Cargando…
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...
Autores principales: | , , , , , , , , , , |
---|---|
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 |
_version_ | 1783745796603117568 |
---|---|
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. |
format | Online Article Text |
id | pubmed-8402467 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT koonpaewsurapong asinglecycleinfluenzaavirusbasedsarscov2vaccineelicitspotentimmuneresponsesinamousemodel AT kaewborisuthchallika asinglecycleinfluenzaavirusbasedsarscov2vaccineelicitspotentimmuneresponsesinamousemodel AT srisutthisamphankanjana asinglecycleinfluenzaavirusbasedsarscov2vaccineelicitspotentimmuneresponsesinamousemodel AT wanitchangasawin asinglecycleinfluenzaavirusbasedsarscov2vaccineelicitspotentimmuneresponsesinamousemodel AT thaweerattanasinptheeradej asinglecycleinfluenzaavirusbasedsarscov2vaccineelicitspotentimmuneresponsesinamousemodel AT saenboonruengjanya asinglecycleinfluenzaavirusbasedsarscov2vaccineelicitspotentimmuneresponsesinamousemodel AT poonsuksukontip asinglecycleinfluenzaavirusbasedsarscov2vaccineelicitspotentimmuneresponsesinamousemodel AT jengarnjuggragarn asinglecycleinfluenzaavirusbasedsarscov2vaccineelicitspotentimmuneresponsesinamousemodel AT viriyakitkosolratchanont asinglecycleinfluenzaavirusbasedsarscov2vaccineelicitspotentimmuneresponsesinamousemodel AT kramyujarin asinglecycleinfluenzaavirusbasedsarscov2vaccineelicitspotentimmuneresponsesinamousemodel AT jongkaewwattanaanan asinglecycleinfluenzaavirusbasedsarscov2vaccineelicitspotentimmuneresponsesinamousemodel AT koonpaewsurapong singlecycleinfluenzaavirusbasedsarscov2vaccineelicitspotentimmuneresponsesinamousemodel AT kaewborisuthchallika singlecycleinfluenzaavirusbasedsarscov2vaccineelicitspotentimmuneresponsesinamousemodel AT srisutthisamphankanjana singlecycleinfluenzaavirusbasedsarscov2vaccineelicitspotentimmuneresponsesinamousemodel AT wanitchangasawin singlecycleinfluenzaavirusbasedsarscov2vaccineelicitspotentimmuneresponsesinamousemodel AT thaweerattanasinptheeradej singlecycleinfluenzaavirusbasedsarscov2vaccineelicitspotentimmuneresponsesinamousemodel AT saenboonruengjanya singlecycleinfluenzaavirusbasedsarscov2vaccineelicitspotentimmuneresponsesinamousemodel AT poonsuksukontip singlecycleinfluenzaavirusbasedsarscov2vaccineelicitspotentimmuneresponsesinamousemodel AT jengarnjuggragarn singlecycleinfluenzaavirusbasedsarscov2vaccineelicitspotentimmuneresponsesinamousemodel AT viriyakitkosolratchanont singlecycleinfluenzaavirusbasedsarscov2vaccineelicitspotentimmuneresponsesinamousemodel AT kramyujarin singlecycleinfluenzaavirusbasedsarscov2vaccineelicitspotentimmuneresponsesinamousemodel AT jongkaewwattanaanan singlecycleinfluenzaavirusbasedsarscov2vaccineelicitspotentimmuneresponsesinamousemodel |