ArticleBiochemical and biophysical research communications2009
Germline-like predecessors of broadly neutralizing antibodies lack measurable binding to HIV-1 envelope glycoproteins: implications for evasion of immune responses and design of vaccine immunogens.
Article in Biochemical and biophysical research communications, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 207 papers.
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Who cites it
207 citing papers in PubMed, 267 citations in OpenAlex.
- Vaccination induces HIV broadly neutralizing antibody precursors in humans.Science (New York, N.Y.) · 2022Trial
- Detection and activation of HIV broadly neutralizing antibody precursor B cells using anti-idiotypes.The Journal of experimental medicine · 2019Trial
- Self-tolerance curtails the B cell repertoire to microbial epitopes.JCI insight · 2019Trial
- Learned young: HIV-1 germline-targeting vaccination in infants.Current opinion in HIV and AIDS · 2026Review
- Article
- Recent advances in HIV-1 envelope-based vaccine designs for guiding broadly neutralizing antibody response.Journal of virology · 2026Review
- High affinity is insufficient for strong B cell activation by HIV broadly neutralising antibodies.NPJ vaccines · 2026Article
- Local antibody feedback enforces a checkpoint on affinity maturation in the germinal center and promotes epitope spreading.Immunity · 2026Article
- Rapidly acquired HIV-1 neutralization breadth in a rhesus V2 apex knockin mouse model after a single bolus immunization.Science immunology · 2026Article
- Divalent HIV-1 gp120 Immunogen Exhibits Selective Avidity for Broadly Neutralizing Antibody VRC01 Precursors.Vaccines · 2026Article
- The Germline Targeting Vaccine Concept: Overview and Updates from HIV Pre-Clinical and Clinical Trials.Current HIV research · 2026Review
- Antibody feedback establishes an affinity brake in the germinal center.bioRxiv : the preprint server for biology · 2025Article
- The HIV-1 envelope glycoprotein: structure, function and interactions with neutralizing antibodies.Nature reviews. Microbiology · 2025Review
- Simultaneous priming of HIV broadly neutralizing antibody precursors to multiple epitopes by germline-targeting mRNA-LNP immunogens in mouse models.Science immunology · 2025Article
- Design and characterization of HIV-1 vaccine candidates to elicit antibodies targeting multiple epitopes.The Journal of experimental medicine · 2025Article
- HIV broadly neutralizing antibody precursors to the Apex epitope induced in nonhuman primates.Science immunology · 2025Article
- Structural insights into VRC01-class bnAb precursors with diverse light chains elicited in the IAVI G001 human vaccine trial.Proceedings of the National Academy of Sciences of the United States of America · 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
- Mechanisms of sterilizing immunity provided by an HIV-1 neutralizing antibody against mucosal infection.PLoS pathogens · 2024Article
- Heterologous prime-boost vaccination drives early maturation of HIV broadly neutralizing antibody precursors in humanized mice.Science translational medicine · 2024Article
147 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Several human monoclonal antibodies (hmAbs) including b12, 2G12, and 2F5 exhibit relatively potent and broad HIV-1-neutralizing activity. However, their elicitation in vivo by vaccine immunogens based on the HIV-1 envelope glycoprotein (Env) has not been successful. We have hypothesized that HIV-1 has evolved a strategy to reduce or eliminate the immunogenicity of the highly conserved epitopes of such antibodies by using "holes" (absence or very weak binding to these epitopes of germline antibodies that is not sufficient to initiate and/or maintain an efficient immune response) in the human germline B cell receptor (BCR) repertoire. To begin to test this hypothesis we have designed germline-like antibodies corresponding most closely to b12, 2G12, and 2F5 as well as to X5, m44, and m46 which are cross-reactive but with relatively modest neutralizing activity as natively occurring antibodies due to size and/or other effects. The germline-like X5, m44, and m46 bound with relatively high affinity to all tested Envs. In contrast, germline-like b12, 2G12, and 2F5 lacked measurable binding to Envs in an ELISA assay although the corresponding mature antibodies did. These results provide initial evidence that Env structures containing conserved vulnerable epitopes may not initiate humoral responses by binding to germline antibodies. Even if such responses are initiated by very weak binding undetectable in our assay it is likely that they will be outcompeted by responses to structures containing the epitopes of X5, m44, m46, and other antibodies that bind germline BCRs with much higher affinity/avidity. This hypothesis, if further supported by data, could contribute to our understanding of how HIV-1 evades immune responses and offer new concepts for design of effective vaccine immunogens.
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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.