Report on the international workshop on alternative methods for human and veterinary rabies vaccine testing: State of the science and planning the way forward

By William Stokes - Richard McFarland - Jodie Kulpa-Eddy - Donna Gatewood - Robin Levis - Marlies Halder - Gayle Pulle - Hajime Kojima - Warren Casey - Alexander Gaydamaka - Timothy Miller - Karen Brown - Charles Lewis - Jean-Michel Chapsal - Lukas Bruckner - Sunil Gairola - Elisabeth Kamphuis - Charles E. Rupprecht - Peter Wunderli - Lorraine McElhinney - Fabrizio De Mattia - Koichiro Gamoh - Richard Hill - David Reed - Vivian Doelling - Nelson Johnson - David Allen - Lori Rinckel - Brett Jones

Potency testing of most human and veterinary rabies vaccines requires vaccination of mice followed by a challenge test using an intracerebral injection of live rabies virus. NICEATM, ICCVAM, and their international partners organized a workshop to review the availability and validation status of alternative methods that might reduce, refine, or replace the use of animals for rabies vaccine potency testing, and to identify research and development efforts to further advance alternative methods. Workshop participants agreed that general anesthesia should be used for intracerebral virus injections and that humane endpoints should be used routinely as the basis for euthanizing animals when conducting the mouse rabies challenge test. Workshop participants recommended as a near-term priority replacement of the mouse challenge with a test validated to ensure potency, such as the mouse antibody serum neutralization test for adjuvanted veterinary rabies vaccines for which an international collaborative study was recently completed. The workshop recommended that an in vitro antigen quantification test should be a high priority for product-specific validation of human and non-adjuvanted veterinary rabies vaccines. Finally, workshop participants recommended greater international cooperation to expedite development, validation, regulatory acceptance, and implementation of alternative test methods for rabies vaccine potency testing.