title: Phase I safety and immunogenicity trial of FMP1/AS02A, a Plasmodium falciparum MSP-1 asexual blood stage vaccine.
abstract: We report the first safety and immunogenicity trial of the Plasmodium falciparum malaria blood stage vaccine candidate, FMP1/AS02A consisting of the FMP1 antigen, an Escherichia coli-expressed His-tagged fusion protein from the 42 kDa C-terminal fragment from the 3D7 clone of the merozoite surface protein 1 formulated in the AS02A adjuvant. An open label, prospective, single-center Phase I dose escalation trial of FMP1/AS02A was conducted in 15 adult malaria-naïve human volunteers to assess safety, reactogenicity, and immunogenicity. The vaccine was safe and well-tolerated and no serious adverse events were observed. The vaccine induced high-titer ELISA and IFA responses in all volunteers. Proliferative and ELISPOT responses were induced to vaccine antigen. Biologically active antibodies were induced as measured by GIA. This study establishes the foundation to further evaluate and measure the vaccine's ability to reduce morbidity and mortality in target populations directly affected by P. falciparum malaria.
authors.affiliation: Department of Immunology, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA. chris.ockenhouse@na.amedd.army.mil
authors.forename: Christian F
authors.initials: CF
authors.lastname: Ockenhouse
authors.forename: Evelina
authors.initials: E
authors.lastname: Angov
authors.forename: Kent E
authors.initials: KE
authors.lastname: Kester
authors.forename: Carter
authors.initials: C
authors.lastname: Diggs
authors.forename: Lorraine
authors.initials: L
authors.lastname: Soisson
authors.forename: James F
authors.initials: JF
authors.lastname: Cummings
authors.forename: Ann V
authors.initials: AV
authors.lastname: Stewart
authors.forename: Dupeh R
authors.initials: DR
authors.lastname: Palmer
authors.forename: Babita
authors.initials: B
authors.lastname: Mahajan
authors.forename: Urszula
authors.initials: U
authors.lastname: Krzych
authors.forename: Nadia
authors.initials: N
authors.lastname: Tornieporth
authors.forename: M
authors.initials: M
authors.lastname: Delchambre
authors.forename: M
authors.initials: M
authors.lastname: Vanhandenhove
authors.forename: Opokua
authors.initials: O
authors.lastname: Ofori-Anyinam
authors.forename: Joe
authors.initials: J
authors.lastname: Cohen
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Lyon
authors.forename: D Gray
authors.initials: DG
authors.lastname: Heppner
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D004338:Drug Combinations; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D008297:Male; D020066:Merozoite Surface Protein 1 / Q000276:immunology*; D008875:Middle Aged; D010963:Plasmodium falciparum / Q000254:growth & development / Q000276:immunology*; D012503:Saponins / Q000008:administration & dosage / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000276:immunology; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
chemical_list: C501939:ASO2A adjuvant; D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D004338:Drug Combinations; D008050:Lipid A; D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1; D012503:Saponins; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; D007371:Interferon-gamma; D007770:L-Lactate Dehydrogenase