title: A semi-synthetic whole parasite vaccine designed to protect against blood stage malaria.
abstract: Although attenuated malaria parasitized red blood cells (pRBCs) are promising vaccine candidates, their application in humans may be restricted for ethical and regulatory reasons. Therefore, we developed an organic microparticle-based delivery platform as a whole parasite malaria-antigen carrier to mimic pRBCs. Killed blood stage parasites were encapsulated within liposomes that are targeted to antigen presenting cells (APCs). Mannosylated lipid core peptides (MLCPs) were used as targeting ligands for the liposome-encapsulated parasite antigens. MLCP-liposomes, but not unmannosylated liposomes, were taken-up efficiently by APCs which then significantly upregulated expression of MHC-ll and costimulatory molecules, CD80 and CD86. Two such vaccines using rodent model systems were constructed - one with Plasmodium chabaudi and the other with P. yoelii. MLCP-liposome vaccines were able to control the parasite burden and extended the survival of mice. Thus, we have demonstrated an alternative delivery system to attenuated pRBCs with similar vaccine efficacy and added clinical advantages. Such liposomes are promising candidates for a human malaria vaccine.
  
  
  
  Attenuated whole parasite-based vaccines, by incorporating all parasite antigens, are very promising candidates, but issues relating to production, storage and safety concerns are significantly slowing their development. We therefore developed a semi-synthetic whole parasite malaria vaccine that is easily manufactured and stored. Two such prototype vaccines (a P. chabaudi and a P. yoelii vaccine) have been constructed. They are non-infectious, highly immunogenic and give good protection profiles. This semi-synthetic delivery platform is an exciting strategy to accelerate the development of a licensed malaria vaccine. Moreover, this strategy can be potentially applied to a wide range of pathogens.
authors.affiliation: The University of Queensland, School of Chemistry and Molecular Biosciences, Australia.
authors.forename: Ashwini Kumar
authors.initials: AK
authors.lastname: Giddam
authors.affiliation: Griffith University, Institute for Glycomics, Australia.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Reiman
authors.affiliation: Griffith University, Institute for Glycomics, Australia.
authors.forename: Mehfuz
authors.initials: M
authors.lastname: Zaman
authors.affiliation: The University of Queensland, School of Chemistry and Molecular Biosciences, Australia.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Skwarczynski
authors.affiliation: The University of Queensland, School of Chemistry and Molecular Biosciences, Australia; The University of Queensland, School of Pharmacy, Australia; The University of Queensland, Institute for Molecular Bioscience, Australia. Electronic address: i.toth@uq.edu.au.
authors.forename: Istvan
authors.initials: I
authors.lastname: Toth
authors.affiliation: Griffith University, Institute for Glycomics, Australia. Electronic address: michael.good@griffith.edu.au.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Good
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D007114:Immunization; D008018:Life Cycle Stages; D008055:Lipids / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry; D008288:Malaria / Q000276:immunology* / Q000469:parasitology*; D017780:Malaria Vaccines / Q000276:immunology*; D008358:Mannose / Q000737:chemistry; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D010271:Parasites / Q000254:growth & development / Q000276:immunology* / Q000469:parasitology*; D010316:Particle Size; D010961:Plasmodium / Q000502:physiology; D016019:Survival Analysis
chemical_list: D008055:Lipids; D008081:Liposomes; D017780:Malaria Vaccines; D008358:Mannose
keywords: Antigen delivery system; Antigen presenting cells; Malaria vaccine; Protective immune response; Targeted liposomes