新型犬噬菌体展示源性狂犬病病毒中和单克隆抗体片段的研制-动脉网

Development of novel canine phage display-derived neutralizing monoclonal antibody fragments against rabies virus from immunized dogs

Nature 等信源发布 2024-10-03 14:52



可切换为仅中文







AbstractAnimal rabies is a potentially fatal infectious disease in mammals, especially dogs. Currently, the number of rabies cases in pet dogs is increasing in several regions of Thailand. However, no passive postexposure prophylaxis (PEP) has been developed to combat rabies infection in animals. As monoclonal antibodies (MAbs) are promising biological therapies for postinfection, we developed a canine-neutralizing MAb against rabies virus (RABV) via the single-chain variable fragment (scFv) platform.

摘要动物狂犬病是哺乳动物特别是狗的潜在致命传染病。目前，在泰国的几个地区，宠物狗中的狂犬病病例正在增加。然而，尚未开发出被动暴露后预防（PEP）来对抗动物中的狂犬病感染。由于单克隆抗体（MAb）是感染后有前途的生物疗法，我们通过单链可变片段（scFv）平台开发了针对狂犬病病毒（RABV）的犬中和MAb。

Immunized phage-displaying scFv libraries were constructed from PBMCs via the pComb3XSS system. Diverse canine VHVLκ and VHVLλ libraries containing 2.4 × 108 and 1.3 × 106 clones, respectively, were constructed. Five unique clones that show binding affinity with the RABV glycoprotein were then selected, of which K9RABVscFv1 and K9RABVscFv16 showed rapid fluorescent foci inhibition test (RFFIT) neutralizing titers above the human protective level of 0.5 IU/ml.

通过pComb3XSS系统从PBMC构建免疫的噬菌体展示scFv文库。构建了分别含有2.4×108和1.3×106个克隆的多种犬VHVLκ和VHVLλ文库。然后选择了五个与RABV糖蛋白具有结合亲和力的独特克隆，其中K9RABVscFv1和K9RABVscFv16显示出快速荧光灶抑制试验（RFFIT）中和滴度，高于0.5 IU/ml的人类保护水平。

Finally, in silico docking predictions revealed that the residues on the CDRs of these neutralizing clones interact mainly with similar antigenic sites II and III on the RABV glycoprotein. These candidates may be used to develop complete anti-RABV MAbs as a novel PEP protocol in pet dogs and other animals..

最后，计算机对接预测显示，这些中和克隆的CDR上的残基主要与RABV糖蛋白上相似的抗原位点II和III相互作用。这些候选物可用于开发完整的抗RABV单克隆抗体，作为宠物狗和其他动物的新型PEP方案。。

IntroductionRabies virus (RABV) is a neurotropic virus that causes rabies in mammals1,2. In particular, the RABV glycoprotein (RABV-G) can induce immune responses and is a major target for neutralizing antibodies3,4. It contains several antigenic sites: I, II, III, IV (G5) and minor site a (G1)5,6,7,8.

简介狂犬病病毒（RABV）是一种嗜神经病毒，可在哺乳动物中引起狂犬病1,2。特别是，RABV糖蛋白（RABV-G）可以诱导免疫反应，并且是中和抗体的主要靶标3,4。它包含几个抗原位点：I，II，III，IV（G5）和次要位点a（G1）5,6,7,8。

Animal rabies is most prevalent in tropical countries such as Thailand, India, Bangladesh, and other Asian countries in Southeast Asia9,10. Thanapongtharm and colleagues reported that 9.9% (848/8,574 samples) and 15.4% (1475/9601) of animals in Thailand tested positive for rabies in 2017 and 2018, respectively.

。Thanapongharm及其同事报告说，2017年和2018年，泰国分别有9.9%（848/8574个样本）和15.4%（1475/9601）的动物检测出狂犬病阳性。

Most of the infected cases were dogs (87% of all positive samples), followed by cattle, cats, and others. More than half of these animals were domesticated, and many were unvaccinated animals (39%) that roam freely or semifreely. Rabies-positive dog clusters are concentrated in the northeastern region, followed by the central and southern provinces of Thailand.

大多数感染病例是狗（占所有阳性样本的87%），其次是牛，猫等。这些动物中有一半以上是驯养的，许多是未接种疫苗的动物（39%），可以自由或半自由地漫游。狂犬病阳性犬群集中在东北地区，其次是泰国中部和南部省份。

Notably, the number of cases increased after June and peaked in January1.Although preexposure rabies vaccination effectively prevents disease in dogs, there is a risk of infection if the dog is not completely vaccinated11,12. Domesticated dogs can also be infected by strays with an unknown history of rabies vaccination1,13,14.

。驯养的狗也可能被狂犬病疫苗接种史未知的流浪狗感染1,13,14。

In general, animals that develop symptomatic signs of rabies should be euthanized by an animal health professional, and the animal’s head or fresh brain tissue should be submitted to the laboratory to confirm rabies virus infection15.The awareness of rabies has increased among pet owners in Thailand because it is a fatal disease caused by inflammation of the brain and spinal cord that can be transmitted from animals to owners16.

一般来说，出现狂犬病症状的动物应该由动物卫生专业人员安乐死，动物的头部或新鲜脑组织应该提交给实验室以确认狂犬病病毒感染15。泰国宠物主人对狂犬病的认识有所提高，因为它是一种致命的疾病，由大脑和脊髓的炎症引起，可以从动物传播给主人16。

Therefore, it is crucial to develop rabies-postexposure t.

因此，开发狂犬病暴露后t至关重要。

Data availability

数据可用性

Primer sequences in “Table 4. The set of primers based on the pComb3XSS phagemid for canine VH and VL chains and scFv amplification, including sequencing primers, were retrieved from Braganza et al. (2011).2) The RABV-G (SQ382) protein sequence and bioinformatics data are provided in the supplementary information file.The RABV-G (SQ382) nucleotide sequence data are available from the GenBank accession number ON808418.3) All protein structure data used as 3D templates for homology model prediction in this study have been deposited in the Worldwide Protein Data Bank (wwPDB):3.1 PDBID no.

引物序列见“表4”。从Braganza等人（2011）中检索到了一组基于犬VH和VL链的pComb3XSS噬菌体和scFv扩增的引物，包括测序引物。2）RABV-G（SQ382）蛋白序列和生物信息学数据在补充信息文件中提供。RABV-G（SQ382）核苷酸序列数据可从GenBank登录号808418获得。3）本研究中用作同源性模型预测的3D模板的所有蛋白质结构数据均已保存在全球蛋白质数据库（wwPDB）中：3.1 PDBID编号。

8DY2.1. A (human GLK1 spFv) was used as a template for K9RABVscFv1. DOI: https://doi.org/10.2210/pdb8DY2/pdb3.2 PDBID no. 1 × 9Q (human anti-fluorescein scFv) was used as a template for K9RABVscFv16.DOI: https://doi.org/10.2210/pdb1 × 9Q/pdb3.3 PDBID no. 7U9G (monomer form of RABV-G) was used as a template for RABV-G (SQ382).

