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TitleFocusing antibody responses to the fusion peptide in rhesus macaques.
Journal, issue, pagesbioRxiv, Year 2023
Publish dateJun 27, 2023
AuthorsChristopher A Cottrell / Payal P Pratap / Kimberly M Cirelli / Diane G Carnathan / Chiamaka A Enemuo / Aleksandar Antanasijevic / Gabriel Ozorowski / Leigh M Sewall / Hongmei Gao / Kelli M Greene / Joel D Allen / Julia T Ngo / Yury Choe / Bartek Nogal / Murillo Silva / Jinal Bhiman / Matthias Pauthner / Darrell J Irvine / David Montefiori / Max Crispin / Dennis R Burton / Guido Silvestri / Shane Crotty / Andrew B Ward /
PubMed AbstractImmunodominance of antibodies targeting non-neutralizing epitopes and the high level of somatic hypermutation within germinal centers (GCs) required for most HIV broadly neutralizing antibodies ...Immunodominance of antibodies targeting non-neutralizing epitopes and the high level of somatic hypermutation within germinal centers (GCs) required for most HIV broadly neutralizing antibodies (bnAbs) are major impediments to the development of an effective HIV vaccine. Rational protein vaccine design and non-conventional immunization strategies are potential avenues to overcome these hurdles. Here, we report using implantable osmotic pumps to continuously deliver a series of epitope-targeted immunogens to rhesus macaques over the course of six months to elicit immune responses against the conserved fusion peptide. Antibody specificities and GC responses were tracked longitudinally using electron microscopy polyclonal epitope mapping (EMPEM) and lymph node fine-needle aspirates, respectively. Application of cryoEMPEM delineated key residues for on-target and off-target responses that can drive the next round of structure-based vaccine design.
External linksbioRxiv / PubMed:37425865 / PubMed Central
MethodsEM (single particle)
Resolution3.73 - 4.5 Å
Structure data

EMDB-40803: BG505 Boost2 SOSIP.664 in complex with NHP polyclonal antibody FP2
Method: EM (single particle) / Resolution: 4.4 Å

EMDB-40804: BG505 Boost2 SOSIP.664 in complex with NHP Polyclonal Antibody FP4
Method: EM (single particle) / Resolution: 4.5 Å

EMDB-40805: BG505 Boost 2 in complex with NHP antibody V1V2
Method: EM (single particle) / Resolution: 4.2 Å

EMDB-40806: BG505 Boost 2 in complex with NHP Polyclonal Antibody N625
Method: EM (single particle) / Resolution: 4.2 Å

EMDB-40807: BG505 Boost2 SOSIP.664 in complex with NHP polyclonal antibody Base1
Method: EM (single particle) / Resolution: 4.2 Å

EMDB-40808: Boost 2 SOSIP.664 in complex with NHP polyclonal antibody Base2
Method: EM (single particle) / Resolution: 4.32 Å

EMDB-40809: BG505 Boost2 SOSIP.664 in complex with NHP polyclonal antibody Base3
Method: EM (single particle) / Resolution: 4.17 Å

40810

8sw7

EMDB-40810, PDB-8sw7:
BG505 Boost2 SOSIP.664 in complex with NHP polyclonal antibody FP1
Method: EM (single particle) / Resolution: 3.73 Å

Chemicals

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

Source
  • human immunodeficiency virus 1
  • Unspecified (others)
  • macaca mulatta (Rhesus monkey)
KeywordsVIRAL PROTEIN/Immune System / HIV-1 / Env / NHP / Antibody / Fusion Peptide / Polyclonal / VIRAL PROTEIN / VIRAL PROTEIN-Immune System complex

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