您的位置:澳门金莎娱乐网址 > 生命科学 > 1新型制剂新进展,新技术增强癌症疫苗的效果

1新型制剂新进展,新技术增强癌症疫苗的效果

发布时间:2019-08-22 03:48编辑:生命科学浏览(89)

    这一结果表明,为了防止HIV-1病毒的传播,需要加强直肠和阴道中中和抗体的量。

    1 The Unit of Anti-Viral Immunity and Genetic Therapy, the Key Laboratory of Molecular Virology and Immunology, the Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200025, China

    NIAID所长Anthony Fauci对比表示同意。Fauci说,“从这项研究中我们获得的认识就是理解奶牛的免疫系统能够制造这些抗体的机制。


    用HIV-1病毒包膜三聚体免疫猴子,它们血液中的抗体能够中和一类HIV-1病毒的变种,而用HIV-1包膜单聚体免疫的人类产生的抗体只能中和较少的HIV-1病毒变种。

    In this study, we constructed single chain Fvs derived from seven human monoclonal antibodies and genetically linked them with or without a glycosyl-phosphatidylinositol attachment signal. We show that with a GPI attachment signal the scFvs are targeted to lipid rafts of plasma membranes. In addition, we demonstrate that four of the GPI-anchored scFvs, but not their secreted counterparts, neutralize HIV-1 with various degrees of breadth and potency. Among them, GPI-anchored scFv exhibits extremely potent and broad neutralization activity against multiple clades of HIV-1 strains tested. Moreover, we show that GPI-anchored scFv also exhibited more potent neutralization activity than its secretory counterpart. Finally, we demonstrate that expression of GPI-anchored scFv in the lipid raft of plasma membrane of human CD4 T cells confers long-term resistance to HIV-1 infection, HIV-1 envelope-mediated cell-cell fusion, and the infection of HIV-1 captured and transferred by human DCs.

    在过去几年里,一些人已发现HIV广谱中和抗体往往是比较大的难以控制的蛋白。除了这一发现之外,其他的科学家们碰巧发现奶牛的抗体往往是类似的较大的和难以控制的。论文第一作者、国际艾滋病疫苗计划(International AIDS Vaccine Initiative)抗体发现与开发主任Devin Sok说,“这是通力合作的结果。我们当中有兽医、奶牛抗体科学家和HIV科学家,大家一起讨论和想法解决这个相对简单的问题。”

    The above story is reprinted from materials provided by Journal of Clinical Investigation, via EurekAlert!, a service of AAAS.

    不过,这些免疫了的猴子在接下来的攻毒实验中只表现出了较弱的保护力。这可能是因为直肠和阴道中的中和抗体滴度比血液中至少低1000倍。

    本研究得到了国家自然科学基金委、国家科技部973项目、国家重大科技专项、上海巴斯德健康研究基金会项目以及阿海珐国际合作项目的资助。

    足够确信的是,利用一种在抗原性上模拟HIV包膜糖蛋白的蛋白免疫原对四只奶牛进行免疫,Sok和他的同事们能够在奶牛中引发他们一直在寻找的HIV广谱中和抗体产生。在免疫头两个月后,他们从这些奶牛体内抽取血液样品,分离出这些血液样品中的抗体,并且在体外证实这些抗体有效地阻断多种HIV毒株感染细胞。

    关键词:抗癌疫苗 免疫反应 中和和抑制反应

    Non-Human Primate Study Generates Information Relevant to HIV-1 Vaccine Strategies

    ScienceDaily — Monkeys repeatedly immunized with a particular form the HIV-1 envelope glycoprotein generated antibodies capable of neutralizing diverse strains of HIV-1, according to a paper published online in the Journal of Experimental Medicine on August 2.

    Antibodies in the blood of monkeys immunized with a HIV-1 envelope trimer neutralized a broader variety of HIV-1 strains than antibodies in the blood of humans immunized with an HIV-1 envelope monomer during the VAX04 phase III clinical trial.

    However, the immunized monkeys showed only weak protection against subsequent rectal infection with a simian HIV virus. This weak protection may be due to the fact that neutralizing antibody titers were at least 1,000-fold lower in rectal and vaginal tissues than in the blood.

    These findings suggest that methods to boost neutralizing antibody abundance in rectal and vaginal tissues might be needed to better prevent HIV-1 transmission.

