title: Safety and enhanced immunogenicity of a hepatitis B core particle Plasmodium falciparum malaria vaccine formulated in adjuvant Montanide ISA 720 in a phase I trial.
abstract: Highly purified subunit vaccines require potent adjuvants in order to elicit optimal immune responses. In a previous phase I trial, an alum formulation of ICC-1132, a malaria vaccine candidate comprising hepatitis B core (HBc) virus-like particle containing Plasmodium falciparum circumsporozoite (CS) protein epitopes, was shown to elicit Plasmodium falciparum-specific antibody and cellular responses. The present study was designed as a single-blind, escalating-dose phase I trial to evaluate the safety and immunogenicity of single intramuscular doses of ICC-1132 formulated in the more potent water-in-oil adjuvant Montanide ISA 720 (ICC-1132/ISA 720). The vaccine was safe and well tolerated, with transient injection site pain as the most frequent complaint. All vaccinees that received either 20 mug or 50 mug of ICC-1132/ISA 720 developed antiimmunogen and anti-HBc antibodies. The majority of volunteers in these two groups developed sporozoite-specific antibodies, predominantly of opsonizing immunoglobulin G subtypes. Peak titers and persistence of parasite-specific antibody following a single injection of the ISA 720 formulated vaccine were comparable to those obtained following two to three immunizations with alum-adsorbed ICC-1132. Peripheral blood mononuclear cells of ICC-1132/ISA 720 vaccinees proliferated and released cytokines (interleukin 2 and gamma interferon) when stimulated with recombinant P. falciparum CS protein, and CS-specific CD4(+) T-cell lines were established from volunteers with high levels of antibodies to the repeat region. The promising results obtained with a single dose of ICC-1132 formulated in Montanide ISA 720 encourage further clinical development of this malaria vaccine candidate.
authors.affiliation: Department of Medical Parasitology, New York University School of Medicine, 341 East 25th Street, New York, NY 10010, USA.
authors.forename: Giane A
authors.initials: GA
authors.lastname: Oliveira
authors.forename: Kristiane
authors.initials: K
authors.lastname: Wetzel
authors.forename: J Mauricio
authors.initials: JM
authors.lastname: Calvo-Calle
authors.forename: Ruth
authors.initials: R
authors.lastname: Nussenzweig
authors.forename: Annette
authors.initials: A
authors.lastname: Schmidt
authors.forename: Ashley
authors.initials: A
authors.lastname: Birkett
authors.forename: Filip
authors.initials: F
authors.lastname: Dubovsky
authors.forename: Eveline
authors.initials: E
authors.lastname: Tierney
authors.forename: Christoph H
authors.initials: CH
authors.lastname: Gleiter
authors.forename: Gabriele
authors.initials: G
authors.lastname: Boehmer
authors.forename: Adrian J F
authors.initials: AJ
authors.lastname: Luty
authors.forename: Michael
authors.initials: M
authors.lastname: Ramharter
authors.forename: George B
authors.initials: GB
authors.lastname: Thornton
authors.forename: Peter G
authors.initials: PG
authors.lastname: Kremsner
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Nardin
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000918:Antibody Specificity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D006512:Hepatitis B Core Antigens / Q000008:administration & dosage*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000145:classification; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D017780:Malaria Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D008353:Mannitol / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D008969:Molecular Sequence Data; D009829:Oleic Acids / Q000008:administration & dosage*; D010963:Plasmodium falciparum / Q000276:immunology*; D016037:Single-Blind Method
chemical_list: D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D006512:Hepatitis B Core Antigens; D007074:Immunoglobulin G; D017780:Malaria Vaccines; D009829:Oleic Acids; C001681:mannide monooleate; D008353:Mannitol; D007371:Interferon-gamma