Preclinical Safety Evaluation: Acute and Repeated-Dose Toxicity of a New Intranasal Recombinant Vector Vaccine TB/FLU-04L Against Tuberculosis.

Background: Vaccination against tuberculosis is one of the most successful medical measures to reduce morbidity and mortality. The BCG vaccine has been in use for more than 100 years, but its efficacy is still controversial. New vaccine candidates may offer better protection than available BCG vaccine. In this work, we studied the acute and the repeated-dose toxicity study of a new vector vaccine TB/Flu-04L against tuberculosis.

Materials And Methods: The study was conducted on 60 BALB/c mice and 150 Wistar rats. The vaccine was administered intranasally and intravenously for the acute toxicity study. For the repeated-dose toxicity study, rats were intranasally immunized by 6.5 log TCID or 7.5 log TCID three times with 21-day intervals. Mortality, temperature, body weight, food and water consumption, hematological and biochemical parameters, urine analysis, as well as cardiovascular, respiratory, and central nervous system parameters were evaluated. A macroscopic examination of internal organs was performed.

Results: The TB/FLU-04L vaccine did not cause death among the mice and rats in the acute toxicity study. There were no pathological abnormalities in animal condition, behavior, food and water consumption, temperature, and body weight during the observation period. The results suggest that intranasal repeated-dose administration of the TB/FLU-04L vaccine does not exhibit significant toxicity in rats.Hematological and biochemistry analysis and the histological examination identified no toxicity-associated changes.

Conclusions: The toxicity study in mice and rats showed that the intranasal vector vaccine TB/FLU-04L had no toxic effect. The tests confirm no adverse effects for laboratory animals in the studied parameters.