title: Boosting of DNA vaccine-elicited gamma interferon responses in humans by exposure to malaria parasites.
abstract: A mixture of DNA plasmids expressing five Plasmodium falciparum pre-erythrocyte-stage antigens was administered with or without a DNA plasmid encoding human granulocyte-macrophage colony-stimulating factor (hGM-CSF) as an immune enhancer. After DNA immunization, antigen-specific gamma interferon (IFN-gamma) responses were detected by ELISPOT in 15/31 volunteers to multiple class I- and/or class II-restricted T-cell epitopes derived from all five antigens. Responses to multiple epitopes (</=7) were detected simultaneously in some volunteers. By 4 weeks after challenge with P. falciparum parasites, 23/31 volunteers had positive IFN-gamma responses and the magnitude of responses was increased from 2- to 143-fold. Nonetheless, none was protected against malaria. Volunteers who received hGM-CSF had a reduced frequency of IFN-gamma responses to class I peptides compared to those who only received plasmids expressing P. falciparum proteins before challenge (3/23 versus 3/8; P = 0.15) or after parasite challenge (4/23 versus 5/8; P = 0.015) but not to class II peptides before or after challenge. The responses to one antigen (P. falciparum circumsporozoite protein [PfCSP]) were similar among volunteers who received the five-gene mixture compared to volunteers who only received the PfCSP DNA plasmid in a previous study. In summary, DNA-primed IFN-gamma responses were boosted in humans by exposure to native antigen on parasites, coadministration of a plasmid expressing hGM-CSF had a negative effect on boosting of class I-restricted IFN-gamma responses, and there was no evidence that immunization with PfCSP DNA in the mixture reduced T-cell responses to PfCSP compared to when it was administered alone.
authors.affiliation: Sanaria, Inc., 12115 Parklawn Drive, Suite L, Rockville, MD 20852, USA.
authors.forename: Ruobing
authors.initials: R
authors.lastname: Wang
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Richie
authors.forename: Maria Fe
authors.initials: MF
authors.lastname: Baraceros
authors.forename: Nancy
authors.initials: N
authors.lastname: Rahardjo
authors.forename: Tanya
authors.initials: T
authors.lastname: Gay
authors.forename: Jo-Glenna
authors.initials: JG
authors.lastname: Banania
authors.forename: Yupin
authors.initials: Y
authors.lastname: Charoenvit
authors.forename: Judith E
authors.initials: JE
authors.lastname: Epstein
authors.forename: Thomas
authors.initials: T
authors.lastname: Luke
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Freilich
authors.forename: Jon
authors.initials: J
authors.lastname: Norman
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hoffman
mesh_terms: D000818:Animals; D000953:Antigens, Protozoan / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D001733:Bites and Stings; D009033:Culicidae; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D006801:Humans; D007114:Immunization; D007371:Interferon-gamma / Q000097:blood*; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology*; D010957:Plasmids; D010963:Plasmodium falciparum / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D019444:Vaccines, DNA; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor