ArticlePloS one2012
Designing and testing broadly-protective filoviral vaccines optimized for cytotoxic T-lymphocyte epitope coverage.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Cellular Phenotyping of Peripheral Blood Mononuclear Cells from Marburg Virus-Infected Animals.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Vaccine Advances against Venezuelan, Eastern, and Western Equine Encephalitis Viruses.Vaccines · 2020Review
- Graph-based optimization of epitope coverage for vaccine antigen design.Statistics in medicine · 2018Article
- Polyvalent vaccine approaches to combat HIV-1 diversity.Immunological reviews · 2017Review
- Towards the knowledge-based design of universal influenza epitope ensemble vaccines.Bioinformatics (Oxford, England) · 2016Article
- Epigraph: A Vaccine Design Tool Applied to an HIV Therapeutic Vaccine and a Pan-Filovirus Vaccine.Scientific reports · 2016Article
- Neglected filoviruses.FEMS microbiology reviews · 2016Review
- Increased Valency of Conserved-mosaic Vaccines Enhances the Breadth and Depth of Epitope Recognition.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- Integrated sequence and immunology filovirus database at Los Alamos.Database : the journal of biological databases and curation · 2016Article
- HIV-1 Subtype C Mosaic Gag Expressed by BCG and MVA Elicits Persistent Effector T Cell Responses in a Prime-Boost Regimen in Mice.PloS one · 2016Article
- Bolstering Components of the Immune Response Compromised by Prior Exposure to Adenovirus: Guided Formulation Development for a Nasal Ebola Vaccine.Molecular pharmaceutics · 2015Article
- Immunological and virological mechanisms of vaccine-mediated protection against SIV and HIV.Nature · 2014Article
- Emerging targets and novel approaches to Ebola virus prophylaxis and treatment.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2013Review
- Vaccine design: emerging concepts and renewed optimism.Current opinion in biotechnology · 2013Review
- Induction of broad cytotoxic T cells by protective DNA vaccination against Marburg and Ebola.Molecular therapy : the journal of the American Society of Gene Therapy · 2013Article
- Hepatitis C genotype 1 mosaic vaccines are immunogenic in mice and induce stronger T-cell responses than natural strains.Clinical and vaccine immunology : CVI · 2013Article
Corrections and comments
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We report the rational design and in vivo testing of mosaic proteins for a polyvalent pan-filoviral vaccine using a computational strategy designed for the Human Immunodeficiency Virus type 1 (HIV-1) but also appropriate for Hepatitis C virus (HCV) and potentially other diverse viruses. Mosaics are sets of artificial recombinant proteins that are based on natural proteins. The recombinants are computationally selected using a genetic algorithm to optimize the coverage of potential cytotoxic T lymphocyte (CTL) epitopes. Because evolutionary history differs markedly between HIV-1 and filoviruses, we devised an adapted computational technique that is effective for sparsely sampled taxa; our first significant result is that the mosaic technique is effective in creating high-quality mosaic filovirus proteins. The resulting coverage of potential epitopes across filovirus species is superior to coverage by any natural variants, including current vaccine strains with demonstrated cross-reactivity. The mosaic cocktails are also robust: mosaics substantially outperformed natural strains when computationally tested against poorly sampled species and more variable genes. Furthermore, in a computational comparison of cross-reactive potential a design constructed prior to the Bundibugyo outbreak performed nearly as well against all species as an updated design that included Bundibugyo. These points suggest that the mosaic designs would be more resilient than natural-variant vaccines against future Ebola outbreaks dominated by novel viral variants. We demonstrate in vivo immunogenicity and protection against a heterologous challenge in a mouse model. This design work delineates the likely requirements and limitations on broadly-protective filoviral CTL vaccines.
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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.