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bioRxiv · 10.1101/2025.10.07.680784

Structural and genetic signatures of two classes of HCV E2 neutralizing face antibodies from non-human primates immunized with a recombinant E1E2

Nguyen, Y. T. K.·Chen, F.·Giang, E.·Saha, S.·Ueno, L. A.·Chen, C.·Watson, C. T.·Tzarum, N.·Wilson, I. A.·Law, M.·Stanfield, R.
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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 E2 conserved 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.

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Nguyen, Y. T. K., Chen, F., Giang, E., Saha, S., Ueno, L. A., Chen, C., Watson, C. T., Tzarum, N., Wilson, I. A., Law, M., Stanfield, R.. 2025-10-07. Structural and genetic signatures of two classes of HCV E2 neutralizing face antibodies from non-human primates immunized with a recombinant E1E2. https://doi.org/10.1101/2025.10.07.680784

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