Protective vaccine efficacy of MTBK_24820, the complete form of PPE39 protein from Mycobacterium tuberculosis Beijing/K strain in mice

Abstract

The aim of this study was to evaluate the protective efficacy of MTBK_24820, the complete form of PPE39 protein derived from a predominant Beijing/K strain of Mycobacterium tuberculosis, in tuberculosis outbreaks in South Korea. Mice were immunized with adjuvant of dimethyl dioctadecyl ammonium bromide and monophospholipid A, Bacilli Calmette-Guérin, or recombinant MTKB_24820 with adjuvant prior to a high-dose Beijing/K strain aerosol infection. After 4 and 9 weeks, bacterial loads were determined and histopathologic and immunologic features in the lungs and spleens of the M. tb-infected mice were analyzed. Putative immunogenic T-cell epitopes were examined using synthetic overlapping peptides. Compared with adjuvant-control mice, MTBK_24820-immunized mice showed increased IgG responses against MTBK_24820 (p<0.05) and recalled antigen-specific IFN-g, IL-2, IL-6, and IL-17 responses in spleens (p<0.01). After challenge with the Beijing/K strain, an approximately 0.5-1.0 log10 reduction in lungs in colony forming units and fewer lung inflammation lesions were observed in MTBK_24820-immunized mice compared with control mice. Moreover, MTBK_24820 immunization elicited significantly higher numbers of CD4+ T cells producing protective cytokines, such as IFN-g and IL-17, in the lungs and spleens (p<0.01) and CD4+ multifunctional T cells producing IFN-g, TNF-a and/or IL-17 (p<0.01) than in control mice, results in comparable protection to BCG against the hypervirulent Beijing/K strain. The dominant immunogenic T-cell epitopes that induced IFN-g production was at the N-terminal (amino acids 85-102 and 217-234). Its vaccine potential along with protective immune responses in vivo may be informative for vaccine development, particularly in regions where the M. tb Beijing/K-strain is frequently isolated from TB patients.