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Is lyophilisation the way forward for lipid nanoparticles-based vaccines?


   Faculty of Biology, Medicine and Health


About the Project

Covid vaccine based on lipid nanoparticles (LNP) have been the success story of the covid pandemic; however, as they are liquid formulation, these vaccines suffer from thermal instability. Our group has been working on the long-term stability of liquid formulation of mRNA like LNP particles in collaboration with the industry. To improve storage and limit the downside of liquid formulation stability, lyophilisation is an appealing approach. Although freeze drying is widely used for live, attenuated virus vaccines (Hansen et al., 2015) and has already been studied for naked mRNA formulations (Jones et al., 2007), there is limited information on mRNA-LNP particles available to the scientific community.

A lyophilized form of a mRNA vaccine (mRNA-1647) used in clinical trial suggests a shelf life at 5 °C of at least 18 months. However, no details on the formulation and production process can be found in the public domain (Moderna, 2021). Thus, lyophilisation can open the door to higher storage temperature for mRNA-LNP particles. However, lyophilization does have its downsides, as it requires reconstitution before administration and is a relatively expensive, energy- and time-consuming process.

Here, in this project, we seek to increase scientific knowledge and understanding of lyophilised LNPs.  Thus, lyophilised LNPs will be produced, their physicochemical properties characterised, their stability over time and their ability to deliver their payload will be characterised and compared against liquid formulations of LNPs. Several techniques will be used including microfluidics, light scattering, zeta potential, electron microscopy, confocal microscopy, cell culture or electrophoresis.

Entry Requirements

Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in a related area/subject. Candidates with previous experience (bio)chemical engineering, chemistry, biochemistry, biophysics, material science, pharmaceutical sciences or related subject. A Master’s degree in a relevant subject and/or experience in (bio)chemical engineering, chemistry, biochemistry, biophysics or related subject is desirable but not necessary. They are also expected to have a strong will to learn different scientific aspects.

Applicants interested in this project should make direct contact with the Primary Supervisor to arrange to discuss the project further as soon as possible.

How To Apply

For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select the appropriate subject title.

For international students, we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences.

Incomplete applications will not be considered and withdrawn.

Equality, Diversity and Inclusion

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/”


Funding Notes

Applications are invited from self-funded students. This project has a Band 3 fee. Details of our different fee bands can be found on our website View Website

References

Hansen et al., 2015: https://doi.org/10.1016/j.vaccine.2015.08.085
Jones et al., 2007: https://doi.org/10.2144/000112593
Moderna, 2021: https://investors.modernatx.com/static-files/693ffcac-b2fc-4f7e-91c5- 0a9164e7c6dc

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