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中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志
中国生物工程杂志  2023, Vol. 43 Issue (9): 46-54    DOI: 10.13523/j.cb.2303035
综述     
HIV-1广谱中和抗体筛选技术的研究进展*
蒋雯玲1,邓婷婷2,李少伟1,2,顾颖1,2,**()
1 厦门大学公共卫生学院 国家传染病诊断试剂与疫苗工程技术研究中心 厦门 361102
2 厦门大学生命科学学院 分子疫苗学与分子诊断学国家重点实验室 厦门 361102
Research Progress of the Screening Technique for HIV- 1 Broad-spectrum Neutralizing Antibodies
JIANG Wen-ling1,DENG Ting-ting2,LI Shao-wei1,2,GU Ying1,2,**()
1 National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, Xiamen University, Xiamen 361102, China
2 State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Life Sciences, Xiamen University, Xiamen 361102, China
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摘要：

HIV-1广谱中和抗体(HIV-1 bNAbs)是一类可以中和大多数流行株的抗体。HIV-1 bNAbs的研究可以为抗艾滋病药物提供候选分子和为艾滋病疫苗设计提供指导,是评估艾滋病疫苗效果的重要指标之一。HIV-1 bNAbs可通过传统筛选技术获得,如杂交瘤技术、EBV转化和展示库技术等。近年来,随着单细胞克隆和分选技术的发展,HIV-1 bNAbs的筛选效率和抗体特异性显著提高。多项技术结合的筛选手段和新型筛选技术LIBRA-seq,以及生物信息学辅助的筛选技术将抗体序列和功能信息统一起来,为HIV-1 bNAbs筛选和疫苗设计提供技术支持。除了HIV-1,这些筛选技术和方法也可用于其他病毒bNAbs的筛选,为疫苗设计和抗病毒药物开发提供了有益启示。综述了广泛应用于HIV-1 bNAbs的筛选技术和最新进展,为后续HIV-1或其他病毒 bNAbs的筛选提供参考。
关键词： HIV-1广谱中和抗体;  筛选技术;  LIBRA-seq;  生物信息学    
Abstract:

HIV-1 broadly neutralizing antibodies (HIV-1 bNAbs) are a class of antibodies that can neutralize most of the circulating strains. The study of HIV-1 bNAbs can provide candidates for anti-AIDS drugs and guide vaccine design, and meanwhile HIV-1 bNAbs is an important indicator for evaluating the efficacy of HIV-1 vaccines. HIV-1 bNAbs can be obtained through traditional screening techniques, such as hybridoma technology, Epstein-Barr virus transformation, and the display library technology. In recent years, with the development of single-cell cloning and sorting technologies, the screening efficiency and antibody specificity of HIV-1 bNAbs have significantly improved. Combined screening methods and novel screening technologies, such as LIBRA-seq and bioinformatics-assisted screening techniques, can unify antibody sequences and functional information, providing technical support for HIV-1 bNAb screening and vaccine design. In addition, these screening techniques and methods for HIV-1 can also be used for the screening of bNAbs against other viruses, providing useful insights into vaccine design and antiviral drug development. This article reviews the widely used screening techniques and latest advances in HIV-1 bNAbs, providing a reference for the screening of HIV-1 or other viruses’ bNAbs in the future.
Key words: HIV-1 broadly neutralizing antibodies    Screening technology    LIBRA-seq    Bioinformatics
收稿日期: 2023-03-13 出版日期: 2023-10-08
ZTFLH:  Q819  
基金资助: * 国家自然科学基金(82171821)
通讯作者: ** 电子信箱:guying@xmu.edu.cn   
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引用本文:

蒋雯玲, 邓婷婷, 李少伟, 顾颖. HIV-1广谱中和抗体筛选技术的研究进展*[J]. 中国生物工程杂志, 2023, 43(9): 46-54.

