Salmonella typhi Ty21a bacterial ghost vector augments HIV-1 gp140 DNA vaccine-induced peripheral and mucosal antibody responses via TLR4 pathway.
Salmonella typhi Ty21a bacterial ghost vector augments HIV-1 gp140 DNA vaccine-induced peripheral and mucosal antibody responses via TLR4 pathway.
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DOI：
10.1016/j.vaccine.2012.07.008
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发表时间：
2012-08
期刊：
影响因子：
5.5
通讯作者：
Jing Wen;Yi Yang;Guangyu Zhao;Shuang Tong;Hong B. Yu;Xia Jin;L. Du;Shibo Jiang;Z. Kou;Yusen Zhou
中科院分区：
文献类型：
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作者：
Jing Wen;Yi Yang;Guangyu Zhao;Shuang Tong;Hong B. Yu;Xia Jin;L. Du;Shibo Jiang;Z. Kou;Yusen Zhou
由于其稳定性和易于操作，DNA疫苗具有相当大的潜力，引发免疫反应。然而，它们受到其弱免疫原性的限制，特别是在人类中。为了应对这一挑战，我们探索了一种新的策略，艾滋病毒疫苗交付使用伤寒沙门氏菌Ty 21 a细菌鬼（BG）。我们发现，Ty 21 a BGs负载HIV gp 140 DNA疫苗（Ty 21 a BG-DNA）很容易被小鼠巨噬细胞RAW 264.7细胞吸收，并且gp 140在这些细胞中有效表达。BGs-DNA疫苗免疫小鼠的外周和肠粘膜抗gp 120抗体应答显著高于裸DNA疫苗免疫小鼠。抗体应答的增强与BG通过TLR 4途径诱导IL-10的产生有关。这些结果表明Ty 21 a BGs是一种新型有效的DNA疫苗载体，因此可以用作HIV疫苗开发的新策略。
Because of their stability and ease of manipulation, DNA vaccines have considerable potential for eliciting immune responses. However, they are limited by their weak immunogenicity, especially in humans. To address this challenge, we explored a new strategy of HIV vaccine delivery using Salmonella typhi Ty21a bacterial ghosts (BGs). We found that Ty21a BGs loaded with an HIV gp140 DNA vaccine (Ty21a BG-DNA) were readily taken up by murine macrophage RAW264.7 cells, and gp140 was efficiently expressed in these cells. Peripheral and intestinal mucosal anti-gp120 antibody responses in mice vaccinated with BGs-DNA vaccine were significantly higher than those in mice immunized with naked DNA vaccine. The enhancement of antibody responses was associated with BG-induced production of IL-10 through TLR4 pathway. These results demonstrate that Ty21a BGs is a novel and effective delivery vehicle for DNA vaccines, which could therefore be used as a new strategy for development of HIV vaccines.