In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 18, No. 11 ( 2022-11-17), p. e1010945-
Abstract:
Broadly neutralizing antibodies (bNAbs) have remarkable breadth and potency against most HIV-1 subtypes and are able to prevent HIV-1 infection in animal models. However, bNAbs are extremely difficult to induce by vaccination. Defining the developmental pathways towards neutralization breadth can assist in the design of strategies to elicit protective bNAb responses by vaccination. Here, HIV-1 envelope glycoproteins (Env)-specific IgG + B cells were isolated at various time points post infection from an HIV-1 infected elite neutralizer to obtain monoclonal antibodies (mAbs). Multiple antibody lineages were isolated targeting distinct epitopes on Env, including the gp120-gp41 interface, CD4-binding site, silent face and V3 region. The mAbs each neutralized a diverse set of HIV-1 strains from different clades indicating that the patient’s remarkable serum breadth and potency might have been the result of a polyclonal mixture rather than a single bNAb lineage. High-resolution cryo-electron microscopy structures of the neutralizing mAbs (NAbs) in complex with an Env trimer generated from the same individual revealed that the NAbs used multiple strategies to neutralize the virus; blocking the receptor binding site, binding to HIV-1 Env N-linked glycans, and disassembly of the trimer. These results show that diverse NAbs can complement each other to achieve a broad and potent neutralizing serum response in HIV-1 infected individuals. Hence, the induction of combinations of moderately broad NAbs might be a viable vaccine strategy to protect against a wide range of circulating HIV-1 viruses.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1010945
DOI:
10.1371/journal.ppat.1010945.g001
DOI:
10.1371/journal.ppat.1010945.g002
DOI:
10.1371/journal.ppat.1010945.g003
DOI:
10.1371/journal.ppat.1010945.g004
DOI:
10.1371/journal.ppat.1010945.g005
DOI:
10.1371/journal.ppat.1010945.g006
DOI:
10.1371/journal.ppat.1010945.g007
DOI:
10.1371/journal.ppat.1010945.s001
DOI:
10.1371/journal.ppat.1010945.s002
DOI:
10.1371/journal.ppat.1010945.s003
DOI:
10.1371/journal.ppat.1010945.s004
DOI:
10.1371/journal.ppat.1010945.s005
DOI:
10.1371/journal.ppat.1010945.s006
DOI:
10.1371/journal.ppat.1010945.s007
DOI:
10.1371/journal.ppat.1010945.s008
DOI:
10.1371/journal.ppat.1010945.s009
DOI:
10.1371/journal.ppat.1010945.s010
DOI:
10.1371/journal.ppat.1010945.s011
DOI:
10.1371/journal.ppat.1010945.s012
DOI:
10.1371/journal.ppat.1010945.s013
DOI:
10.1371/journal.ppat.1010945.s014
DOI:
10.1371/journal.ppat.1010945.r001
DOI:
10.1371/journal.ppat.1010945.r002
DOI:
10.1371/journal.ppat.1010945.r003
DOI:
10.1371/journal.ppat.1010945.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2205412-1
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