@article{d4d6b5efca514b2599af74b8e2270d89,
title = "Altered glycosylation patterns increase immunogenicity of a subunit hepatitis C virus vaccine, inducing neutralizing antibodies which confer protection in mice",
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.",
author = "Dapeng Li and {von Schaewen}, Markus and Xuesong Wang and Wanyin Tao and Yunfang Zhang and Li Li and Brigitte Heller and Gabriela Hrebikova and Qiang Deng and Alexander Ploss and Jin Zhong and Zhong Huang",
note = "Funding Information: We thank Jens Bukh (University of Copenhagen) for providing chimeric HCVcc plasmids, Mansun Law and Dennis Burton (Scripps Research Institute) for providing MAb AR3A, Arvind Patel (University of Glasgow) for providing MAb AP33, and Jenna Gaska for editing the manuscript. The work was supported in part by grants from the Chinese National Science and Technology Major Project (2012ZX10002007-003 to J.Z. and Z.H.), the CAS/SAFEA International Partnership Program for Creative Research Teams (to J.Z.), and the National Institutes of Health (R01 AI079031-05 to A.P.) and by a Research Scholar Grant (RSG-15-048-01 MPC) from the American Cancer Society (to A.P.). A.P. is further supported by an Investigators in the Pathogenesis of Infectious Disease (PATH) Award from the Burroughs Wellcome Fund. M.V.S. is the recipient of a postdoctoral fellowship from the German Research Foundation. This work, including the efforts of Jin Zhong, was funded by the National Natural Science Foundation of China (81330039), the Chinese National 973 Program (2015CB554300), and the CAS-SAFEA International Partnership Program for Creative Research Teams. This work, including the efforts of Zhong Huang, was funded by the Ministry of Science and Technology of the People's Republic of China (MOST) (2012ZX10002007-003). This work, including the efforts of Alexander Ploss, was funded by HHS | National Institutes of Health (NIH) (AI079031-05), the Burroughs Wellcome Fund (BWF), and the American Cancer Society (ACS) (RSG-15-048-01 MPC). This work, including the efforts of Markus von Schaewen, was funded by the German Research Foundation. Publisher Copyright: {\textcopyright} 2016, American Society for Microbiology. All Rights Reserved.",
year = "2016",
doi = "10.1128/JVI.01462-16",
language = "English (US)",
volume = "90",
pages = "10486--10498",
journal = "Journal of virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "23",
}