8g4m › Citations

HIV-1 neutralizing antibodies elicited in humans by a prefusion-stabilized envelope trimer form a reproducible class targeting fusion peptide.

<div class='caption-title'>(A) VRC 018 clinical regimen and a flowchart for B cell sorting and antibody screening.</div>
<div class='caption-title'>(A) Cartoon representation of 2C06 in complex with BG505 DS-SOSIP. 2C06 bound at the fusion-peptide site and interacted with fusion peptide (FP), shown in red. Antibody heavy chain (H) is shown in blue, light chain (L) in pale cyan, gp41 in dark gray, and gp120 in light gray.</div>
<div class='caption-title'>(A) Cartoon representation of 2C09 Fab in complex with BG505 DS-SOSIP. 2C09 bound at the fusion-peptide site and interacted with fusion peptide extensively. Heavy chain (H) is shown in orange, light chain (L) in yellow-orange, fusion peptide (FP) in red, the rest of gp41 in darker gray, and gp120 in lighter gray.</div>
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
OpenAccess logo Cell Rep 42 112755 (2023)
Cited: 7 times
EuropePMC logo PMID: 37436899

Abstract

Elicitation 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.

Articles - 8g4m mentioned but not cited (1)

  1. 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 42 112755 (2023)


Reviews citing this publication (2)

  1. Beyond glycan barriers: non-cognate ligands and protein mimicry approaches to elicit broadly neutralizing antibodies for HIV-1. Walimbwa SI, Maly P, Kafkova LR, Raska M. J Biomed Sci 31 83 (2024)
  2. Cryo-electron microscopy in the study of virus entry and infection. Dutta M, Acharya P. Front Mol Biosci 11 1429180 (2024)

Articles citing this publication (4)



Quick links