Immunogenetic determinants of measles vaccine responses and vaccine failure in children from Australia and Mozambique

Holly Clifford

    Research output: ThesisDoctoral Thesis

    452 Downloads (Pure)

    Abstract

    [Truncated abstract] Background: Measles virus is one of the most highly transmissible pathogens in humans, causing an acute febrile illness with rash that is associated with severe and often fatal complications. Despite the availability of a measles vaccine and global efforts to increase vaccine coverage and eradicate measles, this virus continues to cause the deaths of up to a quarter of a million children every year. Vaccine responses vary between individuals, and among those vaccinated, disease can still occur in up to 10% of children (vaccine failure). Industrialised countries including Australia occasionally encounter measles outbreaks but in underdeveloped countries, the situation is more dire, as measles is endemic and exposure is high, resulting in ongoing severe disease and the deaths of many children. Host immunogenetics play a major role in determining the intrinsic ability of an individual to respond to viruses and vaccines. Responses to measles vaccine in particular have been suggested to have a considerable genetic component. Genes involved in innate immunity are likely to be particularly important as they govern the initial responses to invading pathogens, which can then have downstream effects on subsequent adaptive immune responses. Receptors likely to be involved in measles responses include: the measles cell entry receptors CD46 and SLAM, the measles attachment receptor DC-SIGN, the antiviral toll-like receptors (TLR)3, TLR7 and TLR8, the cytosolic antiviral receptor RIG-I, the TLR co-receptor CD14, and cytokines and their receptors involved in cellular immune responses such as IL-4, IL-13, and IL- 4R!. The contribution of these receptors to measles responses and the functional effects of variations in the genes that encode them have not been fully elucidated.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Publication statusUnpublished - 2010

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