8US0

Human antibody S8V1-157 in complex with the A/American black duck/New Brunswick/00464/2010(H4N6) HA head domain

Summary for 8US0

• Entry DOI: 10.2210/pdb8us0/pdb
• Descriptor: Hemagglutinin, human antibody S8V1-157 light chain, human antibody S8V1-157 heavy chain, ... (7 entities in total)
• Functional Keywords: virus, antibody, influenza, fab, fragment antigen-binding, protection, immune system, viral protein-immune system complex, viral protein/immune system
• Biological source: Influenza A virus; More
• Total number of polymer chains: 18
• Total formula weight: 494575.24

Authors

McCarthy, K.R. (deposition date: 2023-10-27, release date: 2024-10-30, Last modification date: 2025-08-06)

Primary citation

Simmons, H.C.,Finney, J.,Kotaki, R.,Adachi, Y.,Park Moseman, A.,Watanabe, A.,Song, S.,Robinson-McCarthy, L.R.,Le Sage, V.,Kuraoka, M.,Moseman, E.A.,Kelsoe, G.,Takahashi, Y.,McCarthy, K.R.
A protective and broadly binding antibody class engages the influenza virus hemagglutinin head at its stem interface.
Biorxiv, 2024

PubMed Abstract: Influenza infection and vaccination impart strain-specific immunity that protects against neither seasonal antigenic variants nor the next pandemic. However, antibodies directed to conserved sites can confer broad protection. Here we identify and characterize a class of human antibodies that engage a previously undescribed, conserved epitope on the influenza hemagglutinin (HA) protein. Prototype antibody S8V1-157 binds at the normally occluded interface between the HA head and stem. Antibodies to this HA head-stem interface epitope are non-neutralizing but protect against lethal influenza infection in mice. Antibody isotypes that direct clearance of infected cells enhance this protection. Head-stem interface antibodies bind to most influenza A serotypes and seasonal human variants, and are present at low frequencies in the memory B cell populations of multiple human donors. Vaccines designed to elicit these antibodies might contribute to "universal" influenza immunity.

PubMed: 38168412
DOI: 10.1101/2023.12.13.571543

Experimental method

X-RAY DIFFRACTION (3.7 Å)