17 January 2018
DCVMN and the Future Vaccine Manufacturing Hub launched a novel partnership for responsible innovation in emerging countries
[See Milestones above for more detail] London – A new research hub has been set up in the UK to improve vaccine coverage in developing countries and improve the response to life-threatening outbreaks like Ebola and Zika through the rapid deployment of vaccines.
This new effort, called the Future Vaccine Manufacturing Hub, led by Imperial College London and including other world-leading institutions, with a £10million funding by the UK’s Department for Health, will be collaborating with the Developing Countries Vaccine Manufacturers’ Network (DCVMN) on manufacturing projects initially in Bangladesh, China, India, Uganda and Vietnam, with expansion into other countries. The hub will build on new developments in life sciences, immunology and process systems to address challenges.
New approaches to be explored include the rapid production of yeast and bacterially-expressed particles that mimic components of infectious agents; development of synthetic RNA vaccines; manufacturing design and protein stabilization to preserve vaccines at high temperatures, avoiding the need for cold-chain.
There are currently 19.5 million infants that do not have access to basic vaccines and the deaths of one-third of children under five could be prevented with vaccinations. Lead investigator on the project, Professor Robin Shattock, said: “Many of these deaths, whether they are a result of polio, diphtheria measles or other infections, could be prevented through immunization, and the research hub will look to overcome hurdles in this field. We will also help to empower countries most at risk of infections to meet their local vaccine needs.”
“We are privileged to join the Hub’s research and educational efforts, collaborating with the Imperial College London, to advance the incorporation of new vaccine manufacturing technologies in emerging countries to benefit its people” said Dr. Sonia Pagliusi, Executive Secretary of DCVMN International.
Engineering and Physical Sciences Research Council (EPSRC) [U.K.] Grant
Future Vaccine Manufacturing Hub: Advancing the manufacture and deployment of cost effective vaccines
EPSRC Grant Reference: EP/R013764/1 01 December 201 7—31 March 2021 £9,947,570
PI: Shattock, Professor RJ, Imperial College London
Vaccine manufacturing systems have undergone evolutionary optimisation over the last 60 years, with occasional disruptions due to new technology (e.g. mammalian cell cultures replacing egg-based systems for seasonal influenza vaccine manufacture). Global vaccination programmes have been a great success but the production and distribution systems from vaccines still suffer from costs associated with producing and purifying vaccines and the need to store them between 2 and 8 degrees C. This can be a challenge in the rural parts of low and middle income countries where 24 million children do not have access to appropriate vaccinations every year. An additional challenge is the need to rapidly respond to new threats, such as the Ebola and Zika viruses, that continue to emerge.
The development of a “first responder” strategy for the latter means that there are two different types of challenges that future vaccine manufacturing systems will have to overcome:
1. How to design a flexible modular production system, that once a new threat is identified and sequenced, can switch into manufacturing mode and produce of the order of 10,000 doses in a matter of weeks as part of localised containment strategy?
2. How to improve and optimise existing manufacturing processes and change the way vaccines are manufactured, stabilised and stored so that costs are reduced, efficiencies increased and existing and new diseases prevented effectively?
Our proposed programme has been developed with LMIC partners as an integrated approach that will bring quick wins to challenge 2 while building on new developments in life sciences, immunology and process systems to bring concepts addressing challenge 1 to fruition.
Examples of strategies for challenge 1 are RNA vaccines. The significant advantage of synthetic RNA vaccines is the ability to rapidly manufacture many thousands of doses within a matter of weeks. This provides a viable business model not applicable to other technologies with much longer lag phases for production (viral vectors, mammalian cell culture), whereby procurement of the vaccine can be made on a needs basis avoiding the associated costs of stockpiling vaccines for rapid deployment, monitoring their on going stability and implementing a cycle of replacement of expired stock. In addition, low infrastructure and equipment costs make it feasible to establish manufacture in low-income settings, where all required equipment has potential to be run from a generator driven electrical supply in the event of power shortage. This fits the concept of a distributed, flexible platform technology, in that once a threat is identified, the specific genetic code can be provided to the manufacturing process and the doses of the specific vaccine can be produced without delay. Additional concepts that we will explore in this category include the rapid production of yeast and bacterially expressed particles that mimic membrane expressed components of pathogenic viruses and bacteria.
Examples of strategies for challenge 2 build on our work on protein stabilisation which has been shown to preserve the function of delicate protein enzymes at temperatures over 100 degrees C. We shall exploit this knowledge to develop new vaccine stabilisation and formulation platforms. These can be used in two ways: (a) to support the last few miles of delivery from centralised cold chains to patients through reformulation and (b) for direct production of thermally stable forms, i.e. vaccines that retain their activity for months despite being not being refrigerated.
We believe that the best way to deliver these step changes in capability and performance is through a team-based approach that applies deep integration in two dimensions: between UK and LMIC partners to ensure that all the LMIC considerations are “baked in” from the start and between different disciplines accounting for the different expertise that will be required to meet the challenges.