title: Development of a self-assembling protein nanoparticle vaccine targeting Plasmodium falciparum Circumsporozoite Protein delivered in three Army Liposome Formulation adjuvants.
abstract: We have developed FMP014, a vaccine candidate against Plasmodium falciparum malaria, which is comprised of 60 identical monomer protein chains that form an icosahedral shaped self-assembling protein nanoparticle (SAPN). Each monomer contains selected P. falciparum Circumsporozoite Protein (PfCSP) CD4+ and CD8+ epitopes, universal THepitopes, portions of the α-TSR domain, and 6 repeats of the NANP motifs of the PfCSP. Here we describe the conditions that are required for successful scale-up and cGMP manufacturing of FMP014 with a yield of ≈1.5g of drug substance per 100g of wet bacterial paste. When adjuvanted with an Army Liposomal Formulation (ALF) based adjuvant, the nanoparticle vaccine is highly immunogenic and prevents infection of mice by an otherwise lethal dose of transgenic P. berghei sporozoites expressing the full-length PfCSP.
authors.affiliation: Malaria Vaccine Branch, USMMRP-WRAIR, The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., 6720A Rockledge Drive, Bethesda, MD 20817, United States.
authors.forename: Labdhi
authors.initials: L
authors.lastname: Seth
authors.affiliation: Malaria Vaccine Branch, USMMRP-WRAIR, The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., 6720A Rockledge Drive, Bethesda, MD 20817, United States.
authors.forename: Karen M
authors.initials: KM
authors.lastname: Bingham Ferlez
authors.affiliation: Malaria Vaccine Branch, USMMRP-WRAIR, The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., 6720A Rockledge Drive, Bethesda, MD 20817, United States.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Kaba
authors.affiliation: Malaria Vaccine Branch, USMMRP-WRAIR, College Student Leadership Program, 503 Robert Grant Ave, Silver Spring, MD 20910, United States.
authors.forename: Derek M
authors.initials: DM
authors.lastname: Musser
authors.affiliation: Institute of Materials Science, University of Connecticut, Storrs, CT 06269-3136, United States.
authors.forename: Sharareh
authors.initials: S
authors.lastname: Emadi
authors.affiliation: Laboratory of Adjuvant and Antigen Research, US Military HIV Research Program, Walter Reed Army Institute of Research, 503 Robert Grant Ave, Silver Spring, MD 20910, United States.
authors.forename: Gary R
authors.initials: GR
authors.lastname: Matyas
authors.affiliation: US Military HIV Research Program, The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., 6720A Rockledge Drive, Bethesda, MD 20817, United States.
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Beck
authors.affiliation: Laboratory of Adjuvant and Antigen Research, US Military HIV Research Program, Walter Reed Army Institute of Research, 503 Robert Grant Ave, Silver Spring, MD 20910, United States.
authors.forename: Carl R
authors.initials: CR
authors.lastname: Alving
authors.affiliation: Alpha-O Peptides AG, Lörracherstrasse 50, 4125 Riehen, Switzerland.
authors.forename: Peter
authors.initials: P
authors.lastname: Burkhard
authors.affiliation: Malaria Vaccine Branch, USMMRP-WRAIR, Walter Reed Army Institute of Research, 503 Robert Grant Ave, Silver Spring, MD 20910, United States. Electronic address: david.e.lanar.civ@mail.mil.
authors.forename: David E
authors.initials: DE
authors.lastname: Lanar
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D005260:Female; D008081:Liposomes / Q000276:immunology*; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology* / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage*; D010963:Plasmodium falciparum / Q000276:immunology*; D021381:Protein Transport / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D034101:Sporozoites / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D000939:Epitopes; D008081:Liposomes; D017780:Malaria Vaccines; D015800:Protozoan Proteins
keywords: Adjuvant; Malaria; Nanoparticle; Plasmodium falciparum; Scale-up; Vaccine