5UKO

Structure of unliganded anti-gp120 CD4bs antibody DH522IA Fab

Summary for 5UKO

• Entry DOI: 10.2210/pdb5uko/pdb
• Related: 5UKN 5UKP 5UKQ 5UKR
• Descriptor: DH522IA Fab fragment heavy chain, DH522IA Fab fragment light chain (3 entities in total)
• Functional Keywords: hiv gp120 immune system, immune system
• Biological source: Macaca mulatta; More
• Total number of polymer chains: 2
• Total formula weight: 47273.42

Authors

Nicely, N.I. (deposition date: 2017-01-23, release date: 2017-12-06, Last modification date: 2023-10-04)

Primary citation

Williams, W.B.,Zhang, J.,Jiang, C.,Nicely, N.I.,Fera, D.,Luo, K.,Moody, M.A.,Liao, H.X.,Alam, S.M.,Kepler, T.B.,Ramesh, A.,Wiehe, K.,Holland, J.A.,Bradley, T.,Vandergrift, N.,Saunders, K.O.,Parks, R.,Foulger, A.,Xia, S.M.,Bonsignori, M.,Montefiori, D.C.,Louder, M.,Eaton, A.,Santra, S.,Scearce, R.,Sutherland, L.,Newman, A.,Bouton-Verville, H.,Bowman, C.,Bomze, H.,Gao, F.,Marshall, D.J.,Whitesides, J.F.,Nie, X.,Kelsoe, G.,Reed, S.G.,Fox, C.B.,Clary, K.,Koutsoukos, M.,Franco, D.,Mascola, J.R.,Harrison, S.C.,Haynes, B.F.,Verkoczy, L.
Initiation of HIV neutralizing B cell lineages with sequential envelope immunizations.
Nat Commun, 8:1732-1732, 2017

PubMed Abstract: A strategy for HIV-1 vaccine development is to define envelope (Env) evolution of broadly neutralizing antibodies (bnAbs) in infection and to recreate those events by vaccination. Here, we report host tolerance mechanisms that limit the development of CD4-binding site (CD4bs), HCDR3-binder bnAbs via sequential HIV-1 Env vaccination. Vaccine-induced macaque CD4bs antibodies neutralize 7% of HIV-1 strains, recognize open Env trimers, and accumulate relatively modest somatic mutations. In naive CD4bs, unmutated common ancestor knock-in mice EnvB cell clones develop anergy and partial deletion at the transitional to mature B cell stage, but become Env upon receptor editing. In comparison with repetitive Env immunizations, sequential Env administration rescue anergic Env (non-edited) precursor B cells. Thus, stepwise immunization initiates CD4bs-bnAb responses, but immune tolerance mechanisms restrict their development, suggesting that sequential immunogen-based vaccine regimens will likely need to incorporate strategies to expand bnAb precursor pools.

PubMed: 29170366
DOI: 10.1038/s41467-017-01336-3

Experimental method

X-RAY DIFFRACTION (2.3 Å)