9MSC

Structure of Hepatitis C Virus Envelope Glycoprotein HCV-1 E2ecto from genotype 1a bound to neutralizing antibody RM5-16

Summary for 9MSC

• Entry DOI: 10.2210/pdb9msc/pdb
• Descriptor: RM5-16 fab LC, RM5-16 fan HC, HEPC46 fab LC, ... (9 entities in total)
• Functional Keywords: immune system, viral protein-immune system complex, viral protein/immune system
• Biological source: Macaca mulatta (Rhesus monkey); More
• Total number of polymer chains: 5
• Total formula weight: 124466.10

Authors

Nguyen, T.K.Y.,Stanfield, R.L.,Wilson, I.A. (deposition date: 2025-01-09, release date: 2026-01-14, Last modification date: 2026-08-05)

Primary citation

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.L.
Structural and genetic signatures of two classes of HCV E2 neutralizing face antibodies from non-human primates immunized with a recombinant E1E2.
Npj Vaccines, 2026

PubMed 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.

PubMed: 42009696
DOI: 10.1038/s41541-026-01449-1

Experimental method

X-RAY DIFFRACTION (3.39 Å)