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Title: Silica nanoparticles as adjuvants for novel vaccines : a combined immunological, simulation and physical characterisation study
Author: Connell, David James
ISNI:       0000 0004 6349 6381
Awarding Body: University of Strathclyde
Current Institution: University of Strathclyde
Date of Award: 2016
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Vaccines derived from non-pathogenic antigens often have greater safety profiles over live vaccines, whilst still eliciting a specific immune response. However, the decreased immunogenicity of these vaccines means that numerous doses have to be administered or an adjuvant has to be used. In this study gonadotrophin releasing hormone (GnRH), a fertility regulating self-peptide, was used as a model antigen applied to Stober silica nanoparticles (used as an adjuvant) in a vaccine formulation. It is proposed that an inorganic silica nanoparticle can act as a foreign carrier particle for adsorbed peptides, thus stimulating an immune response against these peptides in vivo. This work utilised molecular dynamics simulations of silica substrates and their interaction with peptides for optimal presentation of the peptide to the immune system for antibody production. The interactions at this step allowed the optimum design of the nanoparticle with surface peptides that were free to interact with the surrounding environment, thus having the potential to invoke a biological response. Quartz crystal microbalance and surface plasmon resonance measurements were also used in order to investigate the adsorption of the peptides onto a silica surface. Through running these experiments at various pH levels and ionic strengths the optimum conditions for peptide coverage of silica nanoparticles could be determined, enabling enhanced design of the silica nanoparticle-peptide system and thus providing invaluable data to inform immunisation studies. Following an immunological study in male BALB/c mice it was found that the use of silica as an adjuvant along with bovine serum albumin (BSA) as a carrier protein increased the immunogenicity of GnRH-I peptides in comparison to just BSA alone. It was observed that peptides adsorbed solely onto silica nanoparticles did not elicit a strong antibody response. However, this formulation caused a significant decline in testosterone production, suggesting that silica coated with native GnRH-I peptides could be useful in receptor blocking.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral