A VLP for validation of the Plasmodium falciparum circumsporozoite protein junctional epitope for vaccine development

Abstract Malaria continues to be a pressing global health issue, causing nearly half a million deaths per year. An effective malaria vaccine could radically improve our ability to control and eliminate this pathogen. The most advanced malaria vaccine, RTS,S, confers only 30% protective efficacy unde...

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Autores principales:	Erwan Atcheson, Adrian V. S. Hill, Arturo Reyes-Sandoval
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/8ced57f921af48a3b8a7e7217fdf7c7d
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spelling	oai:doaj.org-article:8ced57f921af48a3b8a7e7217fdf7c7d2021-12-02T14:24:55ZA VLP for validation of the Plasmodium falciparum circumsporozoite protein junctional epitope for vaccine development10.1038/s41541-021-00302-x2059-0105https://doaj.org/article/8ced57f921af48a3b8a7e7217fdf7c7d2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41541-021-00302-xhttps://doaj.org/toc/2059-0105Abstract Malaria continues to be a pressing global health issue, causing nearly half a million deaths per year. An effective malaria vaccine could radically improve our ability to control and eliminate this pathogen. The most advanced malaria vaccine, RTS,S, confers only 30% protective efficacy under field conditions, and hence the search continues for improved vaccines. New antigens and formulations are always first developed at a pre-clinical level. This paper describes the development of a platform to supplement existing tools of pre-clinical malaria vaccine development, by displaying linear peptides on a virus-like particle (VLP). Peptides from PfCSP, particularly from outside the normal target of neutralizing antibodies, the central NANP repeat region, are screened for evidence of protective efficacy. One peptide, recently identified as a target of potent neutralizing antibodies and lying at the junction between the N-terminal domain and the central repeat region of PfCSP, is found to confer protective efficacy against malaria sporozoite challenge in mice when presented on the Qβ VLP. The platform is also used to explore the effects of increasing numbers of NANP unit repeats, and including a universal CD4+ T-cell epitope from tetanus toxin, on immunogenicity and protective efficacy. The VLP-peptide platform is shown to be of use in screening malaria peptides for protective efficacy and answering basic vaccinology questions in a pre-clinical setting.Erwan AtchesonAdrian V. S. HillArturo Reyes-SandovalNature PortfolioarticleImmunologic diseases. AllergyRC581-607Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Vaccines, Vol 6, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Immunologic diseases. Allergy RC581-607 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Erwan Atcheson Adrian V. S. Hill Arturo Reyes-Sandoval A VLP for validation of the Plasmodium falciparum circumsporozoite protein junctional epitope for vaccine development
description	Abstract Malaria continues to be a pressing global health issue, causing nearly half a million deaths per year. An effective malaria vaccine could radically improve our ability to control and eliminate this pathogen. The most advanced malaria vaccine, RTS,S, confers only 30% protective efficacy under field conditions, and hence the search continues for improved vaccines. New antigens and formulations are always first developed at a pre-clinical level. This paper describes the development of a platform to supplement existing tools of pre-clinical malaria vaccine development, by displaying linear peptides on a virus-like particle (VLP). Peptides from PfCSP, particularly from outside the normal target of neutralizing antibodies, the central NANP repeat region, are screened for evidence of protective efficacy. One peptide, recently identified as a target of potent neutralizing antibodies and lying at the junction between the N-terminal domain and the central repeat region of PfCSP, is found to confer protective efficacy against malaria sporozoite challenge in mice when presented on the Qβ VLP. The platform is also used to explore the effects of increasing numbers of NANP unit repeats, and including a universal CD4+ T-cell epitope from tetanus toxin, on immunogenicity and protective efficacy. The VLP-peptide platform is shown to be of use in screening malaria peptides for protective efficacy and answering basic vaccinology questions in a pre-clinical setting.
format	article
author	Erwan Atcheson Adrian V. S. Hill Arturo Reyes-Sandoval
author_facet	Erwan Atcheson Adrian V. S. Hill Arturo Reyes-Sandoval
author_sort	Erwan Atcheson
title	A VLP for validation of the Plasmodium falciparum circumsporozoite protein junctional epitope for vaccine development
title_short	A VLP for validation of the Plasmodium falciparum circumsporozoite protein junctional epitope for vaccine development
title_full	A VLP for validation of the Plasmodium falciparum circumsporozoite protein junctional epitope for vaccine development
title_fullStr	A VLP for validation of the Plasmodium falciparum circumsporozoite protein junctional epitope for vaccine development
title_full_unstemmed	A VLP for validation of the Plasmodium falciparum circumsporozoite protein junctional epitope for vaccine development
title_sort	vlp for validation of the plasmodium falciparum circumsporozoite protein junctional epitope for vaccine development
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/8ced57f921af48a3b8a7e7217fdf7c7d
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A VLP for validation of the Plasmodium falciparum circumsporozoite protein junctional epitope for vaccine development

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