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Thesis

Transcutaneous delivery of T Cell-inducing viral vector Malaria vaccines by microneedle patches

Abstract:

There is an urgent need for improvements to existing vaccine delivery technologies to run parallel with the development of new-generation vaccines. The burdens of needle-based immunisation strategies are exacerbated by poor resource provision in such areas as sub-Saharan Africa, where annual malaria mortality stands at 860,000. Needle-free delivery of vaccine to the skin holds promise for improved immunogenicity with lower doses of vaccine, in addition to significant logistical advantages. Various methods have been described for the transcutaneous delivery of vaccines, including the use of microneedles to overcome the outer stratum corneum of the skin for efficient delivery of liquid or solid, microneedle-coated vaccines into underlying strata rich in antigen-presenting cells. This thesis aims to evaluate two transcutaneous silicon microneedle and microprojection patch technologies for the delivery of live recombinant Adenovirus and Modified Vaccinia Ankara-vectored vaccines encoding pre-erythrocytic malaria antigens in mice. Cellular immunogenicity directed against a well-documented epitope of the Plasmodium berghei circumsporozoite protein is evaluated, as is protection against lethal P. berghei sporozoite challenge. Immunological and logistical benefits of each technology are assessed, as well as mechanisms underlying differences in the generation of a patch-induced immune response to vaccination. These data inform the future development of transcutaneous microneedle patches for the delivery of live vaccine.

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Institution:
University of Oxford
Division:
MSD
Department:
NDM
Research group:
The Jenner Institute
Oxford college:
Mansfield College
Role:
Author

Contributors

Division:
MSD
Department:
NDM
Role:
Supervisor
Division:
MSD
Department:
NDM
Role:
Supervisor


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Funding agency for:
Pearson, FE


Publication date:
2011
DOI:
Type of award:
DPhil
Level of award:
Doctoral
Awarding institution:
University of Oxford


Language:
English
Keywords:
Subjects:
UUID:
uuid:2155c639-bcc8-49e0-b415-a5d353aacba3
Local pid:
ora:9843
Deposit date:
2015-01-30

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