8EQN

BG505 UFO-E2p-L4P nanoparticle reconstructed by focused refinement with a mask around the nanoparticle core

Summary for 8EQN

• Entry DOI: 10.2210/pdb8eqn/pdb
• EMDB information: 28540 28541 28542 28543
• Descriptor: BG505 UFO-E2p-L4P (1 entity in total)
• Functional Keywords: glycoprotein, bg505, ufo, vaccine design, nanoparticle, protein design, viral protein
• Biological source: Human immunodeficiency virus 1
• Total number of polymer chains: 1
• Total formula weight: 109370.85

Authors

Antanasijevic, A.,Zhang, Y.N.,Zhu, J.,Ward, A.B. (deposition date: 2022-10-08, release date: 2023-04-19, Last modification date: 2024-06-19)

Primary citation

Zhang, Y.N.,Paynter, J.,Antanasijevic, A.,Allen, J.D.,Eldad, M.,Lee, Y.Z.,Copps, J.,Newby, M.L.,He, L.,Chavez, D.,Frost, P.,Goodroe, A.,Dutton, J.,Lanford, R.,Chen, C.,Wilson, I.A.,Crispin, M.,Ward, A.B.,Zhu, J.
Single-component multilayered self-assembling protein nanoparticles presenting glycan-trimmed uncleaved prefusion optimized envelope trimmers as HIV-1 vaccine candidates.
Nat Commun, 14:1985-1985, 2023

PubMed Abstract: Uncleaved prefusion-optimized (UFO) design can stabilize diverse HIV-1 envelope glycoproteins (Envs). Single-component, self-assembling protein nanoparticles (1c-SApNP) can display 8 or 20 native-like Env trimers as vaccine candidates. We characterize the biophysical, structural, and antigenic properties of 1c-SApNPs that present the BG505 UFO trimer with wildtype and modified glycans. For 1c-SApNPs, glycan trimming improves recognition of the CD4 binding site without affecting broadly neutralizing antibodies (bNAbs) to major glycan epitopes. In mice, rabbits, and nonhuman primates, glycan trimming increases the frequency of vaccine responders (FVR) and steers antibody responses away from immunodominant glycan holes and glycan patches. The mechanism of vaccine-induced immunity is examined in mice. Compared with the UFO trimer, the multilayered E2p and I3-01v9 1c-SApNPs show 420 times longer retention in lymph node follicles, 20-32 times greater presentation on follicular dendritic cell dendrites, and up-to-4 times stronger germinal center reactions. These findings can inform future HIV-1 vaccine development.

PubMed: 37031217
DOI: 10.1038/s41467-023-37742-z

Experimental method

ELECTRON MICROSCOPY (3.7 Å)