Toxicidad de VA-DIFTET por administración a dosis repetida en ratones.

Considering that the expected immunization schedule for man includes three doses of VA-DIFTET, once demonstrated that this vaccine is safe for two animal species, the study of its toxicity by repeated dosing in mice was imperative, taking into account that in humans a three-dose schedule is used when the pertusis component is contraindicated. Two-hundred and ten OF1 mice of both sexes were used. Experimental groups were similar to those used in the single-dose toxicity study: duplex vaccine, diphtheria toxoid, tetanus toxoid, adjuvant, thiomersal, physiologic saline solution), and a non-treated control group. One group of male and another of female mice were randomly assigned to each treatment to receive 1, 2 or 3 intramuscular doses. Clinical symptoms, body weight increase, water and food intakes and the antibody titers (IgG by indirect ELISA) against the tetanus and diphtheria toxoids were evaluated after each administration. Finally, all mice were sacrificed and anatomopathological studies performed. The relative indexes of spleen and thymus and the spleen/thymus rate were also studied post-mortem. No evidence of toxicity was observed; however, those mice inoculated with the vaccine or the toxoids showed a significant immune response. Final results were considered satisfactory. [ABSTRACT FROM AUTHOR]