Journal article
Single-dose immunogenicity and protective efficacy of simian adenoviral vectors against Plasmodium berghei
European journal of immunology, Vol.38(3), pp.732-741
03/2008
DOI: 10.1002/eji.200737672
PMID: 18266272
Abstract
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.
Details
- Title: Subtitle
- Single-dose immunogenicity and protective efficacy of simian adenoviral vectors against Plasmodium berghei
- Creators
- Arturo Reyes-Sandoval - The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. arturo@well.ox.ac.ukSaranya SridharTamara BerthoudAnne C MooreJohn T HartySarah C Gilbert - University of OxfordGuangping GaoHildegund C J ErtlJames C WilsonAdrian V S Hill
- Resource Type
- Journal article
- Publication Details
- European journal of immunology, Vol.38(3), pp.732-741
- Publisher
- Germany
- DOI
- 10.1002/eji.200737672
- PMID
- 18266272
- ISSN
- 0014-2980
- eISSN
- 1521-4141
- Grant note
- 076438 / Wellcome Trust
- Language
- English
- Date published
- 03/2008
- Academic Unit
- Pathology
- Record Identifier
- 9984047756302771
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