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Structure paper

TitleImmunofocusing on the conserved fusion peptide of HIV envelope glycoprotein in rhesus macaques.
Journal, issue, pagesbioRxiv, Year 2024
Publish dateNov 29, 2024
AuthorsPayal P Pratap / Christopher A Cottrell / James Quinn / Diane G Carnathan / Daniel L V Bader / Andy S Tran / Chiamaka A Enemuo / Julia T Ngo / Sara T Richey / Hongmei Gao / Xiaoying Shen / Kelli M Greene / Jonathan Hurtado / Katarzyna Kaczmarek Michaels / Elana Ben-Akiva / Joel D Allen / Gabriel Ozorowski / Max Crispin / Bryan Briney / David Montefiori / Guido Silvestri / Darrell J Irvine / Shane Crotty / Andrew B Ward
PubMed AbstractDuring infection, the fusion peptide (FP) of HIV envelope glycoprotein (Env) serves a central role in viral fusion with the host cell. As such, the FP is highly conserved and therefore an attractive ...During infection, the fusion peptide (FP) of HIV envelope glycoprotein (Env) serves a central role in viral fusion with the host cell. As such, the FP is highly conserved and therefore an attractive epitope for vaccine design. Here, we describe a vaccination study in non-human primates (NHPs) where glycan deletions were made on soluble HIV Env to increase FP epitope exposure. When delivered via implantable osmotic pumps, this immunogen primed immune responses against the FP, which were then boosted with heterologous trimers resulting in a focused immune response targeting the conserved FP epitope. Although autologous immunizations did not elicit high affinity FP-targeting antibodies, the conserved FP epitope on a heterologous trimer further matured the lower affinity, FP-targeting B cells. This study suggests using epitope conservation strategies on distinct Env trimer immunogens can focus humoral responses on desired neutralizing epitopes and suppress immune-distracting antibody responses against non-neutralizing epitopes.
External linksbioRxiv / PubMed:39651156 / PubMed Central
MethodsEM (single particle)
Resolution3.0 - 25.0 Å
Structure data

EMDB-49411, PDB-9nhh:
AMC016 v4.2 in complex with pAb Base-A isolated from animal RQk18 at week 43
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-49412, PDB-9nhi:
AMC016 v4.2 in complex with Base-C pAb isolated from animal RQk18 at week 43
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-49413, PDB-9nhj:
AMC016 v4.2 in complex with FP-A pAb from animal RQk18 at week 43
Method: EM (single particle) / Resolution: 3.04 Å

EMDB-49414, PDB-9nhk:
BG505-CH505 Env glycoprotein in complex with NHP pAb Base-4 isolated from animal RUu18 at week 14
Method: EM (single particle) / Resolution: 4.1 Å

EMDB-49415, PDB-9nhl:
BG505-CH505 Env glycoprotein in complex with NHP pAb FP-1 isolated from animal RUu18 at week 14
Method: EM (single particle) / Resolution: 3.7 Å

EMDB-49416, PDB-9nhm:
BG505-CH505 Env glycoprotein in complex with NHP pAb V1V2V3-1 isolated from animal RUu18 at week 14
Method: EM (single particle) / Resolution: 4.0 Å

EMDB-49417, PDB-9nhn:
BG505-CH505 Env glycoprotein in complex with NHP pAb V1V2V3-2 isolated from animal RUu18 at week 14
Method: EM (single particle) / Resolution: 3.9 Å

EMDB-49418, PDB-9nho:
BG505-CH505 Env glycoprotein in complex with NHP pAb V1V2V3-5 isolated from animal RUu18 at week 14
Method: EM (single particle) / Resolution: 3.8 Å

EMDB-49457, PDB-9ni9:
BG505-CH505 Env glycoprotein in complex with NHP pAb Base-1 isolated from animal RUu18 at week 14
Method: EM (single particle) / Resolution: 3.8 Å

EMDB-70702: nsEM map of macaque RUu18 week 4 polyclonal Fab in complex with BG505-CH505+N241
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-70703: nsEM map of macaque RMu18 week 4 polyclonal Fab in complex with BG505-CH505+N241
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-70704: nsEM map of macaque RQk18 week 4 polyclonal Fab in complex with BG505-CH505dN241
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-70705: nsEM map of macaque LJ66 week 4 polyclonal Fab in complex with BG505-CH505dN241
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-70706: nsEM map of macaque RUu18 week 14 polyclonal Fab in complex with BG505-CH505+N241
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-70707: nsEM map of macaque RMu18 week 14 polyclonal Fab in complex with BG505-CH505+N241
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-70708: nsEM map of macaque RQk18 week 14 polyclonal Fab in complex with BG505-CH505+N241
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-70709: nsEM map of macaque LJ66 week 14 polyclonal Fab in complex with BG505-CH505+N241
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-70710: nsEM map of macaque RUu18 week 28 polyclonal Fab in complex with BG505-CH505+N241
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-70711: nsEM map of macaque RMu18 week 28 polyclonal Fab in complex with BG505-CH505+N241
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-70712: nsEM map of macaque RQk18 week 28 polyclonal Fab in complex with AMC016
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-70713: nsEM map of macaque LJ66 week 28 polyclonal Fab in complex with AMC016
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-70714: nsEM map of macaque RUu18 week 43 polyclonal Fab in complex with AMC016
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-70715: nsEM map of macaque RMu18 week 43 polyclonal Fab in complex with AMC016
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-70716: nsEM map of macaque RQk18 week 43 polyclonal Fab in complex with AMC016
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-70717: nsEM map of macaque LJ66 week 43 polyclonal Fab in complex with AMC016
Method: EM (single particle) / Resolution: 25.0 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • human immunodeficiency virus 1
  • macaca mulatta (Rhesus monkey)
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / HIV-1 / polyclonal / cryoEMPEM / STRUCTURAL PROTEIN / VIRAL PROTEIN-IMMUNE SYSTEM complex

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