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Phase I randomized, observer-blinded, placebo-controlled study of a SARS-CoV-2 mRNA vaccine PTX-COVID19-B
Access to vaccines against SARS-CoV-2 virus was limited in poor countries during the COVID-19 pandemic. Therefore, a low-cost mRNA vaccine, PTX-COVID19-B, was produced and evaluated in a Phase 1 trial. PTX-COVID19-B encodes Spike protein D614G variant without the proline-proline (986–987) mutation p...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10214351/ https://www.ncbi.nlm.nih.gov/pubmed/37236995 http://dx.doi.org/10.1038/s41598-023-35662-y |
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author | Martin-Orozco, Natalia Vale, Noah Mihic, Alan Amor, Talya Reiter, Lawrence Arita, Yuko Samson, Reuben Hu, Queenie Gingras, Anne-Claude Sorenson, Bradley Thomas Marcusson, Eric Gates Patel, Piyush |
author_facet | Martin-Orozco, Natalia Vale, Noah Mihic, Alan Amor, Talya Reiter, Lawrence Arita, Yuko Samson, Reuben Hu, Queenie Gingras, Anne-Claude Sorenson, Bradley Thomas Marcusson, Eric Gates Patel, Piyush |
author_sort | Martin-Orozco, Natalia |
collection | PubMed |
description | Access to vaccines against SARS-CoV-2 virus was limited in poor countries during the COVID-19 pandemic. Therefore, a low-cost mRNA vaccine, PTX-COVID19-B, was produced and evaluated in a Phase 1 trial. PTX-COVID19-B encodes Spike protein D614G variant without the proline-proline (986–987) mutation present in other COVID-19 vaccines. The aim of the study was to evaluate safety, tolerability, and immunogenicity of PTX-COVID19-B vaccine in healthy seronegative adults 18–64 years old. The trial design was observer-blinded, randomized, placebo-controlled, and tested ascending doses of 16-µg, 40-µg, or 100-µg in a total of 60 subjects who received two intramuscular doses, 4 weeks apart. Participants were monitored for solicited and unsolicited adverse events after vaccination and were provided with a Diary Card and thermometer to report any reactogenicity during the trial. Blood samples were collected on baseline, days 8, 28, 42, 90, and 180 for serum analysis of total IgG anti-receptor binding domain (RBD)/Spike titers by ELISA, and neutralizing antibody titers by pseudovirus assay. Titers in BAU/mL were reported as geometric mean and 95% CI per cohort. After vaccination, few solicited adverse events were observed and were mild to moderate and self-resolved within 48 h. The most common solicited local and systemic adverse event was pain at the injection site, and headache, respectively. Seroconversion was observed in all vaccinated participants, who showed high antibody titers against RBD, Spike, and neutralizing activity against the Wuhan strain. Neutralizing antibody titers were also detected against Alpha, Beta, and Delta variants of concerns in a dose dependent manner. All tested doses of PTX-COVID19-B were safe, well-tolerated, and provided a strong immunogenicity response. The 40-µg dose showed fewer adverse reactions than the 100-µg dose, and therefore was selected for a Phase 2 trial, which is currently ongoing. Clinical Trial Registration number: NCT04765436 (21/02/2021). (https://clinicaltrials.gov/ct2/show/NCT04765436). |
format | Online Article Text |
id | pubmed-10214351 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-102143512023-05-28 Phase I randomized, observer-blinded, placebo-controlled study of a SARS-CoV-2 mRNA vaccine PTX-COVID19-B Martin-Orozco, Natalia Vale, Noah Mihic, Alan Amor, Talya Reiter, Lawrence Arita, Yuko Samson, Reuben Hu, Queenie Gingras, Anne-Claude Sorenson, Bradley Thomas Marcusson, Eric Gates Patel, Piyush Sci Rep Article Access to vaccines against SARS-CoV-2 virus was limited in poor countries during the COVID-19 pandemic. Therefore, a low-cost mRNA vaccine, PTX-COVID19-B, was produced and evaluated in a Phase 1 trial. PTX-COVID19-B encodes Spike protein D614G variant without the proline-proline (986–987) mutation present in other COVID-19 vaccines. The aim of the study was to evaluate safety, tolerability, and immunogenicity of PTX-COVID19-B vaccine in healthy seronegative adults 18–64 years old. The trial design was observer-blinded, randomized, placebo-controlled, and tested ascending doses of 16-µg, 40-µg, or 100-µg in a total of 60 subjects who received two intramuscular doses, 4 weeks apart. Participants were monitored for solicited and unsolicited adverse events after vaccination and were provided with a Diary Card and thermometer to report any reactogenicity during the trial. Blood samples were collected on baseline, days 8, 28, 42, 90, and 180 for serum analysis of total IgG anti-receptor binding domain (RBD)/Spike titers by ELISA, and neutralizing antibody titers by pseudovirus assay. Titers in BAU/mL were reported as geometric mean and 95% CI per cohort. After vaccination, few solicited adverse events were observed and were mild to moderate and self-resolved within 48 h. The most common solicited local and systemic adverse event was pain at the injection site, and headache, respectively. Seroconversion was observed in all vaccinated participants, who showed high antibody titers against RBD, Spike, and neutralizing activity against the Wuhan strain. Neutralizing antibody titers were also detected against Alpha, Beta, and Delta variants of concerns in a dose dependent manner. All tested doses of PTX-COVID19-B were safe, well-tolerated, and provided a strong immunogenicity response. The 40-µg dose showed fewer adverse reactions than the 100-µg dose, and therefore was selected for a Phase 2 trial, which is currently ongoing. Clinical Trial Registration number: NCT04765436 (21/02/2021). (https://clinicaltrials.gov/ct2/show/NCT04765436). Nature Publishing Group UK 2023-05-26 /pmc/articles/PMC10214351/ /pubmed/37236995 http://dx.doi.org/10.1038/s41598-023-35662-y Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Martin-Orozco, Natalia Vale, Noah Mihic, Alan Amor, Talya Reiter, Lawrence Arita, Yuko Samson, Reuben Hu, Queenie Gingras, Anne-Claude Sorenson, Bradley Thomas Marcusson, Eric Gates Patel, Piyush Phase I randomized, observer-blinded, placebo-controlled study of a SARS-CoV-2 mRNA vaccine PTX-COVID19-B |
title | Phase I randomized, observer-blinded, placebo-controlled study of a SARS-CoV-2 mRNA vaccine PTX-COVID19-B |
title_full | Phase I randomized, observer-blinded, placebo-controlled study of a SARS-CoV-2 mRNA vaccine PTX-COVID19-B |
title_fullStr | Phase I randomized, observer-blinded, placebo-controlled study of a SARS-CoV-2 mRNA vaccine PTX-COVID19-B |
title_full_unstemmed | Phase I randomized, observer-blinded, placebo-controlled study of a SARS-CoV-2 mRNA vaccine PTX-COVID19-B |
title_short | Phase I randomized, observer-blinded, placebo-controlled study of a SARS-CoV-2 mRNA vaccine PTX-COVID19-B |
title_sort | phase i randomized, observer-blinded, placebo-controlled study of a sars-cov-2 mrna vaccine ptx-covid19-b |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10214351/ https://www.ncbi.nlm.nih.gov/pubmed/37236995 http://dx.doi.org/10.1038/s41598-023-35662-y |
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