Broadly neutralizing antibodies and vaccine design against HIV-1 infection

doi:10.1007/s11684-019-0721-9

Front. Med.

2020, Vol. 14

Issue (1) : 30-42 https://doi.org/10.1007/s11684-019-0721-9

REVIEW

Broadly neutralizing antibodies and vaccine design against HIV-1 infection

Qian Wang, Linqi Zhang(

)

Comprehensive AIDS Research Center, Beijing Advanced Innovation Center for Structural Biology, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China

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Abstract

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.

Keywords HIV-1 broadly neutralizing antibodies Env conformational states vaccine design SOSIP

Corresponding Author(s): Linqi Zhang

Just Accepted Date: 15 November 2019 Online First Date: 19 December 2019 Issue Date: 02 March 2020

Cite this article:

Qian Wang,Linqi Zhang. Broadly neutralizing antibodies and vaccine design against HIV-1 infection[J]. Front. Med., 2020, 14(1): 30-42.

URL:

https://academic.hep.com.cn/fmd/EN/10.1007/s11684-019-0721-9
https://academic.hep.com.cn/fmd/EN/Y2020/V14/I1/30

Tab.1 Overview of characteristics of representative second-generation bNAbs

Fig.1 Schematic diagram of HIV-1 and epitopes for bNAbs on trimeric HIV envelope spike glycoproteins.

Fig.2 Current status of bNAb development in preclinical and clinical studies.

