Intranasal Immunization with DnaK Protein Induces Protective Mucosal Immunity against Tuberculosis in CD4-Depleted Mice.
Intranasal Immunization with DnaK Protein Induces Protective Mucosal Immunity against Tuberculosis in CD4-Depleted Mice.
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DOI：
10.3389/fcimb.2018.00031
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发表时间：
2018
影响因子：
5.7
通讯作者：
Hung CF
中科院分区：
文献类型：
--
作者：
Chuang YM;Pinn ML;Karakousis PC;Hung CF
结核分枝杆菌（Mtb）仍然是一个全球性的健康挑战，由于目前使用的Mtb疫苗，卡介苗（BCG）的有效性有限。到目前为止，还没有免疫力低下的人可用的疫苗。因此，迫切需要开发一种新的候选疫苗，可以在不同免疫状态的宿主中诱导粘膜免疫。DnaK（HSP 70）已被证明在通过DNA疫苗施用时诱导针对Mtb感染的保护性免疫;然而，保护性不如由BCG疫苗诱导的保护性。在我们的研究中，我们用DnaK蛋白单独接种C57 BL/6 J小鼠。皮下或鼻内接种DnaK在脾脏中产生分泌IFNγ的CD 4 + T细胞，但只有鼻内接种在肺中产生释放IL-17的CD 4 + T细胞，即使循环CD 4 + T细胞减少。此外，用DnaK鼻内接种在肺中产生组织驻留的CD 4 + T细胞。在小鼠中，单独用DnaK接种疫苗产生与BCG接种疫苗相当的针对结核病的保护性免疫。我们的研究结果表明，鼻内接种DnaK可以在免疫功能低下或免疫功能正常的小鼠中产生粘膜免疫，DnaK疫苗接种可以产生类似于BCG的抗Mtb保护，强调其作为人类Mtb疫苗候选物的潜在效用。
Mycobacterium tuberculosis (Mtb) remains a global health challenge due to the limited efficacy of the Mtb vaccine in current use, Bacillus Calmette–Guérin (BCG). To date, there is no available vaccine for immunocompromised individuals. Thus, there is an urgent need to develop a new vaccine candidate which can induce mucosal immunity in hosts with different immune statuses. DnaK (HSP70) has been shown to induce protective immunity against Mtb infection when administered by DNA vaccine; however, the protection is inferior to that induced by the BCG vaccine. In our study, we vaccinated C57BL/6J mice with DnaK protein alone. Subcutaneous or intranasal vaccination with DnaK generated IFNγ-secreting CD4+ T cells in the spleen, but only intranasal vaccination generated IL-17-releasing CD4+ T cells in the lungs, even when circulating CD4+ T cells were diminished. Furthermore, intranasal vaccination with DnaK generated tissue resident CD4+ T cells in the lungs. Vaccination with DnaK alone resulted in protective immunity comparable to BCG vaccination against tuberculosis in mice. Our results demonstrate that intranasal vaccination with DnaK can generate mucosal immunity in immunocompromised or immunocompetent mice and DnaK vaccination can generate protection against Mtb similar to BCG, underscoring its potential utility as an Mtb vaccine candidate in humans.
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影响因子：
168.9
作者：
Black, GF;Weir, RE;Dockrell, HM
通讯作者：
Dockrell, HM
影响因子：
6.7
作者：
Chatterjee S;Dwivedi VP;Singh Y;Siddiqui I;Sharma P;Van Kaer L;Chattopadhyay D;Das G
通讯作者：
Das G
影响因子：
--
作者：
Aguilo, Nacho;Toledo, Ana Maria;Martin, Carlos
通讯作者：
Martin, Carlos
影响因子：
5.5
作者：
Elias, Daniel;Britton, Sven;Akuffo, Hannah
通讯作者：
Akuffo, Hannah
影响因子：
4
作者：
Britton, WJ;Palendira, U
通讯作者：
Palendira, U