JIANG Wen-ling, DENG Ting-ting, LI Shao-wei, GU Ying. Research Progress of the Screening Technique for HIV- 1 Broad-spectrum Neutralizing Antibodies. China Biotechnology, 2023, 43(9): 46-54.

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https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2303035    或    https://manu60.magtech.com.cn/biotech/CN/Y2023/V43/I9/46

广谱中和抗体 识别表位 分离方法 IC50/
(μg/mL)		 测试
毒株数		 中和宽度
/%		 VH-gene
突变		 CDRH3
长度/aa		 参考文献
PGT145 V2 apex B细胞非永生化培养/中和 0.29 162 78 18 31 [38]
PG9 V2 apex B细胞非永生化培养/中和 0.22 162 79 13 28 [39]
PG16 V2 apex B细胞非永生化培养/中和 0.15 162 73 12 28 [39]
PGDM1400 V2 apex B细胞分选和克隆 0.003 106 83 24.3 34 [48]
PGT121 V3 glycan B细胞非永生化培养/中和 0.03 162 70 17 24 [38]
PGT128 V3 glycan B细胞非永生化培养/中和 0.02 162 72 19 19 [38]
10-1074 V3 glycan B细胞分选和克隆 0.039 178 67 28 24 [49]
2G12 V3 glycan 杂交瘤筛选技术 1.45 208 32 21 14 [34]
B12 CD4bs 噬菌体筛选技术 2.204 190 47 13 18 [35]
CH103 CD4bs B细胞分选和克隆 0.699 196 85 16.8 13 [50]
N6 CD4bs B细胞分选和克隆 0.038 181 98 31 15 [72]
N49-P7 CD4bs B细胞分选和克隆 0.100 117 100 24 21 [73]
VRC01 CD4bs B细胞分选和克隆 0.33 208 91 32 14 [51]
3BNC117 CD4bs B细胞分选和克隆 0.097 120 85 30 12 [54]
VRC-PG04 CD4bs B细胞分选和克隆 0.196 178 76 30 14 [53]
8ANC131 CD4bs B细胞分选和克隆 1.832 175 78 26 16 [54]
VRC07 CD4bs B细胞分选和克隆 0.11 179 93 26 18 [74]
VRC13 CD4bs B细胞分选和克隆 0.113 175 82 34 21 [75]
2F5 MPER 杂交瘤筛选技术 1.44 177 67 14 22 [36]
4E10 MPER 杂交瘤筛选技术 1.765 180 98 14 20 [36]
10E8 MPER B细胞非永生化培养/中和 0.299 180 98 21 22 [43]
DH511 MPER B细胞分选和克隆 0.674 210 98 10.6 23 [76]
PG151 gp120-gp41 interface B细胞非永生化培养/中和 0.023 117 66 20 28 [44]
35O22 gp120-gp41 interface B细胞非永生化培养/中和 0.151 181 62 35 14 [45]
ACS202 Fusion peptide B细胞分选和克隆 0.140 75 45 16 22 [52]
SF12 Silent face B细胞分选和克隆 0.20 119 62 17 23 [77]
表1  HIV-1广谱中和抗体及其分离方法
技术 方法 效率 亲和力 轻重链配对 特异性 稳定表达来源
传统筛选技术 杂交瘤筛选技术 低 低 天然 低 永生化细胞
EBV转化技术 低 低 天然 低 永生化细胞
抗体展示库 低 高 重组 低 基因重组
B细胞非永生化培养和
高通量细胞分选技术		 B细胞非永生化培养 中 低 天然 高 基因重组
高通量单个B细胞分选和克隆 中 高 天然 高 基因重组
新型筛选技术 多方法结合的筛选技术 高 高 天然 高 基因重组
抗原特异性连接测序技术 高 高 天然 高 基因重组
生物信息学辅助的筛选技术 高 高 天然 高 基因重组
表2  HIV-1广谱中和抗体筛选技术比较
[1] Lee J H, Crotty S. HIV vaccinology: 2021 update. Seminars in Immunology, 2021, 51: 101470.
doi: 10.1016/j.smim.2021.101470
[2] UNAIDS 2021 Epidemiological Estimates. Global HIV & AIDS statistics. [2022-02-24]. https://www.unaids.org/en/resources/fact-sheet.
