Cell：新技术助推HIV疫苗研发

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图片来源：medicalxpress.com

近日，一项发表于国际著名杂志Cell上的研究论文中，来自墨尔本大学等处的研究人员利用一种新技术向开发潜在有效的HIV疫苗的道路又迈进了一步。文章中，研究者使用了一种类似的系统生物学的工具—系统血清学方法（Systems Serology），该方法将实验和计算分析相结合，可以对开发有效HIV疫苗所需的机体复杂免疫反应进行有效梳理。

文章第一作者Chung表示，这项新型技术可以为我们提供一种空前的深度来帮助理解机体潜在保护性免疫反应的发生机制；抗体是抵御诸如HIV等病毒的重要免疫系统组分，其可以利用多种不同的武器和机制来杀灭病毒，但研究者目前并不清楚是什么样的免疫反应或者组合来帮助机体诱导抵御HIV的免疫力的。

为此，研究人员采用了一种名为系统血清学的方法揭示了独特的基于疫苗的诱导抗体指纹，其可以突出已知的或新型的标志物来帮助保护个体抵御HIV的感染，目前全球大约有3400万人都是因为HIV相关的疾病而死亡，截至到2014年底，全球大约有3690万人感染HIV，其中大约有200万人都为HIV1型感染患者。

研究者指出，开发一种有效的疫苗或可帮助个体有效抵御HIV的感染，尽管目前研究者有多种高效的方法来抑制HIV感染，比如利用抗病毒制剂等，其中就包括暴露前预防等措施，但新型抵御HIV疫苗的开发仍然是首要任务。系统血清学技术的发展是开发疫苗的关键一步，也是分析疫苗有效性的关键步骤，该技术可以帮助鉴别出机体完整的免疫反应组合来消除HIV的传播和感染。

最后研究者表示，新型的分析工具获奖应用于多种感染性疾病的研究中，比如埃博拉病毒感染、结核分枝杆菌的感染中等，其可以帮助评估未来基于抗体的新型疫苗，而当下研究人员还需要进行更多深入的研究来提供大量的数据帮助推动新型HIV疫苗的开发进程。

New technique paves the way for finding a HIV vaccine

Researchers are one step closer to finding an effective vaccine against HIV thanks to a new approach to systematically understanding the immune response to the virus.

The technique, termed 'Systems Serology', was developed by University of Melbourne researcher, Dr Amy Chung, from the Peter Doherty Institute for Infection and Immunity (Doherty Institute) in conjunction with researchers at the Ragon Institute of Massachusetts General Hospital (MGH), Massachusetts Institute of Technology (MIT) and Harvard, Boston in the USA.

Using similar tools to Systems Biology, Systems Serology is a combined experimental and computational analytical method that effectively teases out the complex immune response needed for an effective HIV vaccine. This latest development is described in the paper Systems Serology analysis of vaccine-induced humoral immunity published in Cell today.

Dr Chung, the first author of the study, who helped develop the approach while working with Associate Professor Galit Alter at the Ragon Institute of MGH, MIT and Harvard and Professor Douglas Lauffenburger at MIT as part of her American Australian Association and National Health and Medical Research Council (NHMRC) Early Career Fellowships, said the technique provided an unprecedented depth of understanding to these potentially protective immune responses.

"Antibodies are a key part of protection against viruses like HIV. They can harness a variety of different 'weapons' to eliminate virus," she said, "But the exact immune responses or combinations to induce protective immunity against HIV are still unclear.

"Using Systems Serology we revealed unique, vaccine-induced antibody 'fingerprints', which highlighted known and novel markers of what is needed to protect a person from becoming infected with HIV."

Approximately 34 million people have died due to HIV-related causes worldwide. By the end of 2014, there were an estimated 36.9 million people living with HIV globally, with approximately two million people becoming newly infected with the virus1.

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Dissecting Polyclonal Vaccine-Induced Humoral Immunity against HIV Using Systems Serology

Highlights

• Beyond neutralization, antibodies drive antiviral control via Fc-mediated functions
• Distinct vaccines elicit unique antibody Fc-effector profiles
• Network analyses comprehensively integrating antibody profiles can compare vaccines
• Case:control RV144 analysis points to mechanisms of reduced risk of HIV infection
  

Summary

While antibody titers and neutralization are considered the gold standard for the selection of successful vaccines, these parameters are often inadequate predictors of protective immunity. As antibodies mediate an array of extra-neutralizing Fc functions, when neutralization fails to predict protection, investigating Fc-mediated activity may help identify immunological correlates and mechanism(s) of humoral protection. Here, we used an integrative approach termed Systems Serology to analyze relationships among humoral responses elicited in four HIV vaccine trials. Each vaccine regimen induced a unique humoral “Fc fingerprint.” Moreover, analysis of case:control data from the first moderately protective HIV vaccine trial, RV144, pointed to mechanistic insights into immune complex composition that may underlie protective immunity to HIV. Thus, multi-dimensional relational comparisons of vaccine humoral fingerprints offer a unique approach for the evaluation and design of novel vaccines against pathogens for which correlates of protection remain elusive.