1	RC Gallo, SZ Salahuddin, M Popovic, GM Shearer, M Kaplan, BF Haynes, TJ Palker, R Redfield, J Oleske, B Safai, et al.. Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS. Science 1984; 224(4648): 500–503 https://doi.org/10.1126/science.6200936 pmid: 6200936
2	F Barré-Sinoussi, JC Chermann, F Rey, MT Nugeyre, S Chamaret, J Gruest, C Dauguet, C Axler-Blin, F Vézinet-Brun, C Rouzioux, W Rozenbaum, L Montagnier. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 1983; 220(4599): 868–871 https://doi.org/10.1126/science.6189183 pmid: 6189183
3	A Baghaei Lakeh, N Ghaffarzadegan. Global trends and regional variations in studies of HIV/AIDS. Sci Rep 2017; 7(1): 4170 https://doi.org/10.1038/s41598-017-04527-6 pmid: 28646150
4	UNAIDS. Country factsheets, China 2017.
5	X Hu, B Liang, C Zhou, J Jiang, J Huang, C Ning, J Liu, B Zhou, N Zang, J Lai, R Chen, Y Liao, P Pan, X Liu, G Lan, X Pang, L Ye, Z Shen, H Liang. HIV late presentation and advanced HIV disease among patients with newly diagnosed HIV/AIDS in Southwestern China: a large-scale cross-sectional study. AIDS Res Ther 2019; 16(1): 6 https://doi.org/10.1186/s12981-019-0221-7 pmid: 30876476
6	MJ Buzón, M Massanella, JM Llibre, A Esteve, V Dahl, MC Puertas, JM Gatell, P Domingo, R Paredes, M Sharkey, S Palmer, M Stevenson, B Clotet, J Blanco, J Martinez-Picado. HIV-1 replication and immune dynamics are affected by raltegravir intensification of HAART-suppressed subjects. Nat Med 2010; 16(4): 460–465 https://doi.org/10.1038/nm.2111 pmid: 20228817
7	RC Gallo. A reflection on HIV/AIDS research after 25 years. Retrovirology 2006; 3(1): 72 https://doi.org/10.1186/1742-4690-3-72 pmid: 17054781
8	JD Siliciano, J Kajdas, D Finzi, TC Quinn, K Chadwick, JB Margolick, C Kovacs, SJ Gange, RF Siliciano. Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4+ T cells. Nat Med 2003; 9(6): 727–728 https://doi.org/10.1038/nm880 pmid: 12754504
9	D Finzi, J Blankson, JD Siliciano, JB Margolick, K Chadwick, T Pierson, K Smith, J Lisziewicz, F Lori, C Flexner, TC Quinn, RE Chaisson, E Rosenberg, B Walker, S Gange, J Gallant, RF Siliciano. Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy. Nat Med 1999; 5(5): 512–517 https://doi.org/10.1038/8394 pmid: 10229227
10	Y Gao, PF McKay, JFS Mann. Advances in HIV-1 Vaccine Development. Viruses 2018; 10(4): E167 https://doi.org/10.3390/v10040167 pmid: 29614779
11	S Rerks-Ngarm, P Pitisuttithum, S Nitayaphan, J Kaewkungwal, J Chiu, R Paris, N Premsri, C Namwat, M de Souza, E Adams, M Benenson, S Gurunathan, J Tartaglia, JG McNeil, DP Francis, D Stablein, DL Birx, S Chunsuttiwat, C Khamboonruang, P Thongcharoen, ML Robb, NL Michael, P Kunasol, JH; MOPH-TAVEG Investigators. Kim Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med 2009; 361(23): 2209–2220 https://doi.org/10.1056/NEJMoa0908492 pmid: 19843557
12	JL Excler, ML Robb, JH Kim. HIV-1 vaccines: challenges and new perspectives. Hum Vaccin Immunother 2014; 10(6): 1734–1746 https://doi.org/10.4161/hv.28462 pmid: 24637946
13	PD Kwong, JR Mascola. HIV-1 vaccines based on antibody identification, B cell ontogeny, and epitope structure. Immunity 2018; 48(5): 855–871 https://doi.org/10.1016/j.immuni.2018.04.029 pmid: 29768174
14	M Pancera, A Changela, PD Kwong. How HIV-1 entry mechanism and broadly neutralizing antibodies guide structure-based vaccine design. Curr Opin HIV AIDS 2017; 12(3): 229–240 https://doi.org/10.1097/COH.0000000000000360 pmid: 28422787
15	E Landais, PL Moore. Development of broadly neutralizing antibodies in HIV-1 infected elite neutralizers. Retrovirology 2018; 15(1): 61 https://doi.org/10.1186/s12977-018-0443-0 pmid: 30185183
16	H Mouquet. Antibody B cell responses in HIV-1 infection. Trends Immunol 2014; 35(11): 549–561 https://doi.org/10.1016/j.it.2014.08.007 pmid: 25240985
17	DR Burton, J Pyati, R Koduri, SJ Sharp, GB Thornton, PW Parren, LS Sawyer, RM Hendry, N Dunlop, PL Nara, et al.. Efficient neutralization of primary isolates of HIV-1 by a recombinant human monoclonal antibody. Science 1994; 266(5187): 1024–1027 https://doi.org/10.1126/science.7973652 pmid: 7973652
18	A Trkola, M Purtscher, T Muster, C Ballaun, A Buchacher, N Sullivan, K Srinivasan, J Sodroski, JP Moore, H Katinger. Human monoclonal antibody 2G12 defines a distinctive neutralization epitope on the gp120 glycoprotein of human immunodeficiency virus type 1. J Virol 1996; 70(2): 1100–1108 pmid: 8551569
19	T Muster, F Steindl, M Purtscher, A Trkola, A Klima, G Himmler, F Rüker, H Katinger. A conserved neutralizing epitope on gp41 of human immunodeficiency virus type 1. J Virol 1993; 67(11): 6642–6647 pmid: 7692082
20	MB Zwick, AF Labrijn, M Wang, C Spenlehauer, EO Saphire, JM Binley, JP Moore, G Stiegler, H Katinger, DR Burton, PW Parren. Broadly neutralizing antibodies targeted to the membrane-proximal external region of human immunodeficiency virus type 1 glycoprotein gp41. J Virol 2001; 75(22): 10892–10905 https://doi.org/10.1128/JVI.75.22.10892-10905.2001 pmid: 11602729
21	EO Saphire, PW Parren, R Pantophlet, MB Zwick, GM Morris, PM Rudd, RA Dwek, RL Stanfield, DR Burton, IA Wilson. Crystal structure of a neutralizing human IGG against HIV-1: a template for vaccine design. Science 2001; 293(5532): 1155–1159 https://doi.org/10.1126/science.1061692 pmid: 11498595
22	JR Mascola, MG Lewis, G Stiegler, D Harris, TC VanCott, D Hayes, MK Louder, CR Brown, CV Sapan, SS Frankel, Y Lu, ML Robb, H Katinger, DL Birx. Protection of macaques against pathogenic simian/human immunodeficiency virus 89.6PD by passive transfer of neutralizing antibodies. J Virol 1999; 73(5): 4009–4018 pmid: 10196297
23	JR Mascola, G Stiegler, TC VanCott, H Katinger, CB Carpenter, CE Hanson, H Beary, D Hayes, SS Frankel, DL Birx, MG Lewis. Protection of macaques against vaginal transmission of a pathogenic HIV-1/SIV chimeric virus by passive infusion of neutralizing antibodies. Nat Med 2000; 6(2): 207–210 https://doi.org/10.1038/72318 pmid: 10655111
