The core domain of hepatitis C virus glycoprotein E2 generates potent cross‐neutralizing antibodies in guinea pigs

• DOI: 10.1002/hep.28989
• Publication Date: 2016-12-20T18:30:32Z
• Authors: Patricia T. Vietheer; Irene Boo; Jun Gu; Kathleen McCaffrey; Stirling Edwards; Catherine Owczarek; Matthew P. Hardy; Louis Fabri; Rob J. Center; Pantelis Poumbourios; Heidi E. Drummer
• Keywords: Viral Hepatitis Vaccines; 0301 basic medicine; 570; Genotype; Viral Hepatitis; Guinea Pigs; 610; Enzyme-Linked Immunosorbent Assay; Hepacivirus; Hepatitis C Antibodies; Antibodies, Neutralizing; Hepatitis C; Statistics, Nonparametric; 3. Good health; Disease Models, Animal; Epitopes; Random Allocation; 03 medical and health sciences; Viral Envelope Proteins; Antibody Specificity; Animals

A vaccine that prevents hepatitis C virus (HCV) infection is urgently needed to support an emerging global elimination program. However, development has been confounded because of HCV's high degree antigenic variability and the preferential induction type-specific immune responses with limited potency against heterologous viral strains genotypes. We showed previously deletion three variable regions from E2 receptor-binding domain (Δ123) increases ability human broadly neutralizing antibodies (bNAbs) inhibit E2-CD81 receptor interactions, suggesting improved bNAb epitope exposure. In this study, immunogenicity Δ123 was examined. show high-molecular-weight forms elicit distinct antibody specificities potent broad activity all seven HCV Antibody competition studies revealed sera raised poly specific, given it inhibited binding bNAbs directed major neutralization epitopes on E2. By contrast, monomeric predominantly blocked a non-neutralizing Δ123, while having reduced block E2, largely toward homologous genotype. This increased oligomeric generate correlates occlusion face in glycoprotein form.The results study reveal new information immunogenic potential E2-based immunogens provide pathway for simple, recombinant protein-based prophylactic universal protection. (Hepatology 2017;65:1117-1131).