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Article

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

1
Virology and Cell Technology Research Team, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani 12120, Thailand
2
Faculty of Veterinary Science, Chulalongkorn University, Bangkok 10330, Thailand
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Ralph A. Tripp
Vaccines 2021, 9(8), 850; https://doi.org/10.3390/vaccines9080850
Received: 23 June 2021 / Revised: 24 July 2021 / Accepted: 30 July 2021 / Published: 3 August 2021
(This article belongs to the Section COVID-19 Vaccines and Vaccination)
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. View Full-Text
Keywords: SARS-CoV-2; single-cycle influenza virus-based vaccine; spike RBD; spike-pseudotyped virus SARS-CoV-2; single-cycle influenza virus-based vaccine; spike RBD; spike-pseudotyped virus
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MDPI and ACS Style

Koonpaew, S.; Kaewborisuth, C.; Srisutthisamphan, K.; Wanitchang, A.; Thaweerattanasinp, T.; Saenboonrueng, J.; Poonsuk, S.; Jengarn, J.; Viriyakitkosol, R.; Kramyu, J.; Jongkaewwattana, A. A Single-Cycle Influenza A Virus-Based SARS-CoV-2 Vaccine Elicits Potent Immune Responses in a Mouse Model. Vaccines 2021, 9, 850. https://doi.org/10.3390/vaccines9080850

AMA Style

Koonpaew S, Kaewborisuth C, Srisutthisamphan K, Wanitchang A, Thaweerattanasinp T, Saenboonrueng J, Poonsuk S, Jengarn J, Viriyakitkosol R, Kramyu J, Jongkaewwattana A. A Single-Cycle Influenza A Virus-Based SARS-CoV-2 Vaccine Elicits Potent Immune Responses in a Mouse Model. Vaccines. 2021; 9(8):850. https://doi.org/10.3390/vaccines9080850

Chicago/Turabian Style

Koonpaew, Surapong, Challika Kaewborisuth, Kanjana Srisutthisamphan, Asawin Wanitchang, Theeradej Thaweerattanasinp, Janya Saenboonrueng, Sukontip Poonsuk, Juggragarn Jengarn, Ratchanont Viriyakitkosol, Jarin Kramyu, and Anan Jongkaewwattana. 2021. "A Single-Cycle Influenza A Virus-Based SARS-CoV-2 Vaccine Elicits Potent Immune Responses in a Mouse Model" Vaccines 9, no. 8: 850. https://doi.org/10.3390/vaccines9080850

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