Messenger RNA expressing PfCSP induces functional, protective immune responses against malaria in mice

Abstract Human malaria affects the vast majority of the world’s population with the Plasmodium falciparum species causing the highest rates of morbidity and mortality. With no licensed vaccine and leading candidates achieving suboptimal protection in the field, the need for an effective immunoprophy...

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Autores principales:	Katherine L. Mallory, Justin A. Taylor, Xiaoyan Zou, Ishita N. Waghela, Cosette G. Schneider, Michael Q. Sibilo, Neeraja M. Punde, Leah C. Perazzo, Tatyana Savransky, Martha Sedegah, Sheetij Dutta, Chris J. Janse, Norbert Pardi, Paulo J. C. Lin, Ying K. Tam, Drew Weissman, Evelina Angov
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/e05bb1dcc8a24bf8950c79ee7ff517fc
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spelling	oai:doaj.org-article:e05bb1dcc8a24bf8950c79ee7ff517fc2021-12-02T16:04:30ZMessenger RNA expressing PfCSP induces functional, protective immune responses against malaria in mice10.1038/s41541-021-00345-02059-0105https://doaj.org/article/e05bb1dcc8a24bf8950c79ee7ff517fc2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41541-021-00345-0https://doaj.org/toc/2059-0105Abstract Human malaria affects the vast majority of the world’s population with the Plasmodium falciparum species causing the highest rates of morbidity and mortality. With no licensed vaccine and leading candidates achieving suboptimal protection in the field, the need for an effective immunoprophylactic option continues to motivate the malaria research community to explore alternative technologies. Recent advances in the mRNA discipline have elevated the long-neglected platform to the forefront of infectious disease research. As the immunodominant coat protein of the invasive stage of the malaria parasite, circumsporozoite protein (PfCSP) was selected as the antigen of choice to assess the immunogenic and protective potential of an mRNA malaria vaccine. In mammalian cell transfection experiments, PfCSP mRNA was well expressed and cell associated. In the transition to an in vivo murine model, lipid nanoparticle (LNP) encapsulation was applied to protect and deliver the mRNA to the cell translation machinery and supply adjuvant activity. The immunogenic effect of an array of factors was explored, such as formulation, dose, number, and interval of immunizations. PfCSP mRNA-LNP achieved sterile protection against infection with two P. berghei PfCSP transgenic parasite strains, with mRNA dose and vaccination interval having a greater effect on outcome. This investigation serves as the assessment of pre-erythrocytic malaria, PfCSP mRNA vaccine candidate resulting in sterile protection, with numerous factors affecting protective efficacy, making it a compelling candidate for further investigation.Katherine L. MalloryJustin A. TaylorXiaoyan ZouIshita N. WaghelaCosette G. SchneiderMichael Q. SibiloNeeraja M. PundeLeah C. PerazzoTatyana SavranskyMartha SedegahSheetij DuttaChris J. JanseNorbert PardiPaulo J. C. LinYing K. TamDrew WeissmanEvelina AngovNature PortfolioarticleImmunologic diseases. AllergyRC581-607Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Vaccines, Vol 6, Iss 1, Pp 1-12 (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 Katherine L. Mallory Justin A. Taylor Xiaoyan Zou Ishita N. Waghela Cosette G. Schneider Michael Q. Sibilo Neeraja M. Punde Leah C. Perazzo Tatyana Savransky Martha Sedegah Sheetij Dutta Chris J. Janse Norbert Pardi Paulo J. C. Lin Ying K. Tam Drew Weissman Evelina Angov Messenger RNA expressing PfCSP induces functional, protective immune responses against malaria in mice
description	Abstract Human malaria affects the vast majority of the world’s population with the Plasmodium falciparum species causing the highest rates of morbidity and mortality. With no licensed vaccine and leading candidates achieving suboptimal protection in the field, the need for an effective immunoprophylactic option continues to motivate the malaria research community to explore alternative technologies. Recent advances in the mRNA discipline have elevated the long-neglected platform to the forefront of infectious disease research. As the immunodominant coat protein of the invasive stage of the malaria parasite, circumsporozoite protein (PfCSP) was selected as the antigen of choice to assess the immunogenic and protective potential of an mRNA malaria vaccine. In mammalian cell transfection experiments, PfCSP mRNA was well expressed and cell associated. In the transition to an in vivo murine model, lipid nanoparticle (LNP) encapsulation was applied to protect and deliver the mRNA to the cell translation machinery and supply adjuvant activity. The immunogenic effect of an array of factors was explored, such as formulation, dose, number, and interval of immunizations. PfCSP mRNA-LNP achieved sterile protection against infection with two P. berghei PfCSP transgenic parasite strains, with mRNA dose and vaccination interval having a greater effect on outcome. This investigation serves as the assessment of pre-erythrocytic malaria, PfCSP mRNA vaccine candidate resulting in sterile protection, with numerous factors affecting protective efficacy, making it a compelling candidate for further investigation.
format	article
author	Katherine L. Mallory Justin A. Taylor Xiaoyan Zou Ishita N. Waghela Cosette G. Schneider Michael Q. Sibilo Neeraja M. Punde Leah C. Perazzo Tatyana Savransky Martha Sedegah Sheetij Dutta Chris J. Janse Norbert Pardi Paulo J. C. Lin Ying K. Tam Drew Weissman Evelina Angov
author_facet	Katherine L. Mallory Justin A. Taylor Xiaoyan Zou Ishita N. Waghela Cosette G. Schneider Michael Q. Sibilo Neeraja M. Punde Leah C. Perazzo Tatyana Savransky Martha Sedegah Sheetij Dutta Chris J. Janse Norbert Pardi Paulo J. C. Lin Ying K. Tam Drew Weissman Evelina Angov
author_sort	Katherine L. Mallory
title	Messenger RNA expressing PfCSP induces functional, protective immune responses against malaria in mice
title_short	Messenger RNA expressing PfCSP induces functional, protective immune responses against malaria in mice
title_full	Messenger RNA expressing PfCSP induces functional, protective immune responses against malaria in mice
title_fullStr	Messenger RNA expressing PfCSP induces functional, protective immune responses against malaria in mice
title_full_unstemmed	Messenger RNA expressing PfCSP induces functional, protective immune responses against malaria in mice
title_sort	messenger rna expressing pfcsp induces functional, protective immune responses against malaria in mice
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e05bb1dcc8a24bf8950c79ee7ff517fc
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Messenger RNA expressing PfCSP induces functional, protective immune responses against malaria in mice

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