Single-dose immunogenicity and protective efficacy of simian adenoviral vectors against Plasmodium berghei.
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 adenovir...
| প্রধান লেখক: | , , , , , , , , , |
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| বিন্যাস: | Journal article |
| ভাষা: | English |
| প্রকাশিত: |
2008
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| _version_ | 1826300057365774336 |
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| author | Reyes-Sandoval, A Sridhar, S Berthoud, T Moore, A Harty, J Gilbert, S Gao, G Ertl, H Wilson, J Hill, A |
| author_facet | Reyes-Sandoval, A Sridhar, S Berthoud, T Moore, A Harty, J Gilbert, S Gao, G Ertl, H Wilson, J Hill, A |
| author_sort | Reyes-Sandoval, A |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T05:11:21Z |
| format | Journal article |
| id | oxford-uuid:dba6ac7f-a4da-4e06-ae5a-3c465c738222 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:11:21Z |
| publishDate | 2008 |
| record_format | dspace |
| spelling | oxford-uuid:dba6ac7f-a4da-4e06-ae5a-3c465c7382222022-03-27T09:12:12ZSingle-dose immunogenicity and protective efficacy of simian adenoviral vectors against Plasmodium berghei.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:dba6ac7f-a4da-4e06-ae5a-3c465c738222EnglishSymplectic Elements at Oxford2008Reyes-Sandoval, ASridhar, SBerthoud, TMoore, AHarty, JGilbert, SGao, GErtl, HWilson, JHill, ASimian 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. |
| spellingShingle | Reyes-Sandoval, A Sridhar, S Berthoud, T Moore, A Harty, J Gilbert, S Gao, G Ertl, H Wilson, J Hill, A Single-dose immunogenicity and protective efficacy of simian adenoviral vectors against Plasmodium berghei. |
| title | Single-dose immunogenicity and protective efficacy of simian adenoviral vectors against Plasmodium berghei. |
| title_full | Single-dose immunogenicity and protective efficacy of simian adenoviral vectors against Plasmodium berghei. |
| title_fullStr | Single-dose immunogenicity and protective efficacy of simian adenoviral vectors against Plasmodium berghei. |
| title_full_unstemmed | Single-dose immunogenicity and protective efficacy of simian adenoviral vectors against Plasmodium berghei. |
| title_short | Single-dose immunogenicity and protective efficacy of simian adenoviral vectors against Plasmodium berghei. |
| title_sort | single dose immunogenicity and protective efficacy of simian adenoviral vectors against plasmodium berghei |
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