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rdf:type |
|
|
lifeskim:mentions |
umls-concept:C0023884,
umls-concept:C0024518,
umls-concept:C0032149,
umls-concept:C0039194,
umls-concept:C0085358,
umls-concept:C0127400,
umls-concept:C0205263,
umls-concept:C0232920,
umls-concept:C0332161,
umls-concept:C0456387,
umls-concept:C0678108,
umls-concept:C1306673,
umls-concept:C1332717,
umls-concept:C1413244,
umls-concept:C1545588,
umls-concept:C1706438,
umls-concept:C2698600
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|
pubmed:issue |
4
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pubmed:dateCreated |
2007-7-12
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|
pubmed:abstractText |
At present, radiation-attenuated plasmodia sporozoites ( gamma -spz) is the only vaccine that induces sterile and lasting protection in malaria-naive humans and laboratory rodents. However, gamma -spz are not without risks. For example, the heterogeneity of the gamma -spz could explain occasional breakthrough infections. To avoid this possibility, we constructed a double-knockout P. berghei parasite by removing 2 genes, UIS3 and UIS4, that are up-regulated in infective spz. We evaluated the double-knockout Pbuis3(-)/4(-) parasites for protective efficacy and the contribution of CD8(+) T cells to protection. Pbuis3(-)/4(-) spz induced sterile and protracted protection in C57BL/6 mice. Protection was linked to CD8(+) T cells, given that mice deficient in beta (2)m were not protected. Pbuis3(-)/4(-) spz-immune CD8(+) T cells consisted of effector/memory phenotypes and produced interferon- gamma . On the basis of these observations, we propose that the development of genetically attenuated P. falciparum parasites is warranted for tests in clinical trials as a pre-erythrocytic stage vaccine candidate.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
|
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0022-1899
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pubmed:author |
|
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
196
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
599-607
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pubmed:dateRevised |
2011-5-5
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pubmed:meshHeading |
pubmed-meshheading:17624847-Animals,
pubmed-meshheading:17624847-CD8-Positive T-Lymphocytes,
pubmed-meshheading:17624847-Drug Evaluation, Preclinical,
pubmed-meshheading:17624847-Female,
pubmed-meshheading:17624847-Gene Deletion,
pubmed-meshheading:17624847-Histocompatibility Antigens Class I,
pubmed-meshheading:17624847-Immunization Schedule,
pubmed-meshheading:17624847-Immunologic Memory,
pubmed-meshheading:17624847-Interferon-gamma,
pubmed-meshheading:17624847-Liver,
pubmed-meshheading:17624847-Malaria,
pubmed-meshheading:17624847-Malaria Vaccines,
pubmed-meshheading:17624847-Mice,
pubmed-meshheading:17624847-Mice, Inbred C57BL,
pubmed-meshheading:17624847-Mice, Knockout,
pubmed-meshheading:17624847-Plasmodium berghei,
pubmed-meshheading:17624847-Sporozoites,
pubmed-meshheading:17624847-Vaccination,
pubmed-meshheading:17624847-Vaccines, Attenuated,
pubmed-meshheading:17624847-beta 2-Microglobulin
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|
pubmed:year |
2007
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|
pubmed:articleTitle |
Genetically attenuated Plasmodium berghei liver stages induce sterile protracted protection that is mediated by major histocompatibility complex Class I-dependent interferon-gamma-producing CD8+ T cells.
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pubmed:affiliation |
Division of Malaria Vaccine Development, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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