Vaccine co-display of CSP and Pfs230 on liposomes targeting two Plasmodium falciparum differentiation stages.
Wei-Chiao HuangMoustafa T MabroukLuwen ZhouMinami BabaMayumi TachibanaMotomi ToriiEizo TakashimaEmily LockeJordan PlieskattC Richter KingCamila H CoelhoPatrick Emmet DuffyCarole LongTakafumi TsuboiKazutoyo MiuraYimin WuTomoko IshinoJonathan F LovellPublished in: Communications biology (2022)
A vaccine targeting multiple stages of the Plasmodium falciparum parasite life cycle is desirable. The sporozoite surface Circumsporozoite Protein (CSP) is the target of leading anti-infective P. falciparum pre-erythrocytic vaccines. Pfs230, a sexual-stage P. falciparum surface protein, is currently in trials as the basis for a transmission-blocking vaccine, which inhibits parasite development in the mosquito vector. Here, recombinant full-length CSP and a Pfs230 fragment (Pfs230D1+) are co-displayed on immunogenic liposomes to induce immunity against both infection and transmission. Liposomes contain cobalt-porphyrin phospholipid (CoPoP), monophosphoryl lipid A and QS-21, and rapidly bind His-tagged CSP and Pfs230D1+ upon admixture to form bivalent particles that maintain reactivity with conformational monoclonal antibodies. Use of multicolor fluorophore-labeled antigens reveals liposome binding upon admixture, stability in serum and enhanced uptake in murine macrophages in vitro. Bivalent liposomes induce humoral and cellular responses against both CSP and Pfs230D1+. Vaccine-induced antibodies reduce parasite numbers in mosquito midguts in a standard membrane feeding assay. Mice immunized with liposome-displayed antigens or that passively receive antibodies from immunized rabbits have reduced parasite liver burden following challenge with transgenic sporozoites expressing P. falciparum CSP.
Keyphrases
- plasmodium falciparum
- drug delivery
- drug release
- life cycle
- cancer therapy
- immune response
- aedes aegypti
- dengue virus
- mental health
- molecular dynamics
- protein protein
- amino acid
- photodynamic therapy
- type diabetes
- adipose tissue
- diabetic rats
- oxidative stress
- insulin resistance
- computed tomography
- high glucose
- pet imaging
- single molecule
- metal organic framework
- stress induced