Electroporation of Synthetic DNA Antigens Offers Protection in Nonhuman Primates Challenged with Highly Pathogenic Avian Influenza Virus

Electroporation of Synthetic DNA Antigens Offers Protection in Nonhuman Primates Challenged with Highly Pathogenic Avian Influenza Virus
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DOI:
10.1128/jvi.02335-08
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发表时间:
2009-05-01
影响因子:
5.4
通讯作者:
Weiner, David B.
Weiner, David B.
中科院分区:
医学2区
文献类型:
--
作者:
Laddy, Dominick J.;Yan, Jian;Weiner, David B.

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禽流感突出表明,需要新的疫苗接种技术,以便能够快速设计和生产安全有效的疫苗。一个理想的平台应该能够诱导保护性抗体和强大的细胞免疫反应。由于在大型动物研究和人体试验中缺乏效力,DNA疫苗的这些潜在优势仍然没有实现。关于灵长类动物对流感病毒的细胞免疫反应的潜在效用,问题仍然存在。在这项研究中,通过结构优化和体内电穿孔合成的DNA编码的抗原,我们观察到诱导的交叉反应的细胞和体液免疫反应分别能够提供保护,以防止流感病毒感染恒河猴。这些研究推动了DNA疫苗领域的发展,并提供了一种对禽流感病毒具有广泛免疫原性、更具耐受性的新型疫苗。这种方法似乎对进一步的研究很重要,包括对人类的研究。
Avian influenza highlights the need for novel vaccination techniques that would allow for the rapid design and production of safe and effective vaccines. An ideal platform would be capable of inducing both protective antibodies and potent cellular immune responses. These potential advantages of DNA vaccines remain unrealized due to a lack of efficacy in large animal studies and in human trials. Questions remain regarding the potential utility of cellular immune responses against influenza virus in primates. In this study, by construct optimization and in vivo electroporation of synthetic DNA-encoded antigens, we observed the induction of cross-reactive cellular and humoral immune responses individually capable of providing protection from influenza virus infection in the rhesus macaque. These studies advance the DNA vaccine field and provide a novel, more tolerable vaccine with broad immunogenicity to avian influenza virus. This approach appears important for further investigation, including studies with humans.