Evaluation of the immunotoxicity and allergenicity of a new intranasal influenza vector vaccine against tuberculosis carrying TB10.4 and HspX antigens

OBJECTIVE(S): A new vaccine candidate TB/FLU-05E has been developed at the Smorodintsev Research Institute of Influenza (Russia). The vaccine is based on the attenuated influenza strain A/PR8/NS124-TB10.4-2A-HspX that expresses mycobacterial antigens TB10.4 and HspX. This article describes the results of preclinical immunotoxicity and allergenicity studies of the new vector vaccine TB/FLU-05E against tuberculosis. MATERIALS AND METHODS: The experiments were conducted on male CBA mice, С57/black/6 mice, and guinea pigs. The vaccine candidate was administered intranasally (7.7 lg TCID(50)/animal and 8.0 lg TCID(50)/animal) twice at a 21-day interval. The immunotoxic properties of the vaccine were assessed in mice according to the following parameters: spleen and thymus weight and their organ-to-body weight ratio, splenic and thymic cellularity, hemagglutination titer assay, delayed-type hypersensitivity test, and phagocytic activity of peritoneal macrophages. Histological examination of the thymus and spleen and white blood cell counts were also performed. Allergenicity of the vaccine was assessed in guinea pigs using conjunctival and general anaphylaxis reaction tests. RESULTS: The results showed that double immunization with the TB/FLU-05E vaccine did not affect the phagocytic activity of peritoneal macrophages, cellular and humoral immunity after immunization with a heterologous antigen (sheep red blood cells), or the organ-to-body weight ratio of immunocompetent organs (thymus and spleen). The vaccine candidate demonstrated no allergenic properties. CONCLUSION: According to the results of this study, the TB/FLU-05E vaccine is well-tolerated by the immune system and demonstrates no immunotoxicity or allergenicity.