HCV has a highly heterogeneous RNA genome and can be classified into seven genotypes. Due to the high genetic and resultant antigenic variation among the genotypes, inducing antibodies capable of neutralizing most of the HCV genotypes by experimental vaccination has been challenging. Previous efforts focused on priming humoral immune responses with recombinant HCV envelope E2 protein produced in mammalian cells. Here, we report that a soluble form of HCV E2 (sE2) produced in insect cells possesses different glycosylation patterns and is more immunogenic, as evidenced by the induction of higher titers of broadly neutralizing antibodies (bNAbs) against cell culture-derived HCV (HCVcc) harboring structural proteins from a diverse array of HCV genotypes. We affirm that continuous and discontinuous epitopes of well-characterized bNAbs are conserved, suggesting that sE2 produced in insect cells is properly folded. In a genetically humanized mouse model, active immunization with sE2 efficiently protected against challenge with a heterologous HCV genotype. These data not only demonstrate that sE2 is a promising HCV vaccine candidate, but also highlight the importance of glycosylation patterns in developing subunit viral vaccines.

Original languageEnglish (US)
Pages (from-to)10486-10498
Number of pages13
JournalJournal of virology
Volume90
Issue number23
DOIs
StatePublished - 2016

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Li, D., von Schaewen, M., Wang, X., Tao, W., Zhang, Y., Li, L., Heller, B., Hrebikova, G., Deng, Q., Ploss, A., Zhong, J., & Huang, Z. (2016). Altered glycosylation patterns increase immunogenicity of a subunit hepatitis C virus vaccine, inducing neutralizing antibodies which confer protection in mice. Journal of virology, 90(23), 10486-10498. https://doi.org/10.1128/JVI.01462-16