BHK-21 cell culture rabies vaccine: immunogenicity of a candidate vaccine for humans.

Abstract

Veterinary rabies vaccines produced in BHK-21/C13 permanent cell cultures have been used for a long period of time and have been proven as efficacious and safe. A candidate vaccine for human use (YU BHK Rabivak) was developed at the Pasteur Institute, Novi Sad, Serbia on the basis of the fixed rabies virus strain "L. Pasteur 2061/Vero 15 pas" using BHK 21/C13 as a cell substrate for vaccine production. To test the vaccine immunogenicity, a clinical trial was conducted involving 164 subjects between 18 and 60 years of age, immunized either with the YU BHK Rabivak vaccine candidate orwith a commercially available vaccine (Rabipur). Three groups of subjects were immunized with either vaccine by intramuscular administration in the deltoid region, following a pre-exposure regimen on days 0, 7 and 21, or the Essen or Zagreb post-exposure regimens. Rabies virus neutralizing antibodies (VNA) titres were determined by rapid fluorescent focus inhibition test (RFFIT) 21 and 30-45 days post vaccination. A protective titre of VNAs (>0.5 IU/ml) was found in all subjects vaccinated. Dynamics of the immune response showed that 96.4% of the subjects developed protective VNA titres after two doses, 99.3% after three doses and 100% after four and five doses of the candidate YU BHK Rabivak vaccine. There was a low reactogenicity without serious adverse events indicating a satisfactory safety profile in humans. Results obtained in this study indicate that BHK 21 cells offer the possibility of producing an efficacious and safe cell-culture rabies vaccine for humane use.