ArticleProceedings of the National Academy of Sciences of the United States of America2024
Prevention efficacy of the broadly neutralizing antibody VRC01 depends on HIV-1 envelope sequence features.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. 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, 19 citations in OpenAlex.
- Quantifying how HIV-1 envelope sequence features impact vaccine efficacy in the HVTN 705/HPX2008 randomised trial in southern African women.EBioMedicine · 2026Trial
- Influence of the broadly neutralizing antibody VRC01 on HIV breakthrough virus populations in antibody-mediated prevention trials.Nature communications · 2026Trial
- Trial
- Vaccination with mRNA-encoded nanoparticles drives early maturation of HIV bnAb precursors in humans.Science (New York, N.Y.) · 2025Trial
- Analytical treatment interruption among women with HIV in southern Africa who received VRC01 or placebo in the Antibody Mediated Prevention Study: ATI stakeholder engagement, implementation and early clinical data.Journal of the International AIDS Society · 2025Trial
- Prophylactic treatment with broadly neutralizing antibody VRC01 selects for escape mutants after infection in Antibody-Mediated Prevention trials.Nature microbiology · 2026Article
- Review
- Contemporary HIV-1 envelope pseudovirus panels for detecting and assessing B cell lineages with broadly neutralizing antibody potential.PLoS pathogens · 2026Article
- Current Approaches for Assessments of Neutralizing, Binding, and Effector Functions of Antibodies on the Path to Antibody-Mediated Prevention Strategies for HIV-1.Current HIV research · 2026Review
- Translating viral genetic data to PRRSV-2 cross-neutralization using machine learning.Frontiers in immunology · 2026Article
- Contemporary HIV-1 envelope pseudovirus panels for detecting and assessing B cell lineages with broadly neutralizing antibody potential.bioRxiv : the preprint server for biology · 2025Article
- The Origins and Genetic Diversity of HIV-1: Evolutionary Insights and Global Health Perspectives.International journal of molecular sciences · 2025Review
- VRC01 Selects Rare HIV Escape Mutations After Acquisition in Antibody-Mediated Prevention Trials.bioRxiv : the preprint server for biology · 2025Article
- Valid and efficient inference for nonparametric variable importance in two-phase studies.Biometrics · 2025Article
- Resistance mutations that distinguish HIV-1 envelopes with discordant VRC01 phenotypes from multi-lineage infections in the HVTN703/HPTN081 trial: implications for cross-resistance.Journal of virology · 2025Article
- Rare twin cysteine residues in the HIV-1 envelope variable region 1 link to neutralization escape and breadth development.Cell host & microbe · 2025Article
- Harnessing mRNA for the expression of monoclonal IgG and IgA in non-human primates.Frontiers in immunology · 2025Article
- Preventing perinatal HIV acquisition; current gaps and future perspectives.Current opinion in HIV and AIDS · 2024Review
- Insights from HIV-1 vaccine and passive immunization efficacy trials.Trends in molecular medicine · 2024Article
- Optimized SMRT-UMI protocol produces highly accurate sequence datasets from diverse populations-Application to HIV-1 quasispecies.Virus evolution · 2024Article
Corrections and comments
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Authors and funding
42 authors at 11 institutions in 3 countries.
Funding
Abstract
In the Antibody Mediated Prevention (AMP) trials (HVTN 704/HPTN 085 and HVTN 703/HPTN 081), prevention efficacy (PE) of the monoclonal broadly neutralizing antibody (bnAb) VRC01 (vs. placebo) against HIV-1 acquisition diagnosis varied according to the HIV-1 Envelope (Env) neutralization sensitivity to VRC01, as measured by 80% inhibitory concentration (IC80). Here, we performed a genotypic sieve analysis, a complementary approach to gaining insight into correlates of protection that assesses how PE varies with HIV-1 sequence features. We analyzed HIV-1 Env amino acid (AA) sequences from the earliest available HIV-1 RNA-positive plasma samples from AMP participants diagnosed with HIV-1 and identified Env sequence features that associated with PE. The strongest Env AA sequence correlate in both trials was VRC01 epitope distance that quantifies the divergence of the VRC01 epitope in an acquired HIV-1 isolate from the VRC01 epitope of reference HIV-1 strains that were most sensitive to VRC01-mediated neutralization. In HVTN 704/HPTN 085, the Env sequence-based predicted probability that VRC01 IC80 against the acquired isolate exceeded 1 µg/mL also significantly associated with PE. In HVTN 703/HPTN 081, a physicochemical-weighted Hamming distance across 50 VRC01 binding-associated Env AA positions of the acquired isolate from the most VRC01-sensitive HIV-1 strain significantly associated with PE. These results suggest that incorporating mutation scoring by BLOSUM62 and weighting by the strength of interactions at AA positions in the epitope:VRC01 interface can optimize performance of an Env sequence-based biomarker of VRC01 prevention efficacy. Future work could determine whether these results extend to other bnAbs and bnAb combinations.
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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.