1. HIV-1 neutralizing antibodies elicited in humans by a prefusion-stabilized envelope trimer form a reproducible class targeting fusion peptide.
- Author
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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, and Kwong PD
- Subjects
- Humans, Antibodies, Neutralizing, env Gene Products, Human Immunodeficiency Virus, HIV Antibodies, Peptides, AIDS Vaccines, HIV Infections, HIV Seropositivity, HIV-1
- 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., Competing Interests: Declaration of interests The authors declare no competing interests., (Published by Elsevier Inc.)
- Published
- 2023
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