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Immunization with Transgenic Rodent Malaria Parasites Expressing Pfs25 Induces Potent Transmission-Blocking Activity

An anti-malarial transmission blocking vaccine (TBV) would be an important tool for disease control or elimination, though current candidates have failed to induce high efficacy in clinical studies. The ookinete surface protein P25 is a primary target for TBV development, but heterologous expression...

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Autores principales: Sala, K. A., Angrisano, F., Da, D. F., Taylor, I. J., Churcher, T. S., Blagborough, A. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5785477/
https://www.ncbi.nlm.nih.gov/pubmed/29371619
http://dx.doi.org/10.1038/s41598-017-18831-8
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author Sala, K. A.
Angrisano, F.
Da, D. F.
Taylor, I. J.
Churcher, T. S.
Blagborough, A. M.
author_facet Sala, K. A.
Angrisano, F.
Da, D. F.
Taylor, I. J.
Churcher, T. S.
Blagborough, A. M.
author_sort Sala, K. A.
collection PubMed
description An anti-malarial transmission blocking vaccine (TBV) would be an important tool for disease control or elimination, though current candidates have failed to induce high efficacy in clinical studies. The ookinete surface protein P25 is a primary target for TBV development, but heterologous expression of P25 with appropriate conformation is problematic and a pre-requisite for achieving functional titers. A potential alternative to recombinant/sub-unit vaccine is immunization with a non-pathogenic, whole-parasite vaccine. This study examines the ability of a purified transgenic rodent-malaria parasite (PbPfs25DR3), expressing Plasmodium falciparum P25 in native conformation on the P. berghei ookinete surface, to act as a TBV. Vaccination with purified PbPfs25DR3 ookinetes produces a potent anti-Pfs25 response and high transmission-blocking efficacy in the laboratory, findings that are then translated to experimentation on natural field isolates of P. falciparum from infected individuals in Burkina Faso. Efficacy is demonstrated in the lab and the field (up to 93.3%/97.1% reductions in transmission intensity respectively), with both a homologous strategy with one and two boosts, and as part of a prime-boost regime, providing support for the future development of a whole-parasite TBV.
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spelling pubmed-57854772018-02-07 Immunization with Transgenic Rodent Malaria Parasites Expressing Pfs25 Induces Potent Transmission-Blocking Activity Sala, K. A. Angrisano, F. Da, D. F. Taylor, I. J. Churcher, T. S. Blagborough, A. M. Sci Rep Article An anti-malarial transmission blocking vaccine (TBV) would be an important tool for disease control or elimination, though current candidates have failed to induce high efficacy in clinical studies. The ookinete surface protein P25 is a primary target for TBV development, but heterologous expression of P25 with appropriate conformation is problematic and a pre-requisite for achieving functional titers. A potential alternative to recombinant/sub-unit vaccine is immunization with a non-pathogenic, whole-parasite vaccine. This study examines the ability of a purified transgenic rodent-malaria parasite (PbPfs25DR3), expressing Plasmodium falciparum P25 in native conformation on the P. berghei ookinete surface, to act as a TBV. Vaccination with purified PbPfs25DR3 ookinetes produces a potent anti-Pfs25 response and high transmission-blocking efficacy in the laboratory, findings that are then translated to experimentation on natural field isolates of P. falciparum from infected individuals in Burkina Faso. Efficacy is demonstrated in the lab and the field (up to 93.3%/97.1% reductions in transmission intensity respectively), with both a homologous strategy with one and two boosts, and as part of a prime-boost regime, providing support for the future development of a whole-parasite TBV. Nature Publishing Group UK 2018-01-25 /pmc/articles/PMC5785477/ /pubmed/29371619 http://dx.doi.org/10.1038/s41598-017-18831-8 Text en © The Author(s) 2018 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Sala, K. A.
Angrisano, F.
Da, D. F.
Taylor, I. J.
Churcher, T. S.
Blagborough, A. M.
Immunization with Transgenic Rodent Malaria Parasites Expressing Pfs25 Induces Potent Transmission-Blocking Activity
title Immunization with Transgenic Rodent Malaria Parasites Expressing Pfs25 Induces Potent Transmission-Blocking Activity
title_full Immunization with Transgenic Rodent Malaria Parasites Expressing Pfs25 Induces Potent Transmission-Blocking Activity
title_fullStr Immunization with Transgenic Rodent Malaria Parasites Expressing Pfs25 Induces Potent Transmission-Blocking Activity
title_full_unstemmed Immunization with Transgenic Rodent Malaria Parasites Expressing Pfs25 Induces Potent Transmission-Blocking Activity
title_short Immunization with Transgenic Rodent Malaria Parasites Expressing Pfs25 Induces Potent Transmission-Blocking Activity
title_sort immunization with transgenic rodent malaria parasites expressing pfs25 induces potent transmission-blocking activity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5785477/
https://www.ncbi.nlm.nih.gov/pubmed/29371619
http://dx.doi.org/10.1038/s41598-017-18831-8
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