ArticlePLoS pathogens2015
Vaccine-Elicited Tier 2 HIV-1 Neutralizing Antibodies Bind to Quaternary Epitopes Involving Glycan-Deficient Patches Proximal to the CD4 Binding Site.
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 116 papers, 1 of them a synthesis that pooled it.
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Who cites it
116 citing papers in PubMed, 1 synthesis or guideline pooled it, 145 citations in OpenAlex.
- HIV Genome-Wide Protein Associations: a Review of 30 Years of Research.Microbiology and molecular biology reviews : MMBR · 2016Pooled it
- ViralMap: predicting features in viral proteins from primary sequence.Journal of virology · 2026Article
- Diverse germline-targeting HIV Env immunogens select for distinct mutations in the same knock-in mice B cell receptors.Nature communications · 2026Article
- Dissecting Uricase Immunogenicity: Unveiling the Role of Quaternary Epitopes through In Silico Analysis : Quaternary Epitope Insights in Uricase Immunogenicity.Galen medical journal · 2025Article
- Assessing bnAb potency in the context of HIV-1 envelope conformational plasticity.PLoS pathogens · 2025Article
- Inducible cell lines producing replication-defective human immunodeficiency virus particles containing envelope glycoproteins stabilized in a pretriggered conformation.Journal of virology · 2024Article
- Engineering immunogens that select for specific mutations in HIV broadly neutralizing antibodies.Nature communications · 2024Article
- Impact of glycan depletion, glycan debranching and increased glycan charge on HIV-1 neutralization sensitivity and immunogenicity.Glycobiology · 2024Article
- Exploring HIV Vaccine Progress in the Pre-Clinical and Clinical Setting: From History to Future Prospects.Viruses · 2024Review
- Microsecond dynamics control the HIV-1 Envelope conformation.Science advances · 2024Article
- Impact of stabilizing mutations on the antigenic profile and glycosylation of membrane-expressed HIV-1 envelope glycoprotein.PLoS pathogens · 2023Article
- HIV-1 neutralizing antibodies elicited in humans by a prefusion-stabilized envelope trimer form a reproducible class targeting fusion peptide.Cell reports · 2023Article
- Single-component multilayered self-assembling protein nanoparticles presenting glycan-trimmed uncleaved prefusion optimized envelope trimmers as HIV-1 vaccine candidates.Nature communications · 2023Article
- An engineered HIV-1 Gag-based VLP displaying high antigen density induces strong antibody-dependent functional immune responses.NPJ vaccines · 2023Article
- Characterization of the Human Immunodeficiency Virus (HIV-1) Envelope Glycoprotein Conformational States on Infectious Virus Particles.Journal of virology · 2023Article
- HIV-1 prehairpin intermediate inhibitors show efficacy independent of neutralization tier.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- mRNA-encoded HIV-1 Env trimer ferritin nanoparticles induce monoclonal antibodies that neutralize heterologous HIV-1 isolates in mice.Cell reports · 2022Article
- High thermostability improves neutralizing antibody responses induced by native-like HIV-1 envelope trimers.NPJ vaccines · 2022Article
- Cross-Neutralizing CRF01_AE-Infected Plasma from Malaysia Targets CD4-Binding Site of Human Immunodeficiency Virus Type-1 Envelope Glycoprotein.AIDS research and human retroviruses · 2022Article
- Engineering well-expressed, V2-immunofocusing HIV-1 envelope glycoprotein membrane trimers for use in heterologous prime-boost vaccine regimens.PLoS pathogens · 2021Article
56 more citing papers are in PubMed but not listed here.
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Authors and funding
26 authors at 10 institutions in 3 countries.
Funding
Abstract
Eliciting broad tier 2 neutralizing antibodies (nAbs) is a major goal of HIV-1 vaccine research. Here we investigated the ability of native, membrane-expressed JR-FL Env trimers to elicit nAbs. Unusually potent nAb titers developed in 2 of 8 rabbits immunized with virus-like particles (VLPs) expressing trimers (trimer VLP sera) and in 1 of 20 rabbits immunized with DNA expressing native Env trimer, followed by a protein boost (DNA trimer sera). All 3 sera neutralized via quaternary epitopes and exploited natural gaps in the glycan defenses of the second conserved region of JR-FL gp120. Specifically, trimer VLP sera took advantage of the unusual absence of a glycan at residue 197 (present in 98.7% of Envs). Intriguingly, removing the N197 glycan (with no loss of tier 2 phenotype) rendered 50% or 16.7% (n = 18) of clade B tier 2 isolates sensitive to the two trimer VLP sera, showing broad neutralization via the surface masked by the N197 glycan. Neutralizing sera targeted epitopes that overlap with the CD4 binding site, consistent with the role of the N197 glycan in a putative "glycan fence" that limits access to this region. A bioinformatics analysis suggested shared features of one of the trimer VLP sera and monoclonal antibody PG9, consistent with its trimer-dependency. The neutralizing DNA trimer serum took advantage of the absence of a glycan at residue 230, also proximal to the CD4 binding site and suggesting an epitope similar to that of monoclonal antibody 8ANC195, albeit lacking tier 2 breadth. Taken together, our data show for the first time that strain-specific holes in the glycan fence can allow the development of tier 2 neutralizing antibodies to native spikes. Moreover, cross-neutralization can occur in the absence of protecting glycan. Overall, our observations provide new insights that may inform the future development of a neutralizing antibody vaccine.
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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.