8DY2.1。。内政部：https://doi.org/10.2210/pdb8DY2/pdb3.2使用PDBID no.1××9Q（人抗荧光素scFv）作为K9RABVscFv16.DOI的模板：https://doi.org/10.2210/pdb1 使用9Q/pdb3.3 PDBID号7U9G（RABV-G的单体形式）作为RABV-G（SQ382）的模板。

DOI: https://doi.org/10.2210/pdb7U9G/pdb4) The amino acid sequences of K9RABVscFv1, 2, 12, 15, and 16 are currently under the process of patent registration (patent filing number 2401005189) assigned by the Thailand Department of Intellectual Property (DIP)..

内政部：https://doi.org/10.2210/pdb7U9G/pdb4)K9RABVscFv1、2、12、15和16的氨基酸序列目前正在泰国知识产权局（DIP）指定的专利注册（专利申请号2401005189）过程中。。

ReferencesThanapongtharm, W., Suwanpakdee, S., Chumkaeo, A., Gilbert, M. & Wiratsudakul, A. Current characteristics of animal rabies cases in Thailand and relevant risk factors identified by a spatial modeling approach. PLoS Negl. Trop. Dis.15, e0009980. https://doi.org/10.1371/journal.pntd.0009980 (2021).Article .

参考文献Thanapongharm，W.，Suwanpakdee，S.，Chumkaeo，A.，Gilbert，M。＆Wiratsudakul，A。泰国动物狂犬病病例的当前特征以及通过空间建模方法确定的相关风险因素。公共科学图书馆。托普。Dis.15，e0009980。https://doi.org/10.1371/journal.pntd.0009980（2021年）。文章。

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Niezgoda, M., Hanlon, C. A. & Rupprecht, C. E. Animal rabies. Rabies 163–218 (2003).Dietzschold, B., Tollis, M., Lafon, M., Wunner, W. H. & Koprowski, H. Mechanisms of Rabies virus neutralization by glycoprotein-specific monoclonal antibodies. Virology161, 29–36 (1987).Article

Niezgoda，M.，Hanlon，C.A。和Rupprecht，C.E。动物狂犬病。狂犬病163-218（2003）。Dietzschold，B.，Tollis，M.，Lafon，M.，Wunner，W.H。＆Koprowski，H。通过糖蛋白特异性单克隆抗体中和狂犬病病毒的机制。病毒学161,29-36（1987）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Callaway, H. M. et al. Structure of the Rabies virus glycoprotein trimer bound to a prefusion-specific neutralizing antibody. Sci. Adv.8, eabp9151. https://doi.org/10.1126/sciadv.abp9151 (2022).Article

与融合前特异性中和抗体结合的狂犬病病毒糖蛋白三聚体的结构。科学。Adv.8，eabp9151。https://doi.org/10.1126/sciadv.abp9151（2022年）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Flamand, V. et al. Vaccination with tumor-antigen-pulsed dendritic cells induces in vivo resistance to a B cell lymphoma. Adv. Exp. Med. Biol.329, 611–616. https://doi.org/10.1007/978-1-4615-2930-9_102 (1993).Article

用肿瘤抗原脉冲树突状细胞接种疫苗可诱导体内对B细胞淋巴瘤的抗性。高级实验医学生物学329611-616。https://doi.org/10.1007/978-1-4615-2930-9_102（1993年）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Prehaud, C., Coulon, P., LaFay, F., Thiers, C. & Flamand, A. Antigenic site II of the Rabies virus glycoprotein: structure and role in viral virulence. J. Virol.62, 1–7. https://doi.org/10.1128/JVI.62.1.1-7.1988 (1988).Article

Prehaud，C.，Coulon，P.，LaFay，F.，Thiers，C。＆Flamand，A.狂犬病病毒糖蛋白的抗原位点II：结构和在病毒毒力中的作用。J、 Virol.62，1-7。https://doi.org/10.1128/JVI.62.1.1-7.1988（1988年）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Seif, I., Coulon, P., Rollin, P. E. & Flamand, A. Rabies virulence: effect on pathogenicity and sequence characterization of Rabies virus mutations affecting antigenic site III of the glycoprotein. J. Virol.53, 926–934. https://doi.org/10.1128/JVI.53.3.926-934.1985 (1985).Article

Seif，I.，Coulon，P.，Rollin，P.E。＆Flamand，A。狂犬病毒力：对影响糖蛋白抗原位点III的狂犬病病毒突变的致病性和序列表征的影响。J、 Virol.53926-934。https://doi.org/10.1128/JVI.53.3.926-934.1985（1985年）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Yang, F. et al. Structural analysis of rabies virus glycoprotein reveals pH-dependent conformational changes and interactions with a neutralizing antibody. Cell Host Microbe27, 441–453. https://doi.org/10.1016/j.chom.2019.12.012 (2020).Tenzin & Ward, M. Review of rabies epidemiology and control in South, South East and East Asia: past, present and prospects for elimination.

Yang，F。等人。狂犬病病毒糖蛋白的结构分析揭示了pH依赖性构象变化以及与中和抗体的相互作用。细胞宿主微生物27441-453。https://doi.org/10.1016/j.chom.2019.12.012（2020年）。Tenzin＆Ward，M。南亚，东南亚和东亚狂犬病流行病学和控制综述：过去，现在和消除前景。

Zoonoses Public. Health59, 451–467 (2012).Article .

人畜共患病。Health59451-467（2012）。文章。

CAS

中科院

PubMed

Google Scholar

谷歌学者

World Health Organization (WHO) (2020).Hampson, K. et al. Estimating the global burden of endemic canine rabies. PLoS Negl. Trop. Dis.9, e0003709 (2015).Article

世界卫生组织（WHO）（2020年）。Hampson，K.等人，《估计地方性犬狂犬病的全球负担》。公共科学图书馆。托普。第9部分，e0003709（2015）。文章

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Townsend, S. E. et al. Surveillance guidelines for disease elimination: a case study of canine rabies. Comp. Immunol. Microbiol. Infect. Dis.36, 249–261 (2013).Article

Townsend，S.E.等人，《消除疾病监测指南：犬狂犬病案例研究》。公司。免疫。微生物。感染。。文章

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Leung, T. & Davis, S. A. Rabies vaccination targets for stray dog populations. Front. Veterinary Sci.4, 52 (2017).Article

Leung，T.＆Davis，S.A。针对流浪狗群体的狂犬病疫苗接种目标。正面。。文章

Google Scholar

谷歌学者

Kasempimolporn, S. et al. Prevalence of Rabies virus infection and rabies antibody in stray dogs: A survey in Bangkok, Thailand. Prev. Vet. Med.78, 325–332 (2007).Article

Kasempimolporn，S.等人。流浪狗中狂犬病病毒感染率和狂犬病抗体：泰国曼谷的一项调查。上一页。兽医。Med.78325-332（2007）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Rupprecht, C. E., Fooks, A. R. & Abela-Ridder, B. Laboratory Techniques in Rabies Vol. 1 (WHO, 2018).Premashthira, S. et al. The impact of socioeconomic factors on knowledge, attitudes, and practices of dog owners on dog rabies control in Thailand. Front. Veterinary Sci.8, 699352 (2021).Article .

