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Passive antibody therapy in emerging infectious diseases

《医学前沿（英文）》 doi: 10.1007/s11684-023-1021-y

摘要： The epidemic of corona virus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 and its variants of concern (VOCs) has been ongoing for over 3 years. Antibody therapies encompassing convalescent plasma, hyperimmunoglobulin, and neutralizing monoclonal antibodies (mAbs) applied in passive immunotherapy have yielded positive outcomes and played a crucial role in the early COVID-19 treatment. In this review, the development path, action mechanism, clinical research results, challenges, and safety profile associated with the use of COVID-19 convalescent plasma, hyperimmunoglobulin, and mAbs were summarized. In addition, the prospects of applying antibody therapy against VOCs was assessed, offering insights into the coping strategies for facing new infectious disease outbreaks.

关键词： SARS-CoV-2     COVID-19     convalescent plasma     hyperimmunoglobulin     neutralizing monoclonal antibodies    

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Neutralizing monoclonal antibodies present new prospects to treat SARS-CoV-2 infections

Rongtao Lai, Tianhui Zhou, Xiaogang Xiang, Jie Lu, Haiguang Xin, Qing Xie

《医学前沿（英文）》 2021年 第15卷 第4期   页码 644-648 doi: 10.1007/s11684-021-0847-4

摘要： The coronavirus disease 2019 (COVID-19) has caused global public health and economic crises. Thus, new therapeutic strategies and effective vaccines are urgently needed to cope with this severe pandemic. The development of a broadly neutralizing antibody against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the attractive treatment strategies for COVID-19. Currently, the receptor-binding domain (RBD) of the spike (S) protein is the main target of neutralizing antibodies when SARS-CoV-2 enters human cells through an interaction between the S protein and the angiotensin-converting enzyme 2 expressed on various human cells. A single monoclonal antibody (mAb) treatment is prone to selective pressure due to increased possibility of targeted epitope mutation, leading to viral escape. In addition, the antibody-dependent enhancement effect is a potential risk of enhancing the viral infection. These risks can be reduced using multiple mAbs that nonoverlapping epitopes. Thus, a cocktail therapy combining two or more antibodies that recognize different regions of the viral surface may be the most effective therapeutic strategy.

关键词： neutralizing antibody     antibody cocktail     SARS-CoV-2     COVID-19     therapeutic strategy    

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Recent advances in “universal” influenza virus antibodies: the rise of a hidden trimeric interface in hemagglutinin globular head

Yulu Wang, Dan Hu, Yanling Wu, Tianlei Ying

《医学前沿（英文）》 2020年 第14卷 第2期   页码 149-159 doi: 10.1007/s11684-020-0764-y

摘要： Influenza causes seasonal outbreaks yearly and unpredictable pandemics with high morbidity and mortality rates. Despite significant efforts to address influenza, it remains a major threat to human public health. This issue is partially due to the lack of antiviral drugs with potent antiviral activity and broad reactivity against all influenza virus strains and the rapid emergence of drug-resistant variants. Moreover, designing a universal influenza vaccine that is sufficiently immunogenic to induce universal antibodies is difficult. Some novel epitopes hidden in the hemagglutinin (HA) trimeric interface have been discovered recently, and a number of antibodies targeting these epitopes have been found to be capable of neutralizing a broad range of influenza isolates. These findings may have important implications for the development of universal influenza vaccines and antiviral drugs. In this review, we focused on the antibodies targeting these newly discovered epitopes in the HA domain of the influenza virus to promote the development of universal anti-influenza antibodies or vaccines and extend the discovery to other viruses with similar conformational changes in envelope proteins.

