The process of vaccine development involves discovery, demonstration of immunogenicity and safety, and finally providing evidence of vaccine protection from a clinical or microbiological outcome (immunity). While providing evidence of immunogenicity is often relatively straightforward, providing convincing evidence of in vivo immunity is much more difficult. Randomised controlled trials (RCT) of clinical efficacy remain the gold standard evidence of immunity for vaccine approval. However, a variety of other evidence is often used to support vaccine effectiveness during clinical development, including in vitro assays, animal models, or evidence for immune correlates of protection. In some situations, RCT are not feasible, unethical, or too slow and alternative evidence for vaccine effectiveness is used to support vaccine licensure. For example, my team has provided pivotal evidence of immune correlates of protection that has supported vaccine approval and implementation policy in COVID-19 and mpox, and more recently we have performed similar analyses in HPV and RSV.
The importance of preclinical evidence in vaccine development and assessment has led to the development of the FEEVA project – aiming to develop a Framework for Evidence Evaluation in Vaccine Assessment. This Wellcome / CEPI funded project aims to develop consensus frameworks on how we assess preclinical and early clinical evidence of vaccine effectiveness. We have recently reviewed the types of evidence cited in vaccine approvals by the FDA and EMA, particularly focussing on the different uses of animal models in vaccine assessment and licensure. I will discuss progress towards developing a consensus framework for assessment of animal studies of vaccine effectiveness.