Research roadmap for coronavirus vaccine development

Download 202402 Draft Coronavirus Vaccine research roadmap Final

Identity of mechanisms of protection

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Dependencies

17 Host-pathogen interactions
17A Entry
17B Replication
17C Persistence/ clearance
18 Challenge models

Next steps

12 Identity of protective antigens

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