24	TW Baba, V Liska, R Hofmann-Lehmann, J Vlasak, W Xu, S Ayehunie, LA Cavacini, MR Posner, H Katinger, G Stiegler, BJ Bernacky, TA Rizvi, R Schmidt, LR Hill, ME Keeling, Y Lu, JE Wright, TC Chou, RM Ruprecht. Human neutralizing monoclonal antibodies of the IgG1 subtype protect against mucosal simian-human immunodeficiency virus infection. Nat Med 2000; 6(2): 200–206 https://doi.org/10.1038/72309 pmid: 10655110
25	AJ Hessell, P Poignard, M Hunter, L Hangartner, DM Tehrani, WK Bleeker, PW Parren, PA Marx, DR Burton. Effective, low-titer antibody protection against low-dose repeated mucosal SHIV challenge in macaques. Nat Med 2009; 15(8): 951–954 https://doi.org/10.1038/nm.1974 pmid: 19525965
26	AJ Hessell, EG Rakasz, P Poignard, L Hangartner, G Landucci, DN Forthal, WC Koff, DI Watkins, DR Burton. Broadly neutralizing human anti-HIV antibody 2G12 is effective in protection against mucosal SHIV challenge even at low serum neutralizing titers. PLoS Pathog 2009; 5(5): e1000433 https://doi.org/10.1371/journal.ppat.1000433 pmid: 19436712
27	AJ Hessell, EG Rakasz, DM Tehrani, M Huber, KL Weisgrau, G Landucci, DN Forthal, WC Koff, P Poignard, DI Watkins, DR Burton. Broadly neutralizing monoclonal antibodies 2F5 and 4E10 directed against the human immunodeficiency virus type 1 gp41 membrane-proximal external region protect against mucosal challenge by simian-human immunodeficiency virus SHIVBa-L. J Virol 2010; 84(3): 1302–1313 https://doi.org/10.1128/JVI.01272-09 pmid: 19906907
28	DA Calarese, CN Scanlan, MB Zwick, S Deechongkit, Y Mimura, R Kunert, P Zhu, MR Wormald, RL Stanfield, KH Roux, JW Kelly, PM Rudd, RA Dwek, H Katinger, DR Burton, IA Wilson. Antibody domain exchange is an immunological solution to carbohydrate cluster recognition. Science 2003; 300(5628): 2065–2071 https://doi.org/10.1126/science.1083182 pmid: 12829775
29	G Yang, TM Holl, Y Liu, Y Li, X Lu, NI Nicely, TB Kepler, SM Alam, HX Liao, DW Cain, L Spicer, JL VandeBerg, BF Haynes, G Kelsoe. Identification of autoantigens recognized by the 2F5 and 4E10 broadly neutralizing HIV-1 antibodies. J Exp Med 2013; 210(2): 241–256 https://doi.org/10.1084/jem.20121977 pmid: 23359068
30	BF Haynes, J Fleming, EW St Clair, H Katinger, G Stiegler, R Kunert, J Robinson, RM Scearce, K Plonk, HF Staats, TL Ortel, HX Liao, SM Alam. Cardiolipin polyspecific autoreactivity in two broadly neutralizing HIV-1 antibodies. Science 2005; 308(5730): 1906–1908 https://doi.org/10.1126/science.1111781 pmid: 15860590
31	H Gruell, F Klein. Antibody-mediated prevention and treatment of HIV-1 infection. Retrovirology 2018; 15(1): 73 https://doi.org/10.1186/s12977-018-0455-9 pmid: 30445968
32	NA Doria-Rose, RM Klein, MM Manion, S O’Dell, A Phogat, B Chakrabarti, CW Hallahan, SA Migueles, J Wrammert, R Ahmed, M Nason, RT Wyatt, JR Mascola, M Connors. Frequency and phenotype of human immunodeficiency virus envelope-specific B cells from patients with broadly cross-neutralizing antibodies. J Virol 2009; 83(1): 188–199 https://doi.org/10.1128/JVI.01583-08 pmid: 18922865
33	I Mikell, DN Sather, SA Kalams, M Altfeld, G Alter, L Stamatatos. Characteristics of the earliest cross-neutralizing antibody response to HIV-1. PLoS Pathog 2011; 7(1): e1001251 https://doi.org/10.1371/journal.ppat.1001251 pmid: 21249232
34	ES Gray, MC Madiga, T Hermanus, PL Moore, CK Wibmer, NL Tumba, L Werner, K Mlisana, S Sibeko, C Williamson, SS Abdool Karim, L Morris; CAPRISA002 Study Team. The neutralization breadth of HIV-1 develops incrementally over four years and is associated with CD4+ T cell decline and high viral load during acute infection. J Virol 2011; 85(10): 4828–4840 https://doi.org/10.1128/JVI.00198-11 pmid: 21389135
35	L Stamatatos, L Morris, DR Burton, JR Mascola. Neutralizing antibodies generated during natural HIV-1 infection: good news for an HIV-1 vaccine? Nat Med 2009; 15(8): 866–870 https://doi.org/10.1038/nm.1949 pmid: 19525964
36	DN Sather, J Armann, LK Ching, A Mavrantoni, G Sellhorn, Z Caldwell, X Yu, B Wood, S Self, S Kalams, L Stamatatos. Factors associated with the development of cross-reactive neutralizing antibodies during human immunodeficiency virus type 1 infection. J Virol 2009; 83(2): 757–769 https://doi.org/10.1128/JVI.02036-08 pmid: 18987148
37	NA Doria-Rose, RM Klein, MG Daniels, S O’Dell, M Nason, A Lapedes, T Bhattacharya, SA Migueles, RT Wyatt, BT Korber, JR Mascola, M Connors. Breadth of human immunodeficiency virus-specific neutralizing activity in sera: clustering analysis and association with clinical variables. J Virol 2010; 84(3): 1631–1636 https://doi.org/10.1128/JVI.01482-09 pmid: 19923174
38	AVAC. HIV-specific neutralizing antibodies—targets and research status 2019.
39	AVAC. Broadly neutralizing antibody combinations 2019.
40	JS McLellan, M Pancera, C Carrico, J Gorman, JP Julien, R Khayat, R Louder, R Pejchal, M Sastry, K Dai, S O’Dell, N Patel, S Shahzad-ul-Hussan, Y Yang, B Zhang, T Zhou, J Zhu, JC Boyington, GY Chuang, D Diwanji, I Georgiev, YD Kwon, D Lee, MK Louder, S Moquin, SD Schmidt, ZY Yang, M Bonsignori, JA Crump, SH Kapiga, NE Sam, BF Haynes, DR Burton, WC Koff, LM Walker, S Phogat, R Wyatt, J Orwenyo, LX Wang, J Arthos, CA Bewley, JR Mascola, GJ Nabel, WR Schief, AB Ward, IA Wilson, PD Kwong. Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9. Nature 2011; 480(7377): 336–343 https://doi.org/10.1038/nature10696 pmid: 22113616
41	JP Julien, JH Lee, A Cupo, CD Murin, R Derking, S Hoffenberg, MJ Caulfield, CR King, AJ Marozsan, PJ Klasse, RW Sanders, JP Moore, IA Wilson, AB Ward. Asymmetric recognition of the HIV-1 trimer by broadly neutralizing antibody PG9. Proc Natl Acad Sci USA 2013; 110(11): 4351–4356 https://doi.org/10.1073/pnas.1217537110 pmid: 23426631
42	LM Walker, SK Phogat, PY Chan-Hui, D Wagner, P Phung, JL Goss, T Wrin, MD Simek, S Fling, JL Mitcham, JK Lehrman, FH Priddy, OA Olsen, SM Frey, PW Hammond; Protocol G Principal Investigators, S Kaminsky, T Zamb, M Moyle, WC Koff, P Poignard, DR Burton, DR Burton. Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target. Science 2009; 326(5950): 285–289 https://doi.org/10.1126/science.1178746 pmid: 19729618
