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Chimeric Virus-like Particle-Based COVID-19 Vaccine Confers Strong Protection against SARS-CoV-2 Viremia in K18-hACE2 Mice
Virus-like particles (VLPs) are highly immunogenic and versatile subunit vaccines composed of multimeric viral proteins that mimic the whole virus but lack genetic material. Due to the lack of infectivity, VLPs are being developed as safe and effective vaccines against various infectious diseases. I...
Autores principales: | , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9143195/ https://www.ncbi.nlm.nih.gov/pubmed/35632541 http://dx.doi.org/10.3390/vaccines10050786 |
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author | Kaewborisuth, Challika Wanitchang, Asawin Koonpaew, Surapong Srisutthisamphan, Kanjana Saenboonrueng, Janya Im-Erbsin, Rawiwan Inthawong, Manutsanun Sunyakumthorn, Piyanate Thaweerattanasinp, Theeradej Tanwattana, Nathiphat Jantraphakorn, Yuparat Reed, Matthew C. Lugo-Roman, Luis A. Hunsawong, Taweewun Klungthong, Chonticha Jones, Anthony R. Fernandez, Stefan Teeravechyan, Samaporn Lombardini, Eric D. Jongkaewwattana, Anan |
author_facet | Kaewborisuth, Challika Wanitchang, Asawin Koonpaew, Surapong Srisutthisamphan, Kanjana Saenboonrueng, Janya Im-Erbsin, Rawiwan Inthawong, Manutsanun Sunyakumthorn, Piyanate Thaweerattanasinp, Theeradej Tanwattana, Nathiphat Jantraphakorn, Yuparat Reed, Matthew C. Lugo-Roman, Luis A. Hunsawong, Taweewun Klungthong, Chonticha Jones, Anthony R. Fernandez, Stefan Teeravechyan, Samaporn Lombardini, Eric D. Jongkaewwattana, Anan |
author_sort | Kaewborisuth, Challika |
collection | PubMed |
description | Virus-like particles (VLPs) are highly immunogenic and versatile subunit vaccines composed of multimeric viral proteins that mimic the whole virus but lack genetic material. Due to the lack of infectivity, VLPs are being developed as safe and effective vaccines against various infectious diseases. In this study, we generated a chimeric VLP-based COVID-19 vaccine stably produced by HEK293T cells. The chimeric VLPs contain the influenza virus A matrix (M1) proteins and the SARS-CoV-2 Wuhan strain spike (S) proteins with a deletion of the polybasic furin cleavage motif and a replacement of the transmembrane and cytoplasmic tail with that of the influenza virus hemagglutinin (HA). These resulting chimeric S-M1 VLPs, displaying S and M1, were observed to be enveloped particles that are heterogeneous in shape and size. The intramuscular vaccination of BALB/c mice in a prime-boost regimen elicited high titers of S-specific IgG and neutralizing antibodies. After immunization and a challenge with SARS-CoV-2 in K18-hACE2 mice, the S-M1 VLP vaccination resulted in a drastic reduction in viremia, as well as a decreased viral load in the lungs and improved survival rates compared to the control mice. Balanced Th1 and Th2 responses of activated S-specific T-cells were observed. Moderate degrees of inflammation and viral RNA in the lungs and brains were observed in the vaccinated group; however, brain lesion scores were less than in the PBS control. Overall, we demonstrate the immunogenicity of a chimeric VLP-based COVID-19 vaccine which confers strong protection against SARS-CoV-2 viremia in mice. |
format | Online Article Text |
