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Exploring the potential applications of live viral vaccine encoded small-hairpin-RNAs in improving both vaccine safety and efficacy through RNA-interference and stimulation of the innate immune system

Objective

Live vaccines represent one of the most important and effective interventions against the spread of viral disease. As such, they are instrumental in addressing ongoing societal challenges in areas such as healthcare and global food security. However, their capacity to genetically recombine with wild type (WT) viruses circulating in the field remains a primary safety concern. Modifying live vaccine strains to reduce such occurrences would be highly desirable from a safety perspective. Also efforts to enhance the intrinsic potency of vaccine strains would be very beneficial. This would facilitate the use of much lower doses, while reducing the manufacturing resources required to meet market needs and the cost of vaccination programs.

With this in mind, this project will explore a novel strategy to improve both the safety and efficacy of live viral vaccine strains by modifying them to express small-hairpin-RNAs (shRNAs), which can be designed to:

i) Exclusively inhibit WT virus replication/propagation via RNA-interference (RNAi), thus reducing the levels of WT available for recombination with vaccine strains during vaccination i.e. improving safety

ii) Increase live vaccine strain stimulation of the innate immune system by functioning as potent inducers of Type-1 Interferon (IFN-I) expression during vaccination i.e. enhancing efficacy

This novel strategy will be explored by modifying an existing attenuated Cyprinid herpesvirus-3 vaccine strain to express appropriately designed shRNAs, followed by an assessment of their impact on both WT virus replication and IFN-I expression in-vitro, providing a basis for future progression to in-vivo trials.

Ultimately, if feasible, this novel vaccine design strategy may be applied in the control of many economically important viruses. Also elements of this project are in harmony with the “Strategic European Roadmap for the Vaccines of Tomorrow” launched in 2016 to outline specific EU priorities in future vaccine innovation.

Fields of science (EuroSciVoc)

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Topic(s)

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Funding Scheme

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MSCA-IF-EF-CAR - CAR – Career Restart panel

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2016

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Coordinator

UNIVERSITE DE LIEGE
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 160 800,00
Address
PLACE DU 20 AOUT 7
4000 LIEGE
Belgium

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Region
Région wallonne Prov. Liège Arr. Liège
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 160 800,00
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