关键词： influenza virus     neutralizing antibody     hemagglutinin     globular head region     trimeric interface    

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Neutralization against SARS-CoV-2 Delta/Omicron variants and B cell response after inactivated vaccination among COVID-19 convalescents

《医学前沿（英文）》 2023年 第17卷 第4期   页码 747-757 doi: 10.1007/s11684-022-0954-x

摘要： Emerging SARS-CoV-2 variants have made COVID-19 convalescents susceptible to re-infection and have raised concern about the efficacy of inactivated vaccination in neutralization against emerging variants and antigen-specific B cell response. To this end, a study on a long-term cohort of 208 participants who have recovered from COVID-19 was conducted, and the participants were followed up at 3.3 (Visit 1), 9.2 (Visit 2), and 18.5 (Visit 3) months after SARS-CoV-2 infection. They were classified into three groups (no-vaccination (n = 54), one-dose (n = 62), and two-dose (n = 92) groups) on the basis of the administration of inactivated vaccination. The neutralizing antibody (NAb) titers against the wild-type virus continued to decrease in the no-vaccination group, but they rose significantly in the one-dose and two-dose groups, with the highest NAb titers being observed in the two-dose group at Visit 3. The NAb titers against the Delta variant for the no-vaccination, one-dose, and two-dose groups decreased by 3.3, 1.9, and 2.3 folds relative to the wild-type virus, respectively, and those against the Omicron variant decreased by 7.0, 4.0, and 3.8 folds, respectively. Similarly, the responses of SARS-CoV-2 RBD-specific B cells and memory B cells were boosted by the second vaccine dose. Results showed that the convalescents benefited from the administration of the inactivated vaccine (one or two doses), which enhanced neutralization against highly mutated SARS-CoV-2 variants and memory B cell responses. Two doses of inactivated vaccine among COVID-19 convalescents are therefore recommended for the prevention of the COVID-19 pandemic, and vaccination guidelines and policies need to be updated.

关键词： COVID-19 convalescent     SARS-CoV-2     inactivated vaccination     neutralizing antibody     B cell response    

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Broadly neutralizing antibodies and vaccine design against HIV-1 infection

Qian Wang, Linqi Zhang

《医学前沿（英文）》 2020年 第14卷 第1期   页码 30-42 doi: 10.1007/s11684-019-0721-9

摘要： Remarkable progress has been achieved for prophylactic and therapeutic interventions against human immunodeficiency virus type I (HIV-1) through antiretroviral therapy. However, vaccine development has remained challenging. Recent discoveries in broadly neutralizing monoclonal antibodies (bNAbs) has led to the development of multiple novel vaccine approaches for inducing bNAbs-like antibody response. Structural and dynamic studies revealed several vulnerable sites and states of the HIV-1 envelop glycoprotein (Env) during infection. Our review aims to highlight these discoveries and rejuvenate our endeavor in HIV-1 vaccine design and development.

关键词： HIV-1     broadly neutralizing antibodies     Env conformational states     vaccine design     SOSIP    

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Durability of neutralizing antibodies and T-cell response post SARS-CoV-2 infection

Yun Tan, Feng Liu, Xiaoguang Xu, Yun Ling, Weijin Huang, Mingquan Guo, Ziyu Fu, Dongguo Liang, Miao Xu, Hongzhou Lu, Saijuan Chen

《医学前沿（英文）》 2020年 第14卷 第6期   页码 746-751 doi: 10.1007/s11684-020-0822-5

摘要： The ongoing pandemic of coronavirus disease 19 (COVID-19) is caused by a newly discovered β coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). How long the adaptive immunity triggered by SARS-CoV-2 can last is of critical clinical relevance in assessing the probability of second infection and efficacy of vaccination. Here we examined, using ELISA, the IgG antibodies in serum specimens collected from 17 COVID-19 patients at 6−7 months after diagnosis and the results were compared to those from cases investigated 2 weeks to 2 months post-infection. All samples were positive for IgGs against the S- and N-proteins of SARS-CoV-2. Notably, 14 samples available at 6−7 months post-infection all showed significant neutralizing activities in a pseudovirus assay, with no difference in blocking the cell-entry of the 614D and 614G variants of SARS-CoV-2. Furthermore, in 10 blood samples from cases at 6−7 months post-infection used for memory T-cell tests, we found that interferon γ-producing CD4 and CD8 cells were increased upon SARS-CoV-2 antigen stimulation. Together, these results indicate that durable anti-SARS-CoV-2 immunity is common in convalescent population, and vaccines developed from 614D variant may offer protection from the currently predominant 614D variant of SARS-CoV-2.

关键词： SARS-CoV-2     neutralizing antibodies     T-cell response    

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BGB-A445, a novel non-ligand-blocking agonistic anti-OX40 antibody, exhibits superior immune activation

《医学前沿（英文）》 doi: 10.1007/s11684-023-0996-8

摘要： OX40 is a costimulatory receptor that is expressed primarily on activated CD4+, CD8+, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40–OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.

关键词： BGB-A445     OX40     agonistic antibody     OX40L noncompetitive    

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Production of a polyclonal antibody to the VP26 nucleocapsid protein of white spot syndrome virus (wssv

Suchera LOYPRASERT-THANANIMIT, Akrapon SALEEDANG, Proespichaya KANATHARANA, Panote THAVARUNGKUL, Wilaiwan CHOTIGEAT

《化学科学与工程前沿（英文）》 2012年 第6卷 第2期   页码 216-223 doi: 10.1007/s11705-012-1289-y

摘要： White spot syndrome virus (WSSV) is a major cause of high mortality in cultured shrimp all over the world. VP26 is one of the structural proteins of WSSV that is assumed to assist in recognizing its host and assists the viral nucleocapsid to move toward the nucleus of the host cell. The objective of this work was to produce a polyclonal antibody against VP26 and use it as a biosensor. The recombinant VP26 protein (rVP26) was produced in (BL21), purified and used for immunizing rabbits to obtain a polyclonal antibody. Western blot analysis confirmed that the antiserum had a specific immunoreactivity to the VP26 of WSSV. This VP26 antiserum was immobilized onto a gold electrode for use as the sensing surface to detect WSSV under a flow injection system. The impedance change in the presence of VP26 was monitored in real time. The sensitivity of the biosensor was in the linear range of 160–160000 copies of WSSV, indicating that it is good and sensitive for analysis of WSSV. The specificity of the biosensor was supported by the observation that no impedance change was detected even at high concentrations when using Yellow Head Virus (YHV). This biosensor may be applied to monitor the amount of WSSV in water during shrimp cultivation.

关键词： recombinant protein     polyclonal antibody     label-free biosensor     impedance     white spot syndrome virus (WSSV)    

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Growth suppression of colorectal cancer expressing S492R EGFR by monoclonal antibody CH12

Qiongna Dong, Bizhi Shi, Min Zhou, Huiping Gao, Xiaoying Luo, Zonghai Li, Hua Jiang

《医学前沿（英文）》 2019年 第13卷 第1期   页码 83-93 doi: 10.1007/s11684-019-0682-z

摘要：

Colorectal cancer (CRC) is a common malignant tumor in the digestive tract, and 30%–85% of CRCs express epidermal growth factor receptors (EGFRs). Recently, treatments using cetuximab, also named C225, an anti-EGFR monoclonal antibody, for CRC have been demonstrated to cause an S492R mutation in EGFR. However, little is known about the biological function of S492R EGFR. Therefore, we attempted to elucidate its biological function in CRC cells and explore new treatment strategies for this mutant form. Our study indicated that EGFR and S492R EGFR accelerate the growth of CRC cells in vitro and in vivo and monoclonal antibody CH12, which specifically recognizes an EGFR tumor-specific epitope, can bind efficiently to S492R EGFR. Furthermore, mAb CH12 showed significantly stronger growth suppression activities and induced a more potent antibody-dependent cellular cytotoxicity effect on CRC cells bearing S492R EGFR than mAb C225. mAb CH12 obviously suppressed the growth of CRC xenografts with S492R EGFR mutations in vivo. Thus, mAb CH12 may be a promising therapeutic agent in treating patients with CRC bearing an S492R EGFR mutation.

关键词： S492R EGFR ectodomain mutation     colorectal cancer     mAb CH12     immunnotherapy    

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Preparation of hapten-specific monoclonal antibody for cadmium and its ELISA application to aqueous samples

Huan HE, Bo TANG, Cheng SUN, Shaogui YANG, Weijuan ZHENG, Zichun HUA

《环境科学与工程前沿（英文）》 2011年 第5卷 第3期   页码 409-416 doi: 10.1007/s11783-011-0349-8

摘要： High-affinity and specific monoclonal antibodies against cadmium-ethylene diamine tetraacetic acid (EDTA) complex have been produced using the hybridoma technique. A hapten was synthesized and characterized by Fourier Transform Infrared Spectroscopy (FT-IR) and UV-Vis. Competitive enzyme-linked immunosorbent assay (ELISA) for quantitative detection of cadmium in aqueous sample was developed. The monoclonal antibody with high level of binding affinity for Cd-IEDTA-BSA and high specificity for soluble Cd-EDTA complex showed less than 0.99% cross-reactivity with other 11 metals. The limit of detection was 0.10 μg·L , and the effective linear range was 10 –10 μg·L . The intra- and inter-assay coefficient variations were 1.5%–6.3% and 3.2%–7.4%, respectively. The spike recovery in different water samples were between 98.5% and 110.3%. The detection limit of this assay was well below the allowable concentration of cadmium (3 μg·L ), and the working range was wider than that of other methods which showed the range of 2.19–86.38 and 0–10 μg·L . The competitive ELISA established in this paper was sensitive and accurate in the screening of cadmium in aqueous samples. The results will lay a solid foundation for construction of an immunoassay kit for cadmium.

关键词： cadmium     hapten     monoclonal antibody     enzyme-linked immunosorbent assay (ELISA)    

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CD176 single-chain variable antibody fragment inhibits the adhesion of cancer cells to endothelial cells

null

《医学前沿（英文）》 2016年 第10卷 第2期   页码 204-211 doi: 10.1007/s11684-016-0443-1

摘要：

CD176 (Thomsen-Friedenreich antigen) is a tumor-associated carbohydrate epitope (glycotope) functionally involved in blood spread and liver metastasis of cancer cells by mediating the adhesion of cancer cells to endothelial cells and hepatocytes, respectively. CD176 could be a promising target for antitumor immunotherapy. We applied B lymphocytes obtained from mice immunized with CD176 antigen and constructed a phage display library. A positive clone of CD176 single-chain variable antibody fragment (scFv) was successfully screened from this library. The CD176 scFv was expressed in Escherichia coli and purified. The purified scFv can bind to the natural CD176 expressed on the surface of cancer cells. Furthermore, the CD176 scFv inhibits the adhesion of CD176+ cancer cells to endothelial cells and hepatocytes. This CD176 scFv provides a basis for future development of recombinant CD176-specific antibodies that can be used in therapeutic application.

关键词： CD176     Thomsen-Friedenreich antigen     scFv     cancer     therapy     adhesion     metastasis    

