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A nanoparticle-based HCV vaccine with enhanced potency.

Despite the emergence of new direct-acting antivirals, HCV chronic infection and its consequent fibrosis and hepatocarcinoma remain a significant burden for public health, thus requiring an effective preventive vaccine. We previously showed that a subunit vaccine based on recombinant soluble E2 (sE2) can induce broadly neutralizing antibodies. In order 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 to control HCV.