Rupprecht，C.E.，Fooks，A.R。和Abela Ridder，B。狂犬病实验室技术第1卷（WHO，2018）。Premashthira，S.等人，《社会经济因素对泰国犬只狂犬病控制知识、态度和行为的影响》。正面。兽医科学8699352（2021）。文章。

Google Scholar

谷歌学者

Zhao, X. L., Yin, J., Wang, H., Jiang, M. & Hou, X. J. Construction of human phage-displayed scFv library and selection of the ScFv against Rabies virus. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi20, 243–247 (2004).CAS

Zhao，X.L.，Yin，J.，Wang，H.，Jiang，M。＆Hou，X.J。人噬菌体展示scFv文库的构建和抗狂犬病病毒scFv的选择。《西宝玉芬子面医学杂志》20243-247（2004）。中科院

PubMed

Google Scholar

谷歌学者

Sun, L. et al. Generation and characterization of neutralizing human recombinant antibodies against antigenic site II of Rabies virus glycoprotein. Appl. Microbiol. Biotechnol.96, 357–366. https://doi.org/10.1007/s00253-012-4171-4 (2012).Article

Sun，L.等人。针对狂犬病病毒糖蛋白抗原位点II的中和人重组抗体的产生和表征。应用。微生物。生物技术96357-366。https://doi.org/10.1007/s00253-012-4171-4。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Sparrow, E. et al. Recent advances in the development of monoclonal antibodies for rabies post exposure prophylaxis: a review of the current status of the clinical development pipeline. Vaccine37(Suppl 1), A132–A139. https://doi.org/10.1016/j.vaccine.2018.11.004 (2019).Article

Sparrow，E.等人。狂犬病暴露后预防单克隆抗体开发的最新进展：临床开发管道的现状综述。疫苗37（补充1），A132-A139。https://doi.org/10.1016/j.vaccine.2018.11.004（2019年）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Serum Institute of India PVT. LTD (2018).Yumoto, K. et al. Characterization of single-chain fv fragments of neutralizing antibodies to rabies virus glycoprotein. Viruses13https://doi.org/10.3390/v13112311 (2021).Terryn, S., Francart, A., Rommelaere, H., Stortelers, C. & Van Gucht, S.

印度血清研究所私人有限公司（2018）。Yumoto，K.等人。狂犬病病毒糖蛋白中和抗体单链fv片段的表征。病毒13https://doi.org/10.3390/v13112311（2021年）。Terryn，S.，Francart，A.，Rommelaere，H.，Stortelers，C.＆Van Gucht，S。

Post-exposure treatment with anti-rabies VHH and vaccine significantly improves Protection of mice from Lethal rabies infection. PLoS Negl. Trop. Dis.10, e0004902. https://doi.org/10.1371/journal.pntd.0004902 (2016).Article .

。公共科学图书馆。托普。Dis.10，e0004902。https://doi.org/10.1371/journal.pntd.0004902（2016年）。文章。

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Sun, L., Liu, Y., Li, C., Li, D. & Liang, M. Generation of human ScFv antibodies for antigenic site III of rabies virus glycoprotein from antibody-phage libraries by Chain Shuffling. Bing Du Xue Bao32, 393–398 (2016).PubMed

Sun，L.，Liu，Y.，Li，C.，Li，D。＆Liang，M。通过链改组从抗体噬菌体文库产生狂犬病病毒糖蛋白抗原位点III的人ScFv抗体。《冰毒学报》32393-398（2016）。PubMed出版社

Google Scholar

谷歌学者

Boucher, L. E. et al. Stapling scFv for multispecific biotherapeutics of superior properties. MAbs15, 2195517. https://doi.org/10.1080/19420862.2023.2195517 (2023).Article

Boucher，L.E.等人将scFv用于具有优异特性的多特异性生物治疗。MABS152195517。https://doi.org/10.1080/19420862.2023.2195517（2023年）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Midelfort, K. S. et al. Substantial energetic improvement with minimal structural perturbation in a high affinity mutant antibody. J. Mol. Biol.343, 685–701. https://doi.org/10.1016/j.jmb.2004.08.019 (2004).Article

Midelfort，K.S.等人。在高亲和力突变抗体中，以最小的结构扰动进行了实质性的能量改进。J、分子生物学343685-701。https://doi.org/10.1016/j.jmb.2004.08.019（2004年）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Miandehi, N., Bidoki, S., Ajorloo, M. & Gholami, A. Change in the Basic structure of the rabies Virus Glycoprotein by Reverse Genetics. Iran. J. Med. Microbiol.14, 348–360. https://doi.org/10.30699/ijmm.14.4.348 (2020).Article

Miandehi，N.，Bidoki，S.，Ajorloo，M。＆Gholami，A。通过反向遗传学改变狂犬病病毒糖蛋白的基本结构。伊朗。J、。https://doi.org/10.30699/ijmm.14.4.348（2020年）。文章

Google Scholar

谷歌学者

Shi, C. et al. Research progress on neutralizing epitopes and antibodies for the rabies virus. Infect. Med. (2022).Zhao, X. L. et al. Generation and characterization of human monoclonal antibodies to G5, a linear neutralization epitope on glycoprotein of Rabies virus, by phage display technology.

Shi，C.等人。狂犬病病毒中和表位和抗体的研究进展。感染。。Zhao，X.L.等人。通过噬菌体展示技术产生和表征针对狂犬病病毒糖蛋白上线性中和表位G5的人单克隆抗体。

Microbiol. Immunol.52, 89–93. https://doi.org/10.1111/j.1348-0421.2008.00016.x (2008).Article .

CAS

中科院

PubMed

Google Scholar

谷歌学者

World Health Organization (WHO) (2018).World Health Organization (WHO) (2014).McClain, J. B., Chuang, A., Reid, C., Moore, S. M. & Tsao, E. Rabies virus neutralizing activity, pharmacokinetics, and safety of the monoclonal antibody mixture SYN023 in combination with rabies vaccination: results of a phase 2, randomized, blinded, controlled trial.

世界卫生组织（WHO）（2018）。世界卫生组织（WHO）（2014年）。McClain，J.B.，Chuang，A.，Reid，C.，Moore，S.M。＆Tsao，E。单克隆抗体混合物SYN023联合狂犬病疫苗接种的狂犬病病毒中和活性，药代动力学和安全性：第二阶段随机，盲法对照试验的结果。

Vaccine39, 5822–5830. https://doi.org/10.1016/j.vaccine.2021.08.066 (2021).Article .

疫苗395822-5830。https://doi.org/10.1016/j.vaccine.2021.08.066（2021年）。文章。

CAS

中科院

PubMed

Google Scholar

谷歌学者

Bunn, T., Ridpath, H. & Beard, P. The Relationship Between Rabies Antibody Titers in Dogs and Cats and Protection from Challenge (Centers Disease Control, 1984).Rabies, F. Developing monoclonal antibody cocktails for the passive immunization component of post-exposure prophylaxis. Guidance for Industry (2021).Fan, L., Zhang, L., Li, J.