id | pubmed-9143195 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-91431952022-05-29 Chimeric Virus-like Particle-Based COVID-19 Vaccine Confers Strong Protection against SARS-CoV-2 Viremia in K18-hACE2 Mice Kaewborisuth, Challika Wanitchang, Asawin Koonpaew, Surapong Srisutthisamphan, Kanjana Saenboonrueng, Janya Im-Erbsin, Rawiwan Inthawong, Manutsanun Sunyakumthorn, Piyanate Thaweerattanasinp, Theeradej Tanwattana, Nathiphat Jantraphakorn, Yuparat Reed, Matthew C. Lugo-Roman, Luis A. Hunsawong, Taweewun Klungthong, Chonticha Jones, Anthony R. Fernandez, Stefan Teeravechyan, Samaporn Lombardini, Eric D. Jongkaewwattana, Anan Vaccines (Basel) Article Virus-like particles (VLPs) are highly immunogenic and versatile subunit vaccines composed of multimeric viral proteins that mimic the whole virus but lack genetic material. Due to the lack of infectivity, VLPs are being developed as safe and effective vaccines against various infectious diseases. In this study, we generated a chimeric VLP-based COVID-19 vaccine stably produced by HEK293T cells. The chimeric VLPs contain the influenza virus A matrix (M1) proteins and the SARS-CoV-2 Wuhan strain spike (S) proteins with a deletion of the polybasic furin cleavage motif and a replacement of the transmembrane and cytoplasmic tail with that of the influenza virus hemagglutinin (HA). These resulting chimeric S-M1 VLPs, displaying S and M1, were observed to be enveloped particles that are heterogeneous in shape and size. The intramuscular vaccination of BALB/c mice in a prime-boost regimen elicited high titers of S-specific IgG and neutralizing antibodies. After immunization and a challenge with SARS-CoV-2 in K18-hACE2 mice, the S-M1 VLP vaccination resulted in a drastic reduction in viremia, as well as a decreased viral load in the lungs and improved survival rates compared to the control mice. Balanced Th1 and Th2 responses of activated S-specific T-cells were observed. Moderate degrees of inflammation and viral RNA in the lungs and brains were observed in the vaccinated group; however, brain lesion scores were less than in the PBS control. Overall, we demonstrate the immunogenicity of a chimeric VLP-based COVID-19 vaccine which confers strong protection against SARS-CoV-2 viremia in mice. MDPI 2022-05-16 /pmc/articles/PMC9143195/ /pubmed/35632541 http://dx.doi.org/10.3390/vaccines10050786 Text en © 2022 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 Kaewborisuth, Challika Wanitchang, Asawin Koonpaew, Surapong Srisutthisamphan, Kanjana Saenboonrueng, Janya Im-Erbsin, Rawiwan Inthawong, Manutsanun Sunyakumthorn, Piyanate Thaweerattanasinp, Theeradej Tanwattana, Nathiphat Jantraphakorn, Yuparat Reed, Matthew C. Lugo-Roman, Luis A. Hunsawong, Taweewun Klungthong, Chonticha Jones, Anthony R. Fernandez, Stefan Teeravechyan, Samaporn Lombardini, Eric D. Jongkaewwattana, Anan Chimeric Virus-like Particle-Based COVID-19 Vaccine Confers Strong Protection against SARS-CoV-2 Viremia in K18-hACE2 Mice |
title | Chimeric Virus-like Particle-Based COVID-19 Vaccine Confers Strong Protection against SARS-CoV-2 Viremia in K18-hACE2 Mice |
title_full | Chimeric Virus-like Particle-Based COVID-19 Vaccine Confers Strong Protection against SARS-CoV-2 Viremia in K18-hACE2 Mice |
title_fullStr | Chimeric Virus-like Particle-Based COVID-19 Vaccine Confers Strong Protection against SARS-CoV-2 Viremia in K18-hACE2 Mice |
title_full_unstemmed | Chimeric Virus-like Particle-Based COVID-19 Vaccine Confers Strong Protection against SARS-CoV-2 Viremia in K18-hACE2 Mice |
title_short | Chimeric Virus-like Particle-Based COVID-19 Vaccine Confers Strong Protection against SARS-CoV-2 Viremia in K18-hACE2 Mice |
title_sort | chimeric virus-like particle-based covid-19 vaccine confers strong protection against sars-cov-2 viremia in k18-hace2 mice |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9143195/ https://www.ncbi.nlm.nih.gov/pubmed/35632541 http://dx.doi.org/10.3390/vaccines10050786 |
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