8sw7
BG505 Boost2 SOSIP.664 in complex with NHP polyclonal antibody FP1
Structural highlights
FunctionQ2N0S6_9HIV1 The envelope glyprotein gp160 precursor down-modulates cell surface CD4 antigen by interacting with it in the endoplasmic reticulum and blocking its transport to the cell surface (By similarity).[RuleBase:RU004292][SAAS:SAAS000328_004_020447] The gp120-gp41 heterodimer allows rapid transcytosis of the virus through CD4 negative cells such as simple epithelial monolayers of the intestinal, rectal and endocervical epithelial barriers. Both gp120 and gp41 specifically recognize glycosphingolipids galactosyl-ceramide (GalCer) or 3' sulfo-galactosyl-ceramide (GalS) present in the lipid rafts structures of epithelial cells. Binding to these alternative receptors allows the rapid transcytosis of the virus through the epithelial cells. This transcytotic vesicle-mediated transport of virions from the apical side to the basolateral side of the epithelial cells does not involve infection of the cells themselves (By similarity).[SAAS:SAAS000328_004_240990] Publication Abstract from PubMedImmunodominance 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. Focusing antibody responses to the fusion peptide in rhesus macaques.,Cottrell CA, Pratap PP, Cirelli KM, Carnathan DG, Enemuo CA, Antanasijevic A, Ozorowski G, Sewall LM, Gao H, Greene KM, Allen JD, Ngo JT, Choe Y, Nogal B, Silva M, Bhiman J, Pauthner M, Irvine DJ, Montefiori D, Crispin M, Burton DR, Silvestri G, Crotty S, Ward AB bioRxiv [Preprint]. 2023 Jun 27:2023.06.26.545779. doi: , 10.1101/2023.06.26.545779. PMID:37425865[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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