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Title: Investigation of sugar-membrane vaccine stabilisation for improved vaccine thermostability and delivery
Author: Dulal, Pawan
ISNI:       0000 0004 6495 9157
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2016
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Vaccines and other biomolecules need to be maintained at specified storage temperatures from manufacture through to their end user. To satisfy this requirement an enormous network of fridges and freezers called the "cold chain" throughout the world must exist. This network may account for up to 80% of the total cost of vaccination and is susceptible to failure causing loss of vaccines. Stabilisation strategies for vaccines available in the literature have been limited to a few techniques for a few vaccines. To address this problem a novel, cost-efficient, and simple sugar-membrane technology has been developed. Sugar-membrane technology involves desiccation of biomolecules formulated in stabilising sugars in a fibrous matrix and has previously been demonstrated to thermostabilise live viral vectored vaccines exposed to extremes of temperature for prolonged periods of time. The thesis investigates the applicability of the technology in stabilising a wide range of vaccines. The data reported demonstrate the effectiveness of the technology in thermostabilising the vaccines irrespective of the intrinsic complexities and thermo-sensitivity of the initial product. In addition, the thesis also studies the applicability of the technology in thermostabilisation of vaccines of veterinary importance. An accelerated stability study of sugar-membrane thermostabilised veterinary vaccines also demonstrated that the data are superior to those reported previously for the corresponding vaccines. However, the nature of the current matrix is not suitable for translation to human medicine. This thesis therefore investigates a range of new potentially GMP-compatible fibrous matrices to identify alternative membranes for use clinically. The data indicate that an alternative hydrophobic membrane after physical or chemical surface modification could be considered as an alternative support matrix for the technology. Finally, to understand the reasons for outstanding thermostability delivered by the current membrane in more detail, the physical and chemical properties of the matrix were investigated. Results from this systematic study identified inherent properties of the matrix which could be linked to the superior thermostabilising property of the membrane. These findings will be used for further optimisation of the technology and development towards a more GMP compatible support matrix.
Supervisor: Hill, Adrian ; Cui, Zhanfeng Sponsor: Jenner Institute
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available