Research roadmap for coronavirus vaccine development

Cell-mediated immunity

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Cell-mediated immunity

Research Question

T-cell mediated immune response: Understanding the protective roles of T-cell mediated immune responses. A robust T cell response to CoV may protect against severe disease, however can also have the potential to lead to excessive pro-inflammatory response and enhanced immunopathology
MHC complex variation: The variation in MHC (Major Histocompatibility Complex) molecules between species makes it difficult to generalize findings across animals, as T cell recognition relies heavily on these molecules
Environmental differences: Livestock and pets are often housed in controlled environments, but wildlife are exposed to a broad range of pathogens. This makes it harder to predict how their T cell responses will behave in the wild
Cost and scalability: In livestock, cost and scalability are significant barriers to developing T cell-focused vaccines or treatments
T cell memory and longevity: The duration of T cell memory is hard to quantify, especially in species where long-term studies have not been conducted
Effect of stress and overcrowding: In livestock, animals often experience stress, overcrowding, and poor nutrition, all of which can suppress T cell function and overall immunity, making it difficult to predict how this group will respond to infections

Identification of epitopes: Identify epitopes recognized by CD4 and CD8 T cells in different species that elicit broadly reactive T cell immunity
Role of mucosal immunity: Identify how routes of immunization (internals oral, sublingual, or other mucosal routes) affect the degree of mucosal immunity
Escape from T cell immunity: Explore methods to circumvent virus escape from T cell immunity (optimize peptide presentation or boost responses to subdominant epitopes)
Use of emerging technologies: Efforts to use emerging technologies to reduce reliance on animal models
Multi pathogen vaccines: Develop multi pathogen vaccines as animal are exposed to broad range of pathogens
Memory T cell response: Promote development of memory T cell responses at the site of entry of coronavirus
Better protection from disease: Correlate of protection from disease is most likely the CD8 T cell response, but with more T cell antigens (like N) in the vaccine, would we get a better protection?

Improved, affordable and standardized T cell assays or markers for T cell function are needed. Reagents to characterize pets, livestock and wildlife T cell subsets
Characterize MHC epitopes in pets, livestock and wildlife to better allow assessment of T cell-based vaccines
Basic research to understand T cell responses at different anatomic locations

Eliciting a cell-mediated immune response in addition to an antibody response is likely to improve both protective immunity and viral clearance
Cytotoxic T lymphocytes are critical in the control of infectious bronchitis virus in poultry. (Collisson, E. W. et al. Cytotoxic T lymphocytes are critical in the control of infectious bronchitis virus in poultry. Dev. Comp.Immunol. 24(2–3), 187–200 (2000)