title: Phase I testing of a malaria vaccine composed of hepatitis B virus core particles expressing Plasmodium falciparum circumsporozoite epitopes.
abstract: We report the first phase I trial to assess the safety and immunogenicity of a malaria vaccine candidate, ICC-1132 (Malarivax), composed of a modified hepatitis B virus core protein (HBc) containing minimal epitopes of the Plasmodium falciparum circumsporozoite (CS) protein. When expressed in Escherichia coli, the recombinant ICC-1132 protein forms virus-like particles that were found to be highly immunogenic in preclinical studies of mice and monkeys. Twenty healthy adult volunteers received a 20- or a 50-microg dose of alum-adsorbed ICC-1132 administered intramuscularly at 0, 2, and 6 months. The majority of volunteers in the group receiving the 50-microg dose developed antibodies to CS repeats as well as to HBc. Malaria-specific T cells that secreted gamma interferon were also detected after a single immunization with ICC-1132-alum. These studies support ICC-1132 as a promising malaria vaccine candidate for further clinical testing using more-potent adjuvant formulations and confirm the potential of modified HBc virus-like particles as a delivery platform for vaccines against other human pathogens.
authors.affiliation: New York University School of Medicine, Department of Medical and Molecular Parasitology, 341 East 25th St., New York, NY 10010, USA. nardie01@med.nyu.edu
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Nardin
authors.forename: Giane A
authors.initials: GA
authors.lastname: Oliveira
authors.forename: J Mauricio
authors.initials: JM
authors.lastname: Calvo-Calle
authors.forename: Kristiane
authors.initials: K
authors.lastname: Wetzel
authors.forename: Carolin
authors.initials: C
authors.lastname: Maier
authors.forename: Ashley J
authors.initials: AJ
authors.lastname: Birkett
authors.forename: Pramod
authors.initials: P
authors.lastname: Sarpotdar
authors.forename: Michael L
authors.initials: ML
authors.lastname: Corado
authors.forename: George B
authors.initials: GB
authors.lastname: Thornton
authors.forename: Annette
authors.initials: A
authors.lastname: Schmidt
mesh_terms: D000293:Adolescent; D000328:Adult; D000534:Alum Compounds; D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D004311:Double-Blind Method; D000939:Epitopes; D006509:Hepatitis B / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006512:Hepatitis B Core Antigens / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control; D008875:Middle Aged; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014771:Virion / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D000534:Alum Compounds; D000913:Antibodies, Protozoan; D000939:Epitopes; D006512:Hepatitis B Core Antigens; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D014614:Vaccines, Synthetic; C041595:circumsporozoite protein, Protozoan; C041524:aluminum sulfate; D007371:Interferon-gamma