ArticlePLoS pathogens2015
Well-ordered trimeric HIV-1 subtype B and C soluble spike mimetics generated by negative selection display native-like properties.
Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed, 101 citations in OpenAlex.
- Article
- A modification to heptad repeat 1 of gp41 improves yield and/or quality of soluble pre-fusion HIV-1 envelope glycoprotein trimers.Journal of virology · 2025Article
- Immunofocusing on the conserved fusion peptide of HIV envelope glycoprotein in rhesus macaques.NPJ vaccines · 2025Article
- Article
- Immunofocusing on the conserved fusion peptide of HIV envelope glycoprotein in rhesus macaques.bioRxiv : the preprint server for biology · 2025Article
- Antigen persistence and TLR stimulation contribute to induction of a durable HIV-1-specific neutralizing antibody response.Nature communications · 2025Article
- Exploring distinct modes of inter-spike cross-linking for enhanced neutralization by SARS-CoV-2 antibodies.Nature communications · 2024Article
- Membrane HIV-1 envelope glycoproteins stabilized more strongly in a pretriggered conformation than natural virus Envs.iScience · 2024Article
- RAIN: machine learning-based identification for HIV-1 bNAbs.Nature communications · 2024Article
- Current methods for detecting and assessing HIV-1 antibody resistance.Frontiers in immunology · 2024Review
- Oriented display of HIV-1 Env trimers by a novel coupling strategy enhances B cell activation and phagocytosis.Frontiers in immunology · 2024Article
- mRNA lipid nanoparticles expressing cell-surface cleavage independent HIV Env trimers elicit autologous tier-2 neutralizing antibodies.Frontiers in immunology · 2024Article
- Assessing immunogenicity barriers of the HIV-1 envelope trimer.NPJ vaccines · 2023Article
- Fusion of the molecular adjuvant C3d to cleavage-independent native-like HIV-1 Env trimers improves the elicited antibody response.Frontiers in immunology · 2023Article
- An HIV-1 broadly neutralizing antibody overcomes structural and dynamic variation through highly focused epitope targeting.Npj viruses · 2023Article
- Augmenting glycosylation-directed folding pathways enhances the fidelity of HIV Env immunogen production in plants.Biotechnology and bioengineering · 2022Article
- Functional and Highly Cross-Linkable HIV-1 Envelope Glycoproteins Enriched in a Pretriggered Conformation.Journal of virology · 2022Article
- Structure-guided changes at the V2 apex of HIV-1 clade C trimer enhance elicitation of autologous neutralizing and broad V1V2-scaffold antibodies.Cell reports · 2022Article
- High thermostability improves neutralizing antibody responses induced by native-like HIV-1 envelope trimers.NPJ vaccines · 2022Article
- Asymmetric Structures and Conformational Plasticity of the Uncleaved Full-Length Human Immunodeficiency Virus Envelope Glycoprotein Trimer.Journal of virology · 2021Article
23 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The structure of BG505 gp140 SOSIP, a soluble mimic of the native HIV-1 envelope glycoprotein (Env), marks the beginning of new era in Env structure-based immunogen design. Displaying a well-ordered quaternary structure, these subtype A-derived trimers display an excellent antigenic profile, discriminating recognition by broadly neutralizing antibodies (bNAbs) from non-broadly neutralizing antibodies (non-bNAbs), and provide a solid Env-based immunogenic platform starting point. Even with this important advance, obtaining homogeneous well-ordered soluble SOSIP trimers derived from other subtypes remains challenging. Here, we report the "rescue" of homogeneous well-ordered subtype B and C SOSIP trimers from a heterogeneous Env mixture using CD4 binding site-directed (CD4bs) non-bNAbs in a negative-selection purification process. These non-bNAbs recognize the primary receptor CD4bs only on disordered trimers but not on the native Env spike or well-ordered soluble trimers due to steric hindrance. Following negative selection to remove disordered oligomers, we demonstrated recovery of well-ordered, homogeneous trimers by electron microscopy (EM). We obtained 3D EM reconstructions of unliganded trimers, as well as in complex with sCD4, a panel of CD4bs-directed bNAbs, and the cleavage-dependent, trimer-specific bNAb, PGT151. Using bio-layer light interferometry (BLI) we demonstrated that the well-ordered trimers were efficiently recognized by bNAbs and poorly recognized by non-bNAbs, representing soluble mimics of the native viral spike. Biophysical characterization was consistent with the thermostability of a homogeneous species that could be further stabilized by specific bNAbs. This study revealed that Env trimers generate different frequencies of well-ordered versus disordered aberrant trimers even when they are genetically identical. By negatively selecting the native-like well-ordered trimers, we establish a new means to obtain soluble Env mimetics derived from subtypes B and C for expanded use as candidate vaccine immunogens.
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