Epitope-coated polymer particles elicit neutralising antibodies against Plasmodium falciparum sporozoites

Abstract The current Malaria RTS,S vaccine is based on virus-like particles (VLPs) comprising the NANP repetitive epitopes from the cicumsporozoite protein (CSP) of Plasmodium falciparum. This vaccine has limited efficacy, only preventing severe disease in about 30% of vaccinated individuals. A more...

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Autores principales:	Benjamin J. Evert, Shuxiong Chen, Robyn McConville, Ryan W. J. Steel, Julie Healer, Justin A. Boddey, Lucas Huntimer, Bernd H. A. Rehm
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/20819287a4164343b238a1a5bdf5f86f
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spelling	oai:doaj.org-article:20819287a4164343b238a1a5bdf5f86f2021-12-05T12:05:32ZEpitope-coated polymer particles elicit neutralising antibodies against Plasmodium falciparum sporozoites10.1038/s41541-021-00408-22059-0105https://doaj.org/article/20819287a4164343b238a1a5bdf5f86f2021-11-01T00:00:00Zhttps://doi.org/10.1038/s41541-021-00408-2https://doaj.org/toc/2059-0105Abstract The current Malaria RTS,S vaccine is based on virus-like particles (VLPs) comprising the NANP repetitive epitopes from the cicumsporozoite protein (CSP) of Plasmodium falciparum. This vaccine has limited efficacy, only preventing severe disease in about 30% of vaccinated individuals. A more efficacious vaccine is urgently needed to combat malaria. Here we developed a particulate malaria vaccine based on the same CSP epitopes but using biopolymer particles (BPs) as an antigen carrier system. Specific B- and T-cell epitope-coated BPs were assembled in vivo inside an engineered endotoxin-free mutant of Escherichia coli. A high-yield production process leading to ~27% BP vaccine weight over biomass was established. The epitope-coated BPs were purified and their composition, i.e., the polymer core and epitope identity, was confirmed. Epitope-coated BPs were used alongside soluble peptide epitopes and empty BPs to vaccinate sheep. Epitope-coated BPs showed enhanced immunogenicity by inducing anti-NANP antibody titre of EC50 > 150,000 that were at least 20 times higher than induced by the soluble peptides. We concluded that the additional T-cell epitope was not required as it did not enhance immunogenicity when compared with the B-cell epitope-coated BPs. Antibodies specifically bound to the surface of Plasmodium falciparum sporozoites and efficiently inhibited sporozoite motility and traversal of human hepatocytes. This study demonstrated the utility of biologically self-assembled epitope-coated BPs as an epitope carrier for inclusion in next-generation malaria vaccines.Benjamin J. EvertShuxiong ChenRobyn McConvilleRyan W. J. SteelJulie HealerJustin A. BoddeyLucas HuntimerBernd H. A. RehmNature 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 Benjamin J. Evert Shuxiong Chen Robyn McConville Ryan W. J. Steel Julie Healer Justin A. Boddey Lucas Huntimer Bernd H. A. Rehm Epitope-coated polymer particles elicit neutralising antibodies against Plasmodium falciparum sporozoites
description	Abstract The current Malaria RTS,S vaccine is based on virus-like particles (VLPs) comprising the NANP repetitive epitopes from the cicumsporozoite protein (CSP) of Plasmodium falciparum. This vaccine has limited efficacy, only preventing severe disease in about 30% of vaccinated individuals. A more efficacious vaccine is urgently needed to combat malaria. Here we developed a particulate malaria vaccine based on the same CSP epitopes but using biopolymer particles (BPs) as an antigen carrier system. Specific B- and T-cell epitope-coated BPs were assembled in vivo inside an engineered endotoxin-free mutant of Escherichia coli. A high-yield production process leading to ~27% BP vaccine weight over biomass was established. The epitope-coated BPs were purified and their composition, i.e., the polymer core and epitope identity, was confirmed. Epitope-coated BPs were used alongside soluble peptide epitopes and empty BPs to vaccinate sheep. Epitope-coated BPs showed enhanced immunogenicity by inducing anti-NANP antibody titre of EC50 > 150,000 that were at least 20 times higher than induced by the soluble peptides. We concluded that the additional T-cell epitope was not required as it did not enhance immunogenicity when compared with the B-cell epitope-coated BPs. Antibodies specifically bound to the surface of Plasmodium falciparum sporozoites and efficiently inhibited sporozoite motility and traversal of human hepatocytes. This study demonstrated the utility of biologically self-assembled epitope-coated BPs as an epitope carrier for inclusion in next-generation malaria vaccines.
format	article
author	Benjamin J. Evert Shuxiong Chen Robyn McConville Ryan W. J. Steel Julie Healer Justin A. Boddey Lucas Huntimer Bernd H. A. Rehm
author_facet	Benjamin J. Evert Shuxiong Chen Robyn McConville Ryan W. J. Steel Julie Healer Justin A. Boddey Lucas Huntimer Bernd H. A. Rehm
author_sort	Benjamin J. Evert
title	Epitope-coated polymer particles elicit neutralising antibodies against Plasmodium falciparum sporozoites
title_short	Epitope-coated polymer particles elicit neutralising antibodies against Plasmodium falciparum sporozoites
title_full	Epitope-coated polymer particles elicit neutralising antibodies against Plasmodium falciparum sporozoites
title_fullStr	Epitope-coated polymer particles elicit neutralising antibodies against Plasmodium falciparum sporozoites
title_full_unstemmed	Epitope-coated polymer particles elicit neutralising antibodies against Plasmodium falciparum sporozoites
title_sort	epitope-coated polymer particles elicit neutralising antibodies against plasmodium falciparum sporozoites
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/20819287a4164343b238a1a5bdf5f86f
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Epitope-coated polymer particles elicit neutralising antibodies against Plasmodium falciparum sporozoites

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