[3] Li G D, Wang Y L, De Clercq E. Approved HIV reverse transcriptase inhibitors in the past decade. Acta Pharmaceutica Sinica B, 2022, 12(4): 1567-1590.
doi: 10.1016/j.apsb.2021.11.009 pmid: 35847492
[4] Markham A. Ibalizumab: first global approval. Drugs, 2018, 78(7): 781-785.
doi: 10.1007/s40265-018-0907-5 pmid: 29675744
[5] Mullard A. FDA approves 100th monoclonal antibody product. Nature Reviews Drug Discovery, 2021, 20(7): 491-495.
doi: 10.1038/d41573-021-00079-7 pmid: 33953368
[6] Corey L, Gilbert P B, Juraska M, et al. Two randomized trials of neutralizing antibodies to prevent HIV-1 acquisition. The New England Journal of Medicine, 2021, 384(11): 1003-1014.
doi: 10.1056/NEJMoa2031738 pmid: 33730454
[7] Gaebler C, Nogueira L, Stoffel E, et al. Prolonged viral suppression with anti-HIV-1 antibody therapy. Nature, 2022, 606(7913): 368-374.
doi: 10.1038/s41586-022-04597-1
[8] Gruell H, Gunst J D, Cohen Y Z, et al. Effect of 3BNC117 and romidepsin on the HIV-1 reservoir in people taking suppressive antiretroviral therapy (ROADMAP): a randomised, open-label, phase 2A trial. The Lancet Microbe, 2022, 3(3): e203-e214.
doi: 10.1016/S2666-5247(21)00239-1
[9] Haynes B F, Burton D R, Mascola J R. Multiple roles for HIV broadly neutralizing antibodies. Science Translational Medicine, 2019, 11(516): eaaz2686.
doi: 10.1126/scitranslmed.aaz2686
[10] Julg B, Barouch D. Broadly neutralizing antibodies for HIV-1 prevention and therapy. Seminars in Immunology, 2021, 51: 101475.
doi: 10.1016/j.smim.2021.101475
[11] Prashar P, Swain S, Adhikari N, et al. A novel high-throughput single B-cell cloning platform for isolation and characterization of high-affinity and potent SARS-CoV-2 neutralizing antibodies. Antiviral Research, 2022, 203: 105349.
doi: 10.1016/j.antiviral.2022.105349
[12] Smith S A, Crowe J E Jr. Use of human hybridoma technology to isolate human monoclonal antibodies. Microbiology Spectrum, 2015, 3(1): AID-0027-2014.
[13] Köhler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature, 1975, 256(5517): 495-497.
doi: 10.1038/256495a0
[14] Parray H A, Shukla S, Samal S, et al. Hybridoma technology a versatile method for isolation of monoclonal antibodies, its applicability across species, limitations, advancement and future perspectives. International Immunopharmacology, 2020, 85: 106639.
doi: 10.1016/j.intimp.2020.106639
[15] Stephenson K E, Wagh K, Korber B, et al. Vaccines and broadly neutralizing antibodies for HIV-1 prevention. Annual Review of Immunology, 2020, 38: 673-703.
doi: 10.1146/annurev-immunol-080219-023629 pmid: 32340576
[16] Moraes J Z, Hamaguchi B, Braggion C, et al. Hybridoma technology: is it still useful? Current Research in Immunology, 2021, 2: 32-40.
[17] Mitra S, Tomar P C. Hybridoma technology; advancements, clinical significance, and future aspects. Journal, Genetic Engineering & Biotechnology, 2021, 19(1): 159.
