Abstract
The RTS,S/AS02A protein-based vaccine consistently demonstrates significant protection against infection with Plasmodium falciparum malaria and also against clinical malaria and severe disease in children in areas of endemicity. Here we demonstrate with rhesus macaques that priming with a replication-defective human adenovirus serotype 35 (Ad35) vector encoding circumsporozoite protein (CS) (Ad35.CS), followed by boosting with RTS,S in an improved MPL- and QS21-based adjuvant formulation, AS01B, maintains antibody responses and dramatically increases levels of T cells producing gamma interferon and other Th1 cytokines in response to CS peptides. The increased T-cell responses induced by the combination of Ad35.CS and RTS,S/AS01B are sustained for at least 6 months postvaccination and may translate to improved and more durable protection against P. falciparum infection in humans.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Adenoviridae / classification
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Adenoviridae / genetics*
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Adjuvants, Immunologic
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Animals
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Antibodies, Protozoan / blood
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Female
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Humans
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Immunization
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Immunization Schedule*
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Immunization, Secondary
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Interferon-gamma / metabolism
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Macaca mulatta
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Malaria Vaccines / administration & dosage
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Malaria Vaccines / genetics
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Malaria Vaccines / immunology*
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Malaria, Falciparum / immunology
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Malaria, Falciparum / parasitology
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Malaria, Falciparum / prevention & control*
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Male
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Plasmodium falciparum / immunology
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Protozoan Proteins / administration & dosage
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Protozoan Proteins / genetics
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Protozoan Proteins / immunology*
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Receptors, Thrombopoietin / immunology
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Saponins / immunology
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T-Lymphocytes / immunology
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Th1 Cells
Substances
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Adjuvants, Immunologic
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Antibodies, Protozoan
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Malaria Vaccines
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Protozoan Proteins
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RTS,S-AS02A vaccine
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Receptors, Thrombopoietin
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Saponins
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circumsporozoite protein, Protozoan
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MPL protein, human
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saponin QA-21V1
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Interferon-gamma