RT Journal Article
SR Electronic
T1 A Universal Bacteriophage T4 Nanoparticle Platform to Design Multiplex SARS-CoV-2 Vaccine Candidates by CRISPR Engineering
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.01.19.427310
DO 10.1101/2021.01.19.427310
A1 Jingen Zhu
A1 Neeti Ananthaswamy
A1 Swati Jain
A1 Himanshu Batra
A1 Wei-Chun Tang
A1 Douglass A. Lewry
A1 Michael L. Richards
A1 Sunil A. David
A1 Paul B. Kilgore
A1 Jian Sha
A1 Aleksandra Drelich
A1 Chien-Te K. Tseng
A1 Ashok K. Chopra
A1 Venigalla B. Rao
YR 2021
UL http://biorxiv.org/content/early/2021/01/20/2021.01.19.427310.abstract
AB A “universal” vaccine design platform that can rapidly generate multiplex vaccine candidates is critically needed to control future pandemics. Here, using SARS-CoV-2 pandemic virus as a model, we have developed such a platform by CRISPR engineering of bacteriophage T4. A pipeline of vaccine candidates were 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 is found to be the most potent vaccine candidate in mouse and rabbit models. Without any adjuvant, this vaccine stimulated robust immune responses, both TH1 and TH2 IgG subclasses, blocked virus-receptor interactions, neutralized viral infection, and conferred complete protection against viral challenge. This new type of nanovaccine design framework might allow rapid deployment of effective phage-based vaccines against any emerging pathogen in the future.Competing Interest StatementThe authors have declared no competing interest.