Fukui Masayuki, Shinjo Kikuko, Umemura Masayuki, Shigeno Satoko, Harakuni Tetsuya, Arakawa Takeshi, Matsuzaki Goro
Molecular Microbiology Group.
Department of Host Defense, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
Microbiol Immunol. 2015 Dec;59(12):735-43. doi: 10.1111/1348-0421.12340.
Although the BCG vaccine can prevent tuberculosis (TB) in infants, its ability to prevent adult pulmonary TB is reportedly limited. Therefore, development of a novel effective vaccine against pulmonary TB has become an international research priority. We have previously reported that intranasal vaccination of mice with a mycobacterial heparin-binding hemagglutinin adhesin (HBHA) plus mucosal adjuvant cholera toxin (CT) enhances production of IFN-γ and anti-HBHA antibody and suppresses extrapulmonary bacterial dissemination after intranasal infection with BCG. In the present study, the effects of intranasal HBHA + CT vaccine on murine pulmonary Mycobacterium tuberculosis (Mtb) infection were examined. Intranasal HBHA + CT vaccination alone failed to reduce the bacterial burden in the infected lung. However, a combination vaccine consisting of s.c. BCG priming and an intranasal HBHA + CT booster significantly enhanced protective immunity against pulmonary Mtb infection on day 14 compared with BCG vaccine alone. Further, it was found that intranasal HBHA + CT vaccine enhanced not only IFN-γ but also IL-17A production by HBHA-specific T cells in the lung after pulmonary Mtb infection. Therefore, this combination vaccine may be a good candidate for a new vaccine strategy against pulmonary TB.
尽管卡介苗（BCG）可预防婴儿肺结核（TB），但据报道其预防成人肺结核的能力有限。因此，研发新型有效的抗肺结核疫苗已成为国际研究重点。我们之前报道过，用分枝杆菌肝素结合血凝素粘附素（HBHA）加粘膜佐剂霍乱毒素（CT）对小鼠进行鼻内接种疫苗，可增强IFN-γ和抗HBHA抗体的产生，并抑制鼻内接种卡介苗后肺外细菌的播散。在本研究中，检测了鼻内接种HBHA + CT疫苗对小鼠肺部结核分枝杆菌（Mtb）感染的影响。单独鼻内接种HBHA + CT疫苗未能降低感染肺部的细菌载量。然而，与单独使用卡介苗疫苗相比，由皮下接种卡介苗初免和鼻内接种HBHA + CT加强免疫组成的联合疫苗在第14天显著增强了对肺部Mtb感染的保护性免疫。此外，发现鼻内接种HBHA + CT疫苗不仅增强了IFN-γ的产生，还增强了肺部Mtb感染后HBHA特异性T细胞产生IL-17A的能力。因此，这种联合疫苗可能是抗肺结核新疫苗策略的良好候选者。
