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

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 chimeri...

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Autores principales: Koonpaew, Surapong, Kaewborisuth, Challika, Srisutthisamphan, Kanjana, Wanitchang, Asawin, Thaweerattanasinp, Theeradej, Saenboonrueng, Janya, Poonsuk, Sukontip, Jengarn, Juggragarn, Viriyakitkosol, Ratchanont, Kramyu, Jarin, Jongkaewwattana, Anan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402467/
https://www.ncbi.nlm.nih.gov/pubmed/34451975
http://dx.doi.org/10.3390/vaccines9080850
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author Koonpaew, Surapong
Kaewborisuth, Challika
Srisutthisamphan, Kanjana
Wanitchang, Asawin
Thaweerattanasinp, Theeradej
Saenboonrueng, Janya
Poonsuk, Sukontip
Jengarn, Juggragarn
Viriyakitkosol, Ratchanont
Kramyu, Jarin
Jongkaewwattana, Anan
author_facet Koonpaew, Surapong
Kaewborisuth, Challika
Srisutthisamphan, Kanjana
Wanitchang, Asawin
Thaweerattanasinp, Theeradej
Saenboonrueng, Janya
Poonsuk, Sukontip
Jengarn, Juggragarn
Viriyakitkosol, Ratchanont
Kramyu, Jarin
Jongkaewwattana, Anan
author_sort Koonpaew, Surapong
collection PubMed
description 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.
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spelling pubmed-84024672021-08-29 A Single-Cycle Influenza A Virus-Based SARS-CoV-2 Vaccine Elicits Potent Immune Responses in a Mouse Model Koonpaew, Surapong Kaewborisuth, Challika Srisutthisamphan, Kanjana Wanitchang, Asawin Thaweerattanasinp, Theeradej Saenboonrueng, Janya Poonsuk, Sukontip Jengarn, Juggragarn Viriyakitkosol, Ratchanont Kramyu, Jarin Jongkaewwattana, Anan Vaccines (Basel) Article 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. MDPI 2021-08-03 /pmc/articles/PMC8402467/ /pubmed/34451975 http://dx.doi.org/10.3390/vaccines9080850 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Koonpaew, Surapong
Kaewborisuth, Challika
Srisutthisamphan, Kanjana
Wanitchang, Asawin
Thaweerattanasinp, Theeradej
Saenboonrueng, Janya
Poonsuk, Sukontip
Jengarn, Juggragarn
Viriyakitkosol, Ratchanont
Kramyu, Jarin
Jongkaewwattana, Anan
A Single-Cycle Influenza A Virus-Based SARS-CoV-2 Vaccine Elicits Potent Immune Responses in a Mouse Model
title A Single-Cycle Influenza A Virus-Based SARS-CoV-2 Vaccine Elicits Potent Immune Responses in a Mouse Model
title_full A Single-Cycle Influenza A Virus-Based SARS-CoV-2 Vaccine Elicits Potent Immune Responses in a Mouse Model
title_fullStr A Single-Cycle Influenza A Virus-Based SARS-CoV-2 Vaccine Elicits Potent Immune Responses in a Mouse Model
title_full_unstemmed A Single-Cycle Influenza A Virus-Based SARS-CoV-2 Vaccine Elicits Potent Immune Responses in a Mouse Model
title_short A Single-Cycle Influenza A Virus-Based SARS-CoV-2 Vaccine Elicits Potent Immune Responses in a Mouse Model
title_sort single-cycle influenza a virus-based sars-cov-2 vaccine elicits potent immune responses in a mouse model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402467/
https://www.ncbi.nlm.nih.gov/pubmed/34451975
http://dx.doi.org/10.3390/vaccines9080850
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