title: Expression, purification and refolding of a self-assembling protein nanoparticle (SAPN) malaria vaccine.
abstract: There are many ways to present antigens to the immune system. We have used a repetitive antigen display technology that relies on the self-assembly of 60 protein chains into a spherical self-assembling protein nanoparticle (SAPN) to develop a vaccine against Plasmodium falciparum malaria. The protein sequence contains selected B- and T-cell epitopes of the circumsporozoite protein of P. falciparum (PfCSP) and, when assembled into a nanoparticle induces strong, long-lived and protective immune responses against the PfCSP. Here we describe the conditions needed for promoting self-assembly of a P. falciparum vaccine nanoparticle, PfCSP-KMY-SAPN, and note pitfalls that may occur when determining conditions for other SAPN vaccines. Attention was paid to selecting processes that were amenable to scale up and cGMP manufacturing.
authors.affiliation: Malaria Vaccine Branch, Walter Reed Army Institute of Research, Silver Spring, MD 20910-7500, USA.
authors.forename: Qin
authors.initials: Q
authors.lastname: Guo
authors.forename: Debleena
authors.initials: D
authors.lastname: Dasgupta
authors.forename: Tais A P F
authors.initials: TA
authors.lastname: Doll
authors.forename: Peter
authors.initials: P
authors.lastname: Burkhard
authors.forename: David E
authors.initials: DE
authors.lastname: Lanar
mesh_terms: D000595:Amino Acid Sequence; D000953:Antigens, Protozoan / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D018985:Epitopes, B-Lymphocyte / Q000737:chemistry / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D017780:Malaria Vaccines / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D016778:Malaria, Falciparum / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010963:Plasmodium falciparum / Q000276:immunology*; D058849:Protein Refolding; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D014614:Vaccines, Synthetic
chemical_list: D000953:Antigens, Protozoan; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D014614:Vaccines, Synthetic; C041595:circumsporozoite protein, Protozoan
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