Comparison of long-term and short-term immunogenicity based on two different types of tuberculosis subunit vaccines.

Abstract

Tuberculosis (TB) remains the leading cause of death globally among infectious bacterial pathogens. As the only licensed vaccine for TB prevention, the BCG vaccine fails to deliver comprehensive protection. To address this limitation, this study selected Rv2031c (HspX)-a key antigen in the latent phase of TB-and Rv2428, an essential antigen in the active phase, for synthesis to construct the fusion antigen AH40. We adopted the pET - 28a vector for the expression of the fusion protein, while the pcDNA3.1(+) vector was utilized to construct the fusion gene DNA vaccine. Subsequently, the immunogenicity of the AH40 subunit vaccine and the corresponding DNA vaccine was evaluated and compared through experiments involving Mycobacterium tuberculosis (M.tb)-infected individuals and animal models.The fusion protein AH40 induced high levels of the cytokines IFN-γ, IL-2, and IL-6 in the peripheral blood of individuals infected with Mycobacterium tuberculosis (M.tb). Notably, the secretion levels of these cytokines stimulated by AH40 were higher than those induced by its individual antigen component. Consistent with this observation, AH40 exhibited enhanced immunogenicity compared to the single antigen. In mouse models, immunization with the protein-adjuvant vaccine AH40/Colloidal Manganese Adjuvant (AH40/MnJ) and the DNA vaccine AH40-DNA (AH40-D) both elicited high titers of IgG subclass antibodies. Further analysis revealed that the induced immune responses were biased toward a Th1-type profile. Collectively, these findings demonstrate that both vaccine formulations possess robust immunogenicity.