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.
Highlights
Malaria is a disease caused by the Plasmodium parasite, predominantly P. falciparum, which is transmitted through the bites of infected mosquitoes
As malaria is prevalent in developing countries, the vaccine would ideally be stable at ambient temperatures avoiding cold-chain requirements and it would be subject to cost-effective manufacture
E. coli is generally recognised as a safe (GRAS) production host and is the preferred host for producing numerous therapeutic proteins
Summary
Malaria is a disease caused by the Plasmodium parasite, predominantly P. falciparum, which is transmitted through the bites of infected mosquitoes. The main contributing factors for this are the fact that the RTS,S vaccine shows only about 30% efficacy and drug resistance among parasites and parasite vectors is becoming more widespread[2,3,4] This highlights that a more effective malaria vaccine is urgently needed. As malaria is prevalent in developing countries, the vaccine would ideally be stable at ambient temperatures avoiding cold-chain requirements and it would be subject to cost-effective manufacture. The development of such a vaccine provides the best chance of combating the disease. An important feature of CSP is a repetitive region that contains 25 to 42 copies of the amino acids NANP6
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