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A universal bacteriophage T4 nanoparticle platform to design multiplex SARS-CoV-2 vaccine candidates by CRISPR engineering.
Zhu, Jingen; Ananthaswamy, Neeti; Jain, Swati; Batra, Himanshu; Tang, Wei-Chun; Lewry, Douglass A; Richards, Michael L; David, Sunil A; Kilgore, Paul B; Sha, Jian; Drelich, Aleksandra; Tseng, Chien-Te K; Chopra, Ashok K; Rao, Venigalla B.
  • Zhu J; Bacteriophage Medical Research Center, Department of Biology, The Catholic University of America, Washington, DC 20064, USA.
  • Ananthaswamy N; Bacteriophage Medical Research Center, Department of Biology, The Catholic University of America, Washington, DC 20064, USA.
  • Jain S; Bacteriophage Medical Research Center, Department of Biology, The Catholic University of America, Washington, DC 20064, USA.
  • Batra H; Bacteriophage Medical Research Center, Department of Biology, The Catholic University of America, Washington, DC 20064, USA.
  • Tang WC; Bacteriophage Medical Research Center, Department of Biology, The Catholic University of America, Washington, DC 20064, USA.
  • Lewry DA; Virovax LLC, Lawrence, KS 66047, USA.
  • Richards ML; Virovax LLC, Lawrence, KS 66047, USA.
  • David SA; Virovax LLC, Lawrence, KS 66047, USA.
  • Kilgore PB; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
  • Sha J; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
  • Drelich A; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
  • Tseng CK; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
  • Chopra AK; Center for Biodefense and Emerging Infectious Diseases, University of Texas Medical Branch, Galveston, TX 77555, USA.
  • Rao VB; Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA.
Sci Adv ; 7(37): eabh1547, 2021 Sep 10.
Article in English | MEDLINE | ID: covidwho-1405213
Preprint
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ABSTRACT
A "universal" platform that can rapidly generate multiplex vaccine candidates is critically needed to control pandemics. Using the severe acute respiratory syndrome coronavirus 2 as a model, we have developed such a platform by CRISPR engineering of bacteriophage T4. A pipeline of vaccine candidates was engineered by incorporating various viral components into appropriate compartments of phage nanoparticle structure. These include expressible spike genes in genome, spike and envelope epitopes as surface decorations, and nucleocapsid proteins in packaged core. Phage decorated with spike trimers was found to be the most potent vaccine candidate in animal models. Without any adjuvant, this vaccine stimulated robust immune responses, both T helper cell 1 (TH1) and TH2 immunoglobulin G subclasses, blocked virus-receptor interactions, neutralized viral infection, and conferred complete protection against viral challenge. This new nanovaccine design framework might allow the rapid deployment of effective adjuvant-free phage-based vaccines against any emerging pathogen in the future.

Full text: Available Collection: International databases Database: MEDLINE Topics: Vaccines Language: English Journal: Sci Adv Year: 2021 Document Type: Article Affiliation country: Sciadv.abh1547

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Full text: Available Collection: International databases Database: MEDLINE Topics: Vaccines Language: English Journal: Sci Adv Year: 2021 Document Type: Article Affiliation country: Sciadv.abh1547