43	M Bonsignori, KK Hwang, X Chen, CY Tsao, L Morris, E Gray, DJ Marshall, JA Crump, SH Kapiga, NE Sam, F Sinangil, M Pancera, Y Yongping, B Zhang, J Zhu, PD Kwong, S O’Dell, JR Mascola, L Wu, GJ Nabel, S Phogat, MS Seaman, JF Whitesides, MA Moody, G Kelsoe, X Yang, J Sodroski, GM Shaw, DC Montefiori, TB Kepler, GD Tomaras, SM Alam, HX Liao, BF Haynes. Analysis of a clonal lineage of HIV-1 envelope V2/V3 conformational epitope-specific broadly neutralizing antibodies and their inferred unmutated common ancestors. J Virol 2011; 85(19): 9998–10009 https://doi.org/10.1128/JVI.05045-11 pmid: 21795340
44	LM Walker, M Huber, KJ Doores, E Falkowska, R Pejchal, JP Julien, SK Wang, A Ramos, PY Chan-Hui, M Moyle, JL Mitcham, PW Hammond, OA Olsen, P Phung, S Fling, CH Wong, S Phogat, T Wrin, MD Simek; Protocol G Principal Investigators, WC Koff, IA Wilson, DR Burton, P Poignard, P Poignard. Broad neutralization coverage of HIV by multiple highly potent antibodies. Nature 2011; 477(7365): 466–470 https://doi.org/10.1038/nature10373 pmid: 21849977
45	D Sok, MJ van Gils, M Pauthner, JP Julien, KL Saye-Francisco, J Hsueh, B Briney, JH Lee, KM Le, PS Lee, Y Hua, MS Seaman, JP Moore, AB Ward, IA Wilson, RW Sanders, DR Burton. Recombinant HIV envelope trimer selects for quaternary-dependent antibodies targeting the trimer apex. Proc Natl Acad Sci USA 2014; 111(49): 17624–17629 https://doi.org/10.1073/pnas.1415789111 pmid: 25422458
46	NA Doria-Rose, CA Schramm, J Gorman, PL Moore, JN Bhiman, BJ DeKosky, MJ Ernandes, IS Georgiev, HJ Kim, M Pancera, RP Staupe, HR Altae-Tran, RT Bailer, ET Crooks, A Cupo, A Druz, NJ Garrett, KH Hoi, R Kong, MK Louder, NS Longo, K McKee, M Nonyane, S O’Dell, RS Roark, RS Rudicell, SD Schmidt, DJ Sheward, C Soto, CK Wibmer, Y Yang, Z Zhang; NISC Comparative Sequencing Program, JC Mullikin, JM Binley, RW Sanders, IA Wilson, JP Moore, AB Ward, G Georgiou, C Williamson, SS Abdool Karim, L Morris, PD Kwong, L Shapiro, JR Mascola. Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies. Nature 2014; 509(7498): 55–62 https://doi.org/10.1038/nature13036 pmid: 24590074
47	H Mouquet, L Scharf, Z Euler, Y Liu, C Eden, JF Scheid, A Halper-Stromberg, PN Gnanapragasam, DI Spencer, MS Seaman, H Schuitemaker, T Feizi, MC Nussenzweig, PJ Bjorkman. Complex-type N-glycan recognition by potent broadly neutralizing HIV antibodies. Proc Natl Acad Sci USA 2012; 109(47): E3268–E3277 https://doi.org/10.1073/pnas.1217207109 pmid: 23115339
48	JP Julien, D Sok, R Khayat, JH Lee, KJ Doores, LM Walker, A Ramos, DC Diwanji, R Pejchal, A Cupo, U Katpally, RS Depetris, RL Stanfield, R McBride, AJ Marozsan, JC Paulson, RW Sanders, JP Moore, DR Burton, P Poignard, AB Ward, IA Wilson. Broadly neutralizing antibody PGT121 allosterically modulates CD4 binding via recognition of the HIV-1 gp120 V3 base and multiple surrounding glycans. PLoS Pathog 2013; 9(5): e1003342 https://doi.org/10.1371/journal.ppat.1003342 pmid: 23658524
49	R Pejchal, KJ Doores, LM Walker, R Khayat, PS Huang, SK Wang, RL Stanfield, JP Julien, A Ramos, M Crispin, R Depetris, U Katpally, A Marozsan, A Cupo, S Maloveste, Y Liu, R McBride, Y Ito, RW Sanders, C Ogohara, JC Paulson, T Feizi, CN Scanlan, CH Wong, JP Moore, WC Olson, AB Ward, P Poignard, WR Schief, DR Burton, IA Wilson. A potent and broad neutralizing antibody recognizes and penetrates the HIV glycan shield. Science 2011; 334(6059): 1097–1103 https://doi.org/10.1126/science.1213256 pmid: 21998254
50	D Sok, M Pauthner, B Briney, JH Lee, KL Saye-Francisco, J Hsueh, A Ramos, KM Le, M Jones, JG Jardine, R Bastidas, A Sarkar, CH Liang, SS Shivatare, CY Wu, WR Schief, CH Wong, IA Wilson, AB Ward, J Zhu, P Poignard, DR Burton. 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 https://doi.org/10.1016/j.immuni.2016.06.026 pmid: 27438765
51	AG Dalgleish, PC Beverley, PR Clapham, DH Crawford, MF Greaves, RA Weiss. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature 1984; 312(5996): 763–767 https://doi.org/10.1038/312763a0 pmid: 6096719
52	D Klatzmann, E Champagne, S Chamaret, J Gruest, D Guetard, T Hercend, JC Gluckman, L Montagnier. T-lymphocyte T4 molecule behaves as the receptor for human retrovirus LAV. Nature 1984; 312(5996): 767–768 https://doi.org/10.1038/312767a0 pmid: 6083454
53	T Zhou, L Xu, B Dey, AJ Hessell, D van Ryk, SH Xiang, X Yang, MY Zhang, MB Zwick, J Arthos, DR Burton, DS Dimitrov, J Sodroski, R Wyatt, GJ Nabel, PD Kwong. Structural definition of a conserved neutralization epitope on HIV-1 gp120. Nature 2007; 445(7129): 732–737 https://doi.org/10.1038/nature05580 pmid: 17301785
54	T Zhou, RM Lynch, L Chen, P Acharya, X Wu, NA Doria-Rose, MG Joyce, D Lingwood, C Soto, RT Bailer, MJ Ernandes, R Kong, NS Longo, MK Louder, K McKee, S O’Dell, SD Schmidt, L Tran, Z Yang, A Druz, TS Luongo, S Moquin, S Srivatsan, Y Yang, B Zhang, A Zheng, M Pancera, T Kirys, IS Georgiev, T Gindin, HP Peng, AS Yang; NISC Comparative Sequencing Program, JC Mullikin, MD Gray, L Stamatatos, DR Burton, WC Koff, MS Cohen, BF Haynes, JP Casazza, M Connors, D Corti, A Lanzavecchia, QJ Sattentau, RA Weiss, AP West Jr, PJ Bjorkman, JF Scheid, MC Nussenzweig, L Shapiro, JR Mascola, PD Kwong, PD Kwong. Structural repertoire of HIV-1-neutralizing antibodies targeting the CD4 supersite in 14 donors. Cell 2015; 161(6): 1280–1292 https://doi.org/10.1016/j.cell.2015.05.007 pmid: 26004070
55	MM Sajadi, A Dashti, Z Rikhtegaran Tehrani, WD Tolbert, MS Seaman, X Ouyang, N Gohain, M Pazgier, D Kim, G Cavet, J Yared, RR Redfield, GK Lewis, AL DeVico. Identification of near-Pan-neutralizing antibodies against HIV-1 by deconvolution of plasma humoral responses. Cell 2018; 173(7): 1783–1795.e14
