Structural and genetic signatures of two classes of HCV E2 neutralizing face antibodies from non-human primates immunized with a recombinant E1E2
Year: 2026
Type: article
Abstract: Hepatitis C continues to be a significant public health problem despite advancements in antiviral therapeutics. To eliminate this disease, an effective vaccine against new infections and re-infections is needed. However, to date only one Hepatitis C virus (HCV) envelope protein (E1E2) immunogen, developed by Chiron Inc., has been tested in a Phase I clinical trial (ClinicalTrials.gov identifier NCT00500747). To establish a benchmark for elicitation of broadly neutralizing antibodies (bnAbs) by E1E2, we previously immunized non-human primates (NHPs) with this immunogen and isolated monoclonal nAbs that exhibit neutralization potency comparable to human nAbs. Here we show that NHP nAbs, encoded by germline genes IGHV1-138*01 and IGHV4-NL_5*01 (homologs of human IGHV1-69*10 and IGHV4-59*12, respectively), recognize a relatively conserved E2 region (neutralizing face) proximal to antigenic region 3 (AR3). These NHP AR3-targeting nAbs share highly similar binding modes to human AR3-targeting nAbs, suggesting a similarity in human and NHP immune responses to the same HCV immunogen.
Source: npj Vaccines
Language: English
Topic: Hepatitis C virus research
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,890
Funders: U.S. Department of Energy, National Institutes of Health, Office of Science, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Center for Research Resources, Basic Energy Sciences, Biological and Environmental Research, Office of Research Infrastructure Programs, National Institutes of Health, SLAC National Accelerator Laboratory
Awards: G102163711, G1286251239, G1384768361, G1468070684, G159247434, G1804828992, G1831385526, G2219523378, G222407312, G2287611682, G2363639003, G262962599, G2857925935, Significant upgrade and expansion of the Southwest National Primate Research Center Pathology Unit, G3152346458, G3244038948, G3351052168, G3488436650, G3629260272, G402281873, G409777406, G4259240498, G426311843, G4269941704, A Synchroton Radiation Structural Biology Resource, G4280418065, G4359711755, G4385809619, G4597657575, G4847693919, G4866076653, G498139845, G5368254702, G5387317844, Dual Beckman Coulter DxH 690T and Beckman Coulter DxH 560 AL, G5607048534, G6004781752, G674460504, G6848031779, G6918803902, G7186539832, G7374214904, G7583137537, G7688398576, G8500532866, A Synchrotron Radiation Structural Biology Resource, G9000309569, Broadly Effective HCV Vaccine, The Southwest National Primate Research Center, Understanding human antibody responses to chronic viral hepatitis C, G969889393, G993149817
OpenAlex ID: W4414924501