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Title: Immune responses following DNA vaccination with plasmids encoding antigens of Bordetalla pertussis
Author: Good, J.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2000
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The experiments described in this study showed that DNA vaccines encoding protective antigens of B. pertussis elicit strong immune responses. Plasmids encoding different B. pertussis antigens were constructed, and their immunogenicity tested in different strains of inbred mice. Th1 and Th2 type immune responses could be elicited to plasmids encoding bacterial adhesins. These responses were highly dependent on the vaccination regime. Responses to adenylate cyclase toxin were also obtained. Delivery of a DNA vaccine via the respiratory tract did not elicit detectable systemic immune responses, whereas a native protein delivered by the same route, particularly in the presence of an immunostimulatory oligodeoxynucleotide, was highly immunogenic. To determine whether immune responses to a pertussis antigen following DNA and protein immunisation could be modulated by local cytokine expression, plasmids encoding cytokines were administered with the immunogen. The effect of differential intracellular antigen trafficking on the immune response was determined by constructing translational fusions between adhesins and a secretory leader sequence. The potency of DNA vaccination compared favourably with the protective dose of a whole cell pertussis reference vaccine, and with an acellular vaccine licensed for use in humans. This work has demonstrated that DNA vaccination can indeed be used to elicit immune responses against various antigens of B. pertussis, and indicates how DNA vaccination is now set to become a powerful tool in the further analysis of the functional significance of responses to defined and novel antigens in relation to protection against infection, and the pathogenesis of the disease.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available