56	X Wu, ZY Yang, Y Li, CM Hogerkorp, WR Schief, MS Seaman, T Zhou, SD Schmidt, L Wu, L Xu, NS Longo, K McKee, S O’Dell, MK Louder, DL Wycuff, Y Feng, M Nason, N Doria-Rose, M Connors, PD Kwong, M Roederer, RT Wyatt, GJ Nabel, JR Mascola. Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science 2010; 329(5993): 856–861 https://doi.org/10.1126/science.1187659 pmid: 20616233
57	J Huang, BH Kang, E Ishida, T Zhou, T Griesman, Z Sheng, F Wu, NA Doria-Rose, B Zhang, K McKee, S O’Dell, GY Chuang, A Druz, IS Georgiev, CA Schramm, A Zheng, MG Joyce, M Asokan, A Ransier, S Darko, SA Migueles, RT Bailer, MK Louder, SM Alam, R Parks, G Kelsoe, T Von Holle, BF Haynes, DC Douek, V Hirsch, MS Seaman, L Shapiro, JR Mascola, PD Kwong, M Connors. Identification of a CD4-binding-site antibody to HIV that evolved near-Pan neutralization breadth. Immunity 2016; 45(5): 1108–1121 https://doi.org/10.1016/j.immuni.2016.10.027 pmid: 27851912
58	RS Rudicell, YD Kwon, SY Ko, A Pegu, MK Louder, IS Georgiev, X Wu, J Zhu, JC Boyington, X Chen, W Shi, ZY Yang, NA Doria-Rose, K McKee, S O’Dell, SD Schmidt, GY Chuang, A Druz, C Soto, Y Yang, B Zhang, T Zhou, JP Todd, KE Lloyd, J Eudailey, KE Roberts, BR Donald, RT Bailer, J Ledgerwood; NISC Comparative Sequencing Program, JC Mullikin, L Shapiro, RA Koup, BS Graham, MC Nason, M Connors, BF Haynes, SS Rao, M Roederer, PD Kwong, JR Mascola, GJ Nabel, GJ Nabel. Enhanced potency of a broadly neutralizing HIV-1 antibody in vitro improves protection against lentiviral infection in vivo. J Virol 2014; 88(21): 12669–12682 https://doi.org/10.1128/JVI.02213-14 pmid: 25142607
59	JF Scheid, H Mouquet, B Ueberheide, R Diskin, F Klein, TY Oliveira, J Pietzsch, D Fenyo, A Abadir, K Velinzon, A Hurley, S Myung, F Boulad, P Poignard, DR Burton, F Pereyra, DD Ho, BD Walker, MS Seaman, PJ Bjorkman, BT Chait, MC Nussenzweig. Sequence and structural convergence of broad and potent HIV antibodies that mimic CD4 binding. Science 2011; 333(6049): 1633–1637 https://doi.org/10.1126/science.1207227 pmid: 21764753
60	P Zhou, H Wang, M Fang, Y Li, H Wang, S Shi, Z Li, J Wu, X Han, X Shi, H Shang, T Zhou, L Zhang. Broadly resistant HIV-1 against CD4-binding site neutralizing antibodies. PLoS Pathog 2019; 15(6): e1007819 https://doi.org/10.1371/journal.ppat.1007819 pmid: 31194843
61	J Huang, G Ofek, L Laub, MK Louder, NA Doria-Rose, NS Longo, H Imamichi, RT Bailer, B Chakrabarti, SK Sharma, SM Alam, T Wang, Y Yang, B Zhang, SA Migueles, R Wyatt, BF Haynes, PD Kwong, JR Mascola, M Connors. Broad and potent neutralization of HIV-1 by a gp41-specific human antibody. Nature 2012; 491(7424): 406–412 https://doi.org/10.1038/nature11544 pmid: 23151583
62	SJ Krebs, YD Kwon, CA Schramm, WH Law, G Donofrio, KH Zhou, S Gift, V Dussupt, IS Georgiev, S Schatzle, JR McDaniel, YT Lai, M Sastry, B Zhang, MC Jarosinski, A Ransier, AL Chenine, M Asokan, RT Bailer, M Bose, A Cagigi, EM Cale, GY Chuang, S Darko, JI Driscoll, A Druz, J Gorman, F Laboune, MK Louder, K McKee, L Mendez, MA Moody, AM O'Sullivan, C Owen, D Peng, R Rawi, E Sanders-Buell, CH Shen, AR Shiakolas, T Stephens, Y Tsybovsky, C Tucker, R Verardi, K Wang, J Zhou, T Zhou, G Georgiou, SM Alam, BF Haynes, M Rolland, GR Matyas, VR Polonis, AB McDermott, DC Douek, L Shapiro, S Tovanabutra, NL Michael, JR Mascola, ML Robb, PD Kwong, NA Doria-Rose. 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
63	J Huang, BH Kang, M Pancera, JH Lee, T Tong, Y Feng, H Imamichi, IS Georgiev, GY Chuang, A Druz, NA Doria-Rose, L Laub, K Sliepen, MJ van Gils, AT de la Peña, R Derking, PJ Klasse, SA Migueles, RT Bailer, M Alam, P Pugach, BF Haynes, RT Wyatt, RW Sanders, JM Binley, AB Ward, JR Mascola, PD Kwong, M Connors. Broad and potent HIV-1 neutralization by a human antibody that binds the gp41-gp120 interface. Nature 2014; 515(7525): 138–142 https://doi.org/10.1038/nature13601 pmid: 25186731
64	L Scharf, JF Scheid, JH Lee, AP West Jr, C Chen, H Gao, PN Gnanapragasam, R Mares, MS Seaman, AB Ward, MC Nussenzweig, PJ Bjorkman. Antibody 8ANC195 reveals a site of broad vulnerability on the HIV-1 envelope spike. Cell Reports 2014; 7(3): 785–795 https://doi.org/10.1016/j.celrep.2014.04.001 pmid: 24767986
65	L Scharf, H Wang, H Gao, S Chen, AW McDowall, PJ Bjorkman. Broadly neutralizing antibody 8ANC195 recognizes closed and open states of HIV-1 Env. Cell 2015; 162(6): 1379–1390 https://doi.org/10.1016/j.cell.2015.08.035 pmid: 26359989
66	R Kong, K Xu, T Zhou, P Acharya, T Lemmin, K Liu, G Ozorowski, C Soto, JD Taft, RT Bailer, EM Cale, L Chen, CW Choi, GY Chuang, NA Doria-Rose, A Druz, IS Georgiev, J Gorman, J Huang, MG Joyce, MK Louder, X Ma, K McKee, S O’Dell, M Pancera, Y Yang, SC Blanchard, W Mothes, DR Burton, WC Koff, M Connors, AB Ward, PD Kwong, JR Mascola. Fusion peptide of HIV-1 as a site of vulnerability to neutralizing antibody. Science 2016; 352(6287): 828–833 https://doi.org/10.1126/science.aae0474 pmid: 27174988
67	E Falkowska, KM Le, A Ramos, KJ Doores, JH Lee, C Blattner, A Ramirez, R Derking, MJ van Gils, CH Liang, R Mcbride, B von Bredow, SS Shivatare, CY Wu, PY Chan-Hui, Y Liu, T Feizi, MB Zwick, WC Koff, MS Seaman, K Swiderek, JP Moore, D Evans, JC Paulson, CH Wong, AB Ward, IA Wilson, RW Sanders, P Poignard, DR Burton. Broadly neutralizing HIV antibodies define a glycan-dependent epitope on the prefusion conformation of gp41 on cleaved envelope trimers. Immunity 2014; 40(5): 657–668 https://doi.org/10.1016/j.immuni.2014.04.009 pmid: 24768347
68	MJ van Gils, TLGM van den Kerkhof, G Ozorowski, CA Cottrell, D Sok, M Pauthner, J Pallesen, N de Val, A Yasmeen, SW de Taeye, A Schorcht, S Gumbs, I Johanna, K Saye-Francisco, CH Liang, E Landais, X Nie, LK Pritchard, M Crispin, G Kelsoe, IA Wilson, H Schuitemaker, PJ Klasse, JP Moore, DR Burton, AB Ward, RW Sanders. An HIV-1 antibody from an elite neutralizer implicates the fusion peptide as a site of vulnerability. Nat Microbiol 2016; 2(2): 16199 https://doi.org/10.1038/nmicrobiol.2016.199 pmid: 27841852
