title: A step forward in the quality control testing of inactivated rabies vaccines - extensive evaluation of European vaccines by using alternative methods to the in vivo potency tests.
abstract: The mouse challenge test still remains the reference method for the potency determination of human and animal inactivated rabies vaccines, and it is still widely used throughout the world. This test suffers from many disadvantages - it is expensive and time consuming, uses a large number of mice, causes significant animal distress, and suffers from high variability. Recently, the European Pharmacopoeia has recognised the use of a serological potency assay (SPA) as an alternative method to the challenge test. This new test is based on the determination of rabies neutralising antibody titres in vaccinated mice, by using the modified Rapid Fluorescent Focus Inhibition Test (mRFFIT). With the objective of adopting this new method for the batch release of inactivated rabies vaccines, we evaluated its performance on a large collection of rabies vaccines currently assessed in our laboratory. The Fluorescent Antibody Virus Neutralisation test (FAVNt) was used in parallel with the mRFFIT, and the results were compared to the mouse challenge test. Our results demonstrate that the SPA is capable of estimating the potency of vaccines formulated with a potency margin well above the minimum of 1IU/dose. For low potency vaccines, this new method demonstrated some limitations, due to the recurrent invalidation of the assay. We have also demonstrated the superior sensitivity of the FAVNt when compared to the mRFFIT, and the importance of minimising the risk of detecting non-responders in vaccinated mice.
authors: French Agency for Food, Environmental and Occupational Health Safety (ANSES), Nancy Laboratory for Rabies and Wildlife (EU Reference Laboratory for Rabies, EU Reference Laboratory for Rabies Serology, WHO Collaborating Centre for Research and Management in Zoonoses Control, OIE Reference Laboratory for Rabies), Malzéville, France.
authors: Alexandre
authors: A
authors: Servat
authors: French Agency for Food, Environmental and Occupational Health Safety (ANSES), Nancy Laboratory for Rabies and Wildlife (EU Reference Laboratory for Rabies, EU Reference Laboratory for Rabies Serology, WHO Collaborating Centre for Research and Management in Zoonoses Control, OIE Reference Laboratory for Rabies), Malzéville, France.
authors: Sébastien
authors: S
authors: Kempff
authors: French Agency for Food, Environmental and Occupational Health Safety (ANSES), Nancy Laboratory for Rabies and Wildlife (EU Reference Laboratory for Rabies, EU Reference Laboratory for Rabies Serology, WHO Collaborating Centre for Research and Management in Zoonoses Control, OIE Reference Laboratory for Rabies), Malzéville, France.
authors: Valère
authors: V
authors: Brogat
authors: French Agency for Food, Environmental and Occupational Health Safety (ANSES), Nancy Laboratory for Rabies and Wildlife (EU Reference Laboratory for Rabies, EU Reference Laboratory for Rabies Serology, WHO Collaborating Centre for Research and Management in Zoonoses Control, OIE Reference Laboratory for Rabies), Malzéville, France.
authors: Estelle
authors: E
authors: Litaize
authors: French Agency for Food, Environmental and Occupational Health Safety (ANSES), Nancy Laboratory for Rabies and Wildlife (EU Reference Laboratory for Rabies, EU Reference Laboratory for Rabies Serology, WHO Collaborating Centre for Research and Management in Zoonoses Control, OIE Reference Laboratory for Rabies), Malzéville, France.
authors: Jean-Luc
authors: JL
authors: Schereffer
authors: French Agency for Food, Environmental and Occupational Health Safety (ANSES), Nancy Laboratory for Rabies and Wildlife (EU Reference Laboratory for Rabies, EU Reference Laboratory for Rabies Serology, WHO Collaborating Centre for Research and Management in Zoonoses Control, OIE Reference Laboratory for Rabies), Malzéville, France.
authors: Florence
authors: F
authors: Cliquet
mesh_terms: D000826:Animal Testing Alternatives / Q000379:methods* / Q000592:standards*; D000818:Animals; D001681:Biological Assay / Q000592:standards*; D005060:Europe; D006801:Humans; D051379:Mice; D011786:Quality Control; D011818:Rabies / Q000517:prevention & control*; D011819:Rabies Vaccines / Q000276:immunology*; D015203:Reproducibility of Results
chemical_list: D011819:Rabies Vaccines