Periodic Reporting for period 1 - LaunTeNaBio (Launch Test of Natural Biocides for the Control of Insect Borne Diseases)
Période du rapport: 2019-04-01 au 2021-03-31
Résumé du contexte et des objectifs généraux du projet
‘LaunTeNaBio’: Launch Test of Natural Biocides to prevent Insect Borne Diseases of significance to public health and agriculture
Insect-Borne Diseases (IBDs) are a growing problem, burdening the economy and the social conditions of numerous countries. Climate changes, globalization and increase in travel and trade have fostered the spread of insect populations from tropical and subtropical regions, and with them IBDs are appearing in new areas. Currently, Europe and the USA must face an increasing risk of vector-borne disease outbreaks that in the next future will spread in places where they have never been present. Mosquitoes are the most important vectors injuring public health: Malaria kills 450.000 people annually and filariasis causes chronic diseases. Arboviruses such as Dengue, Chikungunya and West Nile originating from tropics, are appearing in Europe, and Zika fever from Brazil is quickly spreading towards the USA. The whole of these diseases afflicts millions of people. Even though controlling IBDs is a global societal challenge, effective and safe tools are not yet available and new strategies are urgently needed.
The main approach for fighting IBDs is to reduce the insect-vector populations by means of insecticides but insecticide resistance (IR) represents a serious limit of this control method. IR implies new compounds and higher doses of products, demanding huge investments and high production costs. Moreover, many formulations have indirect effects exerting environmental toxicity. Another approach is the release of irradiation-sterilized male insects into the wild, where they compete with wild males to mate with the females, thus reducing the offspring. Since sterile insects are not self-replicating and cannot become established in the environment, constant releases are necessary to have an impact. Hence, the implementation of this strategy in a broad area requires significant initial investments and economic returns are seen only after a very long time. Microbial larvicides represent an additional frontier to fight IBDs, a well-known example is Bacillus thuringiensis used against Diptera. However, its use has some limit as the emergence of tolerance in targeted organisms and indirect effects on the trophic network.
Effective strategies against IBDs should overcome these limits and contribute to the solution in a practical and forward-looking way. Symbiotic Control (SC) exploits microbial symbionts associated with the insect-vectors to render their hosts innocuous. Thanks to antimicrobial properties, symbionts can harm the vector-borne pathogens inside the insect, thus blocking their transmission to humans. This approach is eco-friendly and avoids IR, since it eliminates the pathogens but not the vectors, acting as a biocide instead as a larvicide. Biocide products based on microbial symbionts represent a promising tool for the prevention of IBDs and similar approaches are employed using genetically manipulated bacterial symbionts in the control of Chagas disease and sleeping sickness.
Our discovery of symbiotic yeasts that secrete natural toxins able to kill malaria parasites in the mosquito, has opened a completely new frontier in the SC of IBDs avoiding genetic manipulation of microorganisms and using a costless tool, with zero environmental impact. The exploitation of such ‘killer yeasts’ (KYs) for the development of a biocide product, has posed the bases for the Launtenabio activity. In fact, the project goal has been the implementation of a technology for the development of an innovative product containing KYs. Dried encapsulated KYs-tablets (KysBio) can be released in the environment to prevent the development of pathogens in mosquitoes. Launtenabio has worked on the study of such a product, contributing to the design of the whole pathway of commercialization of KysBio.
KYsBio has potential to contribute to a better quality of life through a sustainable strategy for preventing IBDS. Such a strategy can help numerous communities, thus gaining the interest of entrepreneurs and sponsors for a safe, field applicable and competitively priced technology. Likely end-users, such as national and local healthcare systems, municipal authorities, and private citizens will be attracted by all the benefits of KysBio, but it is necessary to guarantee an industrial production for massive applications.
For this goal, Launtenabio has investigated the KYsBio potential to be inserted step-by-step into the market and managed preparatory contacts with societal organizations, policy makers and governments. The global business associated with products mosquito control (larvicides and repellents) is estimated to have a value of over 35 billion dollars and is mainly developed in Europe and countries such as the United States, Brazil and China under the control of few influential companies (BASF, Bayer, Syngenta, DuPont, Dow and Monsanto). We believe that the absolute originality of this biocide (non-larvicide, non-repellent) can represent an ace in the hole of small companies (SMEs), favoring the growth of their competitiveness. In this frame, searches for the patentability of KysBio have been performed showing an interest from industries working on biological control of insects.
