Project description
Towards improved rabies vaccines
Many antiviral vaccines are designed to target surface glycoproteins that mediate fusion and entry into the host cell. The EU-funded FUSEDESIGN project is focussing on the development of a rabies vaccine based on the rabies virus glycoprotein (RVG). Researchers will employ a structure-guided approach to design mutations to stabilise the RVG pre-fusion protein using a homology model of the protein. Lead candidates will be characterised and used in vivo to immunise mice. Results have the capacity to improve existing rabies vaccines and may also lead to the design of vaccines against other viruses such as herpesviruses.
Objective
This proposal aims to stabilize the pre-fusion form of rabies virus glycoprotein (RVG), the most structurally-tractable clinically-relevant class III fusogen by combining computational biology, immunology, and structural biology.
Rabies virus is fatal; it kills 55,000 people each year and costs billions to control it in animals. Current human rabies vaccines are cumbersome to use and prohibitively costly, thus there is demand for a new generation of rabies vaccines.
Enveloped viruses’ fusion glycoproteins are important subunit vaccine candidates. Structure-guided stabilization of class I fusogens has been a major advance in vaccinology. Many major human pathogens have class III fusogens (notably, all herpesviruses and rabies virus): several post-fusion structures have been reported, but their antigenically critical pre-fusion forms have not been stabilized.
A high-quality homology model of RVG will guide design of mutations to stabilise the trimeric pre-fusion protein. Designed mutants will be transiently expressed in mammalian cells, selected for stability, and characterized immunologically. Lead candidates will be used as immunogens in mouse models and in structural studies. These data will guide design of improved rabies vaccines, and provide insights into RVG’s interaction with neutralizing antibodies and host receptors. Certain structural elements are conserved across class III fusogens, and so the approach may lead towards stabilization of herpesvirus fusogens.
The fellowship will be based between two departments at a world-class host institution. Together, they will offer the Researcher an unusual combination of exposure to both cutting-edge molecular biochemistry and Europe’s leading academic centre for translational vaccine development. This unique training will equip the Researcher with a truly discipline-spanning skill set and position her to make a leading contribution to the development of novel antiviral interventions and public health.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- medical and health sciences health sciences infectious diseases viral diseases RNA viruses
- medical and health sciences health sciences public health
- natural sciences biological sciences microbiology virology
- medical and health sciences basic medicine immunology
- medical and health sciences basic medicine pharmacology and pharmacy pharmaceutical drugs vaccines
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) H2020-MSCA-IF-2018
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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.
OX1 2JD Oxford
United Kingdom
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.