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Immunogenicity of Multiple Doses of pDNA Vaccines against SARS-CoV-2

Since its identification in Wuhan, China, in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has resulted in 46 million cases and more than one million deaths worldwide, as of 30 October 2020. Limited data exist...

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Autores principales: Almansour, Iman, Macadato, Nabela Calamata, Alshammari, Thamer
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825551/
https://www.ncbi.nlm.nih.gov/pubmed/33419184
http://dx.doi.org/10.3390/ph14010039
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author Almansour, Iman
Macadato, Nabela Calamata
Alshammari, Thamer
author_facet Almansour, Iman
Macadato, Nabela Calamata
Alshammari, Thamer
author_sort Almansour, Iman
collection PubMed
description Since its identification in Wuhan, China, in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has resulted in 46 million cases and more than one million deaths worldwide, as of 30 October 2020. Limited data exist on the magnitude and durability of antibodies generated by natural infection with SARS-CoV-2 and whether they can provide long-lasting immunity from reinfection. Vaccination has proven the most effective measure for controlling and preventing pandemics and, thus, development of a vaccine against COVID-19 is a top priority. However, the doses required to induce effective, long-lasting antibody responses against SARS-CoV-2 remain undetermined. Here, we present the development of SARS-CoV-2 vaccine candidates encoding the viral spike (S) gene, generated using plasmid (p)DNA technology, and we demonstrate the eliciting of S-specific antibodies in mice after three and four doses. The magnitude of binding and neutralizing antibody responses with three doses of synthetic, codon-optimized, full-length S (S.opt.FL) vaccine is comparable to that generated after four doses, suggesting that three doses are sufficient to elicit robust immune responses. Conversely, four doses of S1.opt pDNA vaccine, containing the S globular head, are required to elicit high levels of neutralizing antibodies. Furthermore, the S.opt.FL pDNA vaccine induces the highest serum levels of interferon (IFN)-γ, a marker for activation of cellular immune responses. Overall, our data show that three doses of S.FL pDNA vaccine elicit potent neutralizing antibody responses, with preclinical data that support the immunogenicity of these COVID-19 vaccine candidates and provide justification for further translational studies.
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spelling pubmed-78255512021-01-24 Immunogenicity of Multiple Doses of pDNA Vaccines against SARS-CoV-2 Almansour, Iman Macadato, Nabela Calamata Alshammari, Thamer Pharmaceuticals (Basel) Article Since its identification in Wuhan, China, in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has resulted in 46 million cases and more than one million deaths worldwide, as of 30 October 2020. Limited data exist on the magnitude and durability of antibodies generated by natural infection with SARS-CoV-2 and whether they can provide long-lasting immunity from reinfection. Vaccination has proven the most effective measure for controlling and preventing pandemics and, thus, development of a vaccine against COVID-19 is a top priority. However, the doses required to induce effective, long-lasting antibody responses against SARS-CoV-2 remain undetermined. Here, we present the development of SARS-CoV-2 vaccine candidates encoding the viral spike (S) gene, generated using plasmid (p)DNA technology, and we demonstrate the eliciting of S-specific antibodies in mice after three and four doses. The magnitude of binding and neutralizing antibody responses with three doses of synthetic, codon-optimized, full-length S (S.opt.FL) vaccine is comparable to that generated after four doses, suggesting that three doses are sufficient to elicit robust immune responses. Conversely, four doses of S1.opt pDNA vaccine, containing the S globular head, are required to elicit high levels of neutralizing antibodies. Furthermore, the S.opt.FL pDNA vaccine induces the highest serum levels of interferon (IFN)-γ, a marker for activation of cellular immune responses. Overall, our data show that three doses of S.FL pDNA vaccine elicit potent neutralizing antibody responses, with preclinical data that support the immunogenicity of these COVID-19 vaccine candidates and provide justification for further translational studies. MDPI 2021-01-06 /pmc/articles/PMC7825551/ /pubmed/33419184 http://dx.doi.org/10.3390/ph14010039 Text en © 2021 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Almansour, Iman
Macadato, Nabela Calamata
Alshammari, Thamer
Immunogenicity of Multiple Doses of pDNA Vaccines against SARS-CoV-2
title Immunogenicity of Multiple Doses of pDNA Vaccines against SARS-CoV-2
title_full Immunogenicity of Multiple Doses of pDNA Vaccines against SARS-CoV-2
title_fullStr Immunogenicity of Multiple Doses of pDNA Vaccines against SARS-CoV-2
title_full_unstemmed Immunogenicity of Multiple Doses of pDNA Vaccines against SARS-CoV-2
title_short Immunogenicity of Multiple Doses of pDNA Vaccines against SARS-CoV-2
title_sort immunogenicity of multiple doses of pdna vaccines against sars-cov-2
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7825551/
https://www.ncbi.nlm.nih.gov/pubmed/33419184
http://dx.doi.org/10.3390/ph14010039
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