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  • 1
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    Protection against malaria by intravenous immunization with a nonreplicating sporozoite vaccine (2013)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2013-08-10
    Description: Consistent, high-level, vaccine-induced protection against human malaria has only been achieved by inoculation of Plasmodium falciparum (Pf) sporozoites (SPZ) by mosquito bites. We report that the PfSPZ Vaccine--composed of attenuated, aseptic, purified, cryopreserved PfSPZ--was safe and well tolerated when administered four to six times intravenously (IV) to 40 adults. Zero of six subjects receiving five doses and three of nine subjects receiving four doses of 1.35 x 10(5) PfSPZ Vaccine and five of six nonvaccinated controls developed malaria after controlled human malaria infection (P = 0.015 in the five-dose group and P = 0.028 for overall, both versus controls). PfSPZ-specific antibody and T cell responses were dose-dependent. These data indicate that there is a dose-dependent immunological threshold for establishing high-level protection against malaria that can be achieved with IV administration of a vaccine that is safe and meets regulatory standards.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Seder, Robert A -- Chang, Lee-Jah -- Enama, Mary E -- Zephir, Kathryn L -- Sarwar, Uzma N -- Gordon, Ingelise J -- Holman, LaSonji A -- James, Eric R -- Billingsley, Peter F -- Gunasekera, Anusha -- Richman, Adam -- Chakravarty, Sumana -- Manoj, Anita -- Velmurugan, Soundarapandian -- Li, MingLin -- Ruben, Adam J -- Li, Tao -- Eappen, Abraham G -- Stafford, Richard E -- Plummer, Sarah H -- Hendel, Cynthia S -- Novik, Laura -- Costner, Pamela J M -- Mendoza, Floreliz H -- Saunders, Jamie G -- Nason, Martha C -- Richardson, Jason H -- Murphy, Jittawadee -- Davidson, Silas A -- Richie, Thomas L -- Sedegah, Martha -- Sutamihardja, Awalludin -- Fahle, Gary A -- Lyke, Kirsten E -- Laurens, Matthew B -- Roederer, Mario -- Tewari, Kavita -- Epstein, Judith E -- Sim, B Kim Lee -- Ledgerwood, Julie E -- Graham, Barney S -- Hoffman, Stephen L -- VRC 312 Study Team -- 3R44AI055229-06S1/AI/NIAID NIH HHS/ -- 4R44AI055229-08/AI/NIAID NIH HHS/ -- 5R44AI058499-05/AI/NIAID NIH HHS/ -- N01-AI-40096/AI/NIAID NIH HHS/ -- Intramural NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2013 Sep 20;341(6152):1359-65. doi: 10.1126/science.1241800. Epub 2013 Aug 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20852, USA. rseder@mail.nih.gov〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23929949" target="_blank"〉PubMed〈/a〉
    Keywords: Administration, Intravenous ; Adult ; Animals ; Cytokines/immunology ; Female ; Humans ; Immunity, Cellular ; Malaria Vaccines/*administration & dosage/adverse effects/*immunology ; Malaria, Falciparum/*prevention & control ; Male ; Mice ; Plasmodium falciparum/*immunology ; Sporozoites/immunology ; T-Lymphocytes/immunology ; Vaccination/adverse effects/methods
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Live attenuated malaria vaccine designed to protect through hepatic CD8(+) T cell immunity (2011)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2011-09-10
    Description: Our goal is to develop a vaccine that sustainably prevents Plasmodium falciparum (Pf) malaria in 〉/=80% of recipients. Pf sporozoites (PfSPZ) administered by mosquito bites are the only immunogens shown to induce such protection in humans. Such protection is thought to be mediated by CD8(+) T cells in the liver that secrete interferon-gamma (IFN-gamma). We report that purified irradiated PfSPZ administered to 80 volunteers by needle inoculation in the skin was safe, but suboptimally immunogenic and protective. Animal studies demonstrated that intravenous immunization was critical for inducing a high frequency of PfSPZ-specific CD8(+), IFN-gamma-producing T cells in the liver (nonhuman primates, mice) and conferring protection (mice). Our results suggest that intravenous administration of this vaccine will lead to the prevention of infection with Pf malaria.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Epstein, J E -- Tewari, K -- Lyke, K E -- Sim, B K L -- Billingsley, P F -- Laurens, M B -- Gunasekera, A -- Chakravarty, S -- James, E R -- Sedegah, M -- Richman, A -- Velmurugan, S -- Reyes, S -- Li, M -- Tucker, K -- Ahumada, A -- Ruben, A J -- Li, T -- Stafford, R -- Eappen, A G -- Tamminga, C -- Bennett, J W -- Ockenhouse, C F -- Murphy, J R -- Komisar, J -- Thomas, N -- Loyevsky, M -- Birkett, A -- Plowe, C V -- Loucq, C -- Edelman, R -- Richie, T L -- Seder, R A -- Hoffman, S L -- 5R44AI055229-07/AI/NIAID NIH HHS/ -- 5R44AI058375-05/AI/NIAID NIH HHS/ -- 5R44AI058499-05/AI/NIAID NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2011 Oct 28;334(6055):475-80. doi: 10.1126/science.1211548. Epub 2011 Sep 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉U.S. Military