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Nature:美学者利用牛研发对抗HIV中和抗体

摘要 : 2017年7月19日,国际学术权威刊物自然出版集团旗下《Nature》杂志在线发表了美国斯克利普斯研究所Vaughn V. Smider研究员和Dennis R. Burton研究员的一篇研究论文,研究通过往牛注释HIV疫苗获得抗体,并尝试弄清楚相关机制,论文指出牛在免疫接种后可快速产生对抗艾滋病病毒(HIV)的广泛中和抗体。

2017年7月19日,国际学术权威刊物自然出版集团旗下《Nature》杂志在线发表了美国斯克利普斯研究所Vaughn V. Smider研究员和Dennis R. Burton研究员的一篇研究论文,研究通过往牛注释HIV疫苗获得抗体,并尝试弄清楚相关机制,论文指出牛在免疫接种后可快速产生对抗艾滋病病毒(HIV)的广泛中和抗体。新发现不仅有助于HIV疫苗的设计,也为开发新的艾滋病防治手段提供了思路。

在HIV携带者中,约有10%到20%的人会自然产生针对这种病毒的广泛中和抗体,但其通常只在感染两年后才会出现。实验显示,这些抗体能阻止大多数HIV感染人类细胞,并保护动物模型不受感染。但迄今为止,科学家还无法促使人类免疫系统产生这类抗体。

此次研究表明牛或许能帮助人类解决这一难题,其可在注射HIV免疫原后很短时间内产生抗体对抗HIV。研究中,科学家们向4头小牛注射了HIV免疫原——一种BG505 SOSIP三聚体,随后查看它们的免疫反应。他们发现,在进行两次注射后的35天至50天内,4头牛的血液中便产生了针对HIV的广泛中和抗体,其中一种被称为NC-Cow1的抗体能中和约三分之二的HIV。

研究人员指出,虽然少数HIV感染者体内会产生广泛中和抗体,但这些抗体都是在感染很长一段时间后产生,此时体内的病毒已进化到能抵制这些抗体了。而新研究表明,牛能在极短时间内产生广泛中和抗体,并在与HIV的对抗中获得优势。虽然目前牛抗体还不太适合在人类中临床使用,但弄清楚这种快速产生抗体的机制,对于抗艾疫苗的设计非常有用,也有助于开发新的艾滋病防治手段。

原文链接:

Rapid elicitation of broadly neutralizing antibodies to HIV by immunization in cows

原文摘要:

No immunogen to date has reliably elicited broadly neutralizing antibodies to HIV in humans or animal models. Advances in the design of immunogens (BG505 SOSIP) that antigenically mimic the HIV envelope glycoprotein (Env)1 have improved the elicitation of potent isolate-specific antibody responses in rabbits2 and macaques3, but so far failed to induce broadly neutralizing antibodies. One possible contributor to this failure is that the relevant antibody repertoires are poorly suited to target somewhat occluded conserved epitope regions on Env relative to exposed variable epitopes. To test this hypothesis, we immunized four cows with BG505 SOSIP. The antibody repertoire of cows contains long third heavy chain complementarity determining regions (HCDR3) with an ultralong subset that can reach over 70 amino acids in length4–9. Remarkably, BG505 SOSIP immunization resulted in rapid elicitation of broad and potent serum antibody responses in all four cows. Longitudinal serum analysis for one cow showed the development of neutralization breadth (20%, n = 117 cross-clade isolates) in 42 days and 96% breadth (n = 117) at 381 days. A monoclonal antibody isolated from this cow harboured an ultralong HCDR3 of 60 amino acids and neutralized 72% of cross-clade isolates (n = 117) with a potent median IC50 value of 0.028 μg ml−1. We note that breadth was elicited with a single trimer immunogen and did not require additional envelope diversity. Immunization of cows may provide an avenue to rapidly generate antibody prophylactics and therapeutics to address disease agents that have evolved to avoid human antibody responses.

来源: Nature 浏览次数:0

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