A MAPS Vaccine Induces Multipronged Systemic and Tissue-Resident Cellular Responses and Protects Mice against Mycobacterium tuberculosis.
A MAPS Vaccine Induces Multipronged Systemic and Tissue-Resident Cellular Responses and Protects Mice against Mycobacterium tuberculosis.
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作者：
结核病（TB）仍然是全世界发病率和死亡率的主要原因。迄今为止，主要的疫苗接种涉及使用牛分枝杆菌卡介苗（BCG），这是一种减毒活疫苗，可保护婴儿和儿童免受肺外疾病的侵害，但不能预防肺部疾病。因此，迫切需要新的疫苗。在这里，我们表明，多组分无细胞疫苗（TB-MAPS）诱导强大的抗体应答和长期的系统和组织驻留记忆Th 1，Th 17，和细胞毒性CD 4+和CD 8 + T细胞，并促进小鼠γδT和NKT细胞介导的训练先天免疫。当在小鼠气溶胶感染模型中进行测试时，TB-MAPS显着降低了肺和脾中的细菌负荷，其程度与BCG相同。当与BCG结合使用时，TB-MAPS进一步增强BCG介导的保护，特别是在肺中，进一步支持该构建体作为有希望的TB疫苗候选物。
Tuberculosis (TB) remains a leading cause of morbidity and mortality worldwide. To date, the mainstay of vaccination involves the use of Mycobacterium bovis bacillus Calmette-Guérin (BCG), a live-attenuated vaccine that confers protection against extrapulmonary disease in infants and children but not against lung disease. Thus, there is an urgent need for novel vaccines. Here, we show that a multicomponent acellular vaccine (TB-MAPS) induces robust antibody responses and long-lived systemic and tissue-resident memory Th1, Th17, and cytotoxic CD4+ and CD8+ T cells, and promotes trained innate immunity mediated by γδT and NKT cells in mice. When tested in a mouse aerosol infection model, TB-MAPS significantly reduced bacterial loads in the lungs and spleens to the same extent as BCG. When used in conjunction with BCG, TB-MAPS further enhanced BCG-mediated protection, especially in the lungs, further supporting this construct as a promising TB vaccine candidate.
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DOI：
10.1056/nejmoa1714021
发表时间：
2018-07-12
期刊：
The New England journal of medicine
影响因子：
--
作者：
Nemes E;Geldenhuys H;Rozot V;Rutkowski KT;Ratangee F;Bilek N;Mabwe S;Makhethe L;Erasmus M;Toefy A;Mulenga H;Hanekom WA;Self SG;Bekker LG;Ryall R;Gurunathan S;DiazGranados CA;Andersen P;Kromann I;Evans T;Ellis RD;Landry B;Hokey DA;Hopkins R;Ginsberg AM;Scriba TJ;Hatherill M;C-040-404 Study Team
通讯作者：
C-040-404 Study Team
影响因子：
4.6
作者：
Lyadova IV;Panteleev AV
通讯作者：
Panteleev AV
影响因子：
4.4
作者：
Cruz, Andrea;Khader, Shabaana A.;Castro, Antonio G.
通讯作者：
Castro, Antonio G.
影响因子：
1.2
作者：
Mueller, Ann-Kristin;Behrends, Jochen;Schneider, Bianca E.
通讯作者：
Schneider, Bianca E.
影响因子：
7.3
作者：
Huang S
通讯作者：
Huang S