9IA4

Bc8.108 Fab

Summary for 9IA4

• Entry DOI: 10.2210/pdb9ia4/pdb
• Descriptor: Heavy chain, Light chain (3 entities in total)
• Functional Keywords: fab-antigen complex, hbv, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 2
• Total formula weight: 47616.31

Authors

Mechaly, A.E.,Haouz, A.,Beretta, M.,Caillet-Saguy, C.,Mouquet, H. (deposition date: 2025-02-07, release date: 2025-11-26, Last modification date: 2026-05-06)

Primary citation

Beretta, M.,Mechaly, A.,Planchais, C.,Haouz, A.,Caillet-Saguy, C.,Szerman, N.,Aronthippaitoon, Y.,Ungeheuer, M.N.,Pol, S.,Gaudy-Graffin, C.,Sureau, C.,Bourgine, M.,Mouquet, H.
In vivo efficacy of combined human broadly neutralizing antibodies against hepatitis B virus.
Cell Rep, 44:116705-116705, 2025

PubMed Abstract: Antibodies targeting the hepatitis B virus (HBV) surface antigens (HBsAg) are essential for the prevention and control of HBV infection, yet their molecular and functional properties remain incompletely understood. Here, we characterize HBV seroconverter-derived human memory B cell monoclonal antibodies targeting preS1, preS2, and small (S) HBsAg regions. We find that broadly reactive anti-preS2 antibodies neutralize HBV and exert Fc-dependent effector functions that significantly contribute to their in vivo antiviral activity in HBV-carrier mice. Mapping and structural analysis reveal that they target an immunodominant epitope at the N terminus of preS2. Combining anti-preS2 and anti-S broadly neutralizing antibodies (bNAbs) isolated from the same donor profoundly and durably reduces antigenemia and viremia in HBV-carrier mice. These findings underscore the antiviral potential of anti-preS2 antibodies, particularly when combined with potent anti-S bNAbs, emphasizing their relevance for enhancing HBV vaccine efficacy and advancing immunotherapy development.

PubMed: 41405995
DOI: 10.1016/j.celrep.2025.116705

Experimental method

X-RAY DIFFRACTION (2.36 Å)