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Title: The molecular characterization of Plasmodium falciparum infection and development of the humoral immune response in persistently infected Ghanaian infants
Author: Franks, Simon
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2000
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As part of a longitudinal study into the humoral immune response to malaria in infants, 52 out of 156 children were found to be chronically infected with P. falciparum. In 15 of these children, the allelic diversity of these infections was analysed by PCR typing of MSP 1 and MSP 2 alleles followed by sequencing the polymorphic region of MSP 2. The study shows that infants become infected with a number of different allelic types of P. falciparum. These infections were of very low density and were asymptomatic. The number of different genotypes varied over time in each child. Persistent infection in some children was clearly due to multiple new infection, whereas in other children single parasite genotypes persisted for very long periods of time, up to seven months in some children. In order to evaluate serological responses to asexual stage malaria antigens, serum obtained at monthly intervals over the first year of life were tested, by ELISA, against recombinant proteins representing various merozoite antigens, to determine the specific response to MSP 2, novel polymorphic sequences of MSP 2 were expressed as GST fusion proteins. GST fusion proteins representing the conserved and dimorphic sequences of MSP 2 were also constructed. Responses to specific antigens varied between individuals, different children produced antibodies to different agencies at different time points depending on the presence or absence of infection. There were occasions when a decline in a specific antibody titre was associated with infection or reinfection with parasites carrying the same specific polymorphic antigen, which may be indicative of "strain-specific immunity" operating at the level of MSP 2. Interestingly, antibody responses to several different MSP 2 sequences were found to be cross-reactive indicating that the number of serologically identifiable MSP 2 variants may be smaller than the number of sequence variants, intriguingly, we also found that pairs of immunologically cross-reactive variants of msp2 were frequently found together in different children, this data provides evidence in support of the Gupta-Day theory of strain-structuring of malaria parasite populations and indicates that antibody responses to MSP 2 may be able to select for elimination or control of malaria parasites, if so, this would be strong support evidence for the effector role of anti-MSP 2 antibodies and would suggest that MSP 2 might be an important component of a malaria vaccine.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available