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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Autor*in:	Katherine L. Mallory [verfasserIn] Justin A. Taylor [verfasserIn] Xiaoyan Zou [verfasserIn] Ishita N. Waghela [verfasserIn] Cosette G. Schneider [verfasserIn] Michael Q. Sibilo [verfasserIn] Neeraja M. Punde [verfasserIn] Leah C. Perazzo [verfasserIn] Tatyana Savransky [verfasserIn] Martha Sedegah [verfasserIn] Sheetij Dutta [verfasserIn] Chris J. Janse [verfasserIn] Norbert Pardi [verfasserIn] Paulo J. C. Lin [verfasserIn] Ying K. Tam [verfasserIn] Drew Weissman [verfasserIn] Evelina Angov [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2021

Übergeordnetes Werk:	In: npj Vaccines - Nature Portfolio, 2017, 6(2021), 1, Seite 12
Übergeordnetes Werk:	volume:6 ; year:2021 ; number:1 ; pages:12

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.1038/s41541-021-00345-0

Katalog-ID:	DOAJ063216906

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allfieldsSound	10.1038/s41541-021-00345-0 doi (DE-627)DOAJ063216906 (DE-599)DOAJe05bb1dcc8a24bf8950c79ee7ff517fc DE-627 ger DE-627 rakwb eng RC581-607 RC254-282 Katherine L. Mallory verfasserin aut Messenger RNA expressing PfCSP induces functional, protective immune responses against malaria in mice 2021 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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. Immunologic diseases. Allergy Neoplasms. Tumors. Oncology. Including cancer and carcinogens Justin A. Taylor verfasserin aut Xiaoyan Zou verfasserin aut Ishita N. Waghela verfasserin aut Cosette G. Schneider verfasserin aut Michael Q. Sibilo verfasserin aut Neeraja M. Punde verfasserin aut Leah C. Perazzo verfasserin aut Tatyana Savransky verfasserin aut Martha Sedegah verfasserin aut Sheetij Dutta verfasserin aut Chris J. Janse verfasserin aut Norbert Pardi verfasserin aut Paulo J. C. Lin verfasserin aut Ying K. Tam verfasserin aut Drew Weissman verfasserin aut Evelina Angov verfasserin aut In npj Vaccines Nature Portfolio, 2017 6(2021), 1, Seite 12 (DE-627)87811839X (DE-600)2882262-6 20590105 nnns volume:6 year:2021 number:1 pages:12 https://doi.org/10.1038/s41541-021-00345-0 kostenfrei https://doaj.org/article/e05bb1dcc8a24bf8950c79ee7ff517fc kostenfrei https://doi.org/10.1038/s41541-021-00345-0 kostenfrei https://doaj.org/toc/2059-0105 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 6 2021 1 12
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author	Katherine L. Mallory
spellingShingle	Katherine L. Mallory misc RC581-607 misc RC254-282 misc Immunologic diseases. Allergy misc Neoplasms. Tumors. Oncology. Including cancer and carcinogens Messenger RNA expressing PfCSP induces functional, protective immune responses against malaria in mice
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title_sort	messenger rna expressing pfcsp induces functional, protective immune responses against malaria in mice
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title_auth	Messenger RNA expressing PfCSP induces functional, protective immune responses against malaria in mice
abstract	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.
abstractGer	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.
abstract_unstemmed	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.
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title_short	Messenger RNA expressing PfCSP induces functional, protective immune responses against malaria in mice
url	https://doi.org/10.1038/s41541-021-00345-0 https://doaj.org/article/e05bb1dcc8a24bf8950c79ee7ff517fc https://doaj.org/toc/2059-0105
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author2	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
author2Str	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
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doi_str	10.1038/s41541-021-00345-0
callnumber-a	RC581-607
up_date	2024-07-03T16:29:45.700Z
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Messenger RNA expressing PfCSP induces functional, protective immune responses against malaria in mice

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