9Z4P

Crystal structure of VACV-A33 in complex with antibody A35-Ab1

Summary for 9Z4P

• Entry DOI: 10.2210/pdb9z4p/pdb
• Descriptor: Antibody A35-Ab1 light chain, Antibody A35-Ab1 heavy chain, Protein OPG161, ... (5 entities in total)
• Functional Keywords: antibody, vacv, mpxv, a33, a35, antiviral protein, antiviral protein-immune system complex, antiviral protein/immune system
• Biological source: Cricetulus griseus; More
• Total number of polymer chains: 4
• Total formula weight: 72399.82

Authors

Zhang, D.,Wilson, I.A. (deposition date: 2025-11-10, release date: 2026-11-11)

Primary citation

Zhang, D.,Fantin, R.F.,Zhu, X.,Feng, Z.,Park, S.C.,Laghlali, G.,Clark, J.J.,Nobrega, G.M.,Kottkamp, A.C.,Samanovic, M.I.,Mulligan, M.J.,Lim, J.K.,Schotsaert, M.,Yuan, M.,Coelho, C.H.,Wilson, I.A.
Antibodies to distinct epitopes on MPXV enveloped virion provide additive and complete protection.
Sci Immunol, 11:eaee7011-eaee7011, 2026

PubMed Abstract: The continuing evolution of monkeypox virus (MPXV) clades capable of sustained human-to-human transmission poses an escalating global health risk, yet no effective therapy exists for poxvirus infection. Here, we investigate a panel of human monoclonal antibodies (mAbs), derived from an antibody library, which targets A35 and B6 antigens located on the extracellular enveloped virion (EV). Four high-affinity mAbs target the central groove of the A35 dimer, whereas one targets a previously unidentified epitope on the A35 protruding loop. Three other mAbs recognize distinct, previously unmapped epitopes on the multidomain B6 antigen. Those epitopes are conserved across most orthopoxviruses. A combination of an anti-A35 and an anti-B6 antibody provides additive and complete protection from both morbidity and mortality in a lethal VACV mouse model, challenging the previous assumption that targeting both the EV and mature virion (MV) forms is required for full protection. These studies uncover critical information for next-generation therapeutics and vaccines against emerging MPXV as well as other threats.

PubMed: 42962053
DOI: 10.1126/sciimmunol.aee7011

Experimental method

X-RAY DIFFRACTION (2.82 Å)