title: Safety, immunogenicity, and efficacy of a recombinantly produced Plasmodium falciparum circumsporozoite protein-hepatitis B surface antigen subunit vaccine.
abstract: Twenty malaria-naive volunteers received a recombinant Plasmodium falciparum malaria vaccine (RTS,S) containing 19 NANP repeats and the carboxy terminus (amino acids 210-398) of the circumsporozoite (CS) antigen coexpressed in yeast with hepatitis B surface antigen. Ten received vaccine adjuvanted with alum, and 10 received vaccine adjuvanted with alum plus 3-deacylated monophosphoryl lipid A (MPL). Both formulations were well tolerated and immunogenic. MPL enhanced CS antibody levels (measured by ELISA, immunofluorescence, and inhibition of sporozoite invasion assays). After sporozoite challenge, 6 of 6 in the alum group and 6 of 8 in the alum-MPL group developed patent malaria. Protected subjects had higher levels of CS antibody titers on day of challenge than did nonprotected subjects. After immunization, 1 protected subject had increased cytotoxic T lymphocyte activity against CS and recall of memory T cell responses to RTS,S and selected CS.
authors.affiliation: Department of Immunology, Walter Reed Army Institute of Research, Washington, DC, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Gordon
authors.forename: T W
authors.initials: TW
authors.lastname: McGovern
authors.forename: U
authors.initials: U
authors.lastname: Krzych
authors.forename: J C
authors.initials: JC
authors.lastname: Cohen
authors.forename: I
authors.initials: I
authors.lastname: Schneider
authors.forename: R
authors.initials: R
authors.lastname: LaChance
authors.forename: D G
authors.initials: DG
authors.lastname: Heppner
authors.forename: G
authors.initials: G
authors.lastname: Yuan
authors.forename: M
authors.initials: M
authors.lastname: Hollingdale
authors.forename: M
authors.initials: M
authors.lastname: Slaoui
mesh_terms: D000328:Adult; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis*; D003602:Cytotoxicity, Immunologic; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D006801:Humans; D007111:Immunity, Cellular; D017780:Malaria Vaccines / Q000009:adverse effects / Q000276:immunology*; D016778:Malaria, Falciparum / Q000517:prevention & control; D008297:Male; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014614:Vaccines, Synthetic / Q000009:adverse effects / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D006514:Hepatitis B Surface Antigens; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D014614:Vaccines, Synthetic; C041595:circumsporozoite protein, Protozoan