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Rational development of a protective P. vivax vaccine evaluated with transgenic rodent parasite challenge models
Development of a protective and broadly-acting vaccine against the most widely distributed human malaria parasite, Plasmodium vivax, will be a major step towards malaria elimination. However, a P. vivax vaccine has remained elusive by the scarcity of pre-clinical models to test protective efficacy a...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5394459/ https://www.ncbi.nlm.nih.gov/pubmed/28417968 http://dx.doi.org/10.1038/srep46482 |
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author | Salman, Ahmed M. Montoya-Díaz, Eduardo West, Heather Lall, Amar Atcheson, Erwan Lopez-Camacho, Cesar Ramesar, Jai Bauza, Karolis Collins, Katharine A. Brod, Florian Reis, Fernando Pappas, Leontios González-Cerón, Lilia Janse, Chris J. Hill, Adrian V. S. Khan, Shahid M. Reyes-Sandoval, Arturo |
author_facet | Salman, Ahmed M. Montoya-Díaz, Eduardo West, Heather Lall, Amar Atcheson, Erwan Lopez-Camacho, Cesar Ramesar, Jai Bauza, Karolis Collins, Katharine A. Brod, Florian Reis, Fernando Pappas, Leontios González-Cerón, Lilia Janse, Chris J. Hill, Adrian V. S. Khan, Shahid M. Reyes-Sandoval, Arturo |
author_sort | Salman, Ahmed M. |
collection | PubMed |
description | Development of a protective and broadly-acting vaccine against the most widely distributed human malaria parasite, Plasmodium vivax, will be a major step towards malaria elimination. However, a P. vivax vaccine has remained elusive by the scarcity of pre-clinical models to test protective efficacy and support further clinical trials. In this study, we report the development of a highly protective CSP-based P. vivax vaccine, a virus-like particle (VLP) known as Rv21, able to provide 100% sterile protection against a stringent sporozoite challenge in rodent models to malaria, where IgG2a antibodies were associated with protection in absence of detectable PvCSP-specific T cell responses. Additionally, we generated two novel transgenic rodent P. berghei parasite lines, where the P. berghei csp gene coding sequence has been replaced with either full-length P. vivax VK210 or the allelic VK247 csp that additionally express GFP-Luciferase. Efficacy of Rv21 surpassed viral-vectored vaccination using ChAd63 and MVA. We show for the first time that a chimeric VK210/247 antigen can elicit high level cross-protection against parasites expressing either CSP allele, which provide accessible and affordable models suitable to support the development of P. vivax vaccines candidates. Rv21 is progressing to GMP production and has entered a path towards clinical evaluation. |
format | Online Article Text |
id | pubmed-5394459 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-53944592017-04-20 Rational development of a protective P. vivax vaccine evaluated with transgenic rodent parasite challenge models Salman, Ahmed M. Montoya-Díaz, Eduardo West, Heather Lall, Amar Atcheson, Erwan Lopez-Camacho, Cesar Ramesar, Jai Bauza, Karolis Collins, Katharine A. Brod, Florian Reis, Fernando Pappas, Leontios González-Cerón, Lilia Janse, Chris J. Hill, Adrian V. S. Khan, Shahid M. Reyes-Sandoval, Arturo Sci Rep Article Development of a protective and broadly-acting vaccine against the most widely distributed human malaria parasite, Plasmodium vivax, will be a major step towards malaria elimination. However, a P. vivax vaccine has remained elusive by the scarcity of pre-clinical models to test protective efficacy and support further clinical trials. In this study, we report the development of a highly protective CSP-based P. vivax vaccine, a virus-like particle (VLP) known as Rv21, able to provide 100% sterile protection against a stringent sporozoite challenge in rodent models to malaria, where IgG2a antibodies were associated with protection in absence of detectable PvCSP-specific T cell responses. Additionally, we generated two novel transgenic rodent P. berghei parasite lines, where the P. berghei csp gene coding sequence has been replaced with either full-length P. vivax VK210 or the allelic VK247 csp that additionally express GFP-Luciferase. Efficacy of Rv21 surpassed viral-vectored vaccination using ChAd63 and MVA. We show for the first time that a chimeric VK210/247 antigen can elicit high level cross-protection against parasites expressing either CSP allele, which provide accessible and affordable models suitable to support the development of P. vivax vaccines candidates. Rv21 is progressing to GMP production and has entered a path towards clinical evaluation. Nature Publishing Group 2017-04-18 /pmc/articles/PMC5394459/ /pubmed/28417968 http://dx.doi.org/10.1038/srep46482 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Salman, Ahmed M. Montoya-Díaz, Eduardo West, Heather Lall, Amar Atcheson, Erwan Lopez-Camacho, Cesar Ramesar, Jai Bauza, Karolis Collins, Katharine A. Brod, Florian Reis, Fernando Pappas, Leontios González-Cerón, Lilia Janse, Chris J. Hill, Adrian V. S. Khan, Shahid M. Reyes-Sandoval, Arturo Rational development of a protective P. vivax vaccine evaluated with transgenic rodent parasite challenge models |
title | Rational development of a protective P. vivax vaccine evaluated with transgenic rodent parasite challenge models |
title_full | Rational development of a protective P. vivax vaccine evaluated with transgenic rodent parasite challenge models |
title_fullStr | Rational development of a protective P. vivax vaccine evaluated with transgenic rodent parasite challenge models |
title_full_unstemmed | Rational development of a protective P. vivax vaccine evaluated with transgenic rodent parasite challenge models |
title_short | Rational development of a protective P. vivax vaccine evaluated with transgenic rodent parasite challenge models |
title_sort | rational development of a protective p. vivax vaccine evaluated with transgenic rodent parasite challenge models |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5394459/ https://www.ncbi.nlm.nih.gov/pubmed/28417968 http://dx.doi.org/10.1038/srep46482 |
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