Contribution of TLR4 and MyD88 for adjuvant monophosphoryl lipid A (MPLA) activity in a DNA prime-protein boost HIV-1 vaccine.
Contribution of TLR4 and MyD88 for adjuvant monophosphoryl lipid A (MPLA) activity in a DNA prime-protein boost HIV-1 vaccine.
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DOI：
10.1016/j.vaccine.2014.07.010
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发表时间：
2014-09-03
期刊：
影响因子：
5.5
通讯作者：
Lien E
中科院分区：
文献类型：
--
作者：
Pouliot K;Buglione-Corbett R;Marty-Roix R;Montminy-Paquette S;West K;Wang S;Lu S;Lien E
重组蛋白疫苗通常与免疫刺激化合物或佐剂一起配制，以增强对特定抗原的免疫应答。最近的研究表明，通过识别分子基序，先天免疫系统的受体参与佐剂的功能，以产生和指导适应性免疫应答。然而，尚不清楚当佐剂用作新型异源初免-加强免疫过程的一部分时，这些受体在多大程度上也是重要的，其中初免和加强组分不是相同类型的疫苗。在目前的研究中，我们比较了五价HIV-1 DNA引发蛋白加强疫苗在Toll样受体4（TLR 4）或髓样分化初级应答基因88（MyD 88）缺陷小鼠与野生型小鼠中引起的免疫应答。在加强阶段给予的HIV gp 120蛋白与单磷酰脂质A（MPLA）、QS-21或Al（OH）3一起配制。评估终点抗体滴度、血清细胞因子反应和T细胞记忆反应。TLR 4和MyD 88缺陷对给予用QS-21或Al（OH）3配制的疫苗的小鼠的免疫应答都没有显著影响。然而，TLR 4-和MyD 88-缺陷降低了施用MPLA配制的HIV gp 120的小鼠中的抗体和T细胞应答。这些结果进一步加深了我们对在DNA初免/蛋白加强免疫策略的背景下MPLA激活TLR 4和MyD 88的理解。
Recombinant protein vaccines are commonly formulated with an immune-stimulatory compound, or adjuvant, to boost immune responses to a particular antigen. Recent studies have shown that, through recognition of molecular motifs, receptors of the innate immune system are involved in the functions of adjuvants to generate and direct adaptive immune responses. However, it is not clear to which degree those receptors are also important when the adjuvant is used as part of a novel heterologous prime-boost immunization process in which the priming and boosting components are not the same type of vaccines. In the current study, we compared the immune responses elicited by a pentavalent HIV-1 DNA prime–protein boost vaccine in mice deficient in either Toll-like receptor 4 (TLR4) or myeloid differentiation primary response gene 88 (MyD88) to wildtype mice. HIV gp120 protein administered in the boost phase was formulated with either monophosphoryl lipid A (MPLA), QS-21, or Al(OH)3. Endpoint antibody titer, serum cytokine response and T-cell memory response were assessed. Neither TLR4 nor MyD88 deficiency had a significant effect on the immune response of mice given vaccine formulated with QS-21 or Al(OH)3. However, TLR4- and MyD88-deficiency decreased both the antibody and T-cell responses in mice administered HIV gp120 formulated with MPLA. These results further our understanding of the activation of TLR4 and MyD88 by MPLA in the context of a DNA prime/protein boost immunization strategy.
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影响因子：
6.7
作者：
Hajjar AM;Ernst RK;Fortuno ES 3rd;Brasfield AS;Yam CS;Newlon LA;Kollmann TR;Miller SI;Wilson CB
通讯作者：
Wilson CB
DOI：
10.4049/jimmunol.0900164
发表时间：
2009-10-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
McKee AS;Munks MW;MacLeod MK;Fleenor CJ;Van Rooijen N;Kappler JW;Marrack P
通讯作者：
Marrack P
影响因子：
3.7
作者：
Buglione-Corbett R;Pouliot K;Marty-Roix R;West K;Wang S;Lien E;Lu S
通讯作者：
Lu S
影响因子：
56.9
作者：
Mata-Haro, Veronica;Cekic, Caglar;Mitchell, Thomas C.
通讯作者：
Mitchell, Thomas C.
影响因子：
82.9
作者：
Flach, Tracy L.;Ng, Gilbert;Shi, Yan
通讯作者：
Shi, Yan