Context-specific assessment of infectious disease model relevance to human outcomes

DISEASE-04 projects depend on infection and immunological models to support claims about vaccines and interventions. Multiple model systems are often available, each reflecting different components of infection or immune response, making model choice and interpretation a critical scientific decision.

We provide a context-specific, quantitative assessment of infectious disease model relevance to human outcomes, examining how different models relate to the biological features relevant to a given intervention or endpoint. By comparing models at the molecular and pathway level to human disease and immune responses within a systematic and reproducible framework, we clarify which outcomes a model can support, where its limitations lie, and how alternative models complement each other.

In this way, our analyses act as a validation layer linking preclinical models to claims about human outcomes, supporting interpretation without replacing experimental evidence.

This enables consortia to:

• select models aligned with defined human outcomes,

• compare and benchmark alternative models on a question-by-question basis,

• combine models where necessary to cover relevant biology,

• interpret preclinical findings with appropriate scope and confidence.

In addition, the same analyses offer a transparent, evidence-based rationale for model selection and can point to specific aspects where models may be improved or complemented, supporting more targeted experimental strategies.

Our contribution supports DISEASE-04 projects in linking model-based evidence to human outcomes in a structured and quantitative manner, without assuming that any single model is sufficient for all claims.