Research roadmap for coronavirus vaccine development

Identity of immunomodulators

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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

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

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

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?

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.)