Adjuvant and immunogenic properties of pneumolysin of Streptococcus pneumoniae

Ma, Jiang Tao (2006) Adjuvant and immunogenic properties of pneumolysin of Streptococcus pneumoniae. MSc(R) thesis, University of Glasgow.

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Abstract

The Gram-positive bacterium S. pneumoniae (the pneumococcus) is a major pathogen of man causing community -acquired diseases worldwide. The 23-valent polysaccharide (PS) vaccine can protect most of adults and children older than five, but it cannot protect children under age 2, immunodeficiency patients and the elderly. The PS conjugate vaccine which is complementary to the 23-valent PS vaccine is highly immunogenic and protects children under the age of 2 against invasive diseases, but its efficacy is threatened by strain replacement and serotype switching since it only protect against the limited number of serotypes contained within the vaccine. Therefore, it is important to develop new vaccines that can cope with those disadvantages. Pneumococcal virulence proteins have been studied extensively for their possible application in production of an alternative vaccine. A protein-based vaccine is expected to be immunogenic in all age groups including infants and the elderly. Pneumococcal surface adhesin A (PsaA), pneumococcal surface protein A (PspA), pneumococcal surface protein C (PspC), pneumolsyin (PLY) are the current leading candidates, among them PLY is a very promising candidate for developing new vaccines. A promising road to protection against S. pneumoniae would be production of fusion protein-based mucosal vaccine. A mucosal vaccine, which can break the transmission chain of infection by preventing nasopharyngeal colonization, should protect children under 2 and immunodeficiency patients. Prevention of nasopharyngeal colonisation by pneumococci can prevent horizontal spread of the pathogen, thus improving herd immunity to protect non-vaccinated people. Previous work in our group demonstrates that PLY can act as a good adjuvant in PLY fused antigens to induce both systemic and mucosal immunity. The results from this project show truncated PLY lost this adjuvant property in antigen fused with truncated PLY; however, the adjuvant property in antigen fused with truncated PLY was restored in the presence of free PLY. NMR Chemical shift perturbation experiment showed a tryptophan residue maybe involved in the interaction between PLY and water-soluble cholesterol.

Item Type: Thesis (MSc(R))
Qualification Level: Masters
Additional Information: Adviser: Tim J Mitchell
Keywords: Pharmacology
Date of Award: 2006
Depositing User: Enlighten Team
Unique ID: glathesis:2006-71743
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 17 May 2019 09:31
Last Modified: 17 May 2019 09:31
URI: http://theses.gla.ac.uk/id/eprint/71743

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