[18] Lonberg N, Taylor L D, Harding F A, et al. Antigen-specific human antibodies from mice comprising four distinct genetic modifications. Nature, 1994, 368(6474): 856-859.
doi: 10.1038/368856a0
[19] Markham A. Correction to: Ibalizumab: first global approval. Drugs, 2018, 78(8): 859.
doi: 10.1007/s40265-018-0926-2 pmid: 29846911
[20] Wang L W, Shen H Y, Nobre L, et al. Epstein-Barr-virus-induced one-carbon metabolism drives B cell transformation. Cell Metabolism, 2019, 30(3): 539-555.e11.
doi: S1550-4131(19)30306-7 pmid: 31257153
[21] Damania B, Kenney S C, Raab-Traub N. Epstein-Barr virus: biology and clinical disease. Cell, 2022, 185(20): 3652-3670.
doi: 10.1016/j.cell.2022.08.026 pmid: 36113467
[22] Valgardsdottir R, Cattaneo I, Napolitano G, et al. Identification of human SARS-CoV-2 monoclonal antibodies from convalescent patients using EBV immortalization. Antibodies, 2021, 10(3): 26.
doi: 10.3390/antib10030026
[23] Sun Z H, Lu S Q, Yang Z, et al. Isolation and characterization of an HIV-1 envelope glycoprotein-specific B-cell from an immortalized human naïve B-cell library. Journal of General Virology, 2017, 98(4): 791-798.
doi: 10.1099/jgv.0.000706 pmid: 28073404
[24] Miller N L, Clark T, Raman R, et al. Glycans in virus-host interactions: a structural perspective. Frontiers in Molecular Biosciences, 2021, 8: 666756.
doi: 10.3389/fmolb.2021.666756
[25] Krebs S J, Kwon Y D, Schramm C A, et al. Longitudinal analysis reveals early development of three MPER-directed neutralizing antibody lineages from an HIV-1-infected individual. Immunity, 2019, 50(3): 677-691.e13.
doi: S1074-7613(19)30074-3 pmid: 30876875
[26] Mahdavi S Z B, Oroojalian F, Eyvazi S, et al. An overview on display systems (phage, bacterial, and yeast display) for production of anticancer antibodies; advantages and disadvantages. International Journal of Biological Macromolecules, 2022, 208: 421-442.
doi: 10.1016/j.ijbiomac.2022.03.113
[27] Wang Y, Shan Y M, Gao X Y, et al. Screening and expressing HIV-1 specific antibody fragments in Saccharomyces cerevisiae. Molecular Immunology, 2018, 103: 279-285.
doi: 10.1016/j.molimm.2018.10.013
[28] Mathew E, Zhu H, Connelly S M, et al. Display of the HIV envelope protein at the yeast cell surface for immunogen development. PLoS One, 2018, 13(10): e0205756.
doi: 10.1371/journal.pone.0205756
[29] Ledsgaard L, Ljungars A, Rimbault C, et al. Advances in antibody phage display technology. Drug Discovery Today, 2022, 27(8): 2151-2169.
doi: 10.1016/j.drudis.2022.05.002
[30] Jaroszewicz W, Morcinek-Orłowska J, Pierzynowska K, et al. Phage display and other peptide display technologies. FEMS Microbiology Reviews, 2022, 46(2): fuab052.
doi: 10.1093/femsre/fuab052
[31] Muyldermans S. Applications of nanobodies. Annual Review of Animal Biosciences, 2021, 9: 401-421.
doi: 10.1146/annurev-animal-021419-083831 pmid: 33233943
[32] Weiss R A, Verrips C T. Nanobodies that neutralize HIV. Vaccines, 2019, 7(3): 77.
doi: 10.3390/vaccines7030077
[33] Omidfar K, Daneshpour M. Advances in phage display technology for drug discovery. Expert Opinion on Drug Discovery, 2015, 10(6): 651-669.