Bunn，T.，Ridpath，H。＆Beard，P。狗和猫的狂犬病抗体滴度与免受攻击之间的关系（Centers Disease Control，1984）。狂犬病，F。为暴露后预防的被动免疫成分开发单克隆抗体混合物。行业指南（2021年）。范丽，张丽，李洁。

& Zhu, F. Advances in the progress of monoclonal antibodies for rabies. Hum. Vaccines Immunother.18, 2026713 (2022).Article .

&Zhu，F。狂犬病单克隆抗体的进展。嗯，疫苗免疫疗法182026713（2022）。文章。

Google Scholar

谷歌学者

World Health Organization (WHO). Rabies Vaccines and Immunoglobulins: WHO Position: Summary of 2017 Updates (WHO, 2018).Andris-Widhopf, J., Steinberger, P., Fuller, R., Rader, C. & Barbas, C. F. Generation of human Fab antibody libraries: PCR amplification and assembly of light- and heavy-chain coding sequences.

世界卫生组织（WHO）。狂犬病疫苗和免疫球蛋白：世卫组织立场：2017年更新摘要（世卫组织，2018年）。Andris Widhopf，J.，Steinberger，P.，Fuller，R.，Rader，C。＆Barbas，C.F。人Fab抗体文库的产生：PCR扩增和轻链和重链编码序列的组装。

Cold Spring Harb Protoc. https://doi.org/10.1101/pdb.prot065565 (2011).Pruksametanan, N. Production of human monoclonal antibodies against rabies virus using phage display technology (Doctoral dissertation) (School of Biotechnology Institute of Agricultural Technology, Suranaree University of Technology, 2013).Pansri, P., Jaruseranee, N., Rangnoi, K., Kristensen, P.

冷泉Harb Protoc。https://doi.org/10.1101/pdb.prot065565（2011年）。Pruksametanan，N。使用噬菌体展示技术生产抗狂犬病病毒的人单克隆抗体（博士论文）（苏里南理工大学农业技术生物技术学院，2013年）。潘斯利（P.Pansri），北卡罗来纳州（Jaruseranee），K.Rangnoi，克里斯滕森（Kristensen）。

& Yamabhai, M. A compact phage display human scFv library for selection of antibodies to a wide variety of antigens. BMC Biotechnol.9, 6. https://doi.org/10.1186/1472-6750-9-6 (2009).Article .

&Yamabhai，M。一种紧凑的噬菌体展示人scFv文库，用于选择针对多种抗原的抗体。BMC生物技术9，6。https://doi.org/10.1186/1472-6750-9-6（2009年）。文章。

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Aavula, S. M. et al. Generation and characterization of an scFv Directed against Site II of rabies glycoprotein. Biotechnol Res Int 652147. https://doi.org/10.4061/2011/652147 (2011).Kumar, R. et al. A novel strategy for efficient production of anti-V3 human scFvs against HIV-1 clade C.

Aavula，S.M.等人。针对狂犬病糖蛋白位点II的scFv的产生和表征。生物技术研究国际652147。https://doi.org/10.4061/2011/652147（2011年）。Kumar，R。等人。一种有效生产抗HIV-1进化枝C的抗V3人scFv的新策略。

BMC Biotechnol.12, 87. https://doi.org/10.1186/1472-6750-12-87 (2012).Article .

BMC生物技术12，87。https://doi.org/10.1186/1472-6750-12-87(2012).第条。

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Braganza, A. et al. Generation and validation of canine single chain variable fragment phage display libraries. Vet. Immunol. Immunopathol.139, 27–40. https://doi.org/10.1016/j.vetimm.2010.07.026 (2011).Article

Braganza，A。等人。犬单链可变片段噬菌体展示文库的产生和验证。兽医。免疫。免疫病理学139,27-40。https://doi.org/10.1016/j.vetimm.2010.07.026（2011年）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Chiang, Y. L., Sheng-Dong, R., Brow, M. A. & Larrick, J. W. Direct cDNA cloning of the rearranged immunoglobulin variable region. Biotechniques7, 360–366 (1989).CAS

Chiang，Y.L.，Sheng Dong，R.，Brow，M.A。和Larrick，J.W。重排免疫球蛋白可变区的直接cDNA克隆。生物技术7360-366（1989）。中科院

PubMed

Google Scholar

谷歌学者

Yamanaka, H. I. & Inoue, T. Ikeda-Tanaka, O. Chicken monoclonal antibody isolated by a phage display system. J. Immunol.157, 1156–1162 (1996).Article

Yamanaka，H.I。＆Inoue，T。Ikeda Tanaka，O。通过噬菌体展示系统分离的鸡单克隆抗体。J、 Immunol.1571156-1162（1996）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Davies, E. L. et al. Selection of specific phage-display antibodies using libraries derived from chicken immunoglobulin genes. J. Immunol. Methods186, 125–135. https://doi.org/10.1016/0022-1759(95)00143-x (1995).Article

Davies，E.L.等人。使用源自鸡免疫球蛋白基因的文库选择特异性噬菌体展示抗体。J、免疫。方法186125-135。https://doi.org/10.1016/0022-1759（95）00143-x（1995）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Andris-Widhopf, J., Rader, C., Steinberger, P., Fuller, R. & Barbas, C. F. Methods for the generation of chicken monoclonal antibody fragments by phage display. J. Immunol. Methods242, 159–181. https://doi.org/10.1016/s0022-1759(00)00221-0 (2000).Article

Andris Widhopf，J.，Rader，C.，Steinberger，P.，Fuller，R。＆Barbas，C.F。通过噬菌体展示产生鸡单克隆抗体片段的方法。J、免疫。方法242、159-181。https://doi.org/10.1016/s0022-1759（00）00221-0（2000）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Sepulveda, J. & Shoemaker, C. B. Design and testing of PCR primers for the construction of scFv libraries representing the immunoglobulin repertoire of rats. J. Immunol. Methods332, 92–102. https://doi.org/10.1016/j.jim.2007.12.014 (2008).Article

Sepulveda，J。＆Shoemaker，C.B。设计和测试PCR引物，用于构建代表大鼠免疫球蛋白库的scFv文库。J、免疫。方法332,92-102。https://doi.org/10.1016/j.jim.2007.12.014（2008年）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Ridder, R., Schmitz, R., Legay, F. & Gram, H. Generation of rabbit monoclonal antibody fragments from a combinatorial phage display library and their production in the yeast Pichia pastoris. Biotechnol. (N Y)13, 255–260. https://doi.org/10.1038/nbt0395-255 (1995).Article

Ridder，R.，Schmitz，R.，Legay，F。＆Gram，H。从组合噬菌体展示文库产生兔单克隆抗体片段及其在酵母毕赤酵母中的产生。生物技术。。https://doi.org/10.1038/nbt0395-255（1995年）。文章

CAS

中科院

Google Scholar

谷歌学者

Steinberger, P., Sutton, J. K., Rader, C., Elia, M. & Barbas, C. F. Generation and characterization of a recombinant human CCR5-specific antibody. A phage display approach for rabbit antibody humanization. J. Biol. Chem.275, 36073–36078. https://doi.org/10.1074/jbc.M002765200 (2000).Article .