Launtenabio achieved the proof of principle and validated the scientific basis of a breakthrough technology creating all prerequisites for further development of the product. The whole trail includes five objectives that have been in part successfully reached or organized for next improvement: 1. Assessment of effective delivery (AED), 2. Toxicity evaluation (TE), 3. Optimised industrial-scale culturing (OISC), 4. Optimised drying and encapsulation (ODE), 5. Refinement of packaging/storage (RPS).
AED and TE have been fully reached thanks to laboratory tests which demonstrated that the KysBio are an insect-targeted and safe product with potential to be used in the field for the control of mosquito borne diseases and potentially other vector-borne diseases. Also, the project has engaged relationships with industrial partners interested in the product commercialization that can realize a large system of production of KysBio at an industrial level guaranteeing OISC. Lastly, different dried KYsbio formulations have been obtained and final products based on optimised encapsulation are under improvement, thus we partially reach the step of ODE which is preparatory to the final step towards the pathway of commercialization of KysBio through the RPS.
The piece of work carried out represents a launch test of an innovative product at a technology readiness level 4 (TRL4) and the road map per the commercialisation of KYsBio has been traced. Launtenabio has found that SMEs could invest in a cost-competitive product that should be in high demand for large scale use to control IBDs of significant economic and social impact. A phase of technology transfer to partner enterprises has been accomplished with the participation of BioVecBlok Ltd. The spinoff is investing in the refiniment of an infrastructure, the Research Centre (RC), able to offer several specialized services including monitoring and testing of products for the prevention of IBDs in ‘semi-field’ conditions to test products before the use in the field (TRL5). RC will serve national and international customers, providing income for the company and positively impacting the local economic recovery in an area hardly hit in 2016 by devastating earthquakes, which forced a high number of commercial activities to go out of business and have caused a significant part of the population to abandon the Apennine hinterland. Thanks to LaunTeNaBio, BioVecBlok is now ready to push on for the next development of a patentable final product (dried encapsulated KysBio tablets) and proceed with the refinement of packaging and storage. As one of the main objectives of Launtenabio, the experience as a project partner led BioVecBlok to be competitive for the next financing program EIC ‘Transition’ which aims to complete the commercialization pathway of KysBio involving a network of diverse international partners.
Insect-Borne Diseases (IBDs) are a growing problem, burdening the economy and the social conditions of numerous countries. Climate changes, globalization and increase in travel and trade have fostered the spread of insect populations from tropical and subtropical regions, and with them IBDs are appearing in new areas. Currently, Europe and the USA must face an increasing risk of vector-borne disease outbreaks that in the next future will spread in places where they have never been present. Mosquitoes are the most important vectors injuring public health: Malaria kills 450.000 people annually and filariasis causes chronic diseases. Arboviruses such as Dengue, Chikungunya and West Nile originating from tropics, are appearing in Europe, and Zika fever from Brazil is quickly spreading towards the USA. The whole of these diseases afflicts millions of people. Even though controlling IBDs is a global societal challenge, effective and safe tools are not yet available and new strategies are urgently needed.
The main approach for fighting IBDs is to reduce the insect-vector populations by means of insecticides but insecticide resistance (IR) represents a serious limit of this control method. IR implies new compounds and higher doses of products, demanding huge investments and high production costs. Moreover, many formulations have indirect effects exerting environmental toxicity. Another approach is the release of irradiation-sterilized male insects into the wild, where they compete with wild males to mate with the females, thus reducing the offspring. Since sterile insects are not self-replicating and cannot become established in the environment, constant releases are necessary to have an impact. Hence, the implementation of this strategy in a broad area requires significant initial investments and economic returns are seen only after a very long time. Microbial larvicides represent an additional frontier to fight IBDs, a well-known example is Bacillus thuringiensis used against Diptera. However, its use has some limit as the emergence of tolerance in targeted organisms and indirect effects on the trophic network.
Effective strategies against IBDs should overcome these limits and contribute to the solution in a practical and forward-looking way. Symbiotic Control (SC) exploits microbial symbionts associated with the insect-vectors to render their hosts innocuous. Thanks to antimicrobial properties, symbionts can harm the vector-borne pathogens inside the insect, thus blocking their transmission to humans. This approach is eco-friendly and avoids IR, since it eliminates the pathogens but not the vectors, acting as a biocide instead as a larvicide. Biocide products based on microbial symbionts represent a promising tool for the prevention of IBDs and similar approaches are employed using genetically manipulated bacterial symbionts in the control of Chagas disease and sleeping sickness.
