Ionic liquid proteins: a route towards room temperature stable antibodies and vaccines

Lead Research Organisation: Imperial College London
Department Name: Department of Chemical Engineering

Abstract

Vaccines are administered to more than 100 million infants a year, saving three million lives annually. The global health community has recognised the importance of vaccines in the prevention of diseases and are committed to making vaccines available globally. The Centres for Disease Control and Prevention (CDC) recommends that most vaccines should be stored between 2 and 8 Degrees Centigrade, except the oral polio vaccine, to maintain the vaccine efficacy. However, if the storage temperature is lower than the recommended temperature range, then accidental freezing of vaccines can lead to agglomeration, which can reduce the potency of vaccine. Cold chain practices tend to overlook accidental freezing of vaccines because of the associated heat damage at higher temperatures. Despite this, over 31 % of the US$ 439 million UNICEF spent on all vaccines in 2005 are spent on freeze-sensitive vaccines. Therefore, the distribution of vaccines to third-world countries, where electricity and cold storage are limited, puts additional stress on the already fragile 'cold chain'.
A proposed solution to the storage of therapeutic proteins is to increase the thermal stability of proteins and antibodies using ionic liquids (ILs), avoiding the need for refrigeration of vaccines during shipping and storage. The use of ionic liquids have become increasingly popular and have been used for various applications such as material science, catalysis and medicinal chemistry due to their unique and tuneable properties. Ionic liquids have high thermal, chemical and electrochemical stabilities. In addition, most of the interest in ionic liquids is due to their negligible vapour pressures and therefore the possibility of a 'green solvent' to replace volatile organic solvents. Despite these advantages, proteins tend to be highly unstable in anhydrous conditions and poorly soluble in ionic liquids. This study proposes using surface modification of antibodies and viruses to increase their solubility in ionic liquids increasing protein thermal stability whilst retaining their protein biological function.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/N509486/1 01/10/2016 30/09/2021
1854775 Studentship EP/N509486/1 03/10/2016 02/04/2020 Liem Bui-Le
 
Description • Produced protein nanoconjugates through homogenisation of surface charge with diamines and then electrostatic coupling with an anionic surfactant
• Produced avidin nanoconjugates with a half-denaturation temperature of 141 °C and 169 °C, an increase of 73 °C and 101 °C from unmodified avidin in aqueous solution
• Dissolved avidin and antibody nanoconjugates in ionic liquids with a variety of anions. [bmpyrr][OTf] was the most stabilising ionic liquid with a half-denaturation temperature of 113 °C and 126 °C for avidin and antibody nanoconjugate respectively
• Binding studies have shown retention of binding in avidin nanoconjugate and avidin in the cationisation form in aqueous solution with an activity 11.6 % and 94.2 % of the unmodified respectively using HABA as a ligand. In addition, using FTIC-PEG-biotin ligand, the cationised and the modified avidin had an activity of 112 % and 6 % of the unmodified after a 1:1 to binding site ratio.
• Demonstrated that protein stability requires a holistic perspective driven by similar analytical frameworks, as opposed to single-technique assessments that can deliver misleading conclusions. Uncovered unprecedented information regarding site-specific ionic-liquid protein interactions from the point of view of the strongest interactions on both the protein and the ionic liquid.
Exploitation Route This biotechnology has potential as a storage technology for temperature-sensitive therapeutic proteins. The synthesis procedure can be applied to antibodies and viruses to offer the prospect of the elimination of the cold chain, enabling long-term storage and widespread dissemination of life-saving vaccines worldwide. There is vast scope for further research in optimising the synthesis procedure optimising the balance between temperature stability and removal of the surfactant in the reconstitution procedure.
Sectors Chemicals,Energy,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology

URL http://www.imperial.ac.uk/future-vaccine-hub/workstreams/eliminating-the-cold-chain/
 
Title Stabilising biomolecules 
Description Stabilisation of therapeutical antibodies, viruses and nucleic acids to improve the storage lifetime at room temperature, removing the need for a cold chain and thus expanding therapeutic treatments and vaccine coverage. 
IP Reference GB1908914.3 
Protection Patent application published
Year Protection Granted
Licensed No
Impact None