Malaria immunology and vaccine development

Abstract

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

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Identifiers

ORCID for C. Mccormick: orcid.org/0000-0002-6155-9161

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