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Design and Synthesis of a Bifunctional Linker for generating Haptenated Flagellin Bioconjugates for Improving Vaccine Reach and Lifespan (360G-Wellcome-211829_Z_18_Z)

The protein, flagellin, has been shown to enhance vaccine responses in systemic and mucosal sites, and bolster long-lived Ab responses. The ability of flagellin to migrate to mucosa opens up a strategy for delivering other antigens to the gut mucosa to elicit a more robust immune response, which is desirable for a vaccine to maximise its potential to protect. Activated iNKT-cells elicit potent systemic IgG responses but their ability to modulate mucosal antibody responses, including IgA, is less clear. If we could administer iNKT-cell agonists systemically in a way that ensures they reach mucosal sites, we would be able to examine this in depth. We now propose to use flagellin–iNKT-cell agonist conjugates to do just this, by employing flagellin as a carrier to deliver iNKT-cell antigens to the mucosa and in so doing, hopefully induce a robust mucosal antibody response. This Summer research project will focus on the synthesis of a bifunctional molecule which we will use to attach a potent iNKT-cell glycolipid agonist, which we have previously assembled, and then use the second functionality to conjugate the iNKT-cell agonist to the flagellin molecule selectively through surface-exposed Tyr residues that are concentrated in the hypervariable region of the flagellin molecule.

£0

31 May 2018

Grant details
Amount Awarded 0
Applicant Surname ZALESSKY
Approval Committee Internal Decision Panel
Award Date 2018-05-31T00:00:00+00:00
Financial Year 2017/18
Grant Programme: Title Vacation Scholarships
Internal ID 211829/Z/18/Z
Lead Applicant Mr ILLYA ZALESSKY
Planned Dates: End Date 2018-08-31T00:00:00+00:00
Planned Dates: Start Date 2018-07-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region West Midlands
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