title: Immunogenicity of Plasmodium falciparum circumsporozoite protein multiple antigen peptide vaccine formulated with different adjuvants.
abstract: Only low antibody levels were obtained from vaccinating human volunteers with single-chain peptide from the Plasmodium falciparum circumsporozoite protein (PfCSP). This resulted in modest protection against sporozoite challenge. In addition, HLA restriction limits the probability of synthesis of a vaccine effective for a diverse population. We report immunization studies with a multiple antigen peptide (MAP) system consisting of multiple copies of a B-cell epitope from the central repeat region of the PfCSP in combination with a universal T-cell epitope, the P2P30 portion of tetanus toxin. This MAP4(NANP)6P2P30 vaccine was highly immunogenic in four different strains of mice when used with various safe and nontoxic adjuvants. When this MAP vaccine was encapsulated in liposomes with lipid A and adsorbed to aluminium hydroxide and given three times at 4-week intervals, the resultant antibody prevented 100% of sporozoites from invading and developing into liver stage infection. This high degree of immunogenicity of MAP4(NANP)6P2P30 vaccine formulated in liposomes, lipid A and aluminum hydroxide provides the foundation for consideration of human trials with this formulation.
authors.affiliation: Malaria Program, Naval Medical Research Institute, Bethesda, MD, USA.
authors.forename: T P
authors.initials: TP
authors.lastname: Le
authors.forename: L W
authors.initials: LW
authors.lastname: Church
authors.forename: G
authors.initials: G
authors.lastname: Corradin
authors.forename: R L
authors.initials: RL
authors.lastname: Hunter
authors.forename: Y
authors.initials: Y
authors.lastname: Charoenvit
authors.forename: R
authors.initials: R
authors.lastname: Wang
authors.forename: P
authors.initials: P
authors.lastname: de la Vega
authors.forename: J
authors.initials: J
authors.lastname: Sacci
authors.forename: W R
authors.initials: WR
authors.lastname: Ballou
authors.forename: N
authors.initials: N
authors.lastname: Kolodny
authors.forename: S
authors.initials: S
authors.lastname: Kitov
authors.forename: G M
authors.initials: GM
authors.lastname: Glenn
authors.forename: R L
authors.initials: RL
authors.lastname: Richards
authors.forename: C R
authors.initials: CR
authors.lastname: Alving
authors.forename: S L
authors.initials: SL
authors.lastname: Hoffman
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D016782:Apicomplexa / Q000276:immunology; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000953:Antigens, Protozoan; D015800:Protozoan Proteins; C041595:circumsporozoite protein, Protozoan