Direct involvement of neutrophils and Th17 cells in the protective immune response to tuberculosis after vaccination (VAC4P.1067)

Abstract

Abstract Introduction: In 2013, 1.5 million died from TB, the BCG vaccine is the only TB vaccine currently available, but does not protect adults. The mc2CMX vaccine developed by our group was able to generate similar protection in mice, but induced higher levels of Th17 cells when compared with BCG. Objective: To study the role of Th17 cells in the protection induced by mc2CMX vaccine. Methodology: WT, IL22KO, and IL17KO mice were immunized twice with mc2CMX. Mice were challenged with Mycobacterium tuberculosis. Fifteen days after the last immunization, the lesions were collected and stained with HE, and the spleen cells were analyzed by flow cytometry before and after Mtb challenge. Results: Although WT mice induced vaccine lesions showing peripheral neutrophilia, central necrosis and few macrophages, both KO mice strains showed reduced injuries with lower neutrophils migration. Only IL-22KO and WT vaccinated mice presented vaccine specific Th1 and Th17 responses and reduced the lung and spleen bacterial load 30 days after challenging with Mtb. Adoptive transfer of splenocytes from vaccinated WT mice to naïve IL17KO and WT animals restored partially the protection. WT mice neutrophils depletion provoked reduction in lung specific Th1 and Th17 responses after mc2CMX vaccination. Conclusion: The results show for the first time, the protective role of vaccine induced Th17 specific cells, and also the assistance of neutrophils in the generation of such protection against TB.