Adjuvanting a DNA vaccine with a TLR9 ligand plus Flt3 ligand results in enhanced cellular immunity against the simian immunodeficiency virus.
Adjuvanting a DNA vaccine with a TLR9 ligand plus Flt3 ligand results in enhanced cellular immunity against the simian immunodeficiency virus.
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DOI：
10.1084/jem.20071211
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发表时间：
2007-10-29
期刊：
影响因子：
--
通讯作者：
Pulendran B
中科院分区：
文献类型：
--
作者：
Kwissa M;Amara RR;Robinson HL;Moss B;Alkan S;Jabbar A;Villinger F;Pulendran B
DNA疫苗为预防感染提供了有希望的免疫策略。然而，它们的临床应用需要提高免疫原性。我们研究了toll样受体（TLR）配体（TLR- ls）对DNA引物修饰的安卡拉牛痘病毒（MVA）增强疫苗抗SIV免疫原性的增强作用。在恒河猴体内注射fms样酪氨酸激酶3 （Flt3）配体（FL）扩增树突状细胞（DCs），并引物编码免疫缺陷病毒抗原的DNA疫苗与TLR9或TLR7/8配体混合。随后，用DNA和两次表达相同抗原的重组MVA增强动物。TLR9-L （CpG DNA）在体内介导dc的活化，并增强抗原特异性CD8+干扰素(IFN) γ+ T细胞和产生IFN-γ、肿瘤坏死因子α和白细胞介素2的多功能CD8+ T细胞的数量。虽然该试验主要设计为免疫原性研究，但我们用致病性SIVmac251刺激动物，观察到与未接种组相比，TLR9-L加fl佐剂组的峰值病毒血症和累积病毒载量有所降低；然而，研究设计排除了佐剂组和单独接种DNA/MVA组之间的比较。病毒载量与免疫反应的大小和质量呈负相关。因此，TLR9-L加FL可增强DNA疫苗的免疫原性。
DNA vaccines offer promising strategies for immunization against infections. However, their clinical use requires improvements in immunogenicity. We explored the efficacy of Toll-like receptor (TLR) ligands (TLR-Ls) on augmenting the immunogenicity of a DNA prime–modified vaccinia virus Ankara (MVA) boost vaccine against SIV. Rhesus macaques were injected with Fms-like tyrosine kinase 3 (Flt3)–ligand (FL) to expand dendritic cells (DCs) and were primed with a DNA vaccine encoding immunodeficiency virus antigens mixed with ligands for TLR9 or TLR7/8. Subsequently, the animals were boosted with DNA and twice with recombinant MVA expressing the same antigens. TLR9-L (CpG DNA) mediated activation of DCs in vivo and enhanced the magnitude of antigen-specific CD8+ interferon (IFN) γ+ T cells and polyfunctional CD8+ T cells producing IFN-γ, tumor necrosis factor α, and interleukin 2. Although this trial was designed primarily as an immunogenicity study, we challenged the animals with pathogenic SIVmac251 and observed a reduction in peak viremia and cumulative viral loads in the TLR9-L plus FL-adjuvanted group relative to the unvaccinated group; however, the study design precluded comparisons between the adjuvanted groups and the group vaccinated with DNA/MVA alone. Viral loads were inversely correlated with the magnitude and quality of the immune response. Thus, the immunogenicity of DNA vaccines can be augmented with TLR9-L plus FL.
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DOI：
10.1179/096805106x118753
发表时间：
2006-10-01
期刊：
JOURNAL OF ENDOTOXIN RESEARCH
影响因子：
--
作者：
Alderson, Mark R.;McGowan, Patrick;Probst, Peter
通讯作者：
Probst, Peter
FLT3配体处理的小鼠功能成熟的树突状细胞数量的急剧增加：确定的多个树突状细胞亚群。
影响因子：
15.3
作者：
Maraskovsky, E;Brasel, K;Teepe, M;Roux, ER;Lyman, SD;Shortman, K;McKenna, HJ
通讯作者：
McKenna, HJ
影响因子：
5.4
作者：
Loffredo, John T.;Maxwell, Jess;Watkins, David I.
通讯作者：
Watkins, David I.
影响因子：
9.1
作者：
Cooper, CL;Davis, HL;Heathcote, J
通讯作者：
Heathcote, J
影响因子：
20.3
作者：
Betts, Michael R.;Nason, Martha C.;Koup, Richard A.
通讯作者：
Koup, Richard A.