Indexed by: Journal paper

First Author: Jilei Ma，Xindong Teng，Xiaochun Wang

Correspondence Author: Xionglin Fan

Co-author: Yaqi Wu，Maopeng Tian，Zijie Zhou，Longmeng Li

Journal: EBioMedicine

Affiliation of Author(s): 华中科技大学

Discipline: Medicine

First-Level Discipline: Basic Medicine

Document Type: J

Volume: Volume 22

ISSN No.: 2352-3964

Key Words: CMFO-DMT; Latent infection; Primary infection; Reactivation; Subunit vaccine; Tuberculosis.

DOI number: 10.1016/j.ebiom.2017.07.005

Date of Publication: 2017-07-08

Impact Factor: 8.143

Teaching and Research Group: 华中科技大学基础医学院病原生物学系医学微生物学

Abstract: Adult tuberculosis (TB) is the main cause of TB epidemic and death. The infection results mainly by endogenous reactivation of latent TB infection and secondarily transmitted by exogenous infection. There is no vaccine for adult TB. To this end, we first chose antigens from a potential antigenic reservoir. The antigens strongly recognized T cells from latent and active TB infections that responded to antigens expressed by Mycobacterium tuberculosis cultured under different metabolic states. Fusions of single-stage polyprotein CTT3H, two-stage polyprotein A1D4, and multistage CMFO were constructed. C57BL/6 mice vaccinated with DMT adjuvant ed CMFO (CMFO-DMT) were protected more significantly than by CTT3H-DMT, and efficacy was similar to that of the only licensed vaccine, Bacillus Calmette-Guérin (BCG) and A1D4-DMT in the M. tuberculosis primary infection model. In the setting of BCG priming and latent TB infection, M. tuberculosis in the lung and spleen was eliminated more effectively in mice boosted with CMFO-DMT rather than with BCG, A1D4-DMT, or CTT3H-DMT. In particular, sterile immunity was only conferred by CMFO-DMT, which was associated with expedited homing of interferon-gamma+CD4+ TEM and interleukin-2+ TCM cells from the spleen to the infected lung. CMFO-DMT represents a promising candidate to prevent the occurrence of adult TB through both prophylactic and therapeutic methods, and warrants assessment in preclinical and clinical trials.

Note: 8) J. Ma,X. Teng,X. Wang, etal. A Multistage Subunit Vaccine Effectively Protects Mice Against Primary Progressive Tuberculosis, Latency and Reactivation. EBioMedicine, 2017, 22:143-154.

Links to published journals: https://www.sciencedirect.com/science/article/pii/S2352396417302682?via%3Dihub