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

• Published in: Human vaccines & immunotherapeutics 2014-02, Vol.10 (2), p.378-390
• Main Authors: Kong, Hongmei, Dong, Chunsheng, Xiong, Sidong
• Format: Article
• Language: English
• Subjects: Animals; Antigens, Bacterial - genetics; Antigens, Bacterial - immunology; Bacterial Load; Bacterial Proteins - genetics; Bacterial Proteins - immunology; BCG; cellular immunity; Disease Models, Animal; Female; Injections, Intramuscular; Lung - microbiology; Lung - pathology; Lung Injury - pathology; Lung Injury - prevention & control; M. tuberculosis; Mice, Inbred BALB C; Mtb10.4; multifunctional T cells; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - immunology; Research Paper; Rv2660c; Rv3615c; subunit vaccine; T-Lymphocytes - immunology; Tuberculosis Vaccines - administration & dosage; Tuberculosis Vaccines - genetics; Tuberculosis Vaccines - immunology; Tuberculosis, Pulmonary - pathology; Tuberculosis, Pulmonary - prevention & control; Vaccines, DNA - administration & dosage; Vaccines, DNA - genetics; Vaccines, DNA - immunology; Vaccines, Subunit - administration & dosage; Vaccines, Subunit - genetics; Vaccines, Subunit - immunology; Vaccines, Synthetic - administration & dosage; Vaccines, Synthetic - genetics; Vaccines, Synthetic - immunology
• ISSN: 2164-5515; 2164-554X
• DOI: 10.4161/hv.27121

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.