Safety, Immunogenicity, and Efficacy of a Malaria Sporozoite Vaccine Administered with Monophosphoryl Lipid A, Cell Wall Skeleton of Mycobacteria, and Squalane as Adjuvant

Stephen L. Hoffman Malaria Program, Naval Medical Research Institute, Center for Vaccine Development, University of Maryland, Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, Department of Entomology and Department of Immunology, Walter Reed Army Institute of Research, Pan American Health Organization, SmithKline Beecham Pharmaceuticals, Biomedical Research Institute, Division of Infectious Diseases, National Naval Medical Center, Bethesda, Maryland

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Robert Edelman Malaria Program, Naval Medical Research Institute, Center for Vaccine Development, University of Maryland, Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, Department of Entomology and Department of Immunology, Walter Reed Army Institute of Research, Pan American Health Organization, SmithKline Beecham Pharmaceuticals, Biomedical Research Institute, Division of Infectious Diseases, National Naval Medical Center, Bethesda, Maryland

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Joe P. Bryan Malaria Program, Naval Medical Research Institute, Center for Vaccine Development, University of Maryland, Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, Department of Entomology and Department of Immunology, Walter Reed Army Institute of Research, Pan American Health Organization, SmithKline Beecham Pharmaceuticals, Biomedical Research Institute, Division of Infectious Diseases, National Naval Medical Center, Bethesda, Maryland

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Imogene Schneider Malaria Program, Naval Medical Research Institute, Center for Vaccine Development, University of Maryland, Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, Department of Entomology and Department of Immunology, Walter Reed Army Institute of Research, Pan American Health Organization, SmithKline Beecham Pharmaceuticals, Biomedical Research Institute, Division of Infectious Diseases, National Naval Medical Center, Bethesda, Maryland

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Jonathan Davis Malaria Program, Naval Medical Research Institute, Center for Vaccine Development, University of Maryland, Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, Department of Entomology and Department of Immunology, Walter Reed Army Institute of Research, Pan American Health Organization, SmithKline Beecham Pharmaceuticals, Biomedical Research Institute, Division of Infectious Diseases, National Naval Medical Center, Bethesda, Maryland

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Martha Sedegah Malaria Program, Naval Medical Research Institute, Center for Vaccine Development, University of Maryland, Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, Department of Entomology and Department of Immunology, Walter Reed Army Institute of Research, Pan American Health Organization, SmithKline Beecham Pharmaceuticals, Biomedical Research Institute, Division of Infectious Diseases, National Naval Medical Center, Bethesda, Maryland

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Daniel Gordon Malaria Program, Naval Medical Research Institute, Center for Vaccine Development, University of Maryland, Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, Department of Entomology and Department of Immunology, Walter Reed Army Institute of Research, Pan American Health Organization, SmithKline Beecham Pharmaceuticals, Biomedical Research Institute, Division of Infectious Diseases, National Naval Medical Center, Bethesda, Maryland

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Preston Church Malaria Program, Naval Medical Research Institute, Center for Vaccine Development, University of Maryland, Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, Department of Entomology and Department of Immunology, Walter Reed Army Institute of Research, Pan American Health Organization, SmithKline Beecham Pharmaceuticals, Biomedical Research Institute, Division of Infectious Diseases, National Naval Medical Center, Bethesda, Maryland

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Mitchell Gross Malaria Program, Naval Medical Research Institute, Center for Vaccine Development, University of Maryland, Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, Department of Entomology and Department of Immunology, Walter Reed Army Institute of Research, Pan American Health Organization, SmithKline Beecham Pharmaceuticals, Biomedical Research Institute, Division of Infectious Diseases, National Naval Medical Center, Bethesda, Maryland

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Carol Silverman Malaria Program, Naval Medical Research Institute, Center for Vaccine Development, University of Maryland, Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, Department of Entomology and Department of Immunology, Walter Reed Army Institute of Research, Pan American Health Organization, SmithKline Beecham Pharmaceuticals, Biomedical Research Institute, Division of Infectious Diseases, National Naval Medical Center, Bethesda, Maryland

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Michael Hollingdale Malaria Program, Naval Medical Research Institute, Center for Vaccine Development, University of Maryland, Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, Department of Entomology and Department of Immunology, Walter Reed Army Institute of Research, Pan American Health Organization, SmithKline Beecham Pharmaceuticals, Biomedical Research Institute, Division of Infectious Diseases, National Naval Medical Center, Bethesda, Maryland

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David Clyde Malaria Program, Naval Medical Research Institute, Center for Vaccine Development, University of Maryland, Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, Department of Entomology and Department of Immunology, Walter Reed Army Institute of Research, Pan American Health Organization, SmithKline Beecham Pharmaceuticals, Biomedical Research Institute, Division of Infectious Diseases, National Naval Medical Center, Bethesda, Maryland

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Marcelo Sztein Malaria Program, Naval Medical Research Institute, Center for Vaccine Development, University of Maryland, Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, Department of Entomology and Department of Immunology, Walter Reed Army Institute of Research, Pan American Health Organization, SmithKline Beecham Pharmaceuticals, Biomedical Research Institute, Division of Infectious Diseases, National Naval Medical Center, Bethesda, Maryland

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Genevieve Losonsky Malaria Program, Naval Medical Research Institute, Center for Vaccine Development, University of Maryland, Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, Department of Entomology and Department of Immunology, Walter Reed Army Institute of Research, Pan American Health Organization, SmithKline Beecham Pharmaceuticals, Biomedical Research Institute, Division of Infectious Diseases, National Naval Medical Center, Bethesda, Maryland

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Scott Paparello Malaria Program, Naval Medical Research Institute, Center for Vaccine Development, University of Maryland, Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, Department of Entomology and Department of Immunology, Walter Reed Army Institute of Research, Pan American Health Organization, SmithKline Beecham Pharmaceuticals, Biomedical Research Institute, Division of Infectious Diseases, National Naval Medical Center, Bethesda, Maryland

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Trevor R. Jones Malaria Program, Naval Medical Research Institute, Center for Vaccine Development, University of Maryland, Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, Department of Entomology and Department of Immunology, Walter Reed Army Institute of Research, Pan American Health Organization, SmithKline Beecham Pharmaceuticals, Biomedical Research Institute, Division of Infectious Diseases, National Naval Medical Center, Bethesda, Maryland

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A Plasmodium falciparum circumsporozoite protein (PfCSP) recombinant fusion protein, R32NSI81, formulated with monophosphoryl lipid A, cell wall skeleton of mycobacteria, and squalane (Detox™) was administered to 12 volunteers. One volunteer had malaise and self-limited painful induration at the injection site after the second dose and declined further immunization. The other 11 volunteers tolerated the three doses of 1,230 µg of vaccine, but most complained of sore arms; in five cases the pain or malaise was severe enough to interfere with work or sleep. Two weeks after the third dose of vaccine, four of the 11 immunized volunteers had ≥ 14 µg/ml of antibodies to the repeat region of the PfCSP in their serum. Two of these four volunteers did not develop P. falciparum parasitemia when challenged by the bite of five mosquitoes carrying P. falciparum sporozoites. The seven volunteers with lower levels of antibodies and 11 of 11 controls developed parasitemia. These data are consistent with other studies, and indicate that vaccine-induced antibodies against the repeat region of PfCSP can prevent effective sporozoite infection of hepatocytes in humans. The challenge is to improve the immunogenicity of PfCSP-based vaccines, and to develop methods for including PfCSP peptides as components of multitarget malaria vaccines.

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