Coronaviruses roadmap:
Vaccines
Research roadmap for coronavirus vaccine development
Download 202402 Draft Coronavirus Vaccine research roadmap Final14
Identity of immunomodulators
Dependencies
- 17 Host-pathogen interactions
- 17A Entry
- 17B Replication
- 17C Persistence/ clearance
Next steps
Identity of immunomodulators
Research Question
- To identify the coronavirus genes or proteins that modulate the immune response during infection or vaccination in pets, livestock, and wildlife. Understanding how these work can add crucial information for designing effective vaccines (for example by targeting them for knockout) that overcome viral immune-evasion and/or improving protective immunity
Research Gaps and Challenges
- Immune evasion mechanisms: Coronaviruses encode various proteins (e.g., non-structural, accessory proteins from the 3’ of the genome) that modulate innate immune responses, including interferon signalling and cytokine production. However, these may have speciesspecific effects, i.e. behaving differently across species, complicating vaccine design for diverse animal populations
- Characterization of immunomodulator functions: Many of the immunomodulatory functions remain poorly characterized, particularly in non-human coronaviruses – can these functions be easily inferred from viruses like SARS-CoV-2. In addition, there is often a range of different proteins made by the different coronaviruses and so it can be difficult to assign the same function to orthologues
Solution Routes
- In vitro biology: Use reverse genetics to identify and characterize coronavirus immunomodulatory genes, and/or protein-protein interaction studies to map interactions between viral proteins and host immune components to understand their mechanism, also dipping into comparative studies to allow cross-species analysis. Immunemodulating proteins may have conserved and species-specific effects, which may also help to understand determinants of spillover
Dependencies
- Better animal models could help to study coronavirus-host immune interactions across species. What can be learned from SARS2 in hamsters here?
- Elsewhere the development of high throughout assays for rapid identification of viral immune modulators across diverse species could speed up our understanding – is there a role for AI here?
State Of the Art
- SARS2 accessory proteins (e.g., ORF3, ORF6, alternative N transcripts/proteins) are known to inhibit interferon responses – what is the current knowledge for PEDV/ FCV/ BoCV/ IBV and how might this knowledge affect vaccine development (rational attenuation etc.)
Projects
What activities are planned or underway?
Differential susceptibility of SARS-CoV-2 in animals : Evidence of ACE2 host receptor distribution in companion animals, livestock and wildlife by immunohistochemical characterisation
Planned Completion date 26/07/2021
Participating Country(s):
Netherlands
Veterinary Biocontained facility Network for excellence in animal infectiology research and experimentation
Planned Completion date 28/02/2023
Participating Country(s):
Europe