ArticlePLoS pathogens2014
HIV-1 receptor binding site-directed antibodies using a VH1-2 gene segment orthologue are activated by Env trimer immunization.
Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 25 citations in OpenAlex.
- Boosting of HIV envelope CD4 binding site antibodies with long variable heavy third complementarity determining region in the randomized double blind RV305 HIV-1 vaccine trial.PLoS pathogens · 2017Trial
- Necessity of individual VDJ-databases for annotating antibody heavy chain characteristics in non-human primates.Immunogenetics · 2025Article
- Germline-targeting HIV vaccination induces neutralizing antibodies to the CD4 binding site.Science immunology · 2024Article
- CD4 binding site immunogens elicit heterologous anti-HIV-1 neutralizing antibodies in transgenic and wild-type animals.Science immunology · 2023Article
- Structure of an influenza group 2-neutralizing antibody targeting the hemagglutinin stem supersite.Structure (London, England : 1993) · 2022Article
- From structure to sequence: Antibody discovery using cryoEM.Science advances · 2022Article
- Polyclonal antibody responses to HIV Env immunogens resolved using cryoEM.Nature communications · 2021Article
- Polyfunctional Tier 2-Neutralizing Antibodies Cloned following HIV-1 Env Macaque Immunization Mirror Native Antibodies in a Human Donor.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- VDJ Gene Usage in IgM Repertoires of Rhesus and Cynomolgus Macaques.Frontiers in immunology · 2021Article
- Identification of Structurally Related Antibodies in Antibody Sequence Databases Using Rosetta-Derived Position-Specific Scoring.Structure (London, England : 1993) · 2020Article
- HIV-1 gp120-CD4-Induced Antibody Complex Elicits CD4 Binding Site-Specific Antibody Response in Mice.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Extensive dissemination and intraclonal maturation of HIV Env vaccine-induced B cell responses.The Journal of experimental medicine · 2020Article
- Principles of Broad and Potent Antiviral Human Antibodies: Insights for Vaccine Design.Cell host & microbe · 2017Review
- Particulate Array of Well-Ordered HIV Clade C Env Trimers Elicits Neutralizing Antibodies that Display a Unique V2 Cap Approach.Immunity · 2017Article
- Evolution of B cell analysis and Env trimer redesign.Immunological reviews · 2017Review
- An HIV-1 Env-Antibody Complex Focuses Antibody Responses to Conserved Neutralizing Epitopes.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- Repertoire comparison of the B-cell receptor-encoding loci in humans and rhesus macaques by next-generation sequencing.Clinical & translational immunology · 2016Article
- HIV-1 Vaccine-elicited Antibodies Reverted to Their Inferred Naive Germline Reveal Associations between Binding Affinity and in vivo Activation.Scientific reports · 2016Article
- New approaches to HIV vaccine development.Current opinion in immunology · 2015Review
- Diverse antibody genetic and recognition properties revealed following HIV-1 envelope glycoprotein immunization.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
Broadly neutralizing antibodies (bNAbs) isolated from chronically HIV-1 infected individuals reveal important information regarding how antibodies target conserved determinants of the envelope glycoprotein (Env) spike such as the primary receptor CD4 binding site (CD4bs). Many CD4bs-directed bNAbs use the same heavy (H) chain variable (V) gene segment, VH1-2*02, suggesting that activation of B cells expressing this allele is linked to the generation of this type of Ab. Here, we identify the rhesus macaque VH1.23 gene segment to be the closest macaque orthologue to the human VH1-2 gene segment, with 92% homology to VH1-2*02. Of the three amino acids in the VH1-2*02 gene segment that define a motif for VRC01-like antibodies (W50, N58, flanking the HCDR2 region, and R71), the two identified macaque VH1.23 alleles described here encode two. We demonstrate that immunization with soluble Env trimers induced CD4bs-specific VH1.23-using Abs with restricted neutralization breadth. Through alanine scanning and structural studies of one such monoclonal Ab (MAb), GE356, we demonstrate that all three HCDRs are involved in neutralization. This contrasts to the highly potent CD4bs-directed VRC01 class of bNAb, which bind Env predominantly through the HCDR2. Also unlike VRC01, GE356 was minimally modified by somatic hypermutation, its light (L) chain CDRs were of average lengths and it displayed a binding footprint proximal to the trimer axis. These results illustrate that the Env trimer immunogen used here activates B cells encoding a VH1-2 gene segment orthologue, but that the resulting Abs interact distinctly differently with the HIV-1 Env spike compared to VRC01.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.