Safety and Immunogenicity of a Recombinant Sporozoite Malaria Vaccine against Plasmodium Vivax

Deirdre A. Herrington Center for Vaccine Development, Division of Geographic Medicine, Department of Medicine, University of Maryland, Department of Medical and Molecular Parasitology, New York University School of Medicine, Chiron Corporation, Biomedical Research Institute, Baltimore, Maryland

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Elizabeth H. Nardin Center for Vaccine Development, Division of Geographic Medicine, Department of Medicine, University of Maryland, Department of Medical and Molecular Parasitology, New York University School of Medicine, Chiron Corporation, Biomedical Research Institute, Baltimore, Maryland

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Genevieve Losonsky Center for Vaccine Development, Division of Geographic Medicine, Department of Medicine, University of Maryland, Department of Medical and Molecular Parasitology, New York University School of Medicine, Chiron Corporation, Biomedical Research Institute, Baltimore, Maryland

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Ian C. Bathurst Center for Vaccine Development, Division of Geographic Medicine, Department of Medicine, University of Maryland, Department of Medical and Molecular Parasitology, New York University School of Medicine, Chiron Corporation, Biomedical Research Institute, Baltimore, Maryland

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Philip J. Barr Center for Vaccine Development, Division of Geographic Medicine, Department of Medicine, University of Maryland, Department of Medical and Molecular Parasitology, New York University School of Medicine, Chiron Corporation, Biomedical Research Institute, Baltimore, Maryland

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Michael R. Hollingdale Center for Vaccine Development, Division of Geographic Medicine, Department of Medicine, University of Maryland, Department of Medical and Molecular Parasitology, New York University School of Medicine, Chiron Corporation, Biomedical Research Institute, Baltimore, Maryland

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Robert Edelman Center for Vaccine Development, Division of Geographic Medicine, Department of Medicine, University of Maryland, Department of Medical and Molecular Parasitology, New York University School of Medicine, Chiron Corporation, Biomedical Research Institute, Baltimore, Maryland

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Myron M. Levine Center for Vaccine Development, Division of Geographic Medicine, Department of Medicine, University of Maryland, Department of Medical and Molecular Parasitology, New York University School of Medicine, Chiron Corporation, Biomedical Research Institute, Baltimore, Maryland

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A recombinant Plasmodium vivax circumsporozoite (CS) antigen representing approximately 70% of the CS protein was expressed in yeast and adsorbed onto aluminum hydroxide for use as a malaria vaccine. In a study of safety and immunogenicity, 30 volunteers were divided into four groups of 5, 5, 10, and 10 individuals, and inoculated intramuscularly with 50, 100, 200, or 400 µg of vaccine, respectively. Primary vaccinations were followed by two booster immunizations at six weeks and six months. Overall, the vaccine was well tolerated. Following the third vaccination, one volunteer developed acute hepatitis of uncertain etiology that resolved without sequelae. All volunteers in the 400-µg group, and six of 10 in the 200-µg group generated IgG against P. vivax CS protein, as determined by Western blot using recombinant CS protein. However, the magnitude of the antibody response measured by indirect immunofluorescence of intact sporozoites or enzyme-linked immunosorbent assay against the recombinant protein was low, and responses could not be boosted. Antigen-driven replication studies using peripheral blood lymphocytes failed to detect proliferative responses specific to peptide sequences represented in the recombinant vaccine, except in one volunteer. Minimal humoral and cell-mediated immune responses developed in most recipients who received this recombinant CS vaccine.

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