Multi-Stage Tuberculosis Subunit Vaccine Candidate LT69 Provides High Protection against Mycobacterium tuberculosis Infection in Mice.

Abstract

Effective tuberculosis (TB) vaccine should target tubercle bacilli with various metabolic states and confer long-term protective immunity. In this study, we constructed a novel multi-stage TB subunit vaccine based on fusion protein ESAT6-Ag85B-MPT64(190-198)-Mtb8.4-HspX (LT69 for short) which combined early expressed antigens and latency-associated antigen. The fusion protein was mixed with an adjuvant being composed of N, N'-dimethyl-N, N'-dioctadecylammonium bromide (DDA) and polyriboinosinic polyribocytidylic acid (PolyI:C) to construct subunit vaccine, whose immunogenicity and protective ability were evaluated in C57BL/6 mice. The results showed that LT69 had strong immunogenicity and high protective effect against Mycobacterium tuberculosis (M. tuberculosis) H37Rv aerosol challenge. Low-dose (2 μg) of LT69 generated long-term immune memory responses and provided effective protection, which was even higher than traditional vaccine BCG did at 30 weeks post the last vaccination. In conclusion, multistage subunit vaccine LT69 showed high and long-term protection against M. tuberculosis infection in mice, whose effect could be enhanced by using a relative low dosage of antigen.

• Authors: Hongxia Niu, Jinxiu Peng, Chunxiang Bai, Xun Liu, Lina Hu, Yanping Luo, Bingxiang Wang, Ying Zhang, Jianzhu Chen, Hongjuan Yu, Qiaoyang Xian, Bingdong Zhu
• Journal: PloS one (PLoS One) Vol. 10 Issue 6 Pg. e0130641 ( 2015) ISSN: 1932-6203 [Electronic] United States
• PMID: 26098302 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Bacterial
• Bacterial Proteins
• ESAT-6 protein, Mycobacterium tuberculosis
• HspX protein, Mycobacterium tuberculosis
• MPB64 protein, Mycobacterium
• Mtb8.4 protein, Mycobacterium tuberculosis
• Tuberculosis Vaccines
• Vaccines, Synthetic
• Acyltransferases
• antigen 85B, Mycobacterium tuberculosis

Topics

• Acyltransferases (genetics, immunology)
• Animals
• Antigens, Bacterial (genetics, immunology)
• Bacterial Proteins (genetics, immunology)
• Mice
• Mice, Inbred C57BL
• Tuberculosis Vaccines (administration & dosage, genetics, immunology)
• Vaccines, Synthetic (administration & dosage, genetics, immunology)