title: Phase I dose escalation safety and immunogenicity trial of Plasmodium falciparum apical membrane protein (AMA-1) FMP2.1, adjuvanted with AS02A, in malaria-naïve adults at the Walter Reed Army Institute of Research.
abstract: We report the first safety and immunogenicity trial of the Plasmodium falciparum vaccine candidate FMP2.1/AS02A, a recombinant E. coli-expressed protein based upon the apical membrane antigen-1 (AMA-1) of the 3D7 clone formulated with the AS02A adjuvant. We conducted an open-label, staggered-start, dose-escalating Phase I trial in 23 malaria-naïve volunteers who received 8, 20 or 40microg of FMP2.1 in a fixed volume of 0.5mL of AS02A on a 0, 1, and 2 month schedule. Nineteen of 23 volunteers received all three scheduled immunizations. The most frequent solicited local and systemic adverse events associated with immunization were injection site pain (68%) and headache (29%). There were no significant laboratory abnormalities or vaccine-related serious adverse events. All volunteers seroconverted after second immunization as determined by ELISA. Immune sera recognized sporozoites and merozoites by immunofluorescence assay (IFA), and exhibited both growth inhibition and processing inhibition activity against homologous (3D7) asexual stage parasites. Post-immunization, peripheral blood mononuculear cells exhibited FMP2.1-specific lymphoproliferation and IFN-gamma and IL-5 ELISPOT assay responses. This is the first PfAMA-1-based vaccine shown to elicit both potent humoral and cellular immunity in humans. Encouraged by the potential of FMP1/AS02A to target host immunity against PfAMA-1 that is known to be expressed by sporozoite, hepatic and erythrocytic stages, we have initiated field trials of FMP2.1/AS02A in an endemic population in the Republic of Mali.
authors: Walter Reed Army Institute of Research, Silver Spring, MD, United States. mpolhemus@wrp-ksm.org
authors: Mark E
authors: ME
authors: Polhemus
authors: Alan J
authors: AJ
authors: Magill
authors: James F
authors: JF
authors: Cummings
authors: Kent E
authors: KE
authors: Kester
authors: Chris F
authors: CF
authors: Ockenhouse
authors: David E
authors: DE
authors: Lanar
authors: Sheetij
authors: S
authors: Dutta
authors: Arnoldo
authors: A
authors: Barbosa
authors: Lorraine
authors: L
authors: Soisson
authors: Carter L
authors: CL
authors: Diggs
authors: Sally A
authors: SA
authors: Robinson
authors: John D
authors: JD
authors: Haynes
authors: V Ann
authors: VA
authors: Stewart
authors: Lisa A
authors: LA
authors: Ware
authors: Clara
authors: C
authors: Brando
authors: Urszula
authors: U
authors: Krzych
authors: Robert A
authors: RA
authors: Bowden
authors: Joe D
authors: JD
authors: Cohen
authors: Marie-Claude
authors: MC
authors: Dubois
authors: Opokua
authors: O
authors: Ofori-Anyinam
authors: Els
authors: E
authors: De-Kock
authors: W Ripley
authors: WR
authors: Ballou
authors: D Gray
authors: DG
authors: Heppner
mesh_terms: D000276:Adjuvants, Immunologic; D000293:Adolescent; D000328:Adult; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000276:immunology*; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D006224:Cricetinae; D004338:Drug Combinations; D004797:Enzyme-Linked Immunosorbent Assay; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006261:Headache; D006801:Humans; D007117:Immunization, Secondary; D007371:Interferon-gamma / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008050:Lipid A / Q000031:analogs & derivatives* / Q000276:immunology; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D008297:Male; D008565:Membrane Proteins / Q000276:immunology*; D052940:Merozoites / Q000276:immunology; D008647:Mesocricetus; D008875:Middle Aged; D010146:Pain; D010963:Plasmodium falciparum / Q000254:growth & development / Q000276:immunology*; D015800:Protozoan Proteins / Q000276:immunology*; D012503:Saponins / Q000276:immunology*; D034101:Sporozoites / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: C501939:ASO2A adjuvant; D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D004338:Drug Combinations; D015848:Interleukin-5; D008050:Lipid A; D017780:Malaria Vaccines; D008565:Membrane Proteins; D015800:Protozoan Proteins; D012503:Saponins; D014614:Vaccines, Synthetic; C090077:apical membrane antigen I, Plasmodium; D007371:Interferon-gamma