1. Colonic vaccination Vaccine delivery to the colon is rarely considered by researchers. The colon is however an immune inductive site and is appropriate for immunisation as attested by a few publications, including from my group [1-3]. Colonic immunisation - where a vaccine is taken up and processed by the colonic immune cells for the induction of systemic and local mucosal immune responses - is different to oral immunisation, where the vaccine is processed by the immune system in the small intestine, and has important advantages. Vaccine delivery to the colon may be achieved either via the anus or the mouth. The oral route is more convenient and popular, and therefore, I am interested in developing a vaccine formulation which, following swallowing, remains intact until it reaches the colon. At this site, the formulation releases its vaccine cargo, due to its susceptibility to the colonic milieu. The vaccine is then taken up and processed by the local colonic immune cells. Given that antigen delivery in the colon (but not in the small intestine [1]) increases immune responses in the colon and in the vagina, the diseases of interest include animal and human Clostridium difficile infections, sexually transmitted diseases, such as genital Chlamydia trachomatis infection and vertically transmitted infections such as group B Streptococcus infections. 2. Oral immunisation and the compartmentalisation of gut-associated lymphoid tissue (GALT), and mucosal immunology It is known that the mucosa-associated lymphoid tissue (MALT) is compartmentalised into gut-associated lymphoid tissue (GALT), bronchus-associated lymphoid tissue (BALT) and nasopharynx-associated lymphoid tissue (NALT), and that there is further sub-compartmentalisation, such that antigen delivery at one mucosal site does not generate immune responses throughout the whole mucosa, and that vaccines have to be delivered to the correct inductive site for immunity at the target mucosal surface. There is little literature on the sub-compartmentalisation of GALT, and my aim is to plug this gap, in order to identify which sub-compartment should be targeted in specific cases. 3. Formulation and targeting of vaccines My expertise is in the formulation of vaccines, and the physico-chemical characterisation of the formulations. Over the past years, I have formulated various vaccine carriers, such as particles, vesicles and gels. This expertise links in with my interest in formulating vaccines for targeted mucosal delivery and local mucosal immune responses at the desired site (e.g. see 1-2 above). This expertise also links with my experience with different routes of vaccine delivery, such as colonic and ultrasound-assisted transcutaneous routes [1,4]. 3. Gut physiology Related to the above interests in mucosal (especially colonic) immunisation and vaccine formulation for targeting specific sites in the GI tract, we have characterised the gastro-intestinal tract, in terms of pH, fluid content and lymphoid tissue in the mouse, rat, guinea pig, rabbit and pig [5-8]. This work is ongoing, in the drug and vaccine delivery fields. 1. E L McConnell, A W Basit, S Murdan. 2008. Colonic antigen administration induces significantly higher humoral levels of colonic and vaginal IgA, and serum IgG compared to oral administration. Vaccine 26, 639-646. 2. Q Zhu et al., 2008. Immunization with adenovirus at the large intestinal mucosa as an effective vaccination strategy against sexually transmitted viral infection. Mucosal Immunology, 1, 1, 78-88. 3. Q Zhu et al., 2012. Large intestine-targeted, nanoparticle-releasing oral vaccine to control genitorectal viral infection. Nature Medicine, 18, 8, 1291-1296. 4. A Dahlan, HO Alpar, P Stickings, D Sesardic, S Murdan, 2009. Transcutaneous immunisation assisted by low-frequency ultrasound, Int. J. Pharm. 368, 123-128. http://dx.doi.org/10.1016/j.ijpharm.2008.10.014 5. E L McConnell, A W Basit, S Murdan. 2008. Measurements of rat and mouse gastrointestinal pH, fluid and lymphoid tissue, and implications for in vivo experiments. J. Pharm. Pharmacol. 60: 63–70 6. H A Merchant, E L McConnell, F Liu, C Ramaswamy, R K, A W Basit and S Murdan, 2011. Assessment of gastrointestinal pH, fluid and lymphoid tissue in the guinea pig, rabbit and pig, and implications for their use in drug development, Eur. J. Pharm. Sci. 42, 3–10. 7. ACF Vieira, S Murdan, Armenio C Serra, FJ Veiga, AMDR Gonsalves, AW Basit, 2014. Influence of feeding regimens on rat gut fluids and colonic metabolism of diclofenac-beta-cyclodextrin. Carb. Polym., 112, 758-764. 8. E L McConnell, S Murdan, A W Basit. 2008. An investigation into the digestion of chitosan (non-cross-linked and cross-linked) by human colonic bacteria. J. Pharm. Sci. 97: 3820-3829. DOI 10.1002/jps.21271. Link to website. http://www.ucl.ac.uk/pharmacy/people/academic-research-staff-profiles/sudax-murdan