Author(s):
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
Date: 2022
Persistent ID: http://hdl.handle.net/11449/222021
Origin: Oasisbr
Subject(s): AAVP; COVID-19; Gene delivery; Phage display; SARS-CoV-2
Description
Made available in DSpace on 2022-04-28T19:41:58Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-07-27
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.
Rutgers Cancer Institute of New Jersey
Division of Cancer Biology Department of Radiation Oncology Rutgers New Jersey Medical School
Center for Theoretical Biological Physics Rice University
Department of Physics Institute of Biosciences Humanities and Exact Sciences São Paulo State University
Public Health Research Institute Rutgers New Jersey Medical School
Department of Neurology Harvard Medical School
Department of Surgery Rutgers Robert Wood Johnson Medical School
Department of Physics and Center for Theoretical Biological Physics Northeastern University
RCSB Protein Data Bank Institute for Quantitative Biomedicine, Rutgers State University of New Jersey
Department of Chemistry and Chemical Biology Rutgers State University of New Jersey
RCSB Protein Data Bank San Diego Supercomputer Center and Skaggs School of Pharmacy & Pharmaceutical Sciences University of California San Diego
Department of Biosciences Rice University
Department of Chemistry Rice University
Department of Physics and Astronomy Rice University
Division of Hematology/Oncology Department of Medicine Rutgers New Jersey Medical School
Department of Physics Institute of Biosciences Humanities and Exact Sciences São Paulo State University
