ArticlePLoS biology2019
Boosting subdominant neutralizing antibody responses with a computationally designed epitope-focused immunogen.
Article in PLoS biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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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.
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Who cites it
23 citing papers in PubMed, 39 citations in OpenAlex.
- A lipid nanoparticle-based mRNA vaccine elicits immunity against porcine circovirus type 2 in mice.Microbiology spectrum · 2026Article
- Accurate single-domain scaffolding of three nonoverlapping protein epitopes using deep learning.Nature chemical biology · 2026Article
- Article
- Computationally designed stem-epitope mimetics elicit broadly reactive antibodies.bioRxiv : the preprint server for biology · 2025Article
- Article
- Rational structure-guided design of a blood stage malaria vaccine immunogen presenting a single epitope from PfRH5.EMBO molecular medicine · 2024Article
- Opportunities and challenges in design and optimization of protein function.Nature reviews. Molecular cell biology · 2024Review
- Bringing immunofocusing into focus.NPJ vaccines · 2024Review
- An epitope-enriched immunogen expands responses to a conserved viral site.Cell reports · 2022Article
- Antibodies to combat viral infections: development strategies and progress.Nature reviews. Drug discovery · 2022Review
- Recent developments in systems biology and genetic engineering toward design of vaccines for TB.Critical reviews in biotechnology · 2022Review
- RosettaSurf-A surface-centric computational design approach.PLoS computational biology · 2022Article
- Combined Subcutaneous-Intranasal Immunization With Epitope-Based Antigens Elicits Binding and Neutralizing Antibody Responses in Serum and Mucosae Against PRRSV-2 and SARS-CoV-2.Frontiers in immunology · 2022Article
- A Pan-Pneumovirus vaccine based on immunodominant epitopes of the fusion protein.Frontiers in immunology · 2022Article
- Protein engineering strategies for rational immunogen design.NPJ vaccines · 2021Review
- Tensor-structured decomposition improves systems serology analysis.Molecular systems biology · 2021Article
- Deep learning techniques have significantly impacted protein structure prediction and protein design.Current opinion in structural biology · 2021Review
- Bottom-up de novo design of functional proteins with complex structural features.Nature chemical biology · 2021Article
- Flu Universal Vaccines: New Tricks on an Old Virus.Virologica Sinica · 2021Review
- Combinatorial Resurfacing of Dengue Envelope Protein Domain III Antigens Selectively Ablates Epitopes Associated with Serotype-Specific or Infection-Enhancing Antibody Responses.ACS combinatorial science · 2020Article
Corrections and comments
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Authors and funding
18 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Throughout the last several decades, vaccination has been key to prevent and eradicate infectious diseases. However, many pathogens (e.g., respiratory syncytial virus [RSV], influenza, dengue, and others) have resisted vaccine development efforts, largely because of the failure to induce potent antibody responses targeting conserved epitopes. Deep profiling of human B cells often reveals potent neutralizing antibodies that emerge from natural infection, but these specificities are generally subdominant (i.e., are present in low titers). A major challenge for next-generation vaccines is to overcome established immunodominance hierarchies and focus antibody responses on crucial neutralization epitopes. Here, we show that a computationally designed epitope-focused immunogen presenting a single RSV neutralization epitope elicits superior epitope-specific responses compared to the viral fusion protein. In addition, the epitope-focused immunogen efficiently boosts antibodies targeting the palivizumab epitope, resulting in enhanced neutralization. Overall, we show that epitope-focused immunogens can boost subdominant neutralizing antibody responses in vivo and reshape established antibody hierarchies.
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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.