    Email or share this story:| More


    Story Source:

    The above story is reprinted from materials provided by Rockefeller University Press, via EurekAlert!, a service of AAAS.


    Journal Reference:

    1. Christopher Sundling, Mattias N.E. Forsell, Sijy O'Dell, Yu Feng, Bimal Chakrabarti, Srinivas S. Rao, Karin Loré, John R. Mascola, Richard T. Wyatt, Iyadh Douagi, and Gunilla B. Karlsson Hedestam. Soluble HIV-1 Env trimers in adjuvant elicit potent and diverse functional B cell responses in primates. Journal of Experimental Medicine, 2010; DOI: 10.1084/jem.20100025

    关键词:艾滋病疫苗 艾滋病免疫 艾滋病治疗

    2 Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, 77030, USA

    通过采用细胞工程技术,这些奶牛制造的抗体可能有朝一日被用来短期预防或者治疗HIV感染者。美国国家过敏症与传染病研究所疫苗研究主任John Mascola说,理想的情形是制造一种在人体中引发HIV广谱中和抗体产生的疫苗,这一任务迄今为止还没有实现。他说,“这项研究并没有告诉我们如何制造一种在人体中使用的HIV疫苗,但是它确实告诉我们这种病毒如何逃避人体免疫反应。”

    但现在,杜克大学医学中心的Michael Morse领导的研究小组,则通过用甲病毒封装病毒样复制颗粒解决了中和和抑制反应。反复对病人使用这些携带癌胚抗原的颗粒会引起对CEA的确切的免疫反应。而这种反应的存在与病人存活有关,研究者希望这项成果能用于多种癌症的治疗。Boosting the Efficacy of Anticancer Vaccines

    核心提示: 研究人员发现,多次注射HIV-1病毒包膜糖蛋白的猴子,可产生能够中和HIV-1病毒变种的抗体,这一结果发表在了8月2日的Experim

    如何设计免疫原使其诱导出针对HIV-1包膜蛋白的广谱中和抗体反应是当今HIV-1疫苗开发的难点。诱导出这些广谱中和抗体的包膜蛋白表位包括构象依赖的和构象非依赖两种方式。迄今为止发现的约10个广谱中和抗体识别的表位均是构象非依赖的。然而,HIV-1感染靶细胞时,包膜蛋白与靶细胞上的受体和辅助性受体作用后会发生一系列构象改变,从而暴露出构象诱导的瞬时性广谱中和表位。但这些构象诱导的瞬时暴露的广谱中和表位往往很难用常规方法发现和界定。

    图片 1

    Repeated administration of such particles carrying the tumor protein CEA to patients with metastatic cancer expressing CEA induced clinically relevant immune responses targeted to CEA. As the presence of such immune responses was associated with longer overall patient survival, the authors hope their approach might be of therapeutic use in many cancer settings.

    研究人员发现,多次注射HIV-1病毒包膜糖蛋白的猴子,可产生能够中和HIV-1病毒变种的抗体,这一结果发表在了8月2日的Experimental Medicine杂志上。

    Conclusions

    Sok说,“我感到震惊。这真的是疯狂的和非常激动人心的。引发抗体产生的反应非常快速,仅需一到两个月的时间,这远远地超出了我们的预期。”

    Journal Reference:

    Michael Wen1 , Reetakshi Arora2 , Huiqiang Wang1 , Lihong Liu1 , Jason T Kimata2 and Paul Zhou1

    科学家们长期以来就在寻求一种会引起HIV广谱中和抗体(broadly neutralizing antibodies, bNAb)产生的HIV疫苗,这被认为是阻止众多HIV病毒毒株感染的关键。但是这被证实是一项困难的任务;仅大约20%的HIV感染者产生这些抗体。根据一项新的研究,奶牛可能胜任这项任务。相关研究结果于2017年7月20日在线发表在Nature期刊上,论文标题为“Rapid elicitation of broadly neutralizing antibodies to HIV by immunization in cows”。

    Email or share this story:| More

    关键字:HIV-1 包膜蛋白 细胞 研究 上海巴斯德

    想要研制能够激发病人的抗癌免疫反应的治疗性疫苗,需要克服几个挑战。比如,作为肿瘤蛋白载体的病毒本身可能成为病人免疫系统的目标,并引起中和和抑制反应。

    Identification of broad neutralization epitopes in HIV-1 envelope spikes is paramount for HIV-1 vaccine development. A few broad neutralization epitopes identified so far are present on the surface of native HIV-1 envelope spikes whose recognition by antibodies does not depend on conformational changes of the envelope spikes. However, HIV-1 envelope spikes also contain transiently-exposed neutralization epitopes, which are more difficult to identify.