69	M Yuan, CA Cottrell, G Ozorowski, MJ van Gils, S Kumar, NC Wu, A Sarkar, JL Torres, N de Val, J Copps, JP Moore, RW Sanders, AB Ward, IA Wilson. Conformational plasticity in the HIV-1 fusion peptide facilitates recognition by broadly neutralizing antibodies. Cell Host Microbe 2019; 25(6): 873–883.e5
70	K Xu, P Acharya, R Kong, C Cheng, GY Chuang, K Liu, MK Louder, S O’Dell, R Rawi, M Sastry, CH Shen, B Zhang, T Zhou, M Asokan, RT Bailer, M Chambers, X Chen, CW Choi, VP Dandey, NA Doria-Rose, A Druz, ET Eng, SK Farney, KE Foulds, H Geng, IS Georgiev, J Gorman, KR Hill, AJ Jafari, YD Kwon, YT Lai, T Lemmin, K McKee, TY Ohr, L Ou, D Peng, AP Rowshan, Z Sheng, JP Todd, Y Tsybovsky, EG Viox, Y Wang, H Wei, Y Yang, AF Zhou, R Chen, L Yang, DG Scorpio, AB McDermott, L Shapiro, B Carragher, CS Potter, JR Mascola, PD Kwong. Epitope-based vaccine design yields fusion peptide-directed antibodies that neutralize diverse strains of HIV-1. Nat Med 2018; 24(6): 857–867 https://doi.org/10.1038/s41591-018-0042-6 pmid: 29867235
71	R Kong, H Duan, Z Sheng, K Xu, P Acharya, X Chen, C Cheng, AS Dingens, J Gorman, M Sastry, CH Shen, B Zhang, T Zhou, GY Chuang, CW Chao, Y Gu, AJ Jafari, MK Louder, S O’Dell, AP Rowshan, EG Viox, Y Wang, CW Choi, MM Corcoran, AR Corrigan, VP Dandey, ET Eng, H Geng, KE Foulds, Y Guo, YD Kwon, B Lin, K Liu, RD Mason, MC Nason, TY Ohr, L Ou, R Rawi, EK Sarfo, A Schon, JP Todd, S Wang, H Wei, W Wu, NCS Program, JC Mullikin, RT Bailer, NA Doria-Rose, GB Karlsson Hedestam, DG Scorpio, J Overbaugh, JD Bloom, B Carragher, CS Potter, L Shapiro, PD Kwong, JR Mascola. Antibody lineages with vaccine-induced antigen-binding hotspots develop broad HIV neutralization. Cell 2019; 178(3): 567–584.e19
72	T Zhou, A Zheng, U Baxa, GY Chuang, IS Georgiev, R Kong, S O’Dell, S Shahzad-Ul-Hussan, CH Shen, Y Tsybovsky, RT Bailer, SK Gift, MK Louder, K McKee, R Rawi, CH Stevenson, GBE Stewart-Jones, JD Taft, E Waltari, Y Yang, B Zhang, SS Shivatare, VS Shivatare, CD Lee, CY Wu, NCS Program, JC Mullikin, CA Bewley, DR Burton, VR Polonis, L Shapiro, CH Wong, JR Mascola, PD Kwong, X Wu. A neutralizing antibody recognizing primarily N-linked glycan targets the silent face of the HIV envelope. Immunity 2018; 48(3): 500–513.e6
73	T Schoofs, CO Barnes, N Suh-Toma, J Golijanin, P Schommers, H Gruell, AP West, Jr., F Bach, YE Lee, L Nogueira, IS Georgiev, RT Bailer, J Czartoski, JR Mascola, MS Seaman, MJ McElrath, NA Doria-Rose, F Klein, MC Nussenzweig, PJ Bjorkman. Broad and potent neutralizing antibodies recognize the silent face of the HIV envelope. Immunity 2019; 50(6): 1513–1529.e9
74	JR Mascola, BF Haynes. HIV-1 neutralizing antibodies: understanding nature’s pathways. Immunol Rev 2013; 254(1): 225–244 https://doi.org/10.1111/imr.12075 pmid: 23772623
75	F Klein, H Mouquet, P Dosenovic, JF Scheid, L Scharf, MC Nussenzweig. Antibodies in HIV-1 vaccine development and therapy. Science 2013; 341(6151): 1199–1204 https://doi.org/10.1126/science.1241144 pmid: 24031012
76	X Wu, T Zhou, J Zhu, B Zhang, I Georgiev, C Wang, X Chen, NS Longo, M Louder, K McKee, S O’Dell, S Perfetto, SD Schmidt, W Shi, L Wu, Y Yang, ZY Yang, Z Yang, Z Zhang, M Bonsignori, JA Crump, SH Kapiga, NE Sam, BF Haynes, M Simek, DR Burton, WC Koff, NA Doria-Rose, M Connors; Program NISC Comparative Sequencing, JC Mullikin, GJ Nabel, M Roederer, L Shapiro, PD Kwong, JR Mascola, JR Mascola. Focused evolution of HIV-1 neutralizing antibodies revealed by structures and deep sequencing. Science 2011; 333(6049): 1593–1602 https://doi.org/10.1126/science.1207532 pmid: 21835983
77	HX Liao, R Lynch, T Zhou, F Gao, SM Alam, SD Boyd, AZ Fire, KM Roskin, CA Schramm, Z Zhang, J Zhu, L Shapiro; Program NISC Comparative Sequencing, JC Mullikin, S Gnanakaran, P Hraber, K Wiehe, G Kelsoe, G Yang, SM Xia, DC Montefiori, R Parks, KE Lloyd, RM Scearce, KA Soderberg, M Cohen, G Kamanga, MK Louder, LM Tran, Y Chen, F Cai, S Chen, S Moquin, X Du, MG Joyce, S Srivatsan, B Zhang, A Zheng, GM Shaw, BH Hahn, TB Kepler, BT Korber, PD Kwong, JR Mascola, BF Haynes, BF Haynes. Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus. Nature 2013; 496(7446): 469–476 https://doi.org/10.1038/nature12053 pmid: 23552890
78	M Lu, X Ma, LR Castillo-Menendez, J Gorman, N Alsahafi, U Ermel, DS Terry, M Chambers, D Peng, B Zhang, T Zhou, N Reichard, K Wang, JR Grover, BP Carman, MR Gardner, I Nikić-Spiegel, A Sugawara, J Arthos, EA Lemke, AB Smith 3rd, M Farzan, C Abrams, JB Munro, AB McDermott, A Finzi, PD Kwong, SC Blanchard, JG Sodroski, W Mothes. Associating HIV-1 envelope glycoprotein structures with states on the virus observed by smFRET. Nature 2019; 568(7752): 415–419 https://doi.org/10.1038/s41586-019-1101-y pmid: 30971821
79	MS Cohen, GM Shaw, AJ McMichael, BF Haynes. Acute HIV-1 infection. N Engl J Med 2011; 364(20): 1943–1954 https://doi.org/10.1056/NEJMra1011874 pmid: 21591946
80	AJ McMichael, P Borrow, GD Tomaras, N Goonetilleke, BF Haynes. The immune response during acute HIV-1 infection: clues for vaccine development. Nat Rev Immunol 2010; 10(1): 11–23 https://doi.org/10.1038/nri2674 pmid: 20010788
81	F Breden, C Lepik, NS Longo, M Montero, PE Lipsky, JK Scott. Comparison of antibody repertoires produced by HIV-1 infection, other chronic and acute infections, and systemic autoimmune disease. PLoS One 2011; 6(3): e16857 https://doi.org/10.1371/journal.pone.0016857 pmid: 21479208
82	JF Scheid, H Mouquet, N Feldhahn, MS Seaman, K Velinzon, J Pietzsch, RG Ott, RM Anthony, H Zebroski, A Hurley, A Phogat, B Chakrabarti, Y Li, M Connors, F Pereyra, BD Walker, H Wardemann, D Ho, RT Wyatt, JR Mascola, JV Ravetch, MC Nussenzweig. Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals. Nature 2009; 458(7238): 636–640 https://doi.org/10.1038/nature07930 pmid: 19287373
83	T Tiller, M Tsuiji, S Yurasov, K Velinzon, MC Nussenzweig, H Wardemann. Autoreactivity in human IgG+ memory B cells. Immunity 2007; 26(2): 205–213 https://doi.org/10.1016/j.immuni.2007.01.009 pmid: 17306569