Malaria Vaccine Program, Naval Medical Research Center, Silver Spring, MD 20910, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21903775" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; Animals ; Antibodies, Protozoan/blood/immunology ; Antigens, Protozoan/immunology ; CD8-Positive T-Lymphocytes/*immunology ; Humans ; Injections, Intravenous ; Injections, Subcutaneous ; Interferon-gamma/biosynthesis/immunology ; Liver/*immunology ; Macaca mulatta ; Malaria Vaccines/administration & dosage/adverse effects/*immunology ; Malaria, Falciparum/*prevention & control ; Mice ; Middle Aged ; Plasmodium falciparum/*immunology ; Rabbits ; Sporozoites/*immunology ; Vaccines, Attenuated/administration & dosage/adverse effects/immunology ; Young Adult
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 3
    Electronic Resource
    Electronic Resource
    Mapping of the K+/Na+ discrimination locus Kna1 in wheat (1996)
    Springer
    Theoretical and applied genetics 92 (1996), S. 448-454 
    Details
    ISSN: 1432-2242
    Keywords: Key words  Wheat ; Salt tolerance ; Homoeologous recombination ; QTL ; RFLP ; Genetic marker
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract   In saline environments, bread wheat, Triticum aestivum L. (genomes AABBDD), accumulates less Na+ and more K+ in expanding and young leaves than durum wheat, T. turgidum L. (genomes AABB). Higher K+/Na+ ratios in leaves of bread wheat correlate with its higher salt tolerance. Chromosome 4D from bread wheat was shown in previous work to play an important role in the control of this trait and was recombined with chromosome 4B in the absence of the Ph1 locus. A population of plants disomic for 4D/4B recombined chromosomes in the genetic background of T. turgidum was developed to investigate the genetic control of K+/Na+ discrimination by chromosome 4D. Evidence was obtained that the trait is controlled by a single locus, designated Kna1, in the long arm of chromosome 4D. In the present work, K+/Na+ discrimination was determined for additional families with 4D/4B chromosomes. The concentrations of Na+ and K+/Na+ ratios in the youngest leaf blades clustered in two nonoverlapping classes, and all recombinant families could be unequivocally assigned to Kna1 and kna1 classes. The Kna1 locus scored this way was mapped on a short region in the 4DL arm and was completely linked to Xwg199, Xabc305, Xbcd402, Xpsr567, and Xpsr375; it was also mapped as a quantitative trait. The results of the QTL analysis, based on the K+/Na+ ratios in the young leaves of greenhouse-grown plants and flag leaves of field-grown plants, agreed with the position of Kna1 determined as a qualitative trait. Several aspects of gene introgression by manipulation of the Ph1 locus are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001220050148
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  • 4
    Electronic Resource
    Electronic Resource
    Mapping of the K+/Na+ discrimination locus Kna1 in wheat (1996)
    Springer
    Theoretical and applied genetics 92 (1996), S. 448-454 
    Details
    ISSN: 1432-2242
    Keywords: Wheat ; Salt tolerance ; Homoeologous recombination ; QTL ; RFLP ; Genetic marker
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract In saline environments, bread wheat, Triticum aestivum L. (genomes AABBDD), accumulates less Na+ and more K+ in expanding and young leaves than durum wheat, T. turgidum L. (genomes AABB). Higher K+/Na+ ratios in leaves of bread wheat correlate with its higher salt tolerance. Chromosome 4D from bread wheat was shown in previous work to play an important role in the control of this trait and was recombined with chromosome 4B in the absence of the Ph1 locus. A population of plants disomic for 4D/4B recombined chromosomes in the genetic background of T. turgidum was developed to investigate the genetic control of K+/Na+ discrimination by chromosome 4D. Evidence was obtained that the trait is controlled by a single locus, designated Kna1, in the long arm of chromosome 4D. In the present work, K+/Na+ discrimination was determined for additional families with 4D/4B chromosomes. The concentrations of Na+ and K+/Na+ ratios in the youngest leaf blades clustered in two nonoverlapping classes, and all recombinant families could be unequivocally assigned to Kna1 and kna1 classes. The Kna1 locus scored this way was mapped on a short region in the 4DL arm and was completely linked to Xwg199, Xabc305, Xbcd.402, Xpsr567, and Xpsr375; it was also mapped as a quantitative trait. The results of the QTL analysis, based on the K+/Na+ ratios in the young leaves of greenhousegrown plants and flag leaves of field-grown plants, agreed with the position of Knal determined as a qualitative trait. Several aspects of gene introgression by manipulation of the Ph1 locus are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00223692
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