The biological role of akirin in anopheles arabiensis

Letinić, Blaženka Danica
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Anopheles arabiensis is an opportunistic malaria vector that rests and feeds outdoors, circumventing current vector control methods. Furthermore, this vector will readily feed on animal as well as human hosts. Agricultural animals are regularly vaccinated with recombinant proteins, for the control of multiple endo- and ectoparasitic infestations. Targeting An. arabiensis, while feeding on animals, can provide an additional intervention to the current vector control activities. Previously, the use of a subolesin-vaccine showed a mark reduction in tick survival and reproductive fitness. Targeting Akirin (Subolesin ortholog) in An. arabiensis, when performing CRISPR mediated interference or RNA mediated interference, reduced both vector survival and reproductive capacities. This gene regulation function made Akirin a potential antigen for vaccine development against An. arabiensis, which was further investigated. The efficacy of three recombinant Akirin vaccines was evaluated, to determine if Akirin could represent a novel target for the control of An. arabiensis. Immunisation trials were conducted based on the concept that female An. arabiensis, feeding on vaccinated hosts (balb/c mice), would ingest antibodies specific to the target antigen, affecting its function within the vector. All three antigens evaluated, namely recombinant Akirin from An. arabiensis, recombinant Akirin from Aedes albopictus and recombinant Q38 (Akirin/Subolesin chimera), successfully reduced An. arabiensis survivorship and reproductive capacities, with a vaccine efficacy of 68 to 73%. In conclusion, these results were the first to characterise the biological role of Akirin in An. arabiensis survival and reproduction, by performing CRISPRi and RNAi, using an optimised nano-injection protocol. Furthermore, these results were the first to show that blood hosts vaccinated with recombinant Akirin vaccines could aid in the suppression of An. arabiensis vector populations, through the reduction of vector survivorship and reproductive capacities. Therefore, these results provide a step towards the development of a novel target for An. arabiensis vector control
A thesis submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the Faculty of Health Sciences, School of Pathology, University of the Witwatersrand, Johannesburg, 2020