Bridging Animal and Human Data in Pursuit of Vaccine Licensure.

ABSTRACT

The FDA Animal Rule was devised to facilitate approval of candidate vaccines and therapeutics using animal survival data when human efficacy studies are not practical or ethical. This regulatory pathway is critical for candidates against pathogens with high case fatality rates that prohibit human challenge trials, as well as candidates with low and sporadic incidences of outbreaks that make human field trials difficult. Important components of a vaccine development plan for Animal Rule licensure are the identification of an immune correlate of protection and immunobridging to humans. The relationship of vaccine-induced immune responses to survival after vaccination and challenge must be established in validated animal models and then used to infer predictive vaccine efficacy in humans via immunobridging. The Sabin Vaccine Institute is pursuing licensure for candidate filovirus vaccines via the Animal Rule and has convened meetings of key opinion leaders and subject matter experts to define fundamental components for vaccine licensure in the absence of human efficacy data. Here, filoviruses are used as examples to review immune correlates of protection and immunobridging. The points presented herein reflect the presentations and discussions during the second meeting held in October 2021 and are intended to address important considerations for developing immunobridging strategies.