ArticleProceedings of the National Academy of Sciences of the United States of America2014
Vaccine-elicited primate antibodies use a distinct approach to the HIV-1 primary receptor binding site informing vaccine redesign.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 61 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
61 citing papers in PubMed, 71 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
- Rational design of flavivirus E protein vaccine optimizes immunogenicity and mitigates antibody dependent enhancement risk.Nature communications · 2025Article
- Membrane HIV-1 envelope glycoproteins stabilized more strongly in a pretriggered conformation than natural virus Envs.iScience · 2024Article
- Sampling and Scoring in Protein-Protein Docking.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Induction of cross-neutralizing antibodies by a permuted hepatitis C virus glycoprotein nanoparticle vaccine candidate.Nature communications · 2022Article
- Epitope Mapping of Therapeutic Antibodies Targeting Human LAG3.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- From structure to sequence: Antibody discovery using cryoEM.Science advances · 2022Article
- Senecavirus A Entry Into Host Cells Is Dependent on the Cholesterol-Mediated Endocytic Pathway.Frontiers in veterinary science · 2022Article
- Polyclonal antibody responses to HIV Env immunogens resolved using cryoEM.Nature communications · 2021Article
- To bnAb or Not to bnAb: Defining Broadly Neutralising Antibodies Against HIV-1.Frontiers in immunology · 2021Review
- HIV-1 gp120-CD4-Induced Antibody Complex Elicits CD4 Binding Site-Specific Antibody Response in Mice.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Strategies for inducing effective neutralizing antibody responses against HIV-1.Expert review of vaccines · 2019Review
- Star nanoparticles delivering HIV-1 peptide minimal immunogens elicit near-native envelope antibody responses in nonhuman primates.PLoS biology · 2019Article
- The HIV-1 Envelope Glycoprotein C3/V4 Region Defines a Prevalent Neutralization Epitope following Immunization.Cell reports · 2019Article
- HIV-1 immunogens and strategies to drive antibody responses towards neutralization breadth.Retrovirology · 2018Review
- Production of complex viral glycoproteins in plants as vaccine immunogens.Plant biotechnology journal · 2018Review
- Recent advances in retroviruses via cryo-electron microscopy.Retrovirology · 2018Review
- The adjuvant AlhydroGel elicits higher antibody titres than AddaVax when combined with HIV-1 subtype C gp140 from CAP256.PloS one · 2018Article
- HIV-1 Cross-Reactive Primary Virus Neutralizing Antibody Response Elicited by Immunization in Nonhuman Primates.Journal of virology · 2017Article
- Targeted N-glycan deletion at the receptor-binding site retains HIV Env NFL trimer integrity and accelerates the elicited antibody response.PLoS pathogens · 2017Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
- Erratum issuedde Val Alda, Natalia [corrected to de Val, Natalia]
Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
Abstract
HIV-1 neutralization requires Ab accessibility to the functional envelope glycoprotein (Env) spike. We recently reported the isolation of previously unidentified vaccine-elicited, CD4 binding site (CD4bs)-directed mAbs from rhesus macaques immunized with soluble Env trimers, indicating that this region is immunogenic in the context of subunit vaccination. To elucidate the interaction of the trimer-elicited mAbs with gp120 and their insufficient interaction with the HIV-1 primary isolate spike, we crystallized the Fab fragments of two mAbs, GE136 and GE148. Alanine scanning of their complementarity-determining regions, coupled with epitope scanning of their epitopes on gp120, revealed putative contact residues at the Ab/gp120 interface. Docking of the GE136 and GE148 Fabs to gp120, coupled with EM reconstructions of these nonbroadly neutralizing mAbs (non-bNAbs) binding to gp120 monomers and EM modeling to well-ordered trimers, suggested Ab approach to the CD4bs by a vertical angle of access relative to the more lateral mode of interaction used by the CD4bs-directed bNAbs VRC01 and PGV04. Fitting the structures into the available cryo-EM native spike density indicated clashes between these two vaccine-elicited mAbs and the topside variable region spike cap, whereas the bNAbs duck under this quaternary shield to access the CD4bs effectively on primary HIV isolates. These results provide a structural basis for the limited neutralizing breadth observed by current vaccine-induced, CD4bs-directed Abs and highlight the need for better ordered trimer immunogens. The analysis presented here therefore provides valuable information to guide HIV-1 vaccine immunogen redesign.
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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.