Research roadmap for coronavirus vaccine development

Download 202402 Draft Coronavirus Vaccine research roadmap Final

Expression system

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Dependencies

12 Identity of protective antigens

Next steps

9 Adjuvant

Expression system

Research Question

What are we trying to achieve? Development of efficient expression system for recombinant viral glycoproteins, live attenuated virus cell lines or viral vector production
What is the problem? Deciding suitable expression systems for different vaccine platforms, their efficiency and whether they would work in different animal models, particularly when developing a new animal model.

Research Gaps and Challenges

Universality: Not all viral glycoproteins will be as easily expressed, stabilised, pseudotyped, and mono-serotypic as SARS2 spike. We need to turn our attention to more difficult orthologues whose expression and immunization does not always lead to the provision of immunity, e.g. Lassa, HIV. Will spike stabilization strategies like HexaPro be applicable to all coronaviruses?
Cell culture system: Choosing the appropriate cell culture (mammalian, yeast, bacteria, plant-based, insect) system to obtain best expression, optimal yield, purity, minimise contaminants etc
Immune response: Understanding whether different expression systems will result in differential immune response, and whether this is sufficient to provide protection, stop onward transmission etc. This is also important when considering comparing different coronavirus vaccines made using different expression systems – what do we define as a correlate of protection?
Cost: Mammalian expression systems are more costly than e.g., insect expression systems – is one preferable over the other when generating animal vaccines? More vaccines could be produced, the requirement for purity is less stringent than in human vaccines, and it is cheaper to make animal vaccines
Yield: Will one expression system return a greater yield of vaccine over another? Is this as important if the vaccine is not needed urgently? An economical vaccine that requires less investment and can be easily scaled up is of highest priority when designing animal vaccines

Solution Routes

Finding appropriate cell or tissue cultures to study coronaviruses in vitro that best mimic in vivo replication
Alternative methods: Use of ex-vivo tissue and organoid cultures from natural host species when possible
Availability: Broaden access to validated expression systems that are compatible with the first steps in clinical trial

Dependencies

There needs to be a better understanding of coronavirus glycoprotein biology to recognise which expression systems may be appropriate for spike without continuous rounds of trial and error, particularly the more difficult orthologues