Live attenuated Salmonella displaying HIV-1 10E8 epitope on fimbriae: systemic and mucosal immune responses in BALB/c mice by mucosal administration.
Live attenuated Salmonella displaying HIV-1 10E8 epitope on fimbriae: systemic and mucosal immune responses in BALB/c mice by mucosal administration.
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菌毛上展示 HIV-1 10E8 表位的活减毒沙门氏菌：通过粘膜给药对 BALB/c 小鼠产生全身和粘膜免疫反应
DOI：
10.1038/srep29556
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发表时间：
2016-07-14
影响因子：
4.6
通讯作者：
Liu SL
中科院分区：
文献类型：
--
作者：
Li QH;Jin G;Wang JY;Li HN;Liu H;Chang XY;Wang FX;Liu SL
HIV-1膜近端外部区（MPER）被几种广泛中和抗体（BNAb）靶向，被认为是疫苗开发的潜在免疫原。然而，到目前为止，这些BNAb表位的免疫原性还不够充分。在目前的工作中，我们使用减毒活沙门氏菌作为平台，在菌毛中呈现HIV-1 MPER 10 E8表位。将10 E8表位插入菌毛对细菌菌毛的表达和吸收能力没有显著影响，也不影响减毒沙门氏菌的毒力和侵袭力。在将疫苗构建体口服给药于小鼠后，随后进行10 E8表位肽加强，诱导血清和粘膜中的特异性抗体应答以及脾中的记忆淋巴细胞和骨髓中的浆细胞。我们还发现，减毒活沙门氏菌载体将免疫导向Th 1偏好，诱导Th 1和Th 2细胞因子应答，并刺激显著的B细胞分化为GC B、记忆B和浆细胞。因此，构建组成型表达HIV-1BNAb表位的减毒沙门氏菌，将是改善免疫微环境、提高HIV-1表位疫苗免疫原性的有效途径。
The HIV-1 membrane proximal external region (MPER) that is targeted by several broadly neutralizing antibodies (BNAbs) has been considered a potential immunogen for vaccine development. However, to date the immunogenicity of these BNAb epitopes has not been made sufficiently adequate. In the present work, we used live attenuated Salmonella as a platform to present the HIV-1 MPER 10E8 epitope in the fimbriae. The insertion of the 10E8 epitope into the fimbriae had no significant influence on the expression and the absorption capacity of bacterial fimbriae, nor on the virulence and invasiveness of the attenuated Salmonella. After oral administration of the vaccine construct to mice followed by 10E8 epitope peptide boost, specific antibody responses in serum and mucosa as well as memory lymphocytes in spleen and plasma cells in bone marrow were induced. We also found that the live attenuated Salmonella vector directed the immunity toward Th1 bias, induced Th1 and Th2 cytokine responses and stimulated significant B cell differentiation into GC B, memory B and plasma cells. Therefore, we propose that the live attenuated Salmonella constitutively expressing HIV-1 BNAb epitopes on the fimbriae will be an effective approach to improving immune microenvironment and enhancing the immunogenicity of HIV-1 epitope vaccines.