Trial reportPLoS pathogens2013
The effects of somatic hypermutation on neutralization and binding in the PGT121 family of broadly neutralizing HIV antibodies.
Trial report in PLoS pathogens, 2013. 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 137 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
137 citing papers in PubMed, 9 citations in OpenAlex.
- Trial
- The HIV-1 envelope glycoprotein: structure, function and interactions with neutralizing antibodies.Nature reviews. Microbiology · 2025Review
- In vivo antibody diversification targeting a conserved coronavirus epitope.The Journal of experimental medicine · 2025Article
- Monoclonal antibody neutralizesInfection and immunity · 2025Article
- Structural basis for hepatitis E virus neutralization by potent human antibodies.Science advances · 2025Article
- Combining a rhesus cytomegalovirus/SIV vaccine with a neutralizing antibody to protect against SIV challenges in rhesus macaques.Frontiers in microbiology · 2025Article
- Rapid affinity optimization of an anti-TREM2 clinical lead antibody by cross-lineage immune repertoire mining.Nature communications · 2024Article
- Multi-compartmental diversification of neutralizing antibody lineages dissected in SARS-CoV-2 spike-immunized macaques.Nature communications · 2024Article
- The Question of HIV Vaccine: Why Is a Solution Not Yet Available?Journal of immunology research · 2024Review
- B cell phylogenetics in the single cell era.Trends in immunology · 2024Review
- Broadly neutralizing antibodies targeting HIV: Progress and challenges.Clinical immunology (Orlando, Fla.) · 2023Review
- Assessing immunogenicity barriers of the HIV-1 envelope trimer.NPJ vaccines · 2023Article
- Recognition determinants of improved HIV-1 neutralization by a heavy chain matured pediatric antibody.iScience · 2023Article
- Single-component multilayered self-assembling protein nanoparticles presenting glycan-trimmed uncleaved prefusion optimized envelope trimmers as HIV-1 vaccine candidates.Nature communications · 2023Article
- Article
- Molecular insights into antibody-mediated protection against the prototypic simian immunodeficiency virus.Nature communications · 2022Article
- Somatic Hypermutation and Framework Mutations of Variable Region Contribute to Anti-Zika Virus-Specific Monoclonal Antibody Binding and Function.Journal of virology · 2022Article
- Complementary Roles of Antibody Heavy and Light Chain Somatic Hypermutation in Conferring Breadth and Potency to the HIV-1-Specific CAP256-VRC26 bNAb Lineage.Journal of virology · 2022Article
- Moving beyond Titers.Vaccines · 2022Review
- SOSIP Trimer-Specific Antibodies Isolated from a Simian-Human Immunodeficiency Virus-Infected Monkey with versus without a Pre-blocking Step with gp41.Journal of virology · 2022Article
77 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issuedKleinstein, Stephen H [corrected to Kleinstein, Steven H]
Authors and funding
29 authors at 11 institutions in 1 country.
Funding
Abstract
Broadly neutralizing HIV antibodies (bnAbs) are typically highly somatically mutated, raising doubts as to whether they can be elicited by vaccination. We used 454 sequencing and designed a novel phylogenetic method to model lineage evolution of the bnAbs PGT121-134 and found a positive correlation between the level of somatic hypermutation (SHM) and the development of neutralization breadth and potency. Strikingly, putative intermediates were characterized that show approximately half the mutation level of PGT121-134 but were still capable of neutralizing roughly 40-80% of PGT121-134 sensitive viruses in a 74-virus panel at median titers between 15- and 3-fold higher than PGT121-134. Such antibodies with lower levels of SHM may be more amenable to elicitation through vaccination while still providing noteworthy coverage. Binding characterization indicated a preference of inferred intermediates for native Env binding over monomeric gp120, suggesting that the PGT121-134 lineage may have been selected for binding to native Env at some point during maturation. Analysis of glycan-dependent neutralization for inferred intermediates identified additional adjacent glycans that comprise the epitope and suggests changes in glycan dependency or recognition over the course of affinity maturation for this lineage. Finally, patterns of neutralization of inferred bnAb intermediates suggest hypotheses as to how SHM may lead to potent and broad HIV neutralization and provide important clues for immunogen design.
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What OpenQuestion holds
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.