A semi-synthetic whole parasite vaccine designed to protect against blood stage malaria

Giddam, Ashwini Kumar, Reiman, Jennifer M., Zaman, Mehfuz, Skwarczynski, Mariusz, Toth, Istvan and Good, Michael F. (2016) A semi-synthetic whole parasite vaccine designed to protect against blood stage malaria. Acta Biomaterialia, 44 295-303. doi:10.1016/j.actbio.2016.08.020


Author Giddam, Ashwini Kumar
Reiman, Jennifer M.
Zaman, Mehfuz
Skwarczynski, Mariusz
Toth, Istvan
Good, Michael F.
Title A semi-synthetic whole parasite vaccine designed to protect against blood stage malaria
Journal name Acta Biomaterialia   Check publisher's open access policy
ISSN 1742-7061
1878-7568
Publication date 2016-10-15
Year available 2016
Sub-type Article (original research)
DOI 10.1016/j.actbio.2016.08.020
Open Access Status Not yet assessed
Volume 44
Start page 295
End page 303
Total pages 9
Place of publication Amsterdam, Netherlands
Publisher Elsevier BV
Language eng
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.
Formatted 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.
Keyword Antigen delivery system
Antigen presenting cells
Malaria vaccine
Protective immune response
Targeted liposomes
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID NHMRC 496600
Institutional Status UQ

 
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Created: Tue, 27 Sep 2016, 20:40:26 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences