《自然》杂志发表了来自Vir生物技术的新研究，证明了增强

StephenW

Nature Publishes New Research from Vir Biotechnology Demonstrating the Capacity of Enhanced Monoclonal Antibodies to Induce Protective Adaptive Immunity to Viral Infection

Published: Oct 09, 2020

SAN FRANCISCO, Oct. 09, 2020 (GLOBE NEWSWIRE) -- Vir Biotechnology Inc. (Nasdaq: VIR) today announced the publication of preclinical research in an influenza animal model highlighting a new mechanism for enhancing the efficacy of monoclonal antibodies to treat viral infection and induce a protective response. Data demonstrate that selective engagement of an activating Fc receptor on dendritic cells by antiviral monoclonal antibodies induced protective CD8+ T cell adaptive responses. The paper, entitled “Fc-optimized antibodies elicit CD8 immunity to viral respiratory infection,” was published in the October 8, 2020 online edition of Nature.

“In the past several years, we've gained a better understanding of how integral Fc mediated effector functions of monoclonal antibodies are for their therapeutic efficacy in pre-clinical models of neoplastic, infectious and inflammatory diseases,” said Jeffrey V. Ravetch, M.D., Ph.D., study senior author and Theresa and Eugene M. Lang Professor and Head of the Leonard Wagner Laboratory of Molecular Genetics and Immunology at The Rockefeller University. “These approaches have been successfully applied to anti-tumor therapeutics and have resulted in improved clinical outcomes in a variety of oncologic diseases. Our present studies have uncovered a significant new mechanism by which antibodies, through their Fc region, can not only engage innate immune responses but activate adaptive T cell responses, thereby stimulating protective anti-viral immunity in these models.”

The research published in Nature focuses on the role of the Fc domain of monoclonal antibodies, regions with the capacity to bind to other immune cells through a family of receptors (the Fc receptors). By engineering antibodies with modified Fc domains to enhance binding to specific Fc receptors on innate immune cells, investigators observed an enhanced protective immune response. Certain modifications (GAALIE variants) were associated with activation of dendritic cells, as well as antiviral effector T-cells, indicating induction of the adaptive arm of the immune system, which is responsible for long-term immunity. Based on this research, monoclonal antibodies programmed with improved effector function represent a potential new approach in the design of therapeutic antibodies for both the prevention and treatment of infectious diseases.

“By observing and learning from our body’s powerful natural defenses, we have discovered how to maximize the capacity of antibodies through the amplification of key characteristics that may enable more effective treatments for viral diseases,” said Herbert “Skip” Virgin, M.D., Ph.D., study co-author and executive vice president, research, and chief scientific officer of Vir. “These data may have significant implications across a wide range of infectious diseases, and we look forward to exploring the vaccinal potential of the GAALIE-engineered antibodies we are advancing through clinical development – VIR-3434 for chronic hepatitis B and VIR-7832 for SARS-CoV-2.”

The preclinical study was conducted by Dr. Ravetch and Stylianos Bournazos, Ph.D., of the Laboratory of Molecular Genetics and Immunology at The Rockefeller University, in collaboration with Dr. Virgin and Davide Corti, Ph.D., senior vice president of antibody research at Vir’s subsidiary Humabs BioMed SA.

“This type of exceptional collaborative partnership between cutting-edge science and clinical application has the potential to significantly improve our ability to address infectious diseases,” stated Dr. Virgin.

Vir is currently evaluating several monoclonal antibodies that have been Fc engineered to include the XX2 “vaccinal mutation” (or GAALIE variant) for which Vir has licensed exclusive rights for all infectious diseases.

About VIR-3434
VIR-3434 is a subcutaneously administered HBV-neutralizing monoclonal antibody designed to block entry of all 10 genotypes of HBV into hepatocytes and also to reduce the level of virions and subviral particles in the blood. VIR-3434 has been engineered to have an extended half-life as well as to potentially function as a T cell vaccine against HBV in infected patients.

StephenW

《自然》杂志发表了来自Vir生物技术的新研究，证明了增强的单克隆抗体可诱导针对病毒感染的保护性适应性免疫的能力

发布时间：2020年10月9日

旧金山，2020年10月9日（全球新闻）-Vir Biotechnology Inc.（纳斯达克股票代码：VIR）今天宣布发表流感动物模型的临床前研究报告，着重强调了一种增强单克隆抗体治疗病毒感染和免疫的功效的新机制。引起保护性反应。数据表明，抗病毒单克隆抗体选择性激活树突状细胞上的Fc受体，从而诱导保护性CD8 + T细胞适应性反应。该论文题为“ Fc优化的抗体引发CD8对病毒性呼吸道感染的免疫力”，发表在2020年10月8日的《自然》在线版上。

Jeffrey V. Ravetch博士说：“在过去的几年中，我们对单克隆抗体的完整Fc介导的效应子功能如何发挥其在肿瘤前，传染性和炎性疾病的临床前模型中的治疗功效有了更好的了解。”博士，研究高级作者，特雷莎和尤金·朗教授以及洛克菲勒大学分子遗传学和免疫学伦纳德·瓦格纳实验室负责人。这些方法已成功应用于抗肿瘤治疗，并已改善了多种肿瘤疾病的临床疗效。我们目前的研究发现了一种重要的新机制，通过该机制，抗体通过其Fc区不仅可以参与先天免疫应答，而且可以激活适应性T细胞应答，从而在这些模型中刺激保护性抗病毒免疫。”

在《自然》杂志上发表的研究集中在单克隆抗体Fc结构域的作用上，该抗体具有通过一系列受体（Fc受体）与其他免疫细胞结合的能力。通过改造具有修饰的Fc结构域的抗体以增强与先天免疫细胞上特定Fc受体的结合，研究人员观察到了增强的保护性免疫应答。某些修饰（GAALIE变体）与树突状细胞以及抗病毒效应T细胞的激活相关，表明诱导了免疫系统的适应性臂，这负责长期免疫。基于这项研究，具有改善的效应子功能的单克隆抗体代表了设计用于预防和治疗传染病的治疗性抗体的潜在新方法。

“通过观察和学习人体强大的自然防御作用，我们发现了如何通过扩大关键特征来最大化抗体的能力，这些关键特征可以使病毒性疾病得到更有效的治疗，”医学博士赫伯特·“ Skip” Virgin说。 D.，研究合著者，Vir研究执行副总裁，首席科学官。这些数据可能对广泛的传染病具有重要意义，我们期待探索我们正在通过临床开发推进的GAALIE工程抗体的疫苗潜力-VIR-3434用于慢性乙型肝炎和VIR-7832用于SARS-CoV-2。”

临床前研究由洛克菲勒大学分子遗传学和免疫学实验室的Ravetch和Stylianos Bournazos博士与维珍博士和Davide Corti博士（高级副总裁）合作进行。 Vir的子公司Humabs BioMed SA进行抗体研究。

维珍博士说：“尖端科学与临床应用之间的这种特殊的合作伙伴关系有可能显着提高我们应对传染病的能力。”

Vir目前正在评估几种经过Fc工程改造的单克隆抗体，其中包括XX2“疫苗突变”（或GAALIE变体），Vir已为其授予对所有传染病的专有权。

关于VIR-3434
VIR-3434是一种皮下注射的中和HBV的单克隆抗体，旨在阻止HBV的所有10个基因型进入肝细胞，并降低血液中病毒体和亚病毒颗粒的水平。 VIR-3434已被设计为具有延长的半衰期，并可能在感染的患者中充当针对HBV的T细胞疫苗。