Vaccine Development Process Map

Early in vivo - small animal model

Summary of the area

Following in vitro assessment of vaccine immunogenicity in mice/other small animals, it is normally desirable to be able to conduct an early in vivo study to directly assess potential vaccine efficacy in an infectious challenged model in vivo, if a suitable animal model is available. This comes with the caveat that what appears to be efficacious in small animals, may not necessarily be efficacious in man, although the same applies to immunogenicity. Suitable readouts of efficacy need to be determined; this usually means a reduction in pathogen numbers/level of infection following challenge. Where well established correlates of protection already exist (eg serum bactericidal antibody (SBA) for meningococcal vaccines), this stage may not be necessary.

What are the critical steps within the process?

  • candidate vaccine has completed immunogenicity study and shown to be immunogenic without adverse events that halt further progress
  • decision on which animal model to use, vaccination protocol (often the same as for immunogenicity study), dose and route of pathogen challenge, length of challenge and readout of challenge result
  • conduct challenge study
  • analyses data and determine whether pre-set criteria of efficacy have been met

Are there any bottlenecks within this process? Who owns the bottleneck?

  • availability of suitable strains of pathogen for challenge
  • existence of a suitable small animal model
  • experience/licences for small animal work – Home Office approval
  • containment facilities for vaccine challenge (in particular, this step may be rate limiting if Cat 3 or 4 high containment facilities are required, further compounded with then requirement of skilled individuals to conduct the tests)
  • understanding of readout of model and agreement on criteria for efficacy
  • standardisation of models between different groups, including challenge dose and criteria for success

How could the bottlenecks be resolved?

  • experienced small animal challenge group or access to collaborators with such a group
  • review of literature for challenge models and their suitability – central database / information holders known
  • faster turnaround of UK Home Office license approvals

Are there any rate limiting capacity issues?

  • small animal challenge group
  • necessary containment facilities for challenge