Adaptation of a high resolution, high throughput assay of immunoglobulin repertoires for commercial and clinical applications

Lead Research Organisation: Babraham Institute
Department Name: Nuclear Dynamics

Abstract

Our immune system makes millions of different antibodies to fight infection by cutting and pasting together large sets of antibody genes in many different combinations. It is currently not possible to measure them all and it would be extremely useful to be able to do so. First, immunodeficient patients who can't make antibodies could be diagnosed and treated quicker and more accurately. Second many companies are making mouse models that generate human antibodies as powerful therapies against specific infections. They need to know which antibodies are amplified in response to a particular infection. We have developed VDJ-seq, an assay that can identify several hundred thousand different mouse antibody sequences in a sample. We will adapt VDJ-seq to analyse immunodeficient human patient samples and mouse models producing human antibodies in a rapid, high-throughput, cost-effective way that aims to improve patient treatment and accelerate commercial discovery of therapeutic antibodies.
 
Description We have developed a DNA-based next generation sequencing assay that can quantify which genes are used to make antibodies in mouse and human
Exploitation Route We have used the assay to show that immunodeficient patients have large differences in the diversity of their antibody repertoires. this approach can be used to stratify patients for better diagnosis and treatment.
Sectors Healthcare

 
Description They have been used to better understand antibody repertoires in immunodeficient patients
First Year Of Impact 2013
Sector Healthcare
 
Description Babraham KEC TAG
Amount £25,424 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 12/2013 
End 05/2014
 
Description GCRF-IAA
Amount £26,000 (GBP)
Funding ID BB/GCRF-IAA/17/02 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 10/2017 
End 02/2018
 
Description GCRF-IAA
Amount £30,000 (GBP)
Funding ID BB/GCRF-IAA/02 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 12/2016 
End 03/2017
 
Description Addenbrookes 
Organisation Addenbrooke's Hospital
Country United Kingdom 
Sector Hospitals 
PI Contribution High-throughput analysis of patient antibody repertoires
Collaborator Contribution Provision of patient samples, supporting data and clinical expertise
Impact None as yet
Start Year 2012
 
Title Method of identifying VDJ recombination products 
Description A high-throughput, high resolution DNA-based next generation sequencing assay to interrogate the sequences of VDJ recombined gene products resulting from antigen receptor recombination. Patent licence granted in USA and Europe in 2017. Licence application pending in Japan. Undertaking active marketing, no commercial licensee finalised as yet. 
IP Reference EP2820153 
Protection Patent granted
Year Protection Granted 2017
Licensed No
Impact Collaborations with academic, clinical and commercial interests, resulting in 3 grant applications, one of which was successful
 
Title VDJ-seq next generation sequencing assay 
Description Novel DNA-based next generation sequencing assay for analysis of immunoglobulin and T cell receptor repertoires. 
Type Of Technology New/Improved Technique/Technology 
Year Produced 2016 
Impact Interest from companies for licensing; interest from academics in availing of the assay for their research. Pending publication in Nature Protocols. 
 
Title VDJ-seq pipeline - Babraham Linkon 
Description Pipeline to analyse antigene receptor repertoire outputs of VDJseq assay 
Type Of Technology Software 
Year Produced 2017 
Open Source License? Yes  
Impact Publication in Nature Protocols 2018 
 
Description Babraham Institute Schools Day 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact 12 GCSE and A level students spent a day in our lab, doing a small project. Many asked questions about our research and careers in biology. Positive feedback relayed after the visit by teachers.

The feedback afterwards from the students was that biological research was more interesting and scientists more normal than the students expected.
Year(s) Of Engagement Activity 2010,2011,2013,2014,2015
 
Description Primary School visits 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Type Of Presentation Workshop Facilitator
Geographic Reach Local
Primary Audience Schools
Results and Impact Visits were made to a local school. 60 Year 4 to 6 primary school children attended presentations and hands-on practical related to our science.

The teachers reported an increase in understanding and interest in biological research and what real scientists do. We are frequently requested to visit.
Year(s) Of Engagement Activity 2010,2011,2012,2013,2014