In hyperendemic malarious regions adults develop protective immunity to
Plasmodium falciparum infection. In order for this immunity to develop the host
immune system must be able to recognise the parasite. One stage at which this
occurs is prior to red blood cell invasion when the extracellular form of the parasite,
the merozoite, presents the host immune system with a number of potential
immunogens termed merozoite surface antigens. Antibodies to merozoite surface
antigens are able to inhibit the growth and development of the parasite in vitro. This
thesis explores the mechanisms by which merozoite surface antigen -specific
antibodies exert this inhibition.
The affinity, fine specificity and Fc- mediated effects of antibodies may affect their
functional activity. Immortalised B cell lines producing merozoite surface antigen - specific human monoclonal antibodies were generated in order to investigate the
effect of these factors on their growth inhibitory activity in vitro. The preliminary
characterisation of these mAbs is described in chapter 3. However, sufficient
quantities of these mAbs could not be generated for their functional activity to be
investigated in vitro.
Current dogma holds that the primary function of antibodies is to provide a
molecular link between antigen recognition and pathogen destruction. However, all
Abs have the ability to catalyse a reaction between singlet oxygen and water to
generate hydrogen peroxide. This thesis explored the hypothesis that this antibody-catalysed water-oxidation pathway is responsible for the intraerythrocytic growth
inhibition exerted by MSP-1-₁₉-specific Abs. An in vitro ACWO assay was
developed to test this hypothesis and data suggest that ACWO may occur in infected
RBCs associated with an anti- MSP-1-₁₉ monoclonal antibody.
Antibodies specific to an intrinsically unstructured region from the C- terminal half of
merozoite surface protein 3.3, designated MSP3.3C, are highly effective at inhibiting
the in vitro growth of P. falciparum. This thesis explored the mechanisms
responsible for this inhibition. This inhibition is caused by inhibition of the
intraerythrocytic development of the parasite and not by inhibition of merozoite
invasion. MSP3.3C specific Abs can access the intraerythrocytic parasite post
invasion and completely arrest parasite development by inducing parasite death.
The findings presented in this thesis expand current knowledge of the mechanisms
by which MSA- specific Abs inhibit the growth of P. falciparum in vitro. This may
prove informative both in terms of our understanding of naturally acquired antibody
mediated immunity to P. falciparum asexual stages and in furthering effective
vaccine design against this deadly pathogen.