ArticleThe Journal of biological chemistry2017
Structure-based Design of Cyclically Permuted HIV-1 gp120 Trimers That Elicit Neutralizing Antibodies.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 16 citations in OpenAlex.
- Immunogenicity and protection mediated by dmLT and alum adjuvants for an HIV-1 vaccine.Frontiers in immunology · 2025Article
- Multiplexed Epitope Mapping of HIV-1 Neutralizing Antibodies by Coupling Chemical Labeling of Cysteines to Deep Sequencing.Methods in molecular biology (Clifton, N.J.) · 2025Article
- A clade C HIV-1 vaccine protects against heterologous SHIV infection by modulating IgG glycosylation and T helper response in macaques.Science immunology · 2022Article
- Immunogenicity and Protective Efficacy of a Highly Thermotolerant, Trimeric SARS-CoV-2 Receptor Binding Domain Derivative.ACS infectious diseases · 2021Article
- A facile method of mapping HIV-1 neutralizing epitopes using chemically masked cysteines and deep sequencing.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Probing the Structure of the HIV-1 Envelope Trimer Using Aspartate Scanning Mutagenesis.Journal of virology · 2020Article
- VapC21 Toxin Contributes to Drug-Tolerance and Interacts With Non-cognate VapB32 Antitoxin inFrontiers in microbiology · 2020Article
- HIV-1 vaccination by needle-free oral injection induces strong mucosal immunity and protects against SHIV challenge.Nature communications · 2019Article
- Design, display and immunogenicity of HIV1 gp120 fragment immunogens on virus-like particles.Vaccine · 2018Article
- Bacterially expressed HIV-1 gp120 outer-domain fragment immunogens with improved stability and affinity for CD4-binding site neutralizing antibodies.The Journal of biological chemistry · 2018Article
- A Trimeric HIV-1 Envelope gp120 Immunogen Induces Potent and Broad Anti-V1V2 Loop Antibodies against HIV-1 in Rabbits and Rhesus Macaques.Journal of virology · 2018Article
- Design of a highly thermotolerant, immunogenic SARS-CoV-2 spike fragment.The Journal of biological chemistryArticle
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
A major goal for HIV-1 vaccine development is an ability to elicit strong and durable broadly neutralizing antibody (bNAb) responses. The trimeric envelope glycoprotein (Env) spikes on HIV-1 are known to contain multiple epitopes that are susceptible to bNAbs isolated from infected individuals. Nonetheless, all trimeric and monomeric Env immunogens designed to date have failed to elicit such antibodies. We report the structure-guided design of HIV-1 cyclically permuted gp120 that forms homogeneous, stable trimers, and displays enhanced binding to multiple bNAbs, including VRC01, VRC03, VRC-PG04, PGT128, and the quaternary epitope-specific bNAbs PGT145 and PGDM1400. Constructs that were cyclically permuted in the V1 loop region and contained an N-terminal trimerization domain to stabilize V1V2-mediated quaternary interactions, showed the highest homogeneity and the best antigenic characteristics. In guinea pigs, a DNA prime-protein boost regimen with these new gp120 trimer immunogens elicited potent neutralizing antibody responses against highly sensitive Tier 1A isolates and weaker neutralizing antibody responses with an average titer of about 115 against a panel of heterologous Tier 2 isolates. A modest fraction of the Tier 2 virus neutralizing activity appeared to target the CD4 binding site on gp120. These results suggest that cyclically permuted HIV-1 gp120 trimers represent a viable platform in which further modifications may be made to eventually achieve protective bNAb responses.
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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.