84	F Klein, R Diskin, JF Scheid, C Gaebler, H Mouquet, IS Georgiev, M Pancera, T Zhou, RB Incesu, BZ Fu, PN Gnanapragasam, TY Oliveira, MS Seaman, PD Kwong, PJ Bjorkman, MC Nussenzweig. Somatic mutations of the immunoglobulin framework are generally required for broad and potent HIV-1 neutralization. Cell 2013; 153(1): 126–138 https://doi.org/10.1016/j.cell.2013.03.018 pmid: 23540694
85	TB Kepler, HX Liao, SM Alam, R Bhaskarabhatla, R Zhang, C Yandava, S Stewart, K Anasti, G Kelsoe, R Parks, KE Lloyd, C Stolarchuk, J Pritchett, E Solomon, E Friberg, L Morris, SS Karim, MS Cohen, E Walter, MA Moody, X Wu, HR Altae-Tran, IS Georgiev, PD Kwong, SD Boyd, AZ Fire, JR Mascola, BF Haynes. Immunoglobulin gene insertions and deletions in the affinity maturation of HIV-1 broadly reactive neutralizing antibodies. Cell Host Microbe 2014; 16(3): 304–313 https://doi.org/10.1016/j.chom.2014.08.006 pmid: 25211073
86	X Xiao, W Chen, Y Feng, Z Zhu, P Prabakaran, Y Wang, MY Zhang, NS Longo, DS Dimitrov. Germline-like predecessors of broadly neutralizing antibodies lack measurable binding to HIV-1 envelope glycoproteins: implications for evasion of immune responses and design of vaccine immunogens. Biochem Biophys Res Commun 2009; 390(3): 404–409 https://doi.org/10.1016/j.bbrc.2009.09.029 pmid: 19748484
87	HX Liao, X Chen, S Munshaw, R Zhang, DJ Marshall, N Vandergrift, JF Whitesides, X Lu, JS Yu, KK Hwang, F Gao, M Markowitz, SL Heath, KJ Bar, PA Goepfert, DC Montefiori, GC Shaw, SM Alam, DM Margolis, TN Denny, SD Boyd, E Marshal, M Egholm, BB Simen, B Hanczaruk, AZ Fire, G Voss, G Kelsoe, GD Tomaras, MA Moody, TB Kepler, BF Haynes. Initial antibodies binding to HIV-1 gp41 in acutely infected subjects are polyreactive and highly mutated. J Exp Med 2011; 208(11): 2237–2249 https://doi.org/10.1084/jem.20110363 pmid: 21987658
88	A Flemming. HIV: sequential vaccine elicits broadly neutralizing antibodies. Nat Rev Drug Discov 2016; 15(11): 748–749 https://doi.org/10.1038/nrd.2016.228 pmid: 27807354
89	H Wardemann, S Yurasov, A Schaefer, JW Young, E Meffre, MC Nussenzweig. Predominant autoantibody production by early human B cell precursors. Science 2003; 301(5638): 1374–1377 https://doi.org/10.1126/science.1086907 pmid: 12920303
90	H Mouquet, JF Scheid, MJ Zoller, M Krogsgaard, RG Ott, S Shukair, MN Artyomov, J Pietzsch, M Connors, F Pereyra, BD Walker, DD Ho, PC Wilson, MS Seaman, HN Eisen, AK Chakraborty, TJ Hope, JV Ravetch, H Wardemann, MC Nussenzweig. Polyreactivity increases the apparent affinity of anti-HIV antibodies by heteroligation. Nature 2010; 467(7315): 591–595 https://doi.org/10.1038/nature09385 pmid: 20882016
91	P Zhu, J Liu, J Bess Jr, E Chertova, JD Lifson, H Grisé, GA Ofek, KA Taylor, KH Roux. Distribution and three-dimensional structure of AIDS virus envelope spikes. Nature 2006; 441(7095): 847–852 https://doi.org/10.1038/nature04817 pmid: 16728975
92	A Herschhorn, J Sodroski. An entry-competent intermediate state of the HIV-1 envelope glycoproteins. Receptors Clin Investig 2017; 4(1): e1544 pmid: 28752105
93	T Bruel, O Schwartz. HIV-1 envelope FRETted over by antibodies. Cell Host Microbe 2019; 25(6): 767–768 https://doi.org/10.1016/j.chom.2019.05.009 pmid: 31194935
94	X Ma, M Lu, J Gorman, DS Terry, X Hong, Z Zhou, H Zhao, RB Altman, J Arthos, SC Blanchard, PD Kwong, JB Munro, W Mothes. HIV-1 Env trimer opens through an asymmetric intermediate in which individual protomers adopt distinct conformations. eLife 2018; 7:e34271 https://doi.org/10.7554/eLife.34271 pmid: 29561264
95	A Herschhorn, X Ma, C Gu, JD Ventura, L Castillo-Menendez, B Melillo, DS Terry, AB Smith 3rd, SC Blanchard, JB Munro, W Mothes, A Finzi, J Sodroski. Release of gp120 restraints leads to an entry-competent intermediate state of the HIV-1 envelope glycoproteins. MBio 2016; 7(5): e01598-16 https://doi.org/10.1128/mBio.01598-16 pmid: 27795397
96	A Herschhorn, C Gu, F Moraca, X Ma, M Farrell, AB Smith 3rd, M Pancera, PD Kwong, A Schön, E Freire, C Abrams, SC Blanchard, W Mothes, JG Sodroski. The b20-b21 of gp120 is a regulatory switch for HIV-1 Env conformational transitions. Nat Commun 2017; 8(1): 1049 https://doi.org/10.1038/s41467-017-01119-w pmid: 29051495
97	Q Wang, L Liu, W Ren, A Gettie, H Wang, Q Liang, X Shi, DC Montefiori, T Zhou, L Zhang. A single substitution in gp41 modulates the neutralization profile of SHIV during in vivo adaptation. Cell Reports 2019; 27(9): 2593–2607.e5 https://doi.org/10.1016/j.celrep.2019.04.108 pmid: 31141685
98	JB Munro, J Gorman, X Ma, Z Zhou, J Arthos, DR Burton, WC Koff, JR Courter, AB Smith 3rd, PD Kwong, SC Blanchard, W Mothes. Conformational dynamics of single HIV-1 envelope trimers on the surface of native virions. Science 2014; 346(6210): 759–763 https://doi.org/10.1126/science.1254426 pmid: 25298114
99	N Alsahafi, N Bakouche, M Kazemi, J Richard, S Ding, S Bhattacharyya, D Das, SP Anand, J Prevost, WD Tolbert, H Lu, H Medjahed, G Gendron-Lepage, GG Ortega Delgado, S Kirk, B Melillo, W Mothes, J Sodroski, AB Smith, 3rd, DE Kaufmann, X Wu, M Pazgier, I Rouiller, A Finzi, JB Munro. An asymmetric opening of HIV-1 envelope mediates antibody-dependent cellular cytotoxicity. Cell Host Microbe 2019; 25(4): 578–587.e5
100	RW Sanders, R Derking, A Cupo, JP Julien, A Yasmeen, N de Val, HJ Kim, C Blattner, AT de la Peña, J Korzun, M Golabek, K de Los Reyes, TJ Ketas, MJ van Gils, CR King, IA Wilson, AB Ward, PJ Klasse, JP Moore. A next-generation cleaved, soluble HIV-1 Env trimer, BG505 SOSIP.664 gp140, expresses multiple epitopes for broadly neutralizing but not non-neutralizing antibodies. PLoS Pathog 2013; 9(9): e1003618 https://doi.org/10.1371/journal.ppat.1003618 pmid: 24068931
