Abstract
Various Salmonella enterica serovars can cause human diseases that range in severity from a mild gastroenteritis to a severe systemic infection known as typhoid fever. The emergence of antibiotic resistance in S. enterica strains poses a major problem in treatment of patients in many regions of the world. Currently, two licensed vaccines exist, conferring protection against S. enterica serovar Typhi, the causative agent of human typhoid. Unfortunately, these typhoid vaccines are only moderately immunogenic in infants and young children and revaccination is required every few years. Therefore, new vaccines are needed, which not only confer long-term protection against S. Typhi but also other harmful S. enterica serovars.
Conjugate vaccines are among the most effective and safe vaccines against bacterial diseases and have been used in humans for over 30 years. They are composed of an antigenic cell surface polysaccharide, purified from the pathogen, chemically coupled to a carrier protein. Several clinical trials have shown that glycoconjugates are promising vaccine candidates to prevent Salmonella infections. However, manufacturing of conjugate vaccines is a complex, multi-step process. An alternative approach to produce glycoconjugates is based on the bacterial N-linked protein glycosylation system first described in Campylobacter jejuni. This protein modification system was functionally transferred into E. coli, enabling production of customized recombinant glycoproteins in vivo. In this dissertation, the possibilities of using the in vivo conjugation technology for production of conjugate vaccines against various S. enterica serovars causing human diseases were explored.
Wetter, Michael Lukas