doi: 10.1517/17460441.2015.1037738 pmid: 25910798
[34] Doores K J, Fulton Z, Huber M, et al. Antibody 2G 12 recognizes di-mannose equivalently in domain- and nondomain-exchanged forms but only binds the HIV-1 glycan shield if domain exchanged. Journal of Virology, 2010, 84(20): 10690-10699.
doi: 10.1128/JVI.01110-10 pmid: 20702629
[35] Burton D R, Pyati J, Koduri R, et al. Efficient neutralization of primary isolates of HIV-1 by a recombinant human monoclonal antibody. Science, 1994, 266(5187): 1024-1027.
pmid: 7973652
[36] Yang G, Holl T M, Liu Y, et al. Identification of autoantigens recognized by the 2F5 and 4E 10 broadly neutralizing HIV-1 antibodies. The Journal of Experimental Medicine, 2013, 210(2): 241-256.
doi: 10.1084/jem.20121977
[37] McCoy L E, Burton D R. Identification and specificity of broadly neutralizing antibodies against HIV. Immunological Reviews, 2017, 275(1): 11-20.
doi: 10.1111/imr.12484 pmid: 28133814
[38] Walker L M, Huber M, Doores K J, et al. Broad neutralization coverage of HIV by multiple highly potent antibodies. Nature, 2011, 477(7365): 466-470.
doi: 10.1038/nature10373
[39] Walker L M, Phogat S K, Chan-Hui P Y, et al. Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target. Science, 2009, 326(5950): 285-289.
doi: 10.1126/science.1178746 pmid: 19729618
[40] Doria-Rose N A, Bhiman J N, Roark R S, et al. New member of the V1V2-directed CAP256-VRC 26 lineage that shows increased breadth and exceptional potency. Journal of Virology, 2015, 90(1): 76-91.
doi: 10.1128/JVI.01791-15
[41] Bonsignori M, Hwang K K, Chen X, et al. Analysis of a clonal lineage of HIV-1 envelope V2/V3 conformational epitope-specific broadly neutralizing antibodies and their inferred unmutated common ancestors. Journal of Virology, 2011, 85(19): 9998-10009.
doi: 10.1128/JVI.05045-11 pmid: 21795340
[42] Bonsignori M, Zhou T Q, Sheng Z Z, et al. Maturation pathway from germline to broad HIV-1 neutralizer of a CD4-mimic antibody. Cell, 2016, 165(2): 449-463.
doi: 10.1016/j.cell.2016.02.022 pmid: 26949186
[43] Huang J H, Ofek G, Laub L, et al. Broad and potent neutralization of HIV-1 by a gp41-specific human antibody. Nature, 2012, 491(7424): 406-412.
doi: 10.1038/nature11544
[44] Falkowska E, Le K, Ramos A, et al. Broadly neutralizing HIV antibodies define a glycan-dependent epitope on the prefusion conformation of gp 41 on cleaved envelope trimers. Immunity, 2014, 40(5): 657-668.
doi: 10.1016/j.immuni.2014.04.009 pmid: 24768347
[45] Huang J H, Kang B H, Pancera M, et al. Broad and potent HIV-1 neutralization by a human antibody that binds the gp41-gp120 interface. Nature, 2014, 515(7525): 138-142.
doi: 10.1038/nature13601
[46] Perry S T, Keogh E, Morton M, et al. Single-cell screening method for the selection and recovery of antibodies with desired specificities from enriched human memory B cell populations. Journal of Visualized Experiments, 2019(150). DOI: 10.3791/59809.
doi: 10.3791/59809
[47] Starkie D O, Compson J E, Rapecki S, et al. Generation of recombinant monoclonal antibodies from immunised mice and rabbits via flow cytometry and sorting of antigen-specific IgG+ memory B cells. PLoS One, 2016, 11(3): e0152282.
doi: 10.1371/journal.pone.0152282
[48] Sok D, Pauthner M, Briney B, et al. A prominent site of antibody vulnerability on HIV envelope incorporates a motif associated with CCR5 binding and its camouflaging glycans. Immunity, 2016, 45(1): 31-45.
doi: 10.1016/j.immuni.2016.06.026 pmid: 27438765
[49] Mouquet H, Scharf L, Euler Z, et al. Complex-type N-glycan recognition by potent broadly neutralizing HIV antibodies. Proceedings of the National Academy of Sciences of the United States of America, 2012, 109(47): E3268-E3277.
