8g4m
Vaccine-elicited human antibody 2C06 in complex with HIV-1 envelope trimer BG505 DS-SOSIP
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 PubMedElicitation of antibodies that neutralize the tier-2 neutralization-resistant isolates that typify HIV-1 transmission has been a long-sought goal. Success with prefusion-stabilized envelope trimers eliciting autologous neutralizing antibodies has been reported in multiple vaccine-test species, though not in humans. To investigate elicitation of HIV-1 neutralizing antibodies in humans, here, we analyze B cells from a phase I clinical trial of the "DS-SOSIP"-stabilized envelope trimer from strain BG505, identifying two antibodies, N751-2C06.01 and N751-2C09.01 (named for donor-lineage.clone), that neutralize the autologous tier-2 strain, BG505. Though derived from distinct lineages, these antibodies form a reproducible antibody class that targets the HIV-1 fusion peptide. Both antibodies are highly strain specific, which we attribute to their partial recognition of a BG505-specific glycan hole and to their binding requirements for a few BG505-specific residues. Prefusion-stabilized envelope trimers can thus elicit autologous tier-2 neutralizing antibodies in humans, with initially identified neutralizing antibodies recognizing the fusion-peptide site of vulnerability. HIV-1 neutralizing antibodies elicited in humans by a prefusion-stabilized envelope trimer form a reproducible class targeting fusion peptide.,Wang S, Matassoli F, Zhang B, Liu T, Shen CH, Bylund T, Johnston T, Henry AR, Teng IT, Tripathi P, Becker JE, Changela A, Chaudhary R, Cheng C, Gaudinski M, Gorman J, Harris DR, Lee M, Morano NC, Novik L, O'Dell S, Olia AS, Parchment DK, Rawi R, Roberts-Torres J, Stephens T, Tsybovsky Y, Wang D, Van Wazer DJ, Zhou T, Doria-Rose NA, Koup RA, Shapiro L, Douek DC, McDermott AB, Kwong PD Cell Rep. 2023 Jul 25;42(7):112755. doi: 10.1016/j.celrep.2023.112755. Epub 2023 , Jul 11. PMID:37436899[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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