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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2008-2-25
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pubmed:abstractText |
Simian adenoviral vectors (SAd) offer an attractive alternative to standard human adenovirus serotype 5 (AdH5) subunit vaccination, due to pre-existing immunity affecting vaccine performance. We have used a mouse model of liver-stage malaria to test the efficiency of three chimpanzee-origin adenoviral vectors, AdC6, AdC7 and AdC9 containing ME.TRAP as an insert. AdC7 and AdC9 elicited strong immunogenicity ( approximately 20% of CD8(+) T cells in spleen), equivalent to or outperforming AdH5 and inducing sterile protection in 92% (C9), 83% (H5 and C7) and 67% (C6) of the mice, providing the first evidence of single-dose protection to Plasmodium berghei. Protection was afforded by the SAd despite high levels of pre-existing immunity to AdH5. Phenotypic analysis showed that all adenoviral vectors (Ad) elicited CD8(+) T cell responses with an effector memory T cell (T(EM)) phenotype. By contrast, vaccination with poxviral vectors did not confer protection to P. berghei and induced a predominantly CD8(+) central memory T cell (T(CM)) response. Multifunctional CD8(+) T cell responses (co-expressing IFN-gamma, TNF-alpha and IL-2) were also induced by the Ad in higher percentages than the poxviral vectors. Our data suggest that T(EM) cells are important as a first line of defense against fast-replicating pathogens such as murine Plasmodium and demonstrate the potential of replication-defective SAd as future malaria vaccines for humans.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/Epitopes, B-Lymphocyte,
http://linkedlifedata.com/resource/pubmed/chemical/Epitopes, T-Lymphocyte,
http://linkedlifedata.com/resource/pubmed/chemical/Granzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Gzmb protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Malaria Vaccines,
http://linkedlifedata.com/resource/pubmed/chemical/Protozoan Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Vaccines, DNA,
http://linkedlifedata.com/resource/pubmed/chemical/thrombospondin-related adhesive...
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0014-2980
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
38
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
732-41
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pubmed:dateRevised |
2011-6-13
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pubmed:meshHeading |
pubmed-meshheading:18266272-Adenoviruses, Simian,
pubmed-meshheading:18266272-Animals,
pubmed-meshheading:18266272-Antigens, CD,
pubmed-meshheading:18266272-CD8-Positive T-Lymphocytes,
pubmed-meshheading:18266272-Cytokines,
pubmed-meshheading:18266272-Epitopes, B-Lymphocyte,
pubmed-meshheading:18266272-Epitopes, T-Lymphocyte,
pubmed-meshheading:18266272-Female,
pubmed-meshheading:18266272-Genetic Vectors,
pubmed-meshheading:18266272-Granzymes,
pubmed-meshheading:18266272-Injections, Intradermal,
pubmed-meshheading:18266272-Interferon-gamma,
pubmed-meshheading:18266272-Malaria,
pubmed-meshheading:18266272-Malaria Vaccines,
pubmed-meshheading:18266272-Mice,
pubmed-meshheading:18266272-Mice, Inbred BALB C,
pubmed-meshheading:18266272-Mice, Inbred C57BL,
pubmed-meshheading:18266272-Plasmodium berghei,
pubmed-meshheading:18266272-Poxviridae,
pubmed-meshheading:18266272-Protozoan Proteins,
pubmed-meshheading:18266272-Spleen,
pubmed-meshheading:18266272-Survival Analysis,
pubmed-meshheading:18266272-T-Lymphocyte Subsets,
pubmed-meshheading:18266272-Vaccines, DNA
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pubmed:year |
2008
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pubmed:articleTitle |
Single-dose immunogenicity and protective efficacy of simian adenoviral vectors against Plasmodium berghei.
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pubmed:affiliation |
The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. arturo@well.ox.ac.uk
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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