[50] Liao H X, Lynch R, Zhou T Q, et al. Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus. Nature, 2013, 496(7446): 469-476.
doi: 10.1038/nature12053
[51] Zhou T Q, Georgiev I, Wu X L, et al. Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01. Science, 2010, 329(5993): 811-817.
doi: 10.1126/science.1192819 pmid: 20616231
[52] van Gils M J, van den Kerkhof T L G M, Ozorowski G, et al. An HIV-1 antibody from an elite neutralizer implicates the fusion peptide as a site of vulnerability. Nature Microbiology, 2017, 2(2): 1-10.
[53] Wu X L, Zhou T Q, Zhu J, et al. Focused evolution of HIV-1 neutralizing antibodies revealed by structures and deep sequencing. Science, 2011, 333(6049): 1593-1602.
doi: 10.1126/science.1207532 pmid: 21835983
[54] Scheid J F, Mouquet H, Ueberheide B, et al. Sequence and structural convergence of broad and potent HIV antibodies that mimic CD4 binding. Science, 2011, 333(6049): 1633-1637.
doi: 10.1126/science.1207227 pmid: 21764753
[55] Carbonetti S, Oliver B G, Vigdorovich V, et al. A method for the isolation and characterization of functional murine monoclonal antibodies by single B cell cloning. Journal of Immunological Methods, 2017, 448: 66-73.
doi: S0022-1759(17)30067-4 pmid: 28554543
[56] Kreer C, Döring M, Lehnen N, et al. openPrimeR for multiplex amplification of highly diverse templates. Journal of Immunological Methods, 2020, 480: 112752.
doi: 10.1016/j.jim.2020.112752
[57] Gieselmann L, Kreer C, Ercanoglu M S, et al. Effective high-throughput isolation of fully human antibodies targeting infectious pathogens. Nature Protocols, 2021, 16(7): 3639-3671.
doi: 10.1038/s41596-021-00554-w pmid: 34035500
[58] Akagi S, Nakajima C, Tanaka Y, et al. Flow cytometry-based method for rapid and high-throughput screening of hybridoma cells secreting monoclonal antibody. Journal of Bioscience and Bioengineering, 2018, 125(4): 464-469.
doi: S1389-1723(17)30577-7 pmid: 29174537
[59] Xu Z Y, Walker S, Wise M C, et al. Induction of tier-2 neutralizing antibodies in mice with a DNA-encoded HIV envelope native like trimer. Nature Communications, 2022, 13(1): 1-18.
doi: 10.1038/s41467-021-27699-2
[60] Setliff I, Shiakolas A R, Pilewski K A, et al. High-throughput mapping of B cell receptor sequences to antigen specificity. Cell, 2019, 179(7): 1636-1646.e15.
doi: S0092-8674(19)31224-3 pmid: 31787378
[61] Shiakolas A R, Kramer K J, Wrapp D, et al. Cross-reactive coronavirus antibodies with diverse epitope specificities and Fc effector functions. Cell Reports Medicine, 2021, 2(6): 100313.
doi: 10.1016/j.xcrm.2021.100313
[62] Kramer K J, Johnson N V, Shiakolas A R, et al. Potent neutralization of SARS-CoV-2 variants of concern by an antibody with an uncommon genetic signature and structural mode of spike recognition. Cell Reports, 2021, 37(1): 109784.
