project – University of Copenhagen

Project

Production of APC Targeted Allergy Vaccines (APCGlyVac)

Type 1 allergy affects more than 20% of the population with symptoms including hay fever and asthma placing huge costs and demands on health care.
Vaccination is a promising approach to reduce or remove allergic symptoms by inducing tolerance, and may inhibit development of asthma. Currently, allergy vaccines are derived from extracts of natural allergens with the inherent problems of variability and source limitations. The use of recombinant vaccines offers a more controlled and sustainable allergen supply and, importantly, the opportunity for de novo design of vaccines with enhanced efficacy and reduced side-effects.
This proposal involves ALK-Abello, a world-leading pharmaceutical company producing and marketing allergy vaccines, and two University partners, who have developed novel genetically engineered mammalian and plant host cells that can be used to express recombinant glycoproteins with defined carbohydrate structures targeting antigen-presenting immune cells (APCs).
We hypothesize that recombinant allergy vaccines with defined carbohydrates will target APCs and enhance efficiency, induce tolerance at lower dosages, and possibly reduce side-effects. This proposal aims to explore the potential for enhancing efficiency of recombinant allergens vaccines against major allergens by targeting these to APCs through specific glycosylation patterns. We will use Zinc finger nuclease (ZFN) gene targeting strategies to obtain stable glycoengineer host cells to produce different glycovariants of model allergens and test these by well-established in vitro and in vivo models. If successful, the program has huge potential for many other allergens and it will pave the way for a more general concept for next generation vaccine designs.

Dansk resumé

Allergi påvirker 20% af befolkningen med betydelige gener og enorme omkostninger for sundhedsvæsenet. Vaccination er en lovende metode til at inducere tolerance. Dette projekt har til formål at udvikle nye forbedrede allergivacciner. Nuværende allergivacciner bygger på ekstrakter fra naturlige kilder, hvilket indebærer varierende kvalitet og begrænset tilgængelighed. Det er ønskeligt at overgå til rekombinant producerede vacciner med større ensartethed og tilgængelighed. Den grundlæggende idé bag det foreslåede projekt er at udnytte det forhold at nogle kulhydrater har en evne til at binde til lektin-receptorer på immunpræsenterende celler og stimulere immunitet. Vi vil således forsøge at udvikle rekombinante vacciner med kulhydrater som målretter allergenet til immunpræsenterende celler. Sådanne målrettede vacciner forventes at inducere tolerance ved lavere doser og medføre færre bivirkninger. Projektet kræver produktion i dyreceller og planteceller, og de to ansøgergrupper fra to Fakulteter på Københavns Universitet har udviklet genetisk modificerede celler som kan producere vacciner med nogle af disse målsøgende kulhydrater.
Projektet involverer det danske medicinalfirma ALK-Abello, som er internationalt førende i udvikling af allergivacciner og producerer og markedsfører en bred vifte af allergivacciner. Projektet er således et stærkt tværvidenskabeligt samarbejde mellem dansk industri og universitetet. 

This project is financed by The Danish Council for Strategic Research, as represented by the Programme Commission on Strategic Growth Technologies

Project start: April 1, 2013

Work schedule and time table:

2013: Recruitment of PhD-students and Postdocs: 

Participants:

Hans H. Wandall, lektor, Department of Cellular and Molecular Medicine, Copenhagen Center for Glycomics
Hans-Henrik Ipsen, direktør, ALK-Abello A/S
Bent Larsen Petersen, Ass. Prof., Department of Plant- and Environmental science, Plant glycobiology
Henrik Clausen, professor, Department of Cellular and Molecular Medicine, Copenhagen Center for Glycomics