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Title: Formulation strategies for the mucosal delivery of HIV vaccines
Author: Pattani, Aditya Sunil
ISNI:       0000 0004 2725 0712
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2011
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Vaccination seems to be the key to curtailing the HIV epidemic but all efforts to make a clinically effective vaccine have failed to date. Eliciting high titres of neutralising antibodies at the mucosal portals of viral entry is a key goal in HIV vaccine research. Thus, this thesis specifically focuses at the strategic development and evaluation of women-controlled mucosal vaccine delivery systems for HIV envelope based constructs, H4A, gp140 and FP-A for the purpose of eliciting high antibody titres at the vaginal mucosa. Sustained release rod-insert vaginal rings (RiRs) loaded with gp140, quick release rods containing H4A, FP-A loaded liposomal gels and microneedles in conjunction with mucosal inoculations were evaluated for induction of specific antibodies in animal models (sheep/mice/rabbits). The formulations were evaluated mainly using vaginal delivery with nasal route being used as an auxiliary. However, we found that the nasal route was extremely potent compared to the vaginal route for the induction of antibody responses. In addition, we found that there is a definite rationale for sustained vaginal delivery ofvaccines. FP-A loaded gels showed ability to elicit neutralising antibody at mucosal sites and are hence being scaled to GMP production with a view to progressing them to clinical trials. Storage stability of bovine serum albumin (BSA) loaded RiRs and protein loaded immediate release dosage forms were also evaluated. Protein aggregation was found to be the most important route of degradation of BSA in RiRs, while freeze-drying induced changes predominate in the immediate release dosage forms. Finally, a solvent emulsion diffusion based method was developed for the generation of neutral, anionic and cationic liposomes. Homogenisation time was studied as a process parameter; however this was not able to control the particle size significantly.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available