doi: 10.1016/j.celrep.2021.109784
[63] Walker L M, Shiakolas A R, Venkat R, et al. High-throughput B cell epitope determination by next-generation sequencing. Frontiers in Immunology, 2022, 13: 855772.
doi: 10.3389/fimmu.2022.855772
[64] Hu T S, Chitnis N, Monos D, et al. Next-generation sequencing technologies: an overview. Human Immunology, 2021, 82(11): 801-811.
doi: 10.1016/j.humimm.2021.02.012 pmid: 33745759
[65] Sun C J, Zuo T, Wen Z Y. First clinical study of germline-targeting strategy: one step closer to a successful bnAb-based HIV vaccine. The Innovation, 2023, 4(1): 100374.
doi: 10.1016/j.xinn.2023.100374
[66] Burton D R. Advancing an HIV vaccine; advancing vaccinology. Nature Reviews Immunology, 2019, 19(2): 77-78.
doi: 10.1038/s41577-018-0103-6 pmid: 30560910
[67] Yan Q H, He P, Huang X H, et al. Germline IGHV3-53-encoded RBD-targeting neutralizing antibodies are commonly present in the antibody repertoires of COVID-19 patients. Emerging Microbes & Infections, 2021, 10(1): 1097-1111.
[68] Tan T J C, Yuan M, Kuzelka K, et al. Sequence signatures of two public antibody clonotypes that bind SARS-CoV-2 receptor binding domain. Nature Communications, 2021, 12(1): 1-10.
doi: 10.1038/s41467-020-20314-w
[69] Setliff I, McDonnell W J, Raju N, et al. Multi-donor longitudinal antibody repertoire sequencing reveals the existence of public antibody clonotypes in HIV-1 infection. Cell Host & Microbe, 2018, 23(6): 845-854.e6.
[70] Parola C, Neumeier D, Reddy S T. Integrating high-throughput screening and sequencing for monoclonal antibody discovery and engineering. Immunology, 2018, 153(1): 31-41.
doi: 10.1111/imm.12838 pmid: 28898398
[71] Sun Z H, Yan L X, Tang J S, et al. Brief introduction of current technologies in isolation of broadly neutralizing HIV-1 antibodies. Virus Research, 2018, 243: 75-82.
doi: S0168-1702(17)30572-5 pmid: 29051051
[72] Huang J H, Kang B, Ishida E, et al. Identification of a CD4-binding-site antibody to HIV that evolved near-pan neutralization breadth. Immunity, 2016, 45(5): 1108-1121.
doi: S1074-7613(16)30438-1 pmid: 27851912
[73] Sajadi M M, Dashti A, Rikhtegaran Tehrani Z, et al. Identification of near-pan-neutralizing antibodies against HIV-1 by deconvolution of plasma humoral responses. Cell, 2018, 173(7): 1783-1795.e14.
doi: S0092-8674(18)30393-3 pmid: 29731169
[74] Rudicell R S, Do Kwon Y, Ko S Y, et al. Enhanced potency of a broadly neutralizing HIV-1 antibody in vitro improves protection against lentiviral infection in vivo. Journal of Virology, 2014, 88(21): 12669-12682.
doi: 10.1128/JVI.02213-14 pmid: 25142607
[75] Zhou T Q, Lynch R, Chen L, et al. Structural repertoire of HIV-1-neutralizing antibodies targeting the CD 4 supersite in 14 donors. Cell, 2015, 161(6): 1280-1292.
doi: 10.1016/j.cell.2015.05.007
[76] Williams L D, Ofek G, Schätzle S, et al. Potent and broad HIV-neutralizing antibodies in memory B cells and plasma. Science Immunology, 2017, 2(7): eaal2200.
[77] Schoofs T, Barnes C O, Suh-Toma N, et al. Broad and potent neutralizing antibodies recognize the silent face of the HIV envelope. Immunity, 2019, 50(6): 1513-1529.e9.
doi: S1074-7613(19)30194-3 pmid: 31126879
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