Advanced Adjuvants For Antibody Production

Lead Research Organisation: University of Surrey
Department Name: Faculty of Health and Medical Sciences

Abstract

The project aims to rationalise and improve adjuvant technologies for improved vaccine efficacy across the lifespan. Adjuvants are molecules or structured assemblies of molecules or formulations (mixtures of substances) that work together with the vaccine antigens to potentiate the immune response to the vaccine. They do this by stimulating the cellular processes that come together to create the immune response and/or control a sustained delivery of the vaccine antigens. Together we have developed capability to design-in synthesise and encapsulate antigenic peptides into novel, single and multi-layer lipsomes. The student will synthesise and evaluate biological responses of liposomes carrying combinations of active molecules that promote each of the three key steps in peptide-specific antibody production. This project will therefore provide a student with first class interdisciplinary research training at the biology-pharmaceutical chemistry interface in the field of industrial biotechnology.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M017087/1 30/09/2015 30/11/2016
1642137 Studentship BB/M017087/1 30/09/2015 29/09/2019 Matthew Craig Rooney
BB/M017087/2 30/09/2016 29/09/2019
1642137 Studentship BB/M017087/2 30/09/2015 29/09/2019 Matthew Craig Rooney
 
Description We have optimised and characterised two main methods of differentiating THP1 monocytic cells into dendritic cells (DCs) that are key for the initial immune response. This included looking at viability, the expression of specific surface markers and metabolic activity. These models will represent the human model on which our antigens can be tested. We have also optimised a method for making DCs from mouse bone marrow using similar characterisation methods. The mouse DCs have then had their redox state modulated in order to determine the differences in behaviour such as antigen uptake and endosomal pH, and are key to normal DC behaviour. We have found significant changes in surface expression of key surface proteins involved in the immune response with compounds that indirectly reduce reactive oxygen species (ROS).
Since the last submission we have begun research on nanoparticle based vaccine adjuvants both using DC models discussed above and in vivo mouse studies. We are using nanoparticles that use ROS to influence viability which is significant for the three Rs, the expression of specific surface markers and metabolic activity as well as examining antigen uptake and endosomal pH. The in Vivo mouse model has been used to show that key markers of immune stimulation are present at increased levels and antibody titers are being examined.
Exploitation Route The dendritic cell models optimised during this project can be used to replace, reduce and refine the numbers of animals used in future studies for vaccination work. Similarly the newly developed nanoparticles show lower toxicity in vitro compared to previous formulations which could also benefit animal welfare.
Future work will look at how the nanoparticles adjuvants developed in this project can be used to boost immune response for antibody production. These could then go on to be used either in vaccinations intended for immunisation directly or for the production and selection of antibodies for diagnostic purposes.
Sectors Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

 
Description Micro/Biochem Joint Seminar Series 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Other audiences
Results and Impact These meetings consist of presentations followed by question and answer sections, the purpose of these meetings is to present PhD research projects to the wider academic staff at the school of Faculty of Health and Medical Sciences.
Year(s) Of Engagement Activity 2017,2018,2019
 
Description Quarterly internal immunology presentation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Other audiences
Results and Impact Quarterly internal immunology presentation attended by PhD students, supervisors, head of department and executive dean. These meetings consist of presentations followed by question and answer sections, the purpose of these meetings is to present current research and progress from the last presentation.
Year(s) Of Engagement Activity 2017,2018,2019