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

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dc.citation.articleNumbere2105739118en_US
dc.citation.issueNumber30en_US
dc.citation.journalTitleProceedings of the National Academy of Sciencesen_US
dc.citation.volumeNumber118en_US
dc.contributor.authorStaquicini, Daniela I.en_US
dc.contributor.authorTang, Fenny H.F.en_US
dc.contributor.authorMarkosian, Christopheren_US
dc.contributor.authorYao, Virginia J.en_US
dc.contributor.authorStaquicini, Fernanda I.en_US
dc.contributor.authorDodero-Rojas, Estebanen_US
dc.contributor.authorContessoto, Vinícius G.en_US
dc.contributor.authorDavis, Deodateen_US
dc.contributor.authorO’Brien, Paulen_US
dc.contributor.authorHabib, Naziaen_US
dc.contributor.authorSmith, Tracey L.en_US
dc.contributor.authorBruiners, Natalieen_US
dc.contributor.authorSidman, Richard L.en_US
dc.contributor.authorGennaro, Maria L.en_US
dc.contributor.authorLattime, Edmund C.en_US
dc.contributor.authorLibutti, Steven K.en_US
dc.contributor.authorWhitford, Paul C.en_US
dc.contributor.authorBurley, Stephen K.en_US
dc.contributor.authorOnuchic, José Nelsonen_US
dc.contributor.authorArap, Wadihen_US
dc.contributor.authorPasqualini, Renataen_US
dc.contributor.orgCenter for Theoretical Biological Physicsen_US
dc.date.accessioned2021-08-05T15:51:52Zen_US
dc.date.available2021-08-05T15:51:52Zen_US
dc.date.issued2021en_US
dc.description.abstractDevelopment 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.en_US
dc.identifier.citationStaquicini, Daniela I., Tang, Fenny H.F., Markosian, Christopher, et al.. "Design and proof of concept for targeted phage-based COVID-19 vaccination strategies with a streamlined cold-free supply chain." <i>Proceedings of the National Academy of Sciences,</i> 118, no. 30 (2021) National Academy of Sciences: https://doi.org/10.1073/pnas.2105739118.en_US
dc.identifier.digitale2105739118-fullen_US
dc.identifier.doihttps://doi.org/10.1073/pnas.2105739118en_US
dc.identifier.urihttps://hdl.handle.net/1911/111135en_US
dc.language.isoengen_US
dc.publisherNational Academy of Sciencesen_US
dc.rightsThis open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.titleDesign and proof of concept for targeted phage-based COVID-19 vaccination strategies with a streamlined cold-free supply chainen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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