1. Phase I Testing of a Malaria Vaccine Composed of Hepatitis B Virus Core Particles ExpressingPlasmodium falciparumCircumsporozoite Epitopes
- Author
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Giane A. Oliveira, Michael L. Corado, Elizabeth Nardin, Ashley J. Birkett, George B. Thornton, Kristiane Wetzel, Annette Schmidt, Carolin Maier, Pramod Sarpotdar, and J. Mauricio Calvo-Calle
- Subjects
Adult ,Adolescent ,T-Lymphocytes ,Molecular Sequence Data ,Plasmodium falciparum ,Immunology ,Protozoan Proteins ,Antibodies, Protozoan ,medicine.disease_cause ,Microbiology ,Epitope ,Epitopes ,Interferon-gamma ,Double-Blind Method ,Orthohepadnavirus ,Malaria Vaccines ,parasitic diseases ,medicine ,Animals ,Humans ,Amino Acid Sequence ,Malaria, Falciparum ,Hepatitis B virus ,Vaccines, Synthetic ,biology ,Malaria vaccine ,Immunogenicity ,Virion ,Middle Aged ,Hepatitis B ,medicine.disease ,biology.organism_classification ,Hepatitis B Core Antigens ,Virology ,Infectious Diseases ,Hepadnaviridae ,Microbial Immunity and Vaccines ,Alum Compounds ,Parasitology - 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 thePlasmodium falciparumcircumsporozoite (CS) protein. When expressed inEscherichia 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-μg dose of alum-adsorbed ICC-1132 administered intramuscularly at 0, 2, and 6 months. The majority of volunteers in the group receiving the 50-μg 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.
- Published
- 2004