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

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Evert, Benjamin J
Chen, Shuxiong
McConville, Robyn
Steel, Ryan WJ
Healer, Julie
Boddey, Justin A
Huntimer, Lucas
Rehm, Bernd HA
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2021
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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.

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npj Vaccines

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6

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1

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© The Author(s) 2021. 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.

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Medical virology

Medical parasitology

Immunology

Medical microbiology

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Evert, BJ; Chen, S; McConville, R; Steel, RWJ; Healer, J; Boddey, JA; Huntimer, L; Rehm, BHA, Epitope-coated polymer particles elicit neutralising antibodies against Plasmodium falciparum sporozoites, npj Vaccines, 2021, 6 (1), pp. 141

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