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Discovery of four new B-cell protective epitopes for malaria using Q beta virus-like particle as platform

Malaria remains one of the world’s most urgent global health problems, with almost half a million deaths and hundreds of millions of clinical cases each year. Existing interventions by themselves will not be enough to tackle infection in high-transmission areas. The best new intervention would be an...

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Autores principales: Atcheson, Erwan, Cabral-Miranda, Gustavo, Salman, Ahmed M., Reyes-Sandoval, Arturo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546618/
https://www.ncbi.nlm.nih.gov/pubmed/33083027
http://dx.doi.org/10.1038/s41541-020-00242-y
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author Atcheson, Erwan
Cabral-Miranda, Gustavo
Salman, Ahmed M.
Reyes-Sandoval, Arturo
author_facet Atcheson, Erwan
Cabral-Miranda, Gustavo
Salman, Ahmed M.
Reyes-Sandoval, Arturo
author_sort Atcheson, Erwan
collection PubMed
description Malaria remains one of the world’s most urgent global health problems, with almost half a million deaths and hundreds of millions of clinical cases each year. Existing interventions by themselves will not be enough to tackle infection in high-transmission areas. The best new intervention would be an effective vaccine; but the leading P. falciparum and P. vivax vaccine candidates, RTS,S and VMP001, show only modest to low field efficacy. New antigens and improved ways for screening antigens for protective efficacy will be required. This study exploits the potential of Virus-Like Particles (VLP) to enhance immune responses to antigens, the ease of coupling peptides to the Q beta (Qβ) VLP and the existing murine malaria challenge to screen B-cell epitopes for protective efficacy. We screened P. vivax TRAP (PvTRAP) immune sera against individual 20-mer PvTRAP peptides. The most immunogenic peptides associated with protection were loaded onto Qβ VLPs to assess protective efficacy in a malaria sporozoite challenge. A second approach focused on identifying conserved regions within known sporozoite invasion proteins and assessing them as part of the Qβ. Using this VLP as a peptide scaffold, four new protective B-cell epitopes were discovered: three from the disordered region of PvTRAP and one from Thrombospondin-related sporozoite protein (TRSP). Antigenic interference between these and other B-cell epitopes was also explored using the virus-like particle/peptide platform. This approach demonstrates the utility of VLPs to help identifying new B-cell epitopes for inclusion in next-generation malaria vaccines.
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spelling pubmed-75466182020-10-19 Discovery of four new B-cell protective epitopes for malaria using Q beta virus-like particle as platform Atcheson, Erwan Cabral-Miranda, Gustavo Salman, Ahmed M. Reyes-Sandoval, Arturo NPJ Vaccines Article Malaria remains one of the world’s most urgent global health problems, with almost half a million deaths and hundreds of millions of clinical cases each year. Existing interventions by themselves will not be enough to tackle infection in high-transmission areas. The best new intervention would be an effective vaccine; but the leading P. falciparum and P. vivax vaccine candidates, RTS,S and VMP001, show only modest to low field efficacy. New antigens and improved ways for screening antigens for protective efficacy will be required. This study exploits the potential of Virus-Like Particles (VLP) to enhance immune responses to antigens, the ease of coupling peptides to the Q beta (Qβ) VLP and the existing murine malaria challenge to screen B-cell epitopes for protective efficacy. We screened P. vivax TRAP (PvTRAP) immune sera against individual 20-mer PvTRAP peptides. The most immunogenic peptides associated with protection were loaded onto Qβ VLPs to assess protective efficacy in a malaria sporozoite challenge. A second approach focused on identifying conserved regions within known sporozoite invasion proteins and assessing them as part of the Qβ. Using this VLP as a peptide scaffold, four new protective B-cell epitopes were discovered: three from the disordered region of PvTRAP and one from Thrombospondin-related sporozoite protein (TRSP). Antigenic interference between these and other B-cell epitopes was also explored using the virus-like particle/peptide platform. This approach demonstrates the utility of VLPs to help identifying new B-cell epitopes for inclusion in next-generation malaria vaccines. Nature Publishing Group UK 2020-10-08 /pmc/articles/PMC7546618/ /pubmed/33083027 http://dx.doi.org/10.1038/s41541-020-00242-y Text en © The Author(s) 2020 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
Atcheson, Erwan
Cabral-Miranda, Gustavo
Salman, Ahmed M.
Reyes-Sandoval, Arturo
Discovery of four new B-cell protective epitopes for malaria using Q beta virus-like particle as platform
title Discovery of four new B-cell protective epitopes for malaria using Q beta virus-like particle as platform
title_full Discovery of four new B-cell protective epitopes for malaria using Q beta virus-like particle as platform
title_fullStr Discovery of four new B-cell protective epitopes for malaria using Q beta virus-like particle as platform
title_full_unstemmed Discovery of four new B-cell protective epitopes for malaria using Q beta virus-like particle as platform
title_short Discovery of four new B-cell protective epitopes for malaria using Q beta virus-like particle as platform
title_sort discovery of four new b-cell protective epitopes for malaria using q beta virus-like particle as platform
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546618/
https://www.ncbi.nlm.nih.gov/pubmed/33083027
http://dx.doi.org/10.1038/s41541-020-00242-y
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