Steinberger，P.，Sutton，J.K.，Rader，C.，Elia，M。＆Barbas，C.F。重组人CCR5特异性抗体的产生和表征。用于兔抗体人源化的噬菌体展示方法。J、生物。化学27536073–36078。https://doi.org/10.1074/jbc.M002765200（2000年）。文章。

CAS

中科院

PubMed

Google Scholar

谷歌学者

Scripps Research (2020).Rader, C., Cheresh, D. A. & Barbas, C. F. 3rd. A phage display approach for rapid antibody humanization: designed combinatorial V gene libraries. Proc. Natl. Acad. Sci. USA95, 8910–8915. https://doi.org/10.1073/pnas.95.15.8910 (1998)Popkov, M. et al. Rabbit immune repertoires as sources for therapeutic monoclonal antibodies: the impact of kappa allotype-correlated variation in cysteine content on antibody libraries selected by phage display.

斯克里普斯研究（2020）。Rader，C.，Cheresh，D.A。和Barbas，C.F。第三。用于快速抗体人源化的噬菌体展示方法：设计的组合V基因文库。程序。纳特尔。。科学。美国958910-8915。https://doi.org/10.1073/pnas.95.15.8910（1998）Popkov，M。等人。兔免疫库作为治疗性单克隆抗体的来源：半胱氨酸含量的kappa同种异型相关变异对噬菌体展示选择的抗体文库的影响。

J. Mol. Biol.325, 325–335. https://doi.org/10.1016/s0022-2836(02)01232-9 (2003).Article .

CAS

中科院

PubMed

Google Scholar

谷歌学者

Pan, Y. et al. Screening of potent neutralizing antibodies against SARS-CoV-2 using convalescent patients-derived phage-display libraries. Cell Discov.7, 57. https://doi.org/10.1038/s41421-021-00295-w (2021).Article

Pan，Y。等人。使用恢复期患者来源的噬菌体展示文库筛选针对SARS-CoV-2的有效中和抗体。细胞发现7,57。https://doi.org/10.1038/s41421-021-00295-w（2021年）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Ray, K., Embleton, M. J., Jailkhani, B. L., Bhan, M. K. & Kumar, R. Selection of single chain variable fragments (scFv) against the glycoprotein antigen of the Rabies virus from a human synthetic scFv phage display library and their fusion with the fc region of human IgG1. Clin. Exp.

Ray，K.，Embleton，M.J.，Jailkhani，B.L.，Bhan，M.K。＆Kumar，R。从人合成scFv噬菌体展示文库中选择针对狂犬病病毒糖蛋白抗原的单链可变片段（scFv）及其与人IgG1的fc区融合。临床。实验。

Immunol.125, 94–101. https://doi.org/10.1046/j.1365-2249.2001.01515.x (2001).Article .

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Ando, T., Yamashiro, T., Takita-Sonoda, Y., Mannen, K. & Nishizono, A. Construction of human Fab library and isolation of monoclonal fabs with rabies virus-neutralizing ability. Microbiol. Immunol.49, 311–322. https://doi.org/10.1111/j.1348-0421.2005.tb03735.x (2005).Article

Ando，T.，Yamashiro，T.，Takita-Sonoda，Y.，Mannen，K.＆Nishizono，A.人Fab文库的构建和具有狂犬病病毒中和能力的单克隆Fab的分离。微生物。免疫L.49311-322。https://doi.org/10.1111/j.1348-0421.2005.tb03735.x（2005年）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Kramer, R. A. et al. The human antibody repertoire specific for Rabies virus glycoprotein as selected from immune libraries. Eur. J. Immunol.35, 2131–2145. https://doi.org/10.1002/eji.200526134 (2005).Article

Kramer，R.A。等人。从免疫文库中选择的狂犬病病毒糖蛋白特异性人抗体库。《欧洲免疫学杂志》352131-2145。https://doi.org/10.1002/eji.200526134（2005年）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Liu, X. et al. Characterization of a human antibody fragment Fab and its calcium phosphate nanoparticles that inhibit rabies virus infection with vaccine. PLoS ONE6, e19848. https://doi.org/10.1371/journal.pone.0019848 (2011).Article

Liu，X。等人。人抗体片段Fab及其磷酸钙纳米颗粒的表征，其抑制狂犬病病毒感染疫苗。公共科学图书馆ONE6，e19848。https://doi.org/10.1371/journal.pone.0019848（2011年）。文章

ADS

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Pitaksajjakul, P. et al. Fab MAbs specific to HA of influenza virus with H5N1 neutralizing activity selected from immunized chicken phage library. Biochem. Biophys. Res. Commun.395, 496–501. https://doi.org/10.1016/j.bbrc.2010.04.040 (2010).Article

Pitaksajjakul，P。等人。从免疫鸡噬菌体文库中选择具有H5N1中和活性的流感病毒HA特异性Fab单克隆抗体。生物化学。生物物理。公社第395496-501号决议。https://doi.org/10.1016/j.bbrc.2010.04.040（2010年）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Lee, C. H. et al. The bottlenecks of preparing Virus particles by size exclusion for antibody generation. Int. J. Mol. Sci.. https://doi.org/10.3390/ijms232112967 (2022).Reiche, N. et al. Generation and characterization of human monoclonal scFv antibodies against Helicobacter pylori antigens.

Lee，C.H.等人。通过尺寸排阻制备病毒颗粒以产生抗体的瓶颈。国际分子科学杂志。。https://doi.org/10.3390/ijms232112967（2022年）。Reiche，N.等人。针对幽门螺杆菌抗原的人单克隆scFv抗体的产生和表征。

Infect. Immun.70, 4158–4164. https://doi.org/10.1128/IAI.70.8.4158-4164.2002 (2002).Article .

感染。免疫704158-4164。https://doi.org/10.1128/IAI.70.8.4158-4164.2002（2002年）。文章。

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Lee, W., Syed, A. A., Leow, C. Y., Tan, S. C. & Leow, C. H. Isolation and characterization of a novel anti-salbutamol chicken scFv for human doping urinalysis. Anal. Biochem.555, 81–93. https://doi.org/10.1016/j.ab.2018.05.009 (2018).Article

Lee，W.，Syed，A.A.，Leow，C.Y.，Tan，S.C。＆Leow，C.H。用于人类兴奋剂尿液分析的新型抗沙丁胺醇鸡scFv的分离和表征。肛门。生物化学555，81-93。https://doi.org/10.1016/j.ab.2018.05.009（2018年）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Wang, F. et al. Generation and functional analysis of single chain variable fragments (scFvs) targeting the nucleocapsid protein of porcine epidemic diarrhea virus. Appl. Microbiol. Biotechnol.106, 995–1009. https://doi.org/10.1007/s00253-021-11722-z (2022).Article

Wang，F。等人。针对猪流行性腹泻病毒核衣壳蛋白的单链可变片段（scFv）的产生和功能分析。应用。微生物。生物技术.106995-1009。https://doi.org/10.1007/s00253-021-11722-z（2022年）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Li, C. et al. Construction and screening of human immunized phage-display antibody libraries against Rabies virus. Acta Univ. Med. Nanjing (Natural Sci)30, 575–578 (2010).

Li，C。等人。抗狂犬病病毒人免疫噬菌体展示抗体文库的构建和筛选。南京大学学报（自然科学版）30575-578（2010）。

Google Scholar

谷歌学者

Hultberg, A. et al. Llama-derived single domain antibodies to build multivalent, superpotent and broadened neutralizing anti-viral molecules. PLoS One. 6, e17665. https://doi.org/10.1371/journal.pone.0017665 (2011).Article

Hultberg，A。等人。美洲驼衍生的单结构域抗体可构建多价，超能力和拓宽的中和抗病毒分子。PLoS One。6，e17665。https://doi.org/10.1371/journal.pone.0017665（2011年）。文章

ADS

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Zhang, Y. In MAbs. 2213793 (Taylor & Francis).Bao, Y., Guo, Y., Xiao, S. & Zhao, Z. Molecular characterization of the VH repertoire in Canis familiaris. Vet. Immunol. Immunopathol.137, 64–75. https://doi.org/10.1016/j.vetimm.2010.04.011 (2010).Article

张，Y。在单克隆抗体中。2213793（泰勒和弗朗西斯）。Bao，Y.，Guo，Y.，Xiao，S。＆Zhao，Z。熟悉犬VH库的分子表征。兽医。免疫。免疫病理学137,64-75。https://doi.org/10.1016/j.vetimm.2010.04.011（2010年）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Bernat, N. V. Definition of Immunoglobulin Germline Genes by Next Generation Sequencing for Studies of Antigen-Specific B Cell Responses (Karolinska Institutet (Sweden), 2019).Cullen, J. N. et al. Development and application of a next-generation sequencing protocol and bioinformatics pipeline for the comprehensive analysis of the canine immunoglobulin repertoire.

Bernat，N.V。通过下一代测序定义免疫球蛋白种系基因，用于抗原特异性B细胞应答的研究（Karolinska Institutet（瑞典），2019）。Cullen，J.N.等人。用于犬免疫球蛋白库综合分析的下一代测序方案和生物信息学管道的开发和应用。

PLoS ONE17, e0270710. https://doi.org/10.1371/journal.pone.0270710 (2022).Article .

公共科学图书馆ONE17，e027710。https://doi.org/10.1371/journal.pone.0270710（2022年）。文章。

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Steiniger, S. C. et al. Fundamental characteristics of the expressed immunoglobulin VH and VL repertoire in different canine breeds in comparison with those of humans and mice. Mol. Immunol.59, 71–78. https://doi.org/10.1016/j.molimm.2014.01.010 (2014).Article

Steiniger，S.C.等人。与人类和小鼠相比，不同犬种中表达的免疫球蛋白VH和VL库的基本特征。分子免疫学59,71-78。https://doi.org/10.1016/j.molimm.2014.01.010（2014年）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Arndt, K. M., Müller, K. M. & Plückthun, A. Factors influencing the dimer to monomer transition of an antibody single-chain fv fragment. Biochemistry37, 12918–12926. https://doi.org/10.1021/bi9810407 (1998).Article

Arndt，K.M.，Müller，K.M。和Plückthun，A。影响抗体单链fv片段二聚体向单体转变的因素。生物化学3712918-12926。https://doi.org/10.1021/bi9810407（1998年）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Hudson, P. J. & Kortt, A. A. High avidity scFv multimers; diabodies and triabodies. J. Immunol. Methods231, 177–189 (1999).Article

Hudson，P.J。＆Kortt，A.A。高亲和力scFv多聚体；diabodies和triabodies。J、免疫。方法231177-189（1999）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Le Gall, F., Kipriyanov, S. M., Moldenhauer, G. & Little, M. Di-, tri-and tetrameric single chain fv antibody fragments against human CD19: effect of valency on cell binding. FEBS Lett.453, 164–168 (1999).Article

Le Gall，F.，Kipriyanov，S.M.，Moldenhauer，G。＆Little，M。针对人CD19的二聚体，三聚体和四聚体单链fv抗体片段：效价对细胞结合的影响。FEBS Lett.453164-168（1999）。文章

PubMed

Google Scholar

谷歌学者

Arslan, M. et al. Effect of non-repetitive linker on in vitro and in vivo properties of an anti-VEGF scFv. Sci. Rep.12, 5449 (2022).Article

Arslan，M.等人。非重复接头对抗VEGF scFv体外和体内特性的影响。科学。Rep.125449（2022年）。文章

ADS

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Quintero-Hernández, V. et al. The change of the scFv into the Fab format improves the stability and in vivo toxin neutralization capacity of recombinant antibodies. Mol. Immunol.44, 1307–1315. https://doi.org/10.1016/j.molimm.2006.05.009 (2007).Article

Quintero-Hernández，V。等人。将scFv改变为Fab形式可提高重组抗体的稳定性和体内毒素中和能力。分子免疫学441307-1315。https://doi.org/10.1016/j.molimm.2006.05.009（2007年）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Röthlisberger, D., Honegger, A. & Plückthun, A. Domain interactions in the Fab Fragment: A comparative evaluation of the single-chain fv and Fab Format Engineered with Variable domains of different Stability. J. Mol. Biol.347, 773–789. https://doi.org/10.1016/j.jmb.2005.01.053 (2005).Article .

Röthlisberger，D.，Honegger，A。＆Plückthun，A。Fab片段中的域相互作用：用不同稳定性的可变域设计的单链fv和Fab格式的比较评估。J、分子生物学347773-789。https://doi.org/10.1016/j.jmb.2005.01.053（2005年）。文章。

CAS

中科院

PubMed

Google Scholar

谷歌学者

Zhao, X. L. et al. Selection and affinity maturation of human antibodies against Rabies virus from a scFv gene library using ribosome display. J. Biotechnol.144, 253–258. https://doi.org/10.1016/j.jbiotec.2009.09.022 (2009).Article

Zhao，X.L.等人。使用核糖体展示从scFv基因文库中选择和亲和力成熟抗狂犬病病毒的人抗体。J、。https://doi.org/10.1016/j.jbiotec.2009.09.022（2009年）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Muller, T. et al. Development of a mouse monoclonal antibody cocktail for post-exposure rabies prophylaxis in humans. PLoS Negl. Trop. Dis.3, e542. https://doi.org/10.1371/journal.pntd.0000542 (2009).Article

Muller，T.等人开发了一种用于人类暴露后狂犬病预防的小鼠单克隆抗体混合物。公共科学图书馆。托普。图3，e542。https://doi.org/10.1371/journal.pntd.0000542（2009年）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Kim, P. K. et al. A broad-spectrum and highly potent human monoclonal antibody cocktail for rabies prophylaxis. PLoS ONE16, e0256779. https://doi.org/10.1371/journal.pone.0256779 (2021).Article

Kim，P.K.等人。一种用于预防狂犬病的广谱高效人单克隆抗体混合物。公共科学图书馆ONE16，e0256779。https://doi.org/10.1371/journal.pone.0256779（2021年）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Hellert, J. et al. Structure of the prefusion-locking broadly neutralizing antibody RVC20 bound to the Rabies virus glycoprotein. Nat. Commun.11, 596. https://doi.org/10.1038/s41467-020-14398-7 (2020).Article

Hellert，J.等人。与狂犬病病毒糖蛋白结合的融合前锁定广泛中和抗体RVC20的结构。《国家公社》11596。https://doi.org/10.1038/s41467-020-14398-7（2020年）。文章

ADS

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Gogtay, N. J. et al. Comparison of a Novel human rabies monoclonal antibody to human rabies immunoglobulin for Postexposure Prophylaxis: a phase 2/3, Randomized, Single-Blind, Noninferiority, controlled study. Clin. Infect. Dis.66, 387–395. https://doi.org/10.1093/cid/cix791 (2018).Article .

