title: Safety, immunogenicity, and efficacy of a malaria sporozoite vaccine administered with monophosphoryl lipid A, cell wall skeleton of mycobacteria, and squalane as adjuvant.
abstract: A Plasmodium falciparum circumsporozoite protein (PfCSP) recombinant fusion protein, R32NS1(81), formulated with monophosphoryl lipid A, cell wall skeleton of mycobacteria, and squalane (Detox) was administered to 12 volunteers. One volunteer had malaise and self-limited painful induration at the injection site after the second dose and declined further immunization. The other 11 volunteers tolerated the three doses of 1,230 micrograms of vaccine, but most complained of sore arms; in five cases the pain or malaise was severe enough to interfere with work or sleep. Two weeks after the third dose of vaccine, four of the 11 immunized volunteers had > or = 14 micrograms/ml of antibodies to the repeat region of the PfCSP in their serum. Two of these four volunteers did not develop P. falciparum parasitemia when challenged by the bite of five mosquitoes carrying P. falciparum sporozoites. The seven volunteers with lower levels of antibodies and 11 of 11 controls developed parasitemia. These data are consistent with other studies, and indicate that vaccine-induced antibodies against the repeat region of PfCSP can prevent effective sporozoite infection of hepatocytes in humans. The challenge is to improve the immunogenicity of PfCSP-based vaccines, and to develop methods for including PfCSP peptides as components of multitarget malaria vaccines.
authors.affiliation: Malaria Program, Naval Medical Research Institute, Bethesda, Maryland.
authors.forename: S L
authors.initials: SL
authors.lastname: Hoffman
authors.forename: R
authors.initials: R
authors.lastname: Edelman
authors.forename: J P
authors.initials: JP
authors.lastname: Bryan
authors.forename: I
authors.initials: I
authors.lastname: Schneider
authors.forename: J
authors.initials: J
authors.lastname: Davis
authors.forename: M
authors.initials: M
authors.lastname: Sedegah
authors.forename: D
authors.initials: D
authors.lastname: Gordon
authors.forename: P
authors.initials: P
authors.lastname: Church
authors.forename: M
authors.initials: M
authors.lastname: Gross
authors.forename: C
authors.initials: C
authors.lastname: Silverman
mesh_terms: D000276:Adjuvants, Immunologic; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D002473:Cell Wall / Q000276:immunology / Q000648:ultrastructure; D004311:Double-Blind Method; D006801:Humans; D008050:Lipid A / Q000031:analogs & derivatives / Q000276:immunology; D017780:Malaria Vaccines / Q000009:adverse effects / Q000276:immunology; D016778:Malaria, Falciparum / Q000517:prevention & control*; D008875:Middle Aged; D008889:Military Personnel; D008969:Molecular Sequence Data; D009168:Mycobacterium phlei / Q000276:immunology / Q000648:ultrastructure; D018512:Parasitemia / Q000517:prevention & control; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology; D012449:Safety; D013185:Squalene / Q000031:analogs & derivatives / Q000276:immunology; D014481:United States; D014614:Vaccines, Synthetic / Q000009:adverse effects / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D008050:Lipid A; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D014614:Vaccines, Synthetic; C041595:circumsporozoite protein, Protozoan; D013185:Squalene; C019556:squalane; C048436:monophosphoryl lipid A