Adjuvant Activity of the Catalytic A1 Domain of Cholera Toxin for Retroviral Antigens Delivered by GeneGun
Adjuvant Activity of the Catalytic A1 Domain of Cholera Toxin for Retroviral Antigens Delivered by GeneGun
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DOI：
10.1128/cvi.05019-11
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发表时间：
2011-06-01
影响因子：
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通讯作者：
Fouts, Timothy R.
中科院分区：
文献类型：
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作者：
Bagley, Kenneth C.;Lewis, George K.;Fouts, Timothy R.
大多数DNA编码佐剂在小动物中增强对DNA疫苗的免疫反应，但在灵长类动物中效果较差。在这里，我们在小鼠和猕猴中表征了霍乱毒素（CTA1）的催化A1结构域对人类免疫缺陷病毒（HIV）和猴免疫缺陷病毒（SIV）抗原的佐剂活性。CTA1与SIVmac239 Gag的结合显著增强了小鼠的抗Gag抗体反应。CTA1对分泌抗原HIV gp120的佐剂作用远不如Gag的佐剂作用明显，因为在没有佐剂的情况下，对gp120的反应很高。CTA1对Gag的佐剂作用比粒细胞-巨噬细胞集落刺激因子（GM-CSF）更强，在小鼠中的剂量范围也比GM-CSF更大。在猕猴中，CTA1适度增强了对SIV Gag的抗体反应，但有效地引发了重组Gag蛋白的增强。本研究结果表明，CTA1在小鼠中是一种有效的SIV Gag佐剂，并且CTA1在猕猴中提供了一种有效的GeneGun介导的DNA引物，用于异种蛋白的增强。
Most DNA-encoded adjuvants enhance immune responses to DNA vaccines in small animals but are less effective in primates. Here, we characterize the adjuvant activity of the catalytic A1 domain of cholera toxin (CTA1) for human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) antigens in mice and macaques delivered by GeneGun. The inclusion of CTA1 with SIVmac239 Gag dramatically enhanced anti-Gag antibody responses in mice. The adjuvant effects of CTA1 for the secreted antigen HIV gp120 were much less pronounced than those for Gag, as the responses to gp120 were high in the absence of an adjuvant. CTA1 was a stronger adjuvant for Gag than was granulocyte-macrophage colony-stimulating factor (GM-CSF), and it also displayed a wider dose range than GM-CSF in mice. In macaques, CTA1 modestly enhanced the antibody responses to SIV Gag but potently primed for a recombinant Gag protein boost. The results of this study show that CTA1 is a potent adjuvant for SIV Gag when delivered by GeneGun in mice and that CTA1 provides a potent GeneGun-mediated DNA prime for a heterologous protein boost in macaques.