Comparative evaluation for safety & potency of inactivated Cell Culture Rabies Vaccines from four Indian manufacturers

Abstract

Rabies is a fatal but preventable disease. Various cell culture rabies vaccines (CCRV) are recommended by World Health Organization (WHO) for pre- exposure prophylaxis and post-exposure therapeutic application. In the present study, we have evaluated seventy batches of inactivated CCRV, for safety and potency by test for Virus Inactivation and National Institute of Health (NIH) potency test respectively in Swiss albino mice, produced by four manufacturers of India, using different cell substrates, rabies fixed virus strains and inactivation methods. For a single batch evaluation, 0.03ml of undiluted vaccine sample was injected intracerebrally into each of 10 mice weighting between 12-15gms in Virus Inactivation test. In NIH potency test, three fivefold dilutions each of reference and test vaccines were used for immunization of mice. A group of 16 mice were immunized with each dilution on day 0 and 7, followed by a challenge dose of 5-50 LD ₅₀ (Median Lethal dose) of Rabies Challenge Virus Standard (CVS) on day 14. The mice were observed for 14 days after challenge dose for the symptoms of fixed rabies virus. The ED ₅₀ (50 % effective dose) of reference and test vaccine was calculated by Reed and Muench formula and the relative potency is calculated through comparison with the reference vaccine. The relative potency of the all the four rabies vaccines were above the recommended potency of 2.5IU/single human dose. All the vaccines tested were found to be safe and potent irrespective of the strain of rabies virus, substrate and inactivation process used in production.