Our discovery of symbiotic yeasts that secrete natural toxins able to kill malaria parasites in the mosquito, has opened a completely new frontier in the SC of IBDs avoiding genetic manipulation of microorganisms and using a costless tool, with zero environmental impact. The exploitation of such ‘killer yeasts’ (KYs) for the development of a biocide product, has posed the bases for the Launtenabio activity. In fact, the project goal has been the implementation of a technology for the development of an innovative product containing KYs. Dried encapsulated KYs-tablets (KysBio) can be released in the environment to prevent the development of pathogens in mosquitoes. Launtenabio has worked on the study of such a product, contributing to the design of the whole pathway of commercialization of KysBio.
KYsBio has potential to contribute to a better quality of life through a sustainable strategy for preventing IBDS. Such a strategy can help numerous communities, thus gaining the interest of entrepreneurs and sponsors for a safe, field applicable and competitively priced technology. Likely end-users, such as national and local healthcare systems, municipal authorities, and private citizens will be attracted by all the benefits of KysBio, but it is necessary to guarantee an industrial production for massive applications.
For this goal, Launtenabio has investigated the KYsBio potential to be inserted step-by-step into the market and managed preparatory contacts with societal organizations, policy makers and governments. The global business associated with products mosquito control (larvicides and repellents) is estimated to have a value of over 35 billion dollars and is mainly developed in Europe and countries such as the United States, Brazil and China under the control of few influential companies (BASF, Bayer, Syngenta, DuPont, Dow and Monsanto). We believe that the absolute originality of this biocide (non-larvicide, non-repellent) can represent an ace in the hole of small companies (SMEs), favoring the growth of their competitiveness. In this frame, searches for the patentability of KysBio have been performed showing an interest from industries working on biological control of insects.
Launtenabio achieved the proof of principle and validated the scientific basis of a breakthrough technology creating all prerequisites for further development of the product. The whole trail includes five objectives that have been in part successfully reached or organized for next improvement: 1. Assessment of effective delivery (AED), 2. Toxicity evaluation (TE), 3. Optimised industrial-scale culturing (OISC), 4. Optimised drying and encapsulation (ODE), 5. Refinement of packaging/storage (RPS).
AED and TE have been fully reached thanks to laboratory tests which demonstrated that the KysBio are an insect-targeted and safe product with potential to be used in the field for the control of mosquito borne diseases and potentially other vector-borne diseases. Also, the project has engaged relationships with industrial partners interested in the product commercialization that can realize a large system of production of KysBio at an industrial level guaranteeing OISC. Lastly, different dried KYsbio formulations have been obtained and final products based on optimised encapsulation are under improvement, thus we partially reach the step of ODE which is preparatory to the final step towards the pathway of commercialization of KysBio through the RPS.
The piece of work carried out represents a launch test of an innovative product at a technology readiness level 4 (TRL4) and the road map per the commercialisation of KYsBio has been traced. Launtenabio has found that SMEs could invest in a cost-competitive product that should be in high demand for large scale use to control IBDs of significant economic and social impact. A phase of technology transfer to partner enterprises has been accomplished with the participation of BioVecBlok Ltd. The spinoff is investing in the refiniment of an infrastructure, the Research Centre (RC), able to offer several specialized services including monitoring and testing of products for the prevention of IBDs in ‘semi-field’ conditions to test products before the use in the field (TRL5). RC will serve national and international customers, providing income for the company and positively impacting the local economic recovery in an area hardly hit in 2016 by devastating earthquakes, which forced a high number of commercial activities to go out of business and have caused a significant part of the population to abandon the Apennine hinterland. Thanks to LaunTeNaBio, BioVecBlok is now ready to push on for the next development of a patentable final product (dried encapsulated KysBio tablets) and proceed with the refinement of packaging and storage. As one of the main objectives of Launtenabio, the experience as a project partner led BioVecBlok to be competitive for the next financing program EIC ‘Transition’ which aims to complete the commercialization pathway of KysBio involving a network of diverse international partners.