    核心提示: 想要研制能够激发病人的抗癌免疫反应的治疗性疫苗,需要克服几个挑战。比如,作为肿瘤蛋白载体的病毒本身可能成为病人免疫

    在本研究中,研究人员用糖基磷脂酰肌醇锚将构象依赖的单链抗体锚定在HIV-1易感细胞表面介导病毒进入或者释放的脂筏区。研究发现其中4个单链抗体可不同程度地中和HIV-1,并发现一个识别CD4诱导的极为保守表位的GPI锚定的单链抗体X5,能完全抑制本研究中所用的多亚型HIV-1假病毒株以及5个野生型病毒株的感染。此外,该研究还发现细胞表面表达有GPI锚定的单链抗体X5的人T细胞能够长期完全性抑制HIV-1的复制、完全阻止gp120介导的细胞-细胞间融合以及抑制人树突状细胞通过DC-SIGN捕获的HIV-1的感染。更为重要的是,X5的表位对于保持HIV-1生物学活性具有重要作用,也证明了X5表位是抗HIV-1的潜在重要靶点。因此,GPI锚定的单链抗体有可能开发为一种通用且有效的方法来发现并界定HIV-1和其它包膜病毒中构象诱导的瞬时暴露的中和抗体及中和表位。GPI锚定的单链抗体X5,因其抗HIV-1的广谱性、强有力的中和活性及其中和表位不易逃逸的保守性,极有潜力被开发成为抗HIV-1的新型制剂,从而对艾滋病的预防及治疗起到关键作用。

    1. Michael A. Morse, Amy C. Hobeika, Takuya Osada, Peter Berglund, Bolyn Hubby, Sarah Negri, Donna Niedzwiecki, Gayathri R. Devi, Bruce K. Burnett, Timothy M. Clay, Jonathan Smith and H. Kim Lyerly. An alphavirus vector overcomes the presence of neutralizing antibodies and elevated numbers of Tregs to induce immune responses in humans with advanced cancer. Journal of Clinical Investigation, 2010; DOI: 10.1172/JCI42672

    Thus GPI-anchored scFv could be used as a general and effective way to identify antibodies that react with transiently-exposed neutralization epitopes in envelope proteins of HIV-1 and other enveloped viruses. The GPI-anchored scFv , because of its breadth and potency, should have a great potential to be developed into anti-viral agent for HIV-1 prevention and therapy.

    Story Source:

    GPI-anchored single chain Fv - an effective way to capture transiently-exposed neutralization epitopes on HIV-1 envelope spike

    ScienceDaily — There are several challenges to be overcome if therapeutic anticancer vaccines, which are designed to boost the patient's anticancer immune response, are to be successfully developed. For example, the viruses used to deliver the tumor protein to the patient's immune system are themselves targeted by the patient's immune system, inducing neutralizing and suppressive responses.

    Results


    Background

    The research appears in the Journal of Clinical Investigation.

    Retrovirology doi:10.1186/1742-4690-7-79

    But now, a team of researchers, led by Michael Morse, at Duke University Medical Center, Durham, has developed a way to overcome these neutralizing and suppressive responses by using an alphavirus packaged in virus-like replicon particles.

    核心提示:10月,国际学术杂志Retrovirology正式发表了上海巴斯德所研究人员关于有效捕获HIV-1包膜蛋白上瞬间暴露中和表位的研究成果。这项研究由周保罗研究员领导的“抗病毒免疫与遗传治疗”研究组与美国贝勒医学院合作完成。

    10月,国际学术杂志Retrovirology正式发表了上海巴斯德所研究人员关于有效捕获HIV-1包膜蛋白上瞬间暴露中和表位的研究成果。这项研究由周保罗研究员领导的“抗病毒免疫与遗传治疗”研究组与美国贝勒医学院合作完成。

    英文摘要:

    本文由澳门金莎娱乐网址发布于生命科学,转载请注明出处:1新型制剂新进展,新技术增强癌症疫苗的效果

    关键词: