Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 221, Issue 8, Pages 1304-1314Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiz228
Keywords
Hepatitis C virus; vaccine; nanoparticle; neutralizing antibody
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Funding
- Chinese National 973 Program [2015CB554300]
- National Natural Science Foundation of China [31670172]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDPB03]
- National Sciences and Technology Major Projects for Major New Drugs Innovation and Development [2018ZX09711003-001-004]
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Despite the emergence of new direct-acting antivirals, hepatitis C virus (HCV) chronic infection and its consequent fibrosis and hepatocarcinoma remain a significant burden for public health, thus requiring an effective preventive vaccine. Our group previously showed that a subunit vaccine based on recombinant soluble E2 (sE2) can induce broadly neutralizing antibodies. To improve the immunogenicity of sE2, we designed and produced a fusion protein (sE2-ferritin) comprising sE2 and a ferritin unit in Drosophila S2 cells, which self-assembled into a nanoparticle with sE2 displayed on the surface. The sE2 moiety on the sE2-ferritin nanoparticle not only had nearly natural conformation but also had better affinities than the unfused sE2 to neutralizing antibodies, receptor, and patient serum. Mouse immunization studies showed that sE2-ferritin was more potent than sE2 in inducing anti-HCV broadly neutralizing antibodies. Our results demonstrate that sE2- ferritin is a vaccine candidate superior to previously developed sE2, providing a new possibility for controlling HCV.
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