Evaluation of TLR agonists as potential mucosal adjuvants for HIV gp140 and tetanus toxoid in mice.
Evaluation of TLR agonists as potential mucosal adjuvants for HIV gp140 and tetanus toxoid in mice.
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DOI：
10.1371/journal.pone.0050529
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Shattock RJ
中科院分区：
文献类型：
--
作者：
Buffa V;Klein K;Fischetti L;Shattock RJ
在本研究中，我们研究了一系列TLR配体和壳聚糖作为潜在佐剂对小鼠模型中不同的粘膜免疫途径(舌下免疫(SL)、鼻内免疫(IN)、阴道内免疫(IVAG)和肠外免疫(SC))的影响。我们评估了它们在全身和阴道隔间增强对HIV-1CN54gp140(Gp140)和破伤风类毒素(TT)抗体反应的能力。通过给药途径观察到了一些趋势。对于非佐剂抗原，SC>；SL>；在免疫系统的免疫反应中，TT的终点滴度大于gp140。一般来说，与佐剂联合给药会增加 = SC&>SL中的特异性免疫球蛋白应答，而在阴道室中则会增加特异性免疫球蛋白A。相反，在 = SC中，对于单独对SL和GT；抗原的系统和粘膜免疫球蛋白A反应。在一般的IN&gT；SL>；SC免疫中，一些佐剂增加了特异性的全身免疫球蛋白A反应，而在 = SL&>SC中，则增强了粘膜反应。相反，即使在佐剂存在的情况下，直接阴道内免疫也未能诱导对gp140的任何可检测到的全身或粘膜反应。然而，无论有没有佐剂，阴道内免疫都能诱导出对TT的显著的全身免疫球蛋白G反应，当用FSL-1或Poly I：C注射TT时，观察到可检测到的粘膜反应。有趣的是，一些TLRs显示出不同的给药途径。Mpla(TLR4)抑制对SL免疫的全身反应，而增强对IN或SC免疫的反应。CpG B增强了SL和IN的反应，而对SC免疫几乎没有影响。这些数据显示了在设计粘膜疫苗策略时需要考虑的重要途径、抗原和佐剂效应。
In the present study we investigate the impact of a range of TLR ligands and chitosan as potential adjuvants for different routes of mucosal immunisation (sublingual (SL), intranasal (IN), intravaginal (IVag) and a parenteral route (subcutaneous (SC)) in the murine model. We assess their ability to enhance antibody responses to HIV-1 CN54gp140 (gp140) and Tetanus toxoid (TT) in systemic and vaginal compartments. A number of trends were observed by route of administration. For non-adjuvanted antigen, SC>SL>IN immunisation with respect to systemic IgG responses, where endpoint titres were greater for TT than for gp140. In general, co-administration with adjuvants increased specific IgG responses where IN = SC>SL, while in the vaginal compartment IN>SL>SC for specific IgA. In contrast, for systemic and mucosal IgA responses to antigen alone SL>IN = SC. A number of adjuvants increased specific systemic IgA responses where in general IN>SL>SC immunisation, while for mucosal responses IN = SL>SC. In contrast, direct intravaginal immunisation failed to induce any detectable systemic or mucosal responses to gp140 even in the presence of adjuvant. However, significant systemic IgG responses to TT were induced by intravaginal immunisation with or without adjuvant, and detectable mucosal responses IgG and IgA were observed when TT was administered with FSL-1 or Poly I∶C. Interestingly some TLRs displayed differential activity dependent upon the route of administration. MPLA (TLR4) suppressed systemic responses to SL immunisation while enhancing responses to IN or SC immunisation. CpG B enhanced SL and IN responses, while having little or no impact on SC immunisation. These data demonstrate important route, antigen and adjuvant effects that need to be considered in the design of mucosal vaccine strategies.
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影响因子：
4.4
作者：
Black, CA;Rohan, LC;Edwards, RP
通讯作者：
Edwards, RP
影响因子：
3.1
作者：
Lee, SE;Kim, SY;Rhee, JH
通讯作者：
Rhee, JH
影响因子：
5.5
作者：
Hervouet, Catherine;Luci, Carmelo;Anjuere, Fabienne
通讯作者：
Anjuere, Fabienne
DOI：
10.4049/jimmunol.0803740
发表时间：
2009-12-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Cuburu N;Kweon MN;Hervouet C;Cha HR;Pang YY;Holmgren J;Stadler K;Schiller JT;Anjuère F;Czerkinsky C
通讯作者：
Czerkinsky C
影响因子：
3.7
作者：
Huo Z;Bissett SL;Giemza R;Beddows S;Oeser C;Lewis DJ
通讯作者：
Lewis DJ