Design and proof of concept for targeted phage-based COVID-19 vaccination strategies with a streamlined cold-free supply chain

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Autor(es): dc.contributorRutgers Cancer Institute of New Jersey-
Autor(es): dc.contributorRutgers New Jersey Medical School-
Autor(es): dc.contributorRice University-
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorHarvard Medical School-
Autor(es): dc.contributorRutgers Robert Wood Johnson Medical School-
Autor(es): dc.contributorNortheastern University-
Autor(es): dc.contributorState University of New Jersey-
Autor(es): dc.contributorUniversity of California San Diego-
Autor(es): dc.creatorStaquicini, Daniela I.-
Autor(es): dc.creatorTang, Fenny H.F.-
Autor(es): dc.creatorMarkosian, Christopher-
Autor(es): dc.creatorYao, Virginia J.-
Autor(es): dc.creatorStaquicini, Fernanda I.-
Autor(es): dc.creatorDodero-Rojas, Esteban-
Autor(es): dc.creatorContessoto, Vinícius G. [UNESP]-
Autor(es): dc.creatorDavis, Deodate-
Autor(es): dc.creatorO’Brien, Paul-
Autor(es): dc.creatorHabib, Nazia-
Autor(es): dc.creatorSmith, Tracey L.-
Autor(es): dc.creatorBruiners, Natalie-
Autor(es): dc.creatorSidman, Richard L.-
Autor(es): dc.creatorGennaro, Maria L.-
Autor(es): dc.creatorLattime, Edmund C.-
Autor(es): dc.creatorLibutti, Steven K.-
Autor(es): dc.creatorWhitford, Paul C.-
Autor(es): dc.creatorBurley, Stephen K.-
Autor(es): dc.creatorOnuchic, José N.-
Autor(es): dc.creatorArap, Wadih-
Autor(es): dc.creatorPasqualini, Renata-
Data de aceite: dc.date.accessioned2022-08-04T22:10:35Z-
Data de disponibilização: dc.date.available2022-08-04T22:10:35Z-
Data de envio: dc.date.issued2022-04-28-
Data de envio: dc.date.issued2022-04-28-
Data de envio: dc.date.issued2021-07-27-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1073/pnas.2105739118-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/222021-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/222021-
Descrição: dc.descriptionDevelopment of effective vaccines against coronavirus disease 2019 (COVID-19) is a global imperative. Rapid immunization of the entire human population against a widespread, continually evolving, and highly pathogenic virus is an unprecedented challenge, and different vaccine approaches are being pursued. Engineered filamentous bacteriophage (phage) particles have unique potential in vaccine development due to their inherent immunogenicity, genetic plasticity, stability, cost-effectiveness for large-scale production, and proven safety profile in humans. Herein we report the development and initial evaluation of two targeted phage-based vaccination approaches against SARS-CoV-2: dual ligand peptide-targeted phage and adeno-associated virus/phage (AAVP) particles. For peptide-targeted phage, we performed structure-guided antigen design to select six solvent-exposed epitopes of the SARS-CoV-2 spike (S) protein. One of these epitopes displayed on the major capsid protein pVIII of phage induced a specific and sustained humoral response when injected in mice. These phage were further engineered to simultaneously display the peptide CAKSMGDIVC on the minor capsid protein pIII to enable their transport from the lung epithelium into the systemic circulation. Aerosolization of these “dual-display” phage into the lungs of mice generated a systemic and specific antibody response. In the second approach, targeted AAVP particles were engineered to deliver the entire S protein gene under the control of a constitutive CMV promoter. This induced tissue-specific transgene expression, stimulating a systemic S protein-specific antibody response in mice. With these proof-of-concept preclinical experiments, we show that both targeted phage- and AAVP-based particles serve as robust yet versatile platforms that can promptly yield COVID-19 vaccine prototypes for translational development.-
Descrição: dc.descriptionRutgers Cancer Institute of New Jersey-
Descrição: dc.descriptionDivision of Cancer Biology Department of Radiation Oncology Rutgers New Jersey Medical School-
Descrição: dc.descriptionCenter for Theoretical Biological Physics Rice University-
Descrição: dc.descriptionDepartment of Physics Institute of Biosciences Humanities and Exact Sciences São Paulo State University-
Descrição: dc.descriptionPublic Health Research Institute Rutgers New Jersey Medical School-
Descrição: dc.descriptionDepartment of Neurology Harvard Medical School-
Descrição: dc.descriptionDepartment of Surgery Rutgers Robert Wood Johnson Medical School-
Descrição: dc.descriptionDepartment of Physics and Center for Theoretical Biological Physics Northeastern University-
Descrição: dc.descriptionRCSB Protein Data Bank Institute for Quantitative Biomedicine, Rutgers State University of New Jersey-
Descrição: dc.descriptionDepartment of Chemistry and Chemical Biology Rutgers State University of New Jersey-
Descrição: dc.descriptionRCSB Protein Data Bank San Diego Supercomputer Center and Skaggs School of Pharmacy & Pharmaceutical Sciences University of California San Diego-
Descrição: dc.descriptionDepartment of Biosciences Rice University-
Descrição: dc.descriptionDepartment of Chemistry Rice University-
Descrição: dc.descriptionDepartment of Physics and Astronomy Rice University-
Descrição: dc.descriptionDivision of Hematology/Oncology Department of Medicine Rutgers New Jersey Medical School-
Descrição: dc.descriptionDepartment of Physics Institute of Biosciences Humanities and Exact Sciences São Paulo State University-
Idioma: dc.languageen-
Relação: dc.relationProceedings of the National Academy of Sciences of the United States of America-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectAAVP-
Palavras-chave: dc.subjectCOVID-19-
Palavras-chave: dc.subjectGene delivery-
Palavras-chave: dc.subjectPhage display-
Palavras-chave: dc.subjectSARS-CoV-2-
Título: dc.titleDesign and proof of concept for targeted phage-based COVID-19 vaccination strategies with a streamlined cold-free supply chain-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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