Malaria immunology and vaccine development

This thesis describes work undertaken by the author at the University of Oxford. It<br/>begins by providing an introduction to malaria infection and pathophysiology, and<br/>a review of the latest attempts to produce an effective malaria vaccine. It goes on<br/>to describe the rationale behind the vaccines developed by the University of<br/>Oxford and others. A brief introduction to the process of planning and carrying out<br/>clinical trials of vaccines is then provided, and is followed by chapters describing<br/>two clinical trials, designed to test the safety, immunogenicity and then efficacy of<br/>candidate malaria vaccines. These trials were performed in Oxford, to examine<br/>two different vaccination approaches. The first intended to broaden the specificity<br/>of the vaccine induced immune response, by providing multiple antigens in one<br/>vaccine, aiming thereby to improve protection from malaria infection. The second<br/>regimen used a combination vaccine intending to induce both humoral and cellular<br/>immunity simultaneously, thereby providing enhanced efficacy against malaria<br/>infection. Neither approach was sufficient to provide protection from infection in the<br/>challenge studies described; however, some impact on the disease was detected<br/>in the second study. This is examined in detail. The laboratory work described<br/>studies background immune responses (both cellular and humoral) to vaccine<br/>antigens in a malaria exposed population, intended to support the inclusion of<br/>these antigens in the multi-antigen vaccine. The remaining chapters describe work<br/>in parasite life cycle modelling, undertaken to aid interpretation of results of these<br/>clinical trials, and finally an examination of the clinical course of malaria in the<br/>control volunteers who have taken part in the many challenge studies conducted in<br/>Oxford.

Name dc:type.qualificationname

Ph.D.

Level dc:type.qualificationlevel

doctoral

Grantor dc:publisher.institution

University of Southampton

Year dc:date.issued

2008

Author dc:creator

• Thompson, Fiona Mary

Advisors dc:contributor.advisor

• Mccormick, C.
• Hill, A.