Coronaviruses roadmap:
Vaccines
Research roadmap for coronavirus vaccine development
Download 202402 Draft Coronavirus Vaccine research roadmap Final16
Identity of mechanisms of protection
Dependencies
- 17 Host-pathogen interactions
- 17A Entry
- 17B Replication
- 17C Persistence/ clearance
- 18 Challenge models
Next steps
Identity of mechanisms of protection
Research Question
- The goal is to understand the immune mechanisms responsible for long-lasting protection against animal coronaviruses. This will help tailor vaccines that induce both robust humoral and cell-mediated immunity, ensuring durable protection for pets, livestock, and wildlife. An improved understanding of immune responses, especially specific correlates of protection, will optimize vaccine efficacy and provide insights into which immuno-correlates (e.g. the balance of cellular vs. Humoral response) are key for different animal species and viral strains
Research Gaps and Challenges
- Mechanisms underpinning long-lasting protection: A key challenge is defining the immunological mechanisms responsible for long-term protection, particularly in distinguishing when and for which virus cellmediated immunity is more crucial than humoral responses. Understanding these correlates will inform vaccine design
- How pathogens determine the correlates of protection: Currently, it is unclear how much the different animal coronavirus pathogens (PEDV, CCOV, PRCV, FCV etc.) differ, i.e. is vaccine efficacy more closely linked to humoral immunity rather than cell-mediated and is there a general and predictable pattern for such pathogens/vaccines? Measuring more than just nAb responses – T-cell response, mucosal, non-neutralizing Ab responses (ADCC, complement etc). Sometimes see protection without serological response. Considerations of ADE
- Tools for cross-species study: How lacking are we in this area for the main pathogens? Do we have good, validated challenge models for these viruses? Holistic approach to analyzing the immune system
- Antigen conservation across intra-species variants: Identifying conserved viral antigens that can provide protection across all variants, especially in the context of rapid evolution.
Solution Routes
- Memory response research: Improved understanding of memory immune responses, particularly which factors drive long-lasting T-cell and B-cell immunity across different species
- Benchmarking vaccine immunity: Develop standardized benchmarks to assess vaccine efficacy in generating both cell-mediated and humoral immune responses. These benchmarks can be used to compare vaccine platforms across laboratories under consistent conditions
- Host response studies: Investigate the immune responses to both virulent and attenuated strains of coronaviruses to understand the specific immune mechanisms at play. This includes exploring how viral load, antigen presentation, and immune activation differ between strains and host species and will help to determine what sort of immune response is important for vaccine development
- Comparative vaccine platform testing: A wide range of vaccine platforms should be tested using standardized tests and shared SOPs across labs. This should ensure that direct comparisons can be made between vaccines, helping identify which platforms best elicit the desired immune response
- Correlates of protection research: Do we have the necessary tools and models to study correlates of protection in animal species other than humans and mice, which can include studying the balance between neutralizing antibodies and T-cell responses. There is ongoing work on this at places like Pirbright to develop porcine/bovine/chicken tools
- New tools: Expand the use of new computational tools, multiplexing, system immunology using innate signatures, to evaluate immune responses in pets, livestock and wildlife
Dependencies
- Development of research tools: i.e. for studying immune responses to coronaviruses in animals like livestock and wildlife away from classic models. This includes generating new animal models or adapting existing ones to facilitate cross-species immune studies
- Data on conserved antigens: Confirming target antigens so that the relevant tools can be made
State Of the Art
- Humoral and cellular immunity: It is well established now that virus neutralizing antibodies targeting the spike protein are very important for protective immunity following vaccination. However, immune responses, particularly involving T cells, enhance viral clearance and durability of immunity. There are also emerging roles for non-neutralizing mAbs
- Challenges in animal models: For the COVID field there have been some issues, e.g. wild-type mice are less/not permissive to infection by SARS-CoV due to weak binding affinities between murine ACE2 and spike. Is this an issue for animal coronaviruses? Do some host breeds provide a different vaccine responses to others and thus complicate the development of correlates of immunity or protection
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