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A self-amplifying RNA vaccine provides protection in a murine model of bubonic plague
Mice were immunized with a combination of self-amplifying (sa) RNA constructs for the F1 and V antigens of Yersinia pestis at a dose level of 1 μg or 5 μg or with the respective protein sub-units as a reference vaccine. The immunization of outbred OF1 mice on day 0 and day 28 with the lowest dose us...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10652872/ https://www.ncbi.nlm.nih.gov/pubmed/38029221 http://dx.doi.org/10.3389/fmicb.2023.1247041 |
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author | Shattock, Robin John Andrianaivoarimanana, Voahangy McKay, Paul F. Randriantseheno, Lovasoa Nomena Murugaiah, Valarmathy Samnuan, K. Rogers, Paul Tregoning, John S. Rajerison, Minoarisoa Moore, Kristoffer M. Laws, Thomas Robert Williamson, E. Diane |
author_facet | Shattock, Robin John Andrianaivoarimanana, Voahangy McKay, Paul F. Randriantseheno, Lovasoa Nomena Murugaiah, Valarmathy Samnuan, K. Rogers, Paul Tregoning, John S. Rajerison, Minoarisoa Moore, Kristoffer M. Laws, Thomas Robert Williamson, E. Diane |
author_sort | Shattock, Robin John |
collection | PubMed |
description | Mice were immunized with a combination of self-amplifying (sa) RNA constructs for the F1 and V antigens of Yersinia pestis at a dose level of 1 μg or 5 μg or with the respective protein sub-units as a reference vaccine. The immunization of outbred OF1 mice on day 0 and day 28 with the lowest dose used (1 μg) of each of the saRNA constructs in lipid nanoparticles protected 5/7 mice against subsequent sub-cutaneous challenge on day 56 with 180 cfu (2.8 MLD) of a 2021 clinical isolate of Y. pestis termed 10-21/S whilst 5/7 mice were protected against 1800cfu (28MLD) of the same bacteria on day 56. By comparison, only 1/8 or 1/7 negative control mice immunized with 10 μg of irrelevant haemagglutin RNA in lipid nanoparticles (LNP) survived the challenge with 2.8 MLD or 28 MLD Y. pestis 10-21/S, respectively. BALB/c mice were also immunized with the same saRNA constructs and responded with the secretion of specific IgG to F1 and V, neutralizing antibodies for the V antigen and developed a recall response to both F1 and V. These data represent the first report of an RNA vaccine approach using self-amplifying technology and encoding both of the essential virulence antigens, providing efficacy against Y. pestis. This saRNA vaccine for plague has the potential for further development, particularly since its amplifying nature can induce immunity with less boosting. It is also amenable to rapid manufacture with simpler downstream processing than protein sub-units, enabling rapid deployment and surge manufacture during disease outbreaks. |
format | Online Article Text |
id | pubmed-10652872 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-106528722023-11-02 A self-amplifying RNA vaccine provides protection in a murine model of bubonic plague Shattock, Robin John Andrianaivoarimanana, Voahangy McKay, Paul F. Randriantseheno, Lovasoa Nomena Murugaiah, Valarmathy Samnuan, K. Rogers, Paul Tregoning, John S. Rajerison, Minoarisoa Moore, Kristoffer M. Laws, Thomas Robert Williamson, E. Diane Front Microbiol Microbiology Mice were immunized with a combination of self-amplifying (sa) RNA constructs for the F1 and V antigens of Yersinia pestis at a dose level of 1 μg or 5 μg or with the respective protein sub-units as a reference vaccine. The immunization of outbred OF1 mice on day 0 and day 28 with the lowest dose used (1 μg) of each of the saRNA constructs in lipid nanoparticles protected 5/7 mice against subsequent sub-cutaneous challenge on day 56 with 180 cfu (2.8 MLD) of a 2021 clinical isolate of Y. pestis termed 10-21/S whilst 5/7 mice were protected against 1800cfu (28MLD) of the same bacteria on day 56. By comparison, only 1/8 or 1/7 negative control mice immunized with 10 μg of irrelevant haemagglutin RNA in lipid nanoparticles (LNP) survived the challenge with 2.8 MLD or 28 MLD Y. pestis 10-21/S, respectively. BALB/c mice were also immunized with the same saRNA constructs and responded with the secretion of specific IgG to F1 and V, neutralizing antibodies for the V antigen and developed a recall response to both F1 and V. These data represent the first report of an RNA vaccine approach using self-amplifying technology and encoding both of the essential virulence antigens, providing efficacy against Y. pestis. This saRNA vaccine for plague has the potential for further development, particularly since its amplifying nature can induce immunity with less boosting. It is also amenable to rapid manufacture with simpler downstream processing than protein sub-units, enabling rapid deployment and surge manufacture during disease outbreaks. Frontiers Media S.A. 2023-11-02 /pmc/articles/PMC10652872/ /pubmed/38029221 http://dx.doi.org/10.3389/fmicb.2023.1247041 Text en Copyright © 2023 Shattock, Andrianaivoarimanana, McKay, Randriantseheno, Murugaiah, Samnuan, Rogers, Tregoning, Rajerison, Moore, Laws and Williamson. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Microbiology Shattock, Robin John Andrianaivoarimanana, Voahangy McKay, Paul F. Randriantseheno, Lovasoa Nomena Murugaiah, Valarmathy Samnuan, K. Rogers, Paul Tregoning, John S. Rajerison, Minoarisoa Moore, Kristoffer M. Laws, Thomas Robert Williamson, E. Diane A self-amplifying RNA vaccine provides protection in a murine model of bubonic plague |
title | A self-amplifying RNA vaccine provides protection in a murine model of bubonic plague |
title_full | A self-amplifying RNA vaccine provides protection in a murine model of bubonic plague |
title_fullStr | A self-amplifying RNA vaccine provides protection in a murine model of bubonic plague |
title_full_unstemmed | A self-amplifying RNA vaccine provides protection in a murine model of bubonic plague |
title_short | A self-amplifying RNA vaccine provides protection in a murine model of bubonic plague |
title_sort | self-amplifying rna vaccine provides protection in a murine model of bubonic plague |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10652872/ https://www.ncbi.nlm.nih.gov/pubmed/38029221 http://dx.doi.org/10.3389/fmicb.2023.1247041 |
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