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提升疗效的修饰型治疗性抗体国内外研究进展 Review

戴济民, 张雪芹, 戴竞耀, 杨向民, 陈志南

《工程（英文）》 2021年 第7卷 第11期   页码 1529-1540 doi: 10.1016/j.eng.2020.06.030

摘要：

生物治疗药物市场的繁荣反映了治疗性抗体药物用于治疗癌症、炎性疾病和难治性感染的可行性和有效性。随着抗体药物临床试验和转化研究中出现的结合效率不高、效应功能降低和不良反应频发等问题的解决，治疗性抗体的修饰在抗体药物的研发进程中得到了前所未有的蓬勃发展。为了提升抗体的结合活性、循环中的半衰期、靶细胞的有效性，并最终实现改善抗体药物的疗效，抗体可主要通过以下途径修饰：①糖基化修饰；②抗体恒定区（Fc）改造；③抗体亚类重构；④构建抗体-药物偶联物（ADC）；⑤基于单链可变区片段（scFv）的嵌合抗原受体T细胞（CAR-T）；⑥双特异性抗体（bsAb）。过去几十年来全球在修饰型治疗性抗体的领域取得了许多成就，中国作为对于生物治疗药物需求巨大并且拥有巨大研发潜力的国家在该领域亦发挥了积极作用。本文概括了修饰型治疗性抗体在当前国际研究中取得的进展，并在单独的章节中重点介绍了中国在该领域取得的成果。

关键词： 治疗性抗体     抗体修饰     疗效     抗原     抗体-药物偶联物     双特异性抗体    

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使用数据驱动模型优化抗体纯化策略 Article

刘松崧, Lazaros G. Papageorgiou

《工程（英文）》 2019年 第5卷 第6期   页码 1077-1092 doi: 10.1016/j.eng.2019.10.011

摘要：

本工作致力于抗体片段纯化过程的多尺度优化。优化了生产过程中的色谱决策，包括色谱柱的数量及其大小，每批的循环数以及操作流速。使用基于微型实验数据的制造规模模拟数据集，建立了以负载质量、流速和柱床高度为输入的色谱通量数据驱动模型。与其他方法相比，分段线性回归建模方法具有简单、预测精度高的优点。提出了两种混合整数非线性规划（MINLP）模型，结合数据驱动模型，以最小化每克抗体纯化过程的总成本。然后，使用线性化技术和多参数分解将这些MINLP模型重新构造为混合整数线性规划（MILP）模型。研究了两个具有不同色谱柱尺寸替代品的工业相关案例，以证明所提出模型的适用性。

关键词： 抗体纯化     多尺度优化     抗原结合片段     混合整数规划     数据驱动模型     分段线性回归    

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一种通过计算机辅助抗体设计技术获得的靶向人表皮生长因子受体2的新型全人抗体HF Article

乔春霞, 吕明, 李新颖, 郞小玲, 吕守芹, 龙勉, 黎燕, 耿树生, 林周, 沈倍奋, 冯健男

《工程（英文）》 2021年 第7卷 第11期   页码 1566-1576 doi: 10.1016/j.eng.2020.10.024

摘要：

全人抗体免疫原性小、安全性高。目前研究的处于临床试验阶段的大多数抗体药物都是人源化或全人抗体。全人抗体多通过噬菌体展示技术（体外）或转基因小鼠（体内）产生；其他方法包括B淋巴细胞永生化、人-人杂交瘤、单细胞聚合酶链反应等。本文描述了一种基于分子结构的计算机辅助设计新抗体技术，用于获得全人抗体。由于靶向人表皮生长因子受体2（HER2）的注射用曲妥珠单抗（赫赛汀）的结构复杂，我们首先针对赫赛汀识别HER2 的潜在表位设计了6 条短肽。随后，将这些肽作为抗体互补决定区，并采用适合的免疫球蛋白框架，获得名为“HF”的新型抗HER2 抗体。HF比赫赛汀具有更高的亲和力和更有效的抗肿瘤活性。我们的工作为用于机理研究以及免疫相关疾病（如癌症和传染病）的成像和临床应用的新型全人抗体的快速设计和筛选提供了有用工具。

