Mannosylated liposomes formulated with whole parasite P. falciparum blood-stage antigens are highly immunogenic in mice

Development and Evaluation of a Cryopreserved Whole-Parasite Vaccine in a Rodent Model of Blood-Stage Malaria

“…The liposome is a well-recognized delivery system for drugs and antigens for vaccine development and can effectively replace the red blood cell to enable targeting and presentation of the parasite material to antigen-presenting cells. Red blood cell membranes could be removed prior to formulating the parasite material with the liposomes, and we have previously demonstrated that this can be achieved through the use of a novel immunomagnetic method ( 24 ). Liposomes are inherently unstable, with a limited shelf-life when they are in an aqueous dispersion.…”

“…Protective immunity is critically dependent on CD4 + T cells, IFN-γ, and TNF and is not observed in μMT mice. Future work should include removal of the red blood cell membranes from the vaccine formulation using established protocols to determine whether there is any impact on the vaccine’s immunogenicity and protective efficacy ( 24 ). Importantly, we show that this liposomal vaccine approach is compatible with lyophilization or freezing without any loss of vaccine potency.…”

“…They consisted of 1,2-dipalmitoylsn-glycero-3-phosphocholine (DPPC; Avanti Polar Lipids), dimethyldioctadecylammonium bromide (DDAB; Sigma-Aldrich) and cholesterol (Avanti Polar Lipids) in the ratio of 7:2:1. In addition, 3D(6-acyl) PHAD (PHAD; Avanti Polar Lipids) and a mannosylated core peptide, designated “F3” ( 22 , 24 ), were also added ( Fig. 1 ).…”

“…While ring-stage-infected human red cells can be cryopreserved, the low yields of viable parasites following thawing and the difficulties with preserving trophozoite and schizont stages present a significant obstacle to the development of such vaccines. One approach to overcome this is to utilize an alternative delivery system for the malaria parasites, and we have recently investigated liposomes for this purpose ( 22 , 24 ). Liposomes are bilayered lipid vesicles that have flexible physiochemical and biophysical properties that make them an attractive delivery system for both drugs and for antigens for vaccine development.…”

Investigation of liposomal self-adjuvanting peptide epitopes derived from conserved blood-stage Plasmodium antigens

“…Vaccine constructs pL1, pL2 and pL3 conjugates were first synthesised by Boc-SPPS. The mannose receptor targeting moiety, ML-1, was produced as a conjugate of mannose, a short peptide linker (SSKK) and lipid (C16; 2-aminohexadecanoic acid) [20,21], while ML-2 was produced as a conjugate of mannose, PEG linker, and DOPE lipid [26]. Cationic liposomes were produced by lipid film hydration using DPPC, DDAB and cholesterol, as described previously [33].…”