Evaluation of prophylactic therapies for the prevention of campylobacteriosis

Rimmer, Joanna Elizabeth (2020). Evaluation of prophylactic therapies for the prevention of campylobacteriosis. University of Birmingham. M.D.

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Abstract

Campylobacter jejuni, a frequently isolated diarrhoeal pathogen [1], is encapsulated by a polysaccharide capsule. This can be exploited to develop capsule-based conjugate vaccines [2]. Before vaccine implementation, correlates of protection enable efficacy to be measured. This thesis describes the development of a Serum Bactericidal Assay (SBA) to evaluate the bactericidal activity of sera from New Zealand White Rabbits (NZWR) vaccinated with a
GMP grade capsule-based conjugate C. jejuni vaccine ‘CJCV1’; Aotus nancymaae Non-Human Primates (NHP), vaccinated with a research grade vaccine ‘CCV’; and humans, vaccinated with ‘CJCV1’. NZWR and NHP post-vaccination sera demonstrated an increase in serum titre achieving a bactericidal effect. Human sera did not demonstrate a consistent bactericidal effect. These experiments showed variability in readouts, suggesting that for the studies performed, the SBA may be of limited value in assessing vaccine efficacy. This thesis also presents results from a Phase II clinical trial assessing the efficacy of rifaximin in preventing campylobacteriosis in humans; whilst rifaximin prophylaxis does not prevent campylobacteriosis, it reduces the diarrhoeal burden. This study involved the development and use of a successful human challenge model, crucial for testing interventions against
campylobacteriosis. Results from these studies suggest further development of interventions to control this highly problematic pathogen are required.

Type of Work:	Thesis (Doctorates > M.D.)
Award Type:	Doctorates > M.D.
Licence:	All rights reserved
College/Faculty:	Colleges (former) > College of Medical & Dental Sciences
School or Department:	School of Immunity and Infection
Funders:	None/not applicable
URI:	http://etheses.bham.ac.uk/id/eprint/10546

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