关键词： 人表皮生长因子受体2（HER2/erb-B2）     全人抗体     计算机辅助设计（CAD）    

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From SARS to MERS: evidence and speculation

null

《医学前沿（英文）》 2016年 第10卷 第4期   页码 377-382 doi: 10.1007/s11684-016-0466-7

摘要：

The Middle East respiratory syndrome coronavirus (MERS-CoV) is a novel zoonotic pathogen. In 2012, the infectious outbreak caused by MERS-CoV in Saudi Arabia has spread to more than 1600 patients in 26 countries, resulting in over 600 deaths. Without a travel history, few clinical and radiological features can reliably differentiate MERS from SARS. But in real world, comparing with SARS, MERS presents more vaguely defined epidemiology, more severe symptoms, and higher case fatality rate. In this review, we summarize the recent findings in the field of MERS-CoV, especially its molecular virology, interspecies mechanisms, clinical features, antiviral therapies, and the further investigation into this disease. As a newly emerging virus, many questions are not fully answered, including the exact mode of transmission chain, geographical distribution, and animal origins. Furthermore, a new protocol needs to be launched to rapidly evaluate the effects of unproven antiviral drugs and vaccine to fasten the clinical application of new drugs.

关键词： middle east respiratory syndrome     animal origin     cross-species transmission     monoclonal antibody    

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标题 作者 时间 类型 操作

Passive antibody therapy in emerging infectious diseases

期刊论文

Neutralizing monoclonal antibodies present new prospects to treat SARS-CoV-2 infections

Rongtao Lai, Tianhui Zhou, Xiaogang Xiang, Jie Lu, Haiguang Xin, Qing Xie

期刊论文

Recent advances in “universal” influenza virus antibodies: the rise of a hidden trimeric interface in hemagglutinin globular head

Yulu Wang, Dan Hu, Yanling Wu, Tianlei Ying

期刊论文

Neutralization against SARS-CoV-2 Delta/Omicron variants and B cell response after inactivated vaccination among COVID-19 convalescents

期刊论文

Broadly neutralizing antibodies and vaccine design against HIV-1 infection

Qian Wang, Linqi Zhang

期刊论文

Durability of neutralizing antibodies and T-cell response post SARS-CoV-2 infection

Yun Tan, Feng Liu, Xiaoguang Xu, Yun Ling, Weijin Huang, Mingquan Guo, Ziyu Fu, Dongguo Liang, Miao Xu, Hongzhou Lu, Saijuan Chen

期刊论文

BGB-A445, a novel non-ligand-blocking agonistic anti-OX40 antibody, exhibits superior immune activation

期刊论文

Production of a polyclonal antibody to the VP26 nucleocapsid protein of white spot syndrome virus (wssv

Suchera LOYPRASERT-THANANIMIT, Akrapon SALEEDANG, Proespichaya KANATHARANA, Panote THAVARUNGKUL, Wilaiwan CHOTIGEAT

期刊论文

Growth suppression of colorectal cancer expressing S492R EGFR by monoclonal antibody CH12

Qiongna Dong, Bizhi Shi, Min Zhou, Huiping Gao, Xiaoying Luo, Zonghai Li, Hua Jiang

期刊论文

Preparation of hapten-specific monoclonal antibody for cadmium and its ELISA application to aqueous samples

Huan HE, Bo TANG, Cheng SUN, Shaogui YANG, Weijuan ZHENG, Zichun HUA

期刊论文

CD176 single-chain variable antibody fragment inhibits the adhesion of cancer cells to endothelial cells

null

期刊论文

提升疗效的修饰型治疗性抗体国内外研究进展

戴济民, 张雪芹, 戴竞耀, 杨向民, 陈志南

期刊论文

使用数据驱动模型优化抗体纯化策略

刘松崧, Lazaros G. Papageorgiou

期刊论文

一种通过计算机辅助抗体设计技术获得的靶向人表皮生长因子受体2的新型全人抗体HF

乔春霞, 吕明, 李新颖, 郞小玲, 吕守芹, 龙勉, 黎燕, 耿树生, 林周, 沈倍奋, 冯健男

期刊论文

From SARS to MERS: evidence and speculation

null

期刊论文