Gogtay，N.J.等人。新型人狂犬病单克隆抗体与人狂犬病免疫球蛋白在暴露后预防中的比较：2/3期，随机，单盲，非劣效，对照研究。临床。感染。Dis.66387-395。https://doi.org/10.1093/cid/cix791（2018年）。文章。

CAS

中科院

PubMed

Google Scholar

谷歌学者

Bakker, A. B. et al. First administration to humans of a monoclonal antibody cocktail against Rabies virus: safety, tolerability, and neutralizing activity. Vaccine26, 5922–5927. https://doi.org/10.1016/j.vaccine.2008.08.050 (2008).Article

Bakker，A.B.等人首次向人类施用抗狂犬病病毒的单克隆抗体混合物：安全性，耐受性和中和活性。疫苗265922-5927。https://doi.org/10.1016/j.vaccine.2008.08.050（2008年）。文章

CAS

中科院

PubMed

Google Scholar

谷歌学者

Sun, L., Liu, Y., Li, C., Li, D. & Liang, M. [Development of recombinant human monoclonal antibody cocktail for post-exposure rabies Prophylaxis]. Bing Du Xue Bao32, 399–403 (2016).PubMed

Sun，L.，Liu，Y.，Li，C.，Li，D.＆Liang，M.[用于暴露后狂犬病预防的重组人单克隆抗体混合物的开发]。《冰毒学报》32399–403（2016）。PubMed出版社

Google Scholar

谷歌学者

Chao, T. Y. et al. SYN023, a novel humanized monoclonal antibody cocktail, for post-exposure prophylaxis of rabies. PLoS Negl. Trop. Dis.11, e0006133. https://doi.org/10.1371/journal.pntd.0006133 (2017).Article

Chao，T.Y.等人，SYN023，一种新型人源化单克隆抗体混合物，用于暴露后预防狂犬病。公共科学图书馆。托普。Dis.11，e0006133。https://doi.org/10.1371/journal.pntd.0006133（2017年）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

De Benedictis, P. et al. Development of broad-spectrum human monoclonal antibodies for rabies post-exposure prophylaxis. EMBO Mol. Med.8, 407–421. https://doi.org/10.15252/emmm.201505986 (2016).Article

。EMBO分子医学8407-421。https://doi.org/10.15252/emmm.201505986（2016年）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Papaneri, A. B., Wirblich, C., Marissen, W. E. & Schnell, M. J. Alanine scanning of the Rabies virus glycoprotein antigenic site III using recombinant rabies virus: implication for post-exposure treatment. Vaccine31, 5897–5902. https://doi.org/10.1016/j.vaccine.2013.09.038 (2013).Article .

Papaneri，A.B.，Wirblich，C.，Marissen，W.E。＆Schnell，M.J。使用重组狂犬病病毒对狂犬病病毒糖蛋白抗原位点III进行丙氨酸扫描：对暴露后治疗的意义。疫苗315897-5902。https://doi.org/10.1016/j.vaccine.2013.09.038（2013年）。文章。

CAS

中科院

PubMed

Google Scholar

谷歌学者

Chao, T. Y., Zhang, S. F., Chen, L., Tsao, E. & Rupprecht, C. E. In vivo efficacy of SYN023, an anti-rabies monoclonal antibody cocktail, in Post-exposure Prophylaxis Animal models. Trop. Med. Infect. Dis.5https://doi.org/10.3390/tropicalmed5010031 (2020).Tuffereau, C. et al. Arginine or lysine in position 333 of ERA and CVS glycoprotein is necessary for rabies virulence in adult mice.

Chao，T.Y.，Zhang，S.F.，Chen，L.，Tsao，E。＆Rupprecht，C.E。SYN023（一种抗狂犬病单克隆抗体混合物）在暴露后预防动物模型中的体内功效。托普。医学感染。第5部分https://doi.org/10.3390/tropicalmed5010031（2020年）。ERA和CVS糖蛋白333位的精氨酸或赖氨酸是成年小鼠狂犬病毒力所必需的。

Virology172, 206–212. https://doi.org/10.1016/0042-6822(89)90122-0 (1989).Article .

CAS

中科院

PubMed

Google Scholar

谷歌学者

Tanwattana, N. et al. Human BST2 inhibits Rabies virus release independently of cysteine-linked dimerization and asparagine-linked glycosylation. Plos ONE18, e0292833 (2023).Article

Tanwattana，N。等人。人BST2抑制狂犬病病毒的释放，而不依赖于半胱氨酸连接的二聚化和天冬酰胺连接的糖基化。Plos ONE18，e0292833（2023）。文章

CAS

中科院

PubMed

PubMed Central

公共医学中心

Google Scholar

谷歌学者

Download referencesAcknowledgementsThis research was funded by (1) National Research Council of Thailand (NRCT) and Kasetsart University (KU), grant number N42A670624. (2) Research and Researchers for Industries (RRi) Ph.D. scholarships, grant number PHD60I0075 awarded by the National Research Council of Thailand (NRCT); (3) Research Scholarships for Graduate Students of Universities in Thailand, awarded by The KING PRAJADHIPOK and QUEEN RAMBHAIBARNI MEMORIAL FOUNDATION.

