6UR5

Resurfaced influenza hemagglutinin in complex with a broadly neutralizing antibody

Summary for 6UR5

• Entry DOI: 10.2210/pdb6ur5/pdb
• Descriptor: Antibody heavy chain, Antibody light chain, Influenza hemagglutinin HA1, ... (6 entities in total)
• Functional Keywords: hemagglutinin, viral protein, viral protein-immune system complex, viral protein/immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 6
• Total formula weight: 165414.27

Authors

Bajic, G.,Schmidt, A.G. (deposition date: 2019-10-22, release date: 2020-06-10, Last modification date: 2024-10-23)

Primary citation

Bajic, G.,Maron, M.J.,Caradonna, T.M.,Tian, M.,Mermelstein, A.,Fera, D.,Kelsoe, G.,Kuraoka, M.,Schmidt, A.G.
Structure-Guided Molecular Grafting of a Complex Broadly Neutralizing Viral Epitope.
Acs Infect Dis., 6:1182-1191, 2020

PubMed Abstract: Antigenic variation and viral evolution have thwarted traditional influenza vaccination strategies. The broad protection afforded by a "universal" influenza vaccine may come from immunogens that elicit humoral immune responses targeting conserved epitopes on the viral hemagglutinin (HA), such as the receptor-binding site (RBS). Here, we engineered candidate immunogens that use noncirculating, avian influenza HAs as molecular scaffolds to present the broadly neutralizing RBS epitope from historical, circulating H1 influenzas. These "resurfaced" HAs (rsHAs) remove epitopes potentially targeted by strain-specific responses in immune-experienced individuals. Through structure-guided optimization, we improved two antigenically different scaffolds to bind a diverse panel of pan-H1 and H1/H3 cross-reactive bnAbs with high affinity. Subsequent serological and single germinal center B cell analyses from murine prime-boost immunizations show that the rsHAs are both immunogenic and can augment the quality of elicited RBS-directed antibodies. Our structure-guided, RBS grafting approach provides candidate immunogens for selectively presenting a conserved viral epitope.

PubMed: 32267676
DOI: 10.1021/acsinfecdis.0c00008

Experimental method

X-RAY DIFFRACTION (4 Å)