title: A DNA vaccine encoding the 42 kDa C-terminus of merozoite surface protein 1 of Plasmodium falciparum induces antibody, interferon-gamma and cytotoxic T cell responses in rhesus monkeys: immuno-stimulatory effects of granulocyte macrophage-colony stimulating factor.
abstract: We have constructed a DNA plasmid vaccine encoding the C-terminal 42-kDa region of the merozoite surface protein 1 (pMSP1(42)) from the 3D7 strain of Plasmodium falciparum (Pf3D7). This plasmid expressed recombinant MSP1(42) after in vitro transfection in mouse VM92 cells. Rhesus monkeys immunized with pMSP1(42) produced antibodies reactive with Pf3D7 infected erythrocytes by IFAT, and by ELISA against yeast produced MSP1(19) (yMSP1(19)). Immunization also induced antigen specific T cell responses as measured by interferon-gamma production, and by classical CTL chromium release assays. In addition, immunization with pMSP1(42) primed animals for an enhanced antibody response to a subsequent boost with the recombinant yMSP1(19). We also evaluated Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) as an adjuvant for pMSP1(42.) We tested both rhesus GM-CSF expressed from a DNA plasmid, and E. coli produced recombinant human GM-CSF. Plasmids encoding rhesus GM-CSF (prhGM-CSF) and human GM-CSF (phuGM-CSF) were constructed; these plasmids expressed bio-active recombinant GMCSF. Co-immunization with a mixture of prhGM-CSF and pMSP1(42) induced higher specific antibody responses after the first dose of plasmid, but after three doses of DNA monkeys immunized with or without prhGM-CSF had the same final antibody titers and T cell responses. In comparison, rhuGM-CSF protein did not lead to accelerated antibody production after the first DNA dose. However, antibody titers were maintained at a slightly higher level in monkeys receiving GM-CSF protein, and they had a higher response to boosting with recombinant MSP1(19). The GM-CSF plasmid or protein appears to be less potent as an adjuvant in rhesus monkeys than each is in mice, and more work is needed to determine if GM-CSF can be a useful adjuvant in DNA vaccination of primates.
authors.affiliation: Malaria Program, Naval Medical Research Center, Silver Spring, MD 20910, USA. kumars@nmrc.navy.mil
authors.forename: Sanjai
authors.initials: S
authors.lastname: Kumar
authors.forename: Francois
authors.initials: F
authors.lastname: Villinger
authors.forename: Miranda
authors.initials: M
authors.lastname: Oakley
authors.forename: Joao C
authors.initials: JC
authors.lastname: Aguiar
authors.forename: Trevor R
authors.initials: TR
authors.lastname: Jones
authors.forename: Richard C
authors.initials: RC
authors.lastname: Hedstrom
authors.forename: Kalpana
authors.initials: K
authors.lastname: Gowda
authors.forename: John
authors.initials: J
authors.lastname: Chute
authors.forename: Anthony
authors.initials: A
authors.lastname: Stowers
authors.forename: David C
authors.initials: DC
authors.lastname: Kaslow
authors.forename: Elaine K
authors.initials: EK
authors.lastname: Thomas
authors.forename: John
authors.initials: J
authors.lastname: Tine
authors.forename: Dennis
authors.initials: D
authors.lastname: Klinman
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hoffman
authors.forename: Walter W
authors.initials: WW
authors.lastname: Weiss
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology* / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D008253:Macaca mulatta; D017780:Malaria Vaccines / Q000235:genetics / Q000276:immunology; D016778:Malaria, Falciparum / Q000276:immunology* / Q000517:prevention & control*; D020066:Merozoite Surface Protein 1 / Q000235:genetics / Q000276:immunology; D010957:Plasmids; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor