title: Safety, immunogenicity, and efficacy of Plasmodium falciparum repeatless circumsporozoite protein vaccine encapsulated in liposomes.
abstract: Seventeen malaria-naive volunteers received a recombinant Plasmodium falciparum vaccine (RLF) containing the carboxy- and the amino-terminal of the circumsporozoite protein (CSP) antigen without the central tetrapeptide repeats. The vaccine was formulated in liposomes with either a low or high dose of 3-deacylated monophosphoryl lipid A (MPL) and administered with alum by intramuscular injection. Both formulations were well tolerated and immunogenic. MPL increased sporozoite antibody titers measured by ELISA, Western blot, and immunofluorescence assay. One high-dose MPL vaccine formulation recipient developed a CSP-specific cytotoxic T lymphocyte response. After homologous sporozoite challenge, immunized volunteers developed patent malaria. There was no correlation between prepatent period and antibody titers to the amino- or carboxy-terminal. The absence of delay in patency argues against inclusion of the amino-terminal in future vaccines. A significant cytotoxic T lymphocyte response may have been suppressed by the inclusion of alum as an adjuvant.
authors.affiliation: Department of Membrane Biochemistry, Walter Reed Army Institute of Research, Washington, DC, USA.
authors.forename: D G
authors.initials: DG
authors.lastname: Heppner
authors.forename: D M
authors.initials: DM
authors.lastname: Gordon
authors.forename: M
authors.initials: M
authors.lastname: Gross
authors.forename: B
authors.initials: B
authors.lastname: Wellde
authors.forename: W
authors.initials: W
authors.lastname: Leitner
authors.forename: U
authors.initials: U
authors.lastname: Krzych
authors.forename: I
authors.initials: I
authors.lastname: Schneider
authors.forename: R A
authors.initials: RA
authors.lastname: Wirtz
authors.forename: R L
authors.initials: RL
authors.lastname: Richards
authors.forename: A
authors.initials: A
authors.lastname: Trofa
authors.forename: T
authors.initials: T
authors.lastname: Hall
authors.forename: J C
authors.initials: JC
authors.lastname: Sadoff
authors.forename: P
authors.initials: P
authors.lastname: Boerger
authors.forename: C R
authors.initials: CR
authors.lastname: Alving
authors.forename: D R
authors.initials: DR
authors.lastname: Sylvester
authors.forename: T G
authors.initials: TG
authors.lastname: Porter
authors.forename: W R
authors.initials: WR
authors.lastname: Ballou
mesh_terms: D000293:Adolescent; D000328:Adult; D000953:Antigens, Protozoan / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D003602:Cytotoxicity, Immunologic; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D005260:Female; D006801:Humans; D008081:Liposomes; D008213:Lymphocyte Activation; D017780:Malaria Vaccines / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D016778:Malaria, Falciparum / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D015800:Protozoan Proteins / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D012091:Repetitive Sequences, Nucleic Acid; D012449:Safety; D014614:Vaccines, Synthetic / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D000953:Antigens, Protozoan; D004337:Drug Carriers; D008081:Liposomes; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D014614:Vaccines, Synthetic; C041595:circumsporozoite protein, Protozoan