ArticleProceedings of the National Academy of Sciences of the United States of America2026
Deep mining of the human antibody repertoire identifies frequent and genetically diverse CDRH3 topologies targetable by vaccination.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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Who cites it
9 citing papers in PubMed.
- Trial
- Deletions in variable region 1 of the HIV envelope accelerate V3-glycan bNAb induction in SHIV-infected rhesus macaques.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Article
- Nanoparticle Immunoadjuvant Complexes Augment Germinal Center Responses to Vaccination.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Rapidly acquired HIV-1 neutralization breadth in a rhesus V2 apex knockin mouse model after a single bolus immunization.Science immunology · 2026Article
- Env-antibody coevolution identifies B cell priming as the principal bottleneck to HIV V2 apex broadly neutralizing antibody development.Science immunology · 2026Article
- Structural and genetic basis of HIV-1 envelope V2 apex recognition by rhesus broadly neutralizing antibodies.The Journal of experimental medicine · 2025Article
- Transient glycan shield reduction induces CD4-binding site broadly neutralizing antibodies in SHIV-infected macaques.Cell reports · 2025Article
- Rapid acquisition of HIV-1 neutralization breadth in a rhesus V2 apex germline antibody mouse model after a single bolus immunization.bioRxiv : the preprint server for biology · 2025Article
Corrections and comments
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39 authors.
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Abstract
Germline targeting vaccination strategies against highly variable pathogens such as HIV aim to elicit broadly neutralizing antibodies (bnAbs) with particular immunogenetic or structural features. The V2 apex of the HIV Env protein is a promising target for a class of bnAbs that contain conserved structural motifs in the heavy chain complementarity determining region 3 (CDRH3). Here, we show that these structural motifs are targetable by vaccination by characterizing V2 apex "axe-like" CDRH3s in the human repertoire and developing immunogens capable of engaging them. We determined the frequency and diversity of axe-like CDRH3s in healthy human donors using a series of structural informatics approaches, finding these precursors in nearly 90% of donors. Axe-targeting immunogens based on the HIV Env Q23.17 bound axe-like precursors in cryo-electron microscopy structures, induced V2 apex-specific antibody responses in humanized mice, and induced axe-like heterologous neutralizing antibodies in rhesus macaques infected with a germline-targeted simian-HIV. These results illustrate a structure-guided immunoinformatic vaccine design paradigm that can be employed to elicit immunogenetically diverse yet structurally conserved classes of antibodies.
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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 Socratic graph.