Immunogenicity and protective efficacy of Ag85A and truncation of PstS1 fusion protein vaccines against tuberculosis

Abstract

Tuberculosis (TB) is an important public health problem, and the One Health approach is essential for controlling zoonotic tuberculosis. Therefore, a rationally designed and more effective TB vaccine is urgently needed. To enhance vaccine efficacy, it is important to design vaccine candidates that stimulate both cellular and humoral immunity against TB. In this study, we fused the secreted protein Ag85A as the T cell antigen with truncated forms of the mycobacterial cell wall protein PstS1 with B cell epitopes to generate vaccine candidates, Ag85A-tnPstS1 (AP1, AP2, and AP3), and tested their immunogenicity and protective efficacy in mice. The three vaccine candidates induced a significant increase in the levels of T cell-related cytokines such as IFN-γ and IL-17, and AP1 and AP2 can induce more balanced Th1/Th2 responses than AP3. Strong humoral immune responses were also observed in which the production of IgG antibodies including its subclasses IgG1, IgG2c, and IgG3 was tremendously stimulated. AP1 and AP2 induced early antibody responses and more IgG3 isotype antibodies than AP3. Importantly, the mice immunised with the subunit vaccine candidates, particularly AP1 and AP2, had lower bacterial burdens than the control mice. Moreover, the serum from immunised mice can enhance phagocytosis and phagosome-lysosome fusion in macrophages, which can help to eradicate intracellular bacteria. These results indicate that the subunit vaccines Ag85A-tnPstS1 can be promising vaccine candidates for tuberculosis prevention.

Keywords

• Tuberculosis
• One health
• Vaccine
• Humoral immunity
• Cellular immunity
• Ag85A-tnPstS1