6VJT

Co-crystals of broadly neutralizing antibody with the linear epitope from Hepatitis B surface antigen

Summary for 6VJT

• Entry DOI: 10.2210/pdb6vjt/pdb
• Descriptor: Heavy Chain Fab Fragment of Monoclonal Ab15, Light Chain Fab Fragment of Monoclonal antibody A15, antigenic region 139-148 of Hepatitis B surface antigen protein, ... (4 entities in total)
• Functional Keywords: hepatitis b, hepb, fab, ab, antibody, antiviral protein, antiviral protein-immune system complex, antiviral protein/immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 48416.87

Authors

Oren, D.A.,Nussenzweig, M.C.,Wang, Q. (deposition date: 2020-01-17, release date: 2020-08-26, Last modification date: 2024-11-13)

Primary citation

Wang, Q.,Michailidis, E.,Yu, Y.,Wang, Z.,Hurley, A.M.,Oren, D.A.,Mayer, C.T.,Gazumyan, A.,Liu, Z.,Zhou, Y.,Schoofs, T.,Yao, K.H.,Nieke, J.P.,Wu, J.,Jiang, Q.,Zou, C.,Kabbani, M.,Quirk, C.,Oliveira, T.,Chhosphel, K.,Zhang, Q.,Schneider, W.M.,Jahan, C.,Ying, T.,Horowitz, J.,Caskey, M.,Jankovic, M.,Robbiani, D.F.,Wen, Y.,de Jong, Y.P.,Rice, C.M.,Nussenzweig, M.C.
A Combination of Human Broadly Neutralizing Antibodies against Hepatitis B Virus HBsAg with Distinct Epitopes Suppresses Escape Mutations.
Cell Host Microbe, 28:335-349.e6, 2020

PubMed Abstract: Although there is no effective cure for chronic hepatitis B virus (HBV) infection, antibodies are protective and correlate with recovery from infection. To examine the human antibody response to HBV, we screened 124 vaccinated and 20 infected, spontaneously recovered individuals. The selected individuals produced shared clones of broadly neutralizing antibodies (bNAbs) that targeted 3 non-overlapping epitopes on the HBV S antigen (HBsAg). Single bNAbs protected humanized mice against infection but selected for resistance mutations in mice with prior established infection. In contrast, infection was controlled by a combination of bNAbs targeting non-overlapping epitopes with complementary sensitivity to mutations that commonly emerge during human infection. The co-crystal structure of one of the bNAbs with an HBsAg peptide epitope revealed a stabilized hairpin loop. This structure, which contains residues frequently mutated in clinical immune escape variants, provides a molecular explanation for why immunotherapy for HBV infection may require combinations of complementary bNAbs.

PubMed: 32504577
DOI: 10.1016/j.chom.2020.05.010

Experimental method

X-RAY DIFFRACTION (1.782 Å)