A novel vaccine p846 encoding Rv3615c, Mtb10.4, and Rv2660c elicits robust immune response and alleviates lung injury induced by Mycobacterium infection

Abstract

Development of effective anti-tuberculosis (TB) vaccines is one of the important steps to improve control of TB. Cell-mediated immune response significantly affects the control of M. tuberculosis infection. Thus, vaccines able to elicit strong cellular immune response hold special advantages against TB. In this study, three well-defined mycobacterial antigens (Rv3615c, Mtb10.4 [Rv0228], and Rv2660c) were engineered as a novel triple-antigen fusion DNA vaccine p846. The p846 vaccine consists of a high density of CD4⁺ and CD8⁺ T-cell epitopes. Intramuscular immunization of p846 induced robust T cells mediated immune response comparable to that of bacillus Calmette-Guérin (BCG) vaccination but more effective than that of individual antigen vaccination. After mycobacterial challenge, p846 immunization decreased bacterial burden at least 15-fold compared with individual antigen-based vaccination. Notably, the lungs of mice immunized with p846 exhibited fewer inflammatory cell infiltrates and less damage than those of control group mice. Our data demonstrate that the potential of p846 vaccine to protect against TB and the feasibility of this design strategy for further TB vaccine development.

Keywords: :

• M. tuberculosis
• BCG
• multifunctional T cells
• cellular immunity
• subunit vaccine
• Rv3615c
• Mtb10.4
• Rv2660c

10.4161/hv.27121

Disclosure of Potential Conflicts of Interest

The authors declare that there is no conflict of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.

Acknowledgments

The authors appreciate Center for Disease Control of Suzhou and the Fifth People’s Hospital of Suzhou their providing of BCG and inactivated H37Rv strains. This work was supported by grants from Major State Basic Research Development Program of China (2013CB530501, 2013CB531502), the National Science and Technology Key Projects during the Twelveth Five-Year Plan Period of China(2013ZX10003007, 2012ZX10003006-008), the National Natural Science Foundation of China (81072409), Jiangsu “333” project of cultivation of high-level talents, Qing Lan Project of the Jiangsu higher education institutions, Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), Jiangsu Provincial Innovative Research Team and the Program for Changjiang Scholars and Innovative Research Team in University of Ministry of Education of China (PCSIRT-IRT1075), Shanghai STC grant (10JC1400900).