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A Single-Cycle Influenza A Virus-Based SARS-CoV-2 Vaccine Elicits Potent Immune Responses in a Mouse Model

Authors :
Surapong Koonpaew
Challika Kaewborisuth
Kanjana Srisutthisamphan
Asawin Wanitchang
Theeradej Thaweerattanasinp
Janya Saenboonrueng
Sukontip Poonsuk
Juggragarn Jengarn
Ratchanont Viriyakitkosol
Jarin Kramyu
Anan Jongkaewwattana
Source :
Vaccines, Vol 9, Iss 8, p 850 (2021)
Publication Year :
2021
Publisher :
MDPI AG, 2021.

Abstract

The use of virus-vectored platforms has increasingly gained attention in vaccine development as a means for delivering antigenic genes of interest into target hosts. Here, we describe a single-cycle influenza virus-based SARS-CoV-2 vaccine designated as scPR8-RBD-M2. The vaccine utilizes the chimeric gene encoding 2A peptide-based bicistronic protein cassette of the SARS-CoV-2 receptor-binding domain (RBD) and influenza matrix 2 (M2) protein. The C-terminus of the RBD was designed to link with the cytoplasmic domain of the influenza virus hemagglutinin (HA) to anchor the RBD on the surface of producing cells and virus envelope. The chimeric RBD-M2 gene was incorporated in place of the HA open-reading frame (ORF) between the 3′ and 5′ UTR of HA gene for the virus rescue in MDCK cells stably expressing HA. The virus was also constructed with the disrupted M2 ORF in segment seven to ensure that M2 from the RBD-M2 was utilized. The chimeric gene was intact and strongly expressed in infected cells upon several passages, suggesting that the antigen was stably maintained in the vaccine candidate. Mice inoculated with scPR8-RBD-M2 via two alternative prime-boost regimens (intranasal-intranasal or intranasal-intramuscular routes) elicited robust mucosal and systemic humoral immune responses and cell-mediated immunity. Notably, we demonstrated that immunized mouse sera exhibited neutralizing activity against pseudotyped viruses bearing SARS-CoV-2 spikes from various variants, albeit with varying potency. Our study warrants further development of a replication-deficient influenza virus as a promising SARS-CoV-2 vaccine candidate.

Details

Language :
English
ISSN :
2076393X
Volume :
9
Issue :
8
Database :
Directory of Open Access Journals
Journal :
Vaccines
Publication Type :
Academic Journal
Accession number :
edsdoj.70f80266cf475393282b4dc1e9ee74
Document Type :
article
Full Text :
https://doi.org/10.3390/vaccines9080850