The biological role of akirin in anopheles arabiensis
Date
2020
Authors
Letinić, Blaženka Danica
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Abstract
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
Description
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