title: Correlation between ToBI test and in vivo titration for diphtheria and tetanus.
abstract: Alternatives to animal testing for quality control of biologicals have been a goal since 1959. Instituto Butantan has been developing such methods for quality control of biologicals for human use (vaccines and hyperimmune equine sera) for the last 13 years. In this paper we compare the modified ToBI test and the in vivo seroneutralization test to assess immunogenicity of diphtheria and tetanus vaccines and hyperimmune sera. Data from the last 10 years were statistically analyzed to compare the results for in vivo and in vitro titrations (diphtheria, n = 525 and tetanus, n = 455). The agreement between the tests depended on the serum titer range. For both diphtheria and tetanus components, the correlation and concordance coefficient was higher as the serum titer increased. Overall, the in vitro/in vivo titer ratio did not vary systematically over the range of measurements. These results indicate that although the in vitro ToBI test is not completely able to replace the in vivo serum titration, it is a useful tool to guide the tests during the production process, which can reduce the number of animals used for lot release.
authors.affiliation: Quality Control Service, Instituto Butantan, Brazil. Electronic address: wagner.quintilio@butantan.gov.br.
authors.forename: Wagner
authors.initials: W
authors.lastname: Quintilio
authors.affiliation: Quality Control Service, Instituto Butantan, Brazil.
authors.forename: Josana
authors.initials: J
authors.lastname: Kapronezai
authors.affiliation: Regulatory Affairs, Instituto Butantan, Brazil.
authors.forename: Fábio
authors.initials: F
authors.lastname: Alessandro de Freitas
mesh_terms: D000818:Animals; D004168:Diphtheria Toxoid / Q000276:immunology*; D005260:Female; D006168:Guinea Pigs; D008297:Male; D013745:Tetanus Toxoid / Q000276:immunology*
chemical_list: D004168:Diphtheria Toxoid; D013745:Tetanus Toxoid
keywords: Alternative methods; Hyperimmune sera; Quality control; ToBI test; Vaccines