The use of Bacillus subtilis as a mucosal vaccine adjuvant. / Sibley, Laura.

2015. 263 p.

Research output: ThesisDoctoral Thesis

Unpublished

Documents

Abstract

Mucosal vaccines are attracting increasing amounts of attention because of their ability to stimulate immune responses mucosally at the site of pathogen entry as well as systemically. Bacillus subtilis produces spores that are ~1 μM in size and can be modified to carry antigens on the surface, either by binding directly or by genetic modification, and have previously been tested as a vaccine adjuvant. The aim of this thesis was to further investigate the suitability of B. subtilis spores as a mucosal vaccine adjuvant. As an adjuvant carrying Mycobacterium tuberculosis (MTB) antigens (MPT64 and Ag85B-Acr), B. subtilis spores were able to demonstrate immunogenicity by stimulating Th1 cytokine production and provided some degree of protection against MTB challenge in the mouse model. The adjuvant behaviour of spores and initial interactions with host immune cells were investigated. Autoclaved spores were found to interact with different cells to live spores, which was hypothesised to be due to damage to the spore surface proteins prohibiting interactions with cell pattern recognition receptors. The cells that spores interacted with appeared to be dependent on tissue and dosing route and may highlight the differing roles of the lungs, gut and NALT in processing foreign material. The innate immune responses that were examined after nasal dosing demonstrated that spores could activate innate immune responses in the lungs and lymphoid tissue, and suggested that they were able to stimulate dendritic cells that could act as antigen presenting cells to activate adaptive immunity. In conclusion, the data generated provided further evidence on the utility of spores as a mucosal vaccine adjuvant and provided an insight into how they are able to stimulate immune responses.
Original languageEnglish
QualificationPh.D.
Awarding Institution
Supervisors/Advisors
Thesis sponsors
  • Biotechnology&BioSci Research BBSRC
  • Boehringer Ingelheim UK
DOIs
Publication statusUnpublished - 2015
This open access research output is licenced under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License.

ID: 24769126