下载参考文献致谢本研究由（1）泰国国家研究委员会（NRCT）和Kasetsart大学（KU）资助，资助号为N42A670624。（2）泰国国家研究委员会（NRCT）授予工业研究与研究人员（RRi）博士奖学金，资助号PHD60I0075；（3）泰国国王普拉贾德希波克（KING PRAJADHIPOK）和兰巴尼女王纪念基金会（QUEEN Rambaibani MEMORIAL FOUNDATION）授予泰国大学研究生研究奖学金。

We would like to sincerely thank the dogs’ owners and all the dogs used for the sample collection. Special thanks to JICA, who kindly provided the budget for laboratory equipment that was used in this study.Author informationAuthors and AffiliationsDepartment of Social and Environmental Medicine, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, ThailandApidsada Chorpunkul, Pannamthip Pitaksajjakul & Pongrama RamasootaDepartment of Molecular Tropical Medicine and Genetics, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, ThailandUsa BoonyuenDepartment of Tropical Pediatrics, Faculty of Tropical Medicine, Mahidol University, Bangkok, 10400, ThailandKriengsak LimkittikulQueen Saovabha Memorial Institute (WHO Collaborating Center for Research on Rabies), Thai Red Cross Society, Bangkok, 10330, ThailandWachiraporn SaengseesomDepartment of Pathology, Faculty of Veterinary Medicine, Kasetsart University, Bangkok, 10900, ThailandWallaya Phongphaew & Iyarath PutchongDepartment of Microbiology and Immunology, Faculty of Veterinary Medicine, Kasetsart University, Bangkok, 10900, ThailandPenpitcha Chankeeree & Porntippa LekcharoensukDepartment of Anatomy, Faculty of Veterinary Medicine, Kasetsart University, Bangkok, 10900, ThailandSirin TheerawatanasirikulCancer Ph.

我们要衷心感谢狗的主人和所有用于样本采集的狗。特别感谢JICA，他为本研究中使用的实验室设备提供了预算。，曼谷Kasetsart大学兽医学院，10900，Thailand Sirin TheerawatanasirikulCancer Ph。

PubMed Google ScholarUsa BoonyuenView author publicationsYou can also search for this author in

PubMed Google ScholarUsa BoonyuenView作者出版物您也可以在

PubMed Google ScholarKriengsak LimkittikulView author publicationsYou can also search for this author in

PubMed谷歌奖学金Kriengsak Limkittikul查看作者出版物您也可以在

PubMed Google ScholarWachiraporn SaengseesomView author publicationsYou can also search for this author in

PubMed Google ScholarWachiraporn SaengseesomView作者出版物您也可以在

PubMed Google ScholarWallaya PhongphaewView author publicationsYou can also search for this author in

PubMed Google ScholarWallaya PhongphaewView作者出版物您也可以在

PubMed Google ScholarIyarath PutchongView author publicationsYou can also search for this author in

PubMed谷歌学术评论PutchongView作者出版物您也可以在

PubMed Google ScholarPenpitcha ChankeereeView author publicationsYou can also search for this author in

PubMed Google ScholarPenpitcha Chankeereview作者出版物您也可以在

PubMed Google ScholarSirin TheerawatanasirikulView author publicationsYou can also search for this author in

PubMed Google ScholarSirin TheerawatanasirikulView作者出版物您也可以在

PubMed Google ScholarAmin HajitouView author publicationsYou can also search for this author in

PubMed Google ScholarAmin HajitouView作者出版物您也可以在

PubMed Google ScholarSurachet BenjathummarakView author publicationsYou can also search for this author in

PubMed Google ScholarSurachet BenjathummarakView作者出版物您也可以在

PubMed Google ScholarPannamthip PitaksajjakulView author publicationsYou can also search for this author in

PubMed Google ScholarPannamthip PitaksajjakulView作者出版物您也可以在

PubMed Google ScholarPorntippa LekcharoensukView author publicationsYou can also search for this author in

PubMed Google ScholarPorntippa LekcharoensukView作者出版物您也可以在

PubMed Google ScholarPongrama RamasootaView author publicationsYou can also search for this author in

PubMed Google ScholarPongrama RamasootaView作者出版物您也可以在

PubMed Google ScholarContributionsConceptualization, P.R., P.P., P.L., A.C., S.B., U.B., K.L. ; methodology, A.C., P.C., W.S., W.P., and I.P.; Software, A.C., U.B., and S.T.; validation, A.C., P.P. and P.L. ; formal analysis, P.R.; investigation, A.C. ; resources, P.R., P.P., P.L., W.P., A.H.

PubMed谷歌学术贡献概念化，P.R.，P.P.，P.L.，A.C.，S.B.，U.B.，K.L；方法论，A.C.，P.C.，W.S.，W.P。和I.P。；软件，A.C.，U.B。和S.T。；验证，A.C.，P.P.和P.L；形式分析，P.R。；调查，A.C；资源，P.R.，P.P.，P.L.，W.P.，A.H。

; data curation, P.R., P.P., P.L.; writing—original draft preparation, A.C. ; writing-review and editing, P.R., S.B., and P.P.; visualization, A.C., S.T., P.L., P.P. and P.R.; supervision, P.R., P.L., P.P., and A.H.; project administration, P.L., and P.R. ; funding acquisition, P.L. All authors have read and agreed to the published version of the manuscript.Corresponding authorCorrespondence to.

；数据管理，P.R.，P.P.，P.L。；；写作评论和编辑，P.R.，S.B。和P.P。；可视化，A.C.，S.T.，P.L.，P.P.和P.R。；监督，P.R.，P.L.，P.P。和A.H。；项目管理，P.L。和P.R；资助获取，P.L。所有作者都阅读并同意稿件的发布版本。对应作者对应。

Pongrama Ramasoota.Ethics declarations

蓬拉马·拉马苏塔。道德宣言

Competing interests

相互竞争的利益

The authors declare no competing interests.

作者声明没有利益冲突。

Additional informationPublisher’s noteSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Electronic supplementary materialBelow is the link to the electronic supplementary material.Supplementary Material 1Rights and permissions

Additional informationPublisher的noteSpringer Nature在已发布地图和机构隶属关系中的管辖权主张方面保持中立。电子补充材料流是指向电子补充材料的链接。补充材料1权利和许可

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material.

。

You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.

To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/..

要查看此许可证的副本，请访问http://creativecommons.org/licenses/by-nc-nd/4.0/..

Reprints and permissionsAbout this articleCite this articleChorpunkul, A., Boonyuen, U., Limkittikul, K. et al. Development of novel canine phage display-derived neutralizing monoclonal antibody fragments against rabies virus from immunized dogs.

转载和许可本文引用本文Chorpunkul，A.，Boonyuen，U.，Limkittikul，K。等人开发了新型犬噬菌体展示衍生的抗免疫犬狂犬病病毒中和单克隆抗体片段。

Sci Rep 14, 22939 (2024). https://doi.org/10.1038/s41598-024-73339-2Download citationReceived: 23 May 2024Accepted: 16 September 2024Published: 03 October 2024DOI: https://doi.org/10.1038/s41598-024-73339-2Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

科学报告1422939（2024）。https://doi.org/10.1038/s41598-024-73339-2Download引文接收日期：2024年5月23日接受日期：2024年9月16日发布日期：2024年10月3日OI：https://doi.org/10.1038/s41598-024-73339-2Share本文与您共享以下链接的任何人都可以阅读此内容：获取可共享链接对不起，本文目前没有可共享的链接。。

Provided by the Springer Nature SharedIt content-sharing initiative

由Springer Nature SharedIt内容共享计划提供

CommentsBy submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

评论通过提交评论，您同意遵守我们的条款和社区指南。如果您发现有虐待行为或不符合我们的条款或准则，请将其标记为不合适。

全球产业链接平台

重庆市渝北区金星科技大厦A区5楼512室

联系电话：023-67139735（重庆）

关于我们

产品服务