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TitleSingle-component multilayered self-assembling protein nanoparticles presenting glycan-trimmed uncleaved prefusion optimized envelope trimmers as HIV-1 vaccine candidates.
Journal, issue, pagesNat Commun, Vol. 14, Issue 1, Page 1985, Year 2023
Publish dateApr 8, 2023
AuthorsYi-Nan Zhang / Jennifer Paynter / Aleksandar Antanasijevic / Joel D Allen / Mor Eldad / Yi-Zong Lee / Jeffrey Copps / Maddy L Newby / Linling He / Deborah Chavez / Pat Frost / Anna Goodroe / John Dutton / Robert Lanford / Christopher Chen / Ian A Wilson / Max Crispin / Andrew B Ward / Jiang Zhu /
PubMed AbstractUncleaved 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- ...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.
External linksNat Commun / PubMed:37031217 / PubMed Central
MethodsEM (single particle)
Resolution3.7 - 10.4 Å
Structure data

EMDB-28540, PDB-8eqn:
BG505 UFO-E2p-L4P nanoparticle reconstructed by focused refinement with a mask around the nanoparticle core
Method: EM (single particle) / Resolution: 3.7 Å

EMDB-28541: BG505 UFO trimer map reconstructed from BG505 UFO-E2p-L4P nanoparticle by localized reconstruction
Method: EM (single particle) / Resolution: 7.4 Å

EMDB-28542: BG505 UFO-10GS-I3-01v9-L7P nanoparticle reconstructed by focused refinement with a mask around the nanoparticle core
Method: EM (single particle) / Resolution: 6.0 Å

EMDB-28543: BG505 UFO trimer map reconstructed from BG505 UFO-10GS-I3-01v9-L7P nanoparticle by localized reconstruction
Method: EM (single particle) / Resolution: 10.4 Å

Source
  • human immunodeficiency virus 1
KeywordsVIRAL PROTEIN / glycoprotein / BG505 / UFO / vaccine design / nanoparticle / protein design

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