title: Use of adjuvant containing mycobacterial cell-wall skeleton, monophosphoryl lipid A, and squalane in malaria circumsporozoite protein vaccine.
abstract: Human immune responses to modern synthetic and recombinant peptide vaccines administered with the standard adjuvant, aluminum hydroxide, tend to be poor, hence the search for better adjuvants. Antibody responses to a Plasmodium falciparum circumsporozoite (CS) protein vaccine, R32NS1(81), administered with an adjuvant containing cell-wall skeleton of mycobacteria and monophosphoryl lipid A in squalane (MPL/CWS) have been compared to responses to the same immunogen administered with aluminum hydroxide. 2 weeks after the third dose the following indices were greater in the 5 patients who received MPL/CWS than in controls (p less than 0.05): the geometric mean concentration (2.0 vs 25.4 microgram/ml) and avidity index of antibodies to the P falciparum CS protein by ELISA, the geometric mean titre to P falciparum sporozoites by IFAT (1/115 vs 1/1600), and the geometric mean inhibition of sporozoite invasion of hepatoma cells in vitro (37.6 vs 90.3%). For R32NS1(81) MPL/CWS is superior to aluminum hydroxide as an adjuvant, and the data support the evaluation of this complex as an adjuvant for other vaccines.
authors.affiliation: Division of Infectious Diseases, National Naval Medical Center, Bethesda, Maryland 20852.
authors.forename: L S
authors.initials: LS
authors.lastname: Rickman
authors.forename: D M
authors.initials: DM
authors.lastname: Gordon
authors.forename: R
authors.initials: R
authors.lastname: Wistar
authors.forename: U
authors.initials: U
authors.lastname: Krzych
authors.forename: M
authors.initials: M
authors.lastname: Gross
authors.forename: M R
authors.initials: MR
authors.lastname: Hollingdale
authors.forename: J E
authors.initials: JE
authors.lastname: Egan
authors.forename: J D
authors.initials: JD
authors.lastname: Chulay
authors.forename: S L
authors.initials: SL
authors.lastname: Hoffman
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000328:Adult; D000818:Animals; D000913:Antibodies, Protozoan / Q000032:analysis; D000915:Antibody Affinity / Q000187:drug effects; D002473:Cell Wall / Q000382:microbiology; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives; D017780:Malaria Vaccines; D008297:Male; D009161:Mycobacterium / Q000166:cytology; D010963:Plasmodium falciparum / Q000276:immunology*; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D011993:Recombinant Fusion Proteins; D013185:Squalene / Q000008:administration & dosage; D014614:Vaccines, Synthetic / Q000009:adverse effects / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D008050:Lipid A; D017780:Malaria Vaccines; D016052:Protozoan Vaccines; C068418:R 32NS1(81); D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; D013185:Squalene; C048436:monophosphoryl lipid A