气候变化领域集成服务门户(CCPortal): Design and proof of concept for targeted phage-based COVID-19 vaccination strategies with a streamlined cold-free supply chain

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DOI	10.1073/pnas.2105739118
	Design and proof of concept for targeted phage-based COVID-19 vaccination strategies with a streamlined cold-free supply chain
	Staquicini D.I.; Tang F.H.F.; Markosian C.; Yao V.J.; Staquicini F.I.; Dodero-Rojas E.; Contessoto V.G.; Davis D.; O’Brien P.; Habib N.; Smith T.L.; Bruiners N.; Sidman R.L.; Gennaro M.L.; Lattime E.C.; Libutti S.K.; Whitford P.C.; Burley S.K.; Onuchic J.N.; Arap W.; Pasqualini R.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:30
英文摘要	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. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	AAVP; COVID-19; Gene delivery; Phage display; SARS-CoV-2
语种	英语
scopus关键词	administration and dosage; animal; bacteriophage; Bagg albino mouse; chemistry; Dependoparvovirus; drug storage; female; genetics; immunology; inhalational drug administration; mouse; prevention and control; preventive health service; procedures; proof of concept; temperature; vaccine immunogenicity; Administration, Inhalation; Animals; Bacteriophages; COVID-19; COVID-19 Vaccines; Dependovirus; Drug Storage; Female; Immunization Programs; Immunogenicity, Vaccine; Mice; Mice, Inbred BALB C; Proof of Concept Study; Temperature
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/238856
作者单位	Rutgers Cancer Institute of New Jersey, Newark, NJ 07101, United States; Division of Cancer Biology, Department of Radiation Oncology, Rutgers New Jersey Medical School, Newark, NJ 07103, United States; Center for Theoretical Biological Physics, Rice University, Houston, TX 77005, United States; Department of Physics, Institute of Biosciences, Humanities and Exact Sciences, São Paulo State University, São José do Rio Preto, SP 15054, Brazil; Public Health Research Institute, Rutgers New Jersey Medical School, Newark, NJ 07103, United States; Department of Neurology, Harvard Medical School, Boston, MA 02115, United States; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08901, United States; Department of Surgery, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, United States; Department of Physics and Center for Theoretical Biological Physics, Northeastern University, Boston, MA 02115, United States; RCSB Protein Data Bank, Institute for Quantitative Biomedicine,, Rut...
推荐引用方式 GB/T 7714	Staquicini D.I.,Tang F.H.F.,Markosian C.,et al. Design and proof of concept for targeted phage-based COVID-19 vaccination strategies with a streamlined cold-free supply chain[J],2021,118(30).
APA	Staquicini D.I..,Tang F.H.F..,Markosian C..,Yao V.J..,Staquicini F.I..,...&Pasqualini R..(2021).Design and proof of concept for targeted phage-based COVID-19 vaccination strategies with a streamlined cold-free supply chain.Proceedings of the National Academy of Sciences of the United States of America,118(30).
MLA	Staquicini D.I.,et al."Design and proof of concept for targeted phage-based COVID-19 vaccination strategies with a streamlined cold-free supply chain".Proceedings of the National Academy of Sciences of the United States of America 118.30(2021).