Our phase I study with recombinant HCV E1/E2 envelope glycoprotein (EnvGPs) as a candidate vaccine did not induce a strong immune response in volunteers.
We used long-read, deep-sequenced data of full-length HCV envelope glycoprotein, longitudinally sampled from acute to chronic HCV infection to investigate the underlying viral population and evolutionary dynamics.
However, this effort has proven challenging because HCV evades neutralizing antibodies (NAbs) through molecular features of viral envelope glycoprotein E2, including hypervariable region 1 (HVR1) and N-linked glycans.
Assembly of infectious hepatitis C virus (HCV) particles is known to involve host lipoproteins, giving rise to unique lipo-viro-particles (LVPs), but proteome studies now suggest that additional cellular proteins are associated with HCV virions or other particles containing the viral envelope glycoprotein E2.
In the present study, we constructed genetic vaccines based on novel recombinant adeno‑associated viral (rAAV) vectors (AAV2/8 or AAV2/rh32.33) that express the envelope glycoprotein E2 from the HCV genotype 1b.
NEURL3 inhibits HCV assembly by directly binding viral E1 envelope glycoprotein to disrupt its interaction with E2, an action that requires its Neuralized homology repeat (NHR) domain but not the RING domain.
The occurrence of five sense mutations [S391A, G397A, L402F and M405T in the hypervariable region 1 (HVR1) of envelope glycoprotein 2 and I2750M in NS5B] suggested that HCV undergoes genetic evolution during culture.
In this study, we rescued a recombinant PR8 influenza viral vector, called rgFLU-HCV<sub>CE1E2</sub>, carrying the core and envelope glycoprotein (C/E1/E2) epitopes of HCV inserted into the influenza nonstructural protein 1 gene.
Using the structure of a broadly neutralizing antibody in complex with a conserved linear epitope from the HCV E2 envelope glycoprotein (residues 412 to 423; epitope I), we performed structure-based design of immunogens to induce antibody responses to this epitope.
Here, we report the generation and application of a combinatorial library of HCV strain JFH1 envelope glycoprotein to profile the antibody response in four HCV chronically infected individuals.