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曼氏血吸虫可溶性虫卵抗原增强单核细胞增生李斯特菌载体HIV-1疫苗诱导的细胞毒性T细胞。

Schistosoma mansoni soluble egg antigens enhance Listeria monocytogenes vector HIV-1 vaccine induction of cytotoxic T cells.

作者信息

Bui Cac T, Shollenberger Lisa M, Paterson Yvonne, Harn Donald A

机构信息

Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, Georgia, USA.

Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

出版信息

Clin Vaccine Immunol. 2014 Sep;21(9):1232-9. doi: 10.1128/CVI.00138-14. Epub 2014 Jul 2.

Abstract

Vaccines are an important public health measure for prevention and treatment of diseases. In addition to the vaccine immunogen, many vaccines incorporate adjuvants to stimulate the recipient's immune system and enhance vaccine-specific responses. While vaccine development has advanced from attenuated organism to recombinant protein or use of plasmid DNA, the development of new adjuvants that safely increase immune responses has not kept pace. Previous studies have shown that the complex mixture of molecules that comprise saline soluble egg antigens (SEA) from Schistosoma mansoni eggs functions to promote CD4(+) T helper 2 (Th2) responses. Therefore, we hypothesized that coadministration of SEA with a Listeria vector HIV-1 Gag (Lm-Gag) vaccine would suppress host cytotoxic T lymphocyte (CTL) and T helper 1 (Th1) responses to HIV-1 Gag epitopes. Surprisingly, instead of driving HIV-1 Gag-specific responses toward Th2 type, we found that coadministration of SEA with Lm-Gag vaccine significantly increased the frequency of gamma interferon (IFN-γ)-producing Gag-specific Th1 and CTL responses over that seen in mice administered Lm-Gag only. Analysis of the functionality and durability of vaccine responses suggested that SEA not only enlarged different memory T cell compartments but induced functional and long-lasting vaccine-specific responses as well. These results suggest there are components in SEA that can synergize with potent inducers of strong and durable Th1-type responses such as those to Listeria. We hypothesize that SEA contains moieties that, if defined, can be used to expand type 1 proinflammatory responses for use in vaccines.

摘要

疫苗是疾病预防和治疗的一项重要公共卫生措施。除疫苗免疫原外,许多疫苗还加入佐剂以刺激接受者的免疫系统并增强疫苗特异性反应。尽管疫苗开发已从减毒生物体发展到重组蛋白或使用质粒DNA,但安全增强免疫反应的新型佐剂的开发却未能跟上步伐。先前的研究表明,构成曼氏血吸虫卵盐水可溶性卵抗原(SEA)的复杂分子混合物具有促进CD4(+)辅助性T细胞2(Th2)反应的作用。因此,我们推测将SEA与李斯特菌载体HIV-1 Gag(Lm-Gag)疫苗共同给药会抑制宿主对HIV-1 Gag表位的细胞毒性T淋巴细胞(CTL)和辅助性T细胞1(Th1)反应。令人惊讶的是,我们发现SEA与Lm-Gag疫苗共同给药并未使HIV-1 Gag特异性反应趋向Th2型,反而与仅接种Lm-Gag的小鼠相比,显著增加了产生γ干扰素(IFN-γ)的Gag特异性Th1和CTL反应的频率。对疫苗反应的功能性和持久性分析表明,SEA不仅扩大了不同的记忆性T细胞区室,还诱导了功能性和持久性的疫苗特异性反应。这些结果表明,SEA中存在一些成分,它们可以与强大而持久的Th1型反应的有效诱导剂(如针对李斯特菌的诱导剂)协同作用。我们推测SEA含有一些部分,如果能够确定,可用于扩大1型促炎反应以用于疫苗。

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