Development of a mucosal vaccine delivery system

Vaccine delivery systems that target the mucosal immune system carry important advantages in terms of accessibility and acceptability. Lipid based nanoparticles with and without the incorporation of bile salts were formulated by novel preparation methods in order to provide suitable immunogen carriers for delivery to mucosal surfaces. The nanoparticles were physically characterised by determination of size, zeta potential, and morphological appearance using a variety of analytical tools. A new method for the analysis of the chemical lipid components by HPLC separation was implemented, which can be adopted for quality control in future. The adjuvant and delivery properties of the nanoparticles were evaluated with different immunogens incuding non-pathogenic peptides and immunogenic proteins originating from pathogenic organisms. In particular, the reproductive self-hormone gonadotrophin releasing hormone (GnRH) conjugated with different carrier proteins was used as an immunogen in in vivo studies. Various mucosal administration routes were compared against parenteral vaccination, including oral, nasal and vaginal. Systemic and local specific antibodies (IgG, IgG subclasses and IgA) were evaluated in body fluids obtained from immunised mice. The effect of immunisation was evaluated by assessment of reproductive hormone levels after immunisation. In addition, pathogen-derived immunogens were used to evaluate whether the lipid nanoparticles were suitable for vaccination via mucosal surfaces. The results showed that lipid-based nanoparticles enhanced antigen delivery via subcutaneous and nasal routes with nasal delivery proving to be successful in terms of producing systemic and mucosal antibodies. Whereas, vaginal and oral routes showed a very low immune responses when using GnRH conjugates. However, oral administration of pathogen-derived antigens showed promising results. The possible reasons for the limited capability of orally delivered nanoparticles were investigated using LC/MS analysis and fluorescent multiphoton microscopy. The study suggests that lipid based nanoparticles possess adjuvant properties and can be potential candidate for enabling vaccine delivery via the nasal route.

Name dc:type.qualificationname

phd

Level dc:type.qualificationlevel

doctoral-pg

Grantor dc:publisher.institution

University of Strathclyde

Year dc:date.issued

2013

Author dc:creator

• Gebril, Ayman Mohamed

DOI

10.48730/rw3b-kr05

Identifier

T13791

OAI identifier oai:identifier

oai:strathclyde:cc08hf642