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

Detalhes bibliográficos
Autor(a) principal: Staquicini, Daniela I.
Data de Publicação: 2021
Outros Autores: Tang, Fenny H.F., Markosian, Christopher, Yao, Virginia J., Staquicini, Fernanda I., Dodero-Rojas, Esteban, Contessoto, Vinícius G. [UNESP], Davis, Deodate, O’Brien, Paul, Habib, Nazia, Smith, Tracey L., Bruiners, Natalie, Sidman, Richard L., Gennaro, Maria L., Lattime, Edmund C., Libutti, Steven K., Whitford, Paul C., Burley, Stephen K., Onuchic, José N., Arap, Wadih, Pasqualini, Renata
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1073/pnas.2105739118
http://hdl.handle.net/11449/222021
Resumo: Development 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.
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spelling Design and proof of concept for targeted phage-based COVID-19 vaccination strategies with a streamlined cold-free supply chainAAVPCOVID-19Gene deliveryPhage displaySARS-CoV-2Development 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.Rutgers Cancer Institute of New JerseyDivision of Cancer Biology Department of Radiation Oncology Rutgers New Jersey Medical SchoolCenter for Theoretical Biological Physics Rice UniversityDepartment of Physics Institute of Biosciences Humanities and Exact Sciences São Paulo State UniversityPublic Health Research Institute Rutgers New Jersey Medical SchoolDepartment of Neurology Harvard Medical SchoolDepartment of Surgery Rutgers Robert Wood Johnson Medical SchoolDepartment of Physics and Center for Theoretical Biological Physics Northeastern UniversityRCSB Protein Data Bank Institute for Quantitative Biomedicine, Rutgers State University of New JerseyDepartment of Chemistry and Chemical Biology Rutgers State University of New JerseyRCSB Protein Data Bank San Diego Supercomputer Center and Skaggs School of Pharmacy & Pharmaceutical Sciences University of California San DiegoDepartment of Biosciences Rice UniversityDepartment of Chemistry Rice UniversityDepartment of Physics and Astronomy Rice UniversityDivision of Hematology/Oncology Department of Medicine Rutgers New Jersey Medical SchoolDepartment of Physics Institute of Biosciences Humanities and Exact Sciences São Paulo State UniversityRutgers Cancer Institute of New JerseyRutgers New Jersey Medical SchoolRice UniversityUniversidade Estadual Paulista (UNESP)Harvard Medical SchoolRutgers Robert Wood Johnson Medical SchoolNortheastern UniversityState University of New JerseyUniversity of California San DiegoStaquicini, Daniela I.Tang, Fenny H.F.Markosian, ChristopherYao, Virginia J.Staquicini, Fernanda I.Dodero-Rojas, EstebanContessoto, Vinícius G. [UNESP]Davis, DeodateO’Brien, PaulHabib, NaziaSmith, Tracey L.Bruiners, NatalieSidman, Richard L.Gennaro, Maria L.Lattime, Edmund C.Libutti, Steven K.Whitford, Paul C.Burley, Stephen K.Onuchic, José N.Arap, WadihPasqualini, Renata2022-04-28T19:41:58Z2022-04-28T19:41:58Z2021-07-27info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1073/pnas.2105739118Proceedings of the National Academy of Sciences of the United States of America, v. 118, n. 30, 2021.1091-64900027-8424http://hdl.handle.net/11449/22202110.1073/pnas.21057391182-s2.0-85110992529Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengProceedings of the National Academy of Sciences of the United States of Americainfo:eu-repo/semantics/openAccess2022-04-28T19:41:59Zoai:repositorio.unesp.br:11449/222021Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T14:11:19.905372Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Design and proof of concept for targeted phage-based COVID-19 vaccination strategies with a streamlined cold-free supply chain
title Design and proof of concept for targeted phage-based COVID-19 vaccination strategies with a streamlined cold-free supply chain
spellingShingle Design and proof of concept for targeted phage-based COVID-19 vaccination strategies with a streamlined cold-free supply chain
Staquicini, Daniela I.
AAVP
COVID-19
Gene delivery
Phage display
SARS-CoV-2
title_short Design and proof of concept for targeted phage-based COVID-19 vaccination strategies with a streamlined cold-free supply chain
title_full Design and proof of concept for targeted phage-based COVID-19 vaccination strategies with a streamlined cold-free supply chain
title_fullStr Design and proof of concept for targeted phage-based COVID-19 vaccination strategies with a streamlined cold-free supply chain
title_full_unstemmed Design and proof of concept for targeted phage-based COVID-19 vaccination strategies with a streamlined cold-free supply chain
title_sort Design and proof of concept for targeted phage-based COVID-19 vaccination strategies with a streamlined cold-free supply chain
author Staquicini, Daniela I.
author_facet Staquicini, Daniela I.
Tang, Fenny H.F.
Markosian, Christopher
Yao, Virginia J.
Staquicini, Fernanda I.
Dodero-Rojas, Esteban
Contessoto, Vinícius G. [UNESP]
Davis, Deodate
O’Brien, Paul
Habib, Nazia
Smith, Tracey L.
Bruiners, Natalie
Sidman, Richard L.
Gennaro, Maria L.
Lattime, Edmund C.
Libutti, Steven K.
Whitford, Paul C.
Burley, Stephen K.
Onuchic, José N.
Arap, Wadih
Pasqualini, Renata
author_role author
author2 Tang, Fenny H.F.
Markosian, Christopher
Yao, Virginia J.
Staquicini, Fernanda I.
Dodero-Rojas, Esteban
Contessoto, Vinícius G. [UNESP]
Davis, Deodate
O’Brien, Paul
Habib, Nazia
Smith, Tracey L.
Bruiners, Natalie
Sidman, Richard L.
Gennaro, Maria L.
Lattime, Edmund C.
Libutti, Steven K.
Whitford, Paul C.
Burley, Stephen K.
Onuchic, José N.
Arap, Wadih
Pasqualini, Renata
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Rutgers Cancer Institute of New Jersey
Rutgers New Jersey Medical School
Rice University
Universidade Estadual Paulista (UNESP)
Harvard Medical School
Rutgers Robert Wood Johnson Medical School
Northeastern University
State University of New Jersey
University of California San Diego
dc.contributor.author.fl_str_mv Staquicini, Daniela I.
Tang, Fenny H.F.
Markosian, Christopher
Yao, Virginia J.
Staquicini, Fernanda I.
Dodero-Rojas, Esteban
Contessoto, Vinícius G. [UNESP]
Davis, Deodate
O’Brien, Paul
Habib, Nazia
Smith, Tracey L.
Bruiners, Natalie
Sidman, Richard L.
Gennaro, Maria L.
Lattime, Edmund C.
Libutti, Steven K.
Whitford, Paul C.
Burley, Stephen K.
Onuchic, José N.
Arap, Wadih
Pasqualini, Renata
dc.subject.por.fl_str_mv AAVP
COVID-19
Gene delivery
Phage display
SARS-CoV-2
topic AAVP
COVID-19
Gene delivery
Phage display
SARS-CoV-2
description Development 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.
publishDate 2021
dc.date.none.fl_str_mv 2021-07-27
2022-04-28T19:41:58Z
2022-04-28T19:41:58Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1073/pnas.2105739118
Proceedings of the National Academy of Sciences of the United States of America, v. 118, n. 30, 2021.
1091-6490
0027-8424
http://hdl.handle.net/11449/222021
10.1073/pnas.2105739118
2-s2.0-85110992529
url http://dx.doi.org/10.1073/pnas.2105739118
http://hdl.handle.net/11449/222021
identifier_str_mv Proceedings of the National Academy of Sciences of the United States of America, v. 118, n. 30, 2021.
1091-6490
0027-8424
10.1073/pnas.2105739118
2-s2.0-85110992529
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Proceedings of the National Academy of Sciences of the United States of America
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
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