Tackling vector-borne diseases using Non-Replicating Virus Particles

Vector-borne diseases (VBD) pose a major health and socio-economic burden particularly on countries in tropical and sub-tropical areas. Arthropod-borne viruses (arboviruses) such as dengue, Zika, chikungunya and yellow fever virus are a major contributor to the overall burden of VBD and both the emergence of new and re-emergence of known arboviruses are noted with concern due to their epidemic and even pandemic potential. Climate, economic and social factors expand the global distribution of their vectors and thereby extend the geographical range of arboviruses. To date, the most effective way to control transmission of arboviruses is vector control, predominantly by use of insecticides. However, concerns over insecticide resistance plus their detrimental effect on the ecosystem has prompted research into more sustainable and eco-friendly solutions. The most advanced of these next-generation strategies that are currently under development uses various mechanisms to force traits through a target vector population (e.g. gene drives) which can be used either to reduce the mosquito population or to replace the population with individuals less competent to transmit arboviruses. Depending on the specific technology, possible issues are the very narrow range of viruses they work against (mostly just one), insufficient efficiency for field use, high costs, and the risk of resistance development due to fitness effects of the integrated genetic information on the mosquito. Here I am proposing a completely novel approach to vector control - a two-component system leveraging the replication strategy of the virus. It combines the advantages of the above-mentioned conventional and novel control strategies, while mitigating the stated drawbacks. Only if both two components come together in the mosquito cell will the system take effect and kill the vector. This allows widespread application of the first component to target a large number of mosquitoes (as insecticides do), while the second component, a limiting factor, will provide the system with specificity and flexibility. I aim to develop two different application strategies of this technology, one will provide large-scale population suppression, the other will target only vectors infected with specific viruses. Both are sustainable, eco-friendly, likely to be cheaper than some currently used/developed technologies and have a lower risk of resistance development as the mosquitoes will not carry a cargo affecting their fitness. Over 150 countries are located in the tropical and subtropical zones of our planet. The approximately 3.9 billion people living in these regions are particularly affected by diseases  vectored by mosquitoes and would substantially benefit from improved vector control. Particularly in densely populated areas and megacities, application of the first strategy of my proposed technology could provide relief not only from the disease vector but also from the health risk insecticides pose to the residents as well as to beneficial insect species. The second strategy is a highly cost-effective alternative and would be particularly beneficial around transport hubs such as airports, ports, or large train stations, in urbanised areas during an outbreak scenario or as a long-term control measure in zones with increased virus spill-over risk such as deforestation areas. This version of my proposed technology can also be utilized for surveillance using a visual marker protein. In summary, if applied, my technology would significantly advance the vector-control field, positively impact human health, reduce environmental degradation and likely do this more economically than currently developed mosquito control technologies.