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.articleNumbere2105739118
dc.citation.issueNumber30
dc.citation.journalTitleProceedings of the National Academy of Sciences
dc.citation.volumeNumber118
dc.contributor.authorStaquicini, Daniela I.
dc.contributor.authorTang, Fenny H.F.
dc.contributor.authorMarkosian, Christopher
dc.contributor.authorYao, Virginia J.
dc.contributor.authorStaquicini, Fernanda I.
dc.contributor.authorDodero-Rojas, Esteban
dc.contributor.authorContessoto, Vinícius G.
dc.contributor.authorDavis, Deodate
dc.contributor.authorO’Brien, Paul
dc.contributor.authorHabib, Nazia
dc.contributor.authorSmith, Tracey L.
dc.contributor.authorBruiners, Natalie
dc.contributor.authorSidman, Richard L.
dc.contributor.authorGennaro, Maria L.
dc.contributor.authorLattime, Edmund C.
dc.contributor.authorLibutti, Steven K.
dc.contributor.authorWhitford, Paul C.
dc.contributor.authorBurley, Stephen K.
dc.contributor.authorOnuchic, José Nelson
dc.contributor.authorArap, Wadih
dc.contributor.authorPasqualini, Renata
dc.contributor.orgCenter for Theoretical Biological Physics
dc.date.accessioned2021-08-05T15:51:52Z
dc.date.available2021-08-05T15:51:52Z
dc.date.issued2021
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.
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.
dc.identifier.digitale2105739118-full
dc.identifier.doihttps://doi.org/10.1073/pnas.2105739118
dc.identifier.urihttps://hdl.handle.net/1911/111135
dc.language.isoeng
dc.publisherNational Academy of Sciences
dc.rightsThis open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.titleDesign and proof of concept for targeted phage-based COVID-19 vaccination strategies with a streamlined cold-free supply chain
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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