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首页> 外文期刊>Vaccine >SIV antigen-specific effects on immune responses induced by vaccination with DNA electroporation and plasmid IL-12.
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SIV antigen-specific effects on immune responses induced by vaccination with DNA electroporation and plasmid IL-12.

机译：SIV抗原对DNA电穿孔和质粒IL-12疫苗接种诱导的免疫反应的特异性影响。

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Molecular adjuvants are important for augmenting or modulating immune responses induced by DNA vaccination. Promising results have been obtained using IL-12 expression plasmids in a variety of disease models including the SIV model of HIV infection. We used a mouse model to evaluate plasmid IL-12 (pIL-12) in a DNA prime, recombinant adenovirus serotype 5 (rAd5) boost regimen specifically to evaluate the effect of IL-12 expression on cellular and humoral immunity induced against both SIVmac239 Gag and Env antigens. Priming with electroporated (EP) DNA+pIL-12 resulted in a 2-4-fold enhanced frequency of Gag-specific CD4 T cells which was maintained through the end of the study irrespective of the pIL-12 dose, while memory Env-specific CD4+ T cells were maintained only at the low dose of pIL-12. There was little positive effect of pIL-12 on the humoral response to Env, and in fact, high dose pIL-12 dramatically reduced SIV Env-specific IgG. Additionally, both doses of pIL-12 diminished the frequency of CD8 T-cells after DNA prime, although a rAd5 boost recovered CD8 responses regardless of the pIL-12 dose. In this prime-boost regimen, we have shown that a high dose pIL-12 can systemically reduce Env-specific humoral responses and CD4T cell frequency, but not Gag-specific CD4+ T cells. These data indicate that it is important to independently characterize individual SIV or HIV antigen immunogenicity in multi-antigenic vaccines as a function of adjuvant dose.Digital Object Identifier http://dx.doi.org/10.1016/j.vaccine.2013.08.011
机译：分子佐剂对于增强或调节DNA疫苗诱导的免疫反应非常重要。使用IL-12表达质粒已在包括HIV感染的SIV模型在内的多种疾病模型中获得了令人鼓舞的结果。我们使用小鼠模型来评估DNA初免重组腺病毒血清型5（rAd5）增强方案中的质粒IL-12（pIL-12），以评估IL-12表达对针对SIVmac239 Gag诱导的细胞和体液免疫的影响和Env抗原。用电穿孔（EP）DNA + pIL-12引发导致Gag特异性CD4 T细胞的频率提高了2到4倍，无论pIL-12剂量如何，该频率在研究结束之前一直保持，而记忆Env特异性CD4 + T细胞仅维持在低剂量的pIL-12下。 pIL-12对Env的体液反应几乎没有积极作用，实际上，高剂量的pIL-12大大降低了SIV Env特异性IgG。另外，两种剂量的pIL-12都减少了DNA引发后CD8 T细胞的频率，尽管无论pIL-12剂量如何，rAd5增强都能恢复CD8反应。在这种初免-加强方案中，我们已经表明，高剂量的pIL-12可以系统地降低Env特异性的体液反应和CD4T细胞的频率，但不能降低Gag特异性的CD4 + T细胞。这些数据表明，根据佐剂剂量独立表征多抗原疫苗中的个体SIV或HIV抗原免疫原性很重要。数字对象标识符http://dx.doi.org/10.1016/j.vaccine.2013.08.011

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