9CB1

Cryo-EM Structure of the Human Neutralizing Antibody 5-1 in Complex with Prefusion Human Metapneumovirus F Glycoprotein

Summary for 9CB1

• Entry DOI: 10.2210/pdb9cb1/pdb
• EMDB information: 45412
• Descriptor: 5-1 Fab Heavy Chain Variable Domain, 5-1 Fab Light Chain Variable Domain, Fusion glycoprotein F0, ... (4 entities in total)
• Functional Keywords: hmpv f, 5-1 antibody, antibody, viral protein-immune system, viral protein-immune system complex, viral protein/immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 9
• Total formula weight: 323014.23

Authors

Guo, L.Q.,McLellan, J.S. (deposition date: 2024-06-18, release date: 2025-05-28, Last modification date: 2026-03-25)

Primary citation

Abu-Shmais, A.A.,Guo, L.,Khalil, A.M.,Leonard, S.E.,Miller, R.J.,Janke, A.K.,Vukovich, M.J.,Bass, L.E.,Suresh, Y.P.,Rush, S.A.,Wolters, R.M.,Kose, N.,Carnahan, R.H.,Crowe Jr., J.E.,Bonami, R.H.,Mousa, J.J.,McLellan, J.S.,Georgiev, I.S.
A potently neutralizing and protective human antibody targeting antigenic site V on RSV and hMPV fusion glycoprotein.
Cell Rep Med, 7:102564-102564, 2026

PubMed Abstract: Human respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are frequent drivers of morbidity and mortality in susceptible populations. The primary target of neutralizing antibodies is the fusion (F) glycoprotein on the surface of the RSV and hMPV virion. As a result of the structural conservation between RSV and hMPV F, three antigenic regions are known to induce cross-neutralizing responses: sites III, IV, and V. Leveraging LIBRA-seq, we identify five RSV/hMPV cross-reactive human antibodies. One antibody, RM 5-1, potently neutralizes all tested viruses from the major subgroups of RSV and hMPV and provides protection against RSV and hMPV in a mouse challenge model. Structural analysis reveals that RM 5-1 utilizes an uncommon genetic signature to bind an epitope that spans sites Ø, II, and V. These findings highlight the molecular and structural elements influencing RSV and hMPV cross-reactivity as well as the potential of antibody RM 5-1 for translational development.

PubMed: 41547352
DOI: 10.1016/j.xcrm.2025.102564

Experimental method

ELECTRON MICROSCOPY (4.24 Å)