101	YD Kwon, M Pancera, P Acharya, IS Georgiev, ET Crooks, J Gorman, MG Joyce, M Guttman, X Ma, S Narpala, C Soto, DS Terry, Y Yang, T Zhou, G Ahlsen, RT Bailer, M Chambers, GY Chuang, NA Doria-Rose, A Druz, MA Hallen, A Harned, T Kirys, MK Louder, S O’Dell, G Ofek, K Osawa, M Prabhakaran, M Sastry, GB Stewart-Jones, J Stuckey, PV Thomas, T Tittley, C Williams, B Zhang, H Zhao, Z Zhou, BR Donald, LK Lee, S Zolla-Pazner, U Baxa, A Schön, E Freire, L Shapiro, KK Lee, J Arthos, JB Munro, SC Blanchard, W Mothes, JM Binley, AB McDermott, JR Mascola, PD Kwong. Crystal structure, conformational fixation and entry-related interactions of mature ligand-free HIV-1 Env. Nat Struct Mol Biol 2015; 22(7): 522–531 https://doi.org/10.1038/nsmb.3051 pmid: 26098315
102	JH Lee, G Ozorowski, AB Ward. Cryo-EM structure of a native, fully glycosylated, cleaved HIV-1 envelope trimer. Science 2016; 351(6277): 1043–1048 https://doi.org/10.1126/science.aad2450 pmid: 26941313
103	SK Sharma, N de Val, S Bale, J Guenaga, K Tran, Y Feng, V Dubrovskaya, AB Ward, RT Wyatt. Cleavage-independent HIV-1 Env trimers engineered as soluble native spike mimetics for vaccine design. Cell Reports 2015; 11(4): 539–550 https://doi.org/10.1016/j.celrep.2015.03.047 pmid: 25892233
104	J Guenaga, F Garces, N de Val, RL Stanfield, V Dubrovskaya, B Higgins, B Carrette, AB Ward, IA Wilson, RT Wyatt. Glycine substitution at helix-to-coil transitions facilitates the structural determination of a stabilized subtype C HIV envelope glycoprotein. Immunity 2017; 46(5): 792–803.e3
105	L Kong, L He, N de Val, N Vora, CD Morris, P Azadnia, D Sok, B Zhou, DR Burton, AB Ward, IA Wilson, J Zhu. Uncleaved prefusion-optimized gp140 trimers derived from analysis of HIV-1 envelope metastability. Nat Commun 2016; 7(1): 12040 https://doi.org/10.1038/ncomms12040 pmid: 27349805
106	JP Julien, A Cupo, D Sok, RL Stanfield, D Lyumkis, MC Deller, PJ Klasse, DR Burton, RW Sanders, JP Moore, AB Ward, IA Wilson. Crystal structure of a soluble cleaved HIV-1 envelope trimer. Science 2013; 342(6165): 1477–1483 https://doi.org/10.1126/science.1245625 pmid: 24179159
107	D Lyumkis, JP Julien, N de Val, A Cupo, CS Potter, PJ Klasse, DR Burton, RW Sanders, JP Moore, B Carragher, IA Wilson, AB Ward. Cryo-EM structure of a fully glycosylated soluble cleaved HIV-1 envelope trimer. Science 2013; 342(6165): 1484–1490 https://doi.org/10.1126/science.1245627 pmid: 24179160
108	L He, S Kumar, JD Allen, D Huang, X Lin, CJ Mann, KL Saye-Francisco, J Copps, A Sarkar, GS Blizard, G Ozorowski, D Sok, M Crispin, AB Ward, D Nemazee, DR Burton, IA Wilson, J Zhu. HIV-1 vaccine design through minimizing envelope metastability. Sci Adv 2018; 4(11): eaau6769
109	A Sarkar, S Bale, AJ Behrens, S Kumar, SK Sharma, N de Val, J Pallesen, A Irimia, DC Diwanji, RL Stanfield, AB Ward, M Crispin, RT Wyatt, IA Wilson. Structure of a cleavage-independent HIV Env recapitulates the glycoprotein architecture of the native cleaved trimer. Nat Commun 2018; 9(1): 1956 https://doi.org/10.1038/s41467-018-04272-y pmid: 29769533
110	H Wang, X Chen, D Wang, C Yao, Q Wang, J Xie, X Shi, Y Xiang, W Liu, L Zhang. Epitope-focused immunogens against the CD4-binding site of HIV-1 envelope protein induce neutralizing antibodies against auto- and heterologous viruses. J Biol Chem 2018; 293(3): 830–846 https://doi.org/10.1074/jbc.M117.816447 pmid: 29187598
111	T Zhou, I Georgiev, X Wu, ZY Yang, K Dai, A Finzi, YD Kwon, JF Scheid, W Shi, L Xu, Y Yang, J Zhu, MC Nussenzweig, J Sodroski, L Shapiro, GJ Nabel, JR Mascola, PD Kwong. Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01. Science 2010; 329(5993): 811–817 https://doi.org/10.1126/science.1192819 pmid: 20616231
112	NT Freund, JA Horwitz, L Nogueira, SA Sievers, L Scharf, JF Scheid, A Gazumyan, C Liu, K Velinzon, A Goldenthal, RW Sanders, JP Moore, PJ Bjorkman, MS Seaman, BD Walker, F Klein, MC Nussenzweig. A new glycan-dependent CD4-binding site neutralizing antibody exerts pressure on HIV-1 in vivo. PLoS Pathog 2015; 11(10): e1005238 https://doi.org/10.1371/journal.ppat.1005238 pmid: 26516768
113	AJ Borst, CE Weidle, MD Gray, B Frenz, J Snijder, MG Joyce, IS Georgiev, GB Stewart-Jones, PD Kwong, AT McGuire, F DiMaio, L Stamatatos, M Pancera, D Veesler. Germline VRC01 antibody recognition of a modified clade C HIV-1 envelope trimer and a glycosylated HIV-1 gp120 core. eLife 2018; 7: e37688 https://doi.org/10.7554/eLife.37688 pmid: 30403372
114	J Jardine, JP Julien, S Menis, T Ota, O Kalyuzhniy, A McGuire, D Sok, PS Huang, S MacPherson, M Jones, T Nieusma, J Mathison, D Baker, AB Ward, DR Burton, L Stamatatos, D Nemazee, IA Wilson, WR Schief. Rational HIV immunogen design to target specific germline B cell receptors. Science 2013; 340(6133): 711–716 https://doi.org/10.1126/science.1234150 pmid: 23539181
115	JG Jardine, DW Kulp, C Havenar-Daughton, A Sarkar, B Briney, D Sok, F Sesterhenn, J Ereño-Orbea, O Kalyuzhniy, I Deresa, X Hu, S Spencer, M Jones, E Georgeson, Y Adachi, M Kubitz, AC deCamp, JP Julien, IA Wilson, DR Burton, S Crotty, WR Schief. HIV-1 broadly neutralizing antibody precursor B cells revealed by germline-targeting immunogen. Science 2016; 351(6280): 1458–1463 https://doi.org/10.1126/science.aad9195 pmid: 27013733
116	M Pauthner, C Havenar-Daughton, D Sok, JP Nkolola, R Bastidas, AV Boopathy, DG Carnathan, A Chandrashekar, KM Cirelli, CA Cottrell, AM Eroshkin, J Guenaga, K Kaushik, DW Kulp, J Liu, LE McCoy, AL Oom, G Ozorowski, KW Post, SK Sharma, JM Steichen, SW de Taeye, T Tokatlian, A Torrents de la Pena, ST Butera, CC LaBranche, DC Montefiori, G Silvestri, IA Wilson, DJ Irvine, RW Sanders, WR Schief, AB Ward, RT Wyatt, DH Barouch, S Crotty, DR Burton. Elicitation of robust Tier 2 neutralizing antibody responses in nonhuman primates by HIV envelope trimer immunization using optimized approaches. Immunity 2017; 46(6): 1073–1088.e6
117	A Torrents de la Peña, SW de Taeye, K Sliepen, CC LaBranche, JA Burger, EE Schermer, DC Montefiori, JP Moore, PJ Klasse, RW Sanders. Immunogenicity in rabbits of HIV-1 SOSIP trimers from clades A, B, and C, given individually, sequentially, or in combination. J Virol 2018; 92(8): e01957-17 https://doi.org/10.1128/JVI.01957-17 pmid: 29367243
118	RW Sanders, MJ van Gils, R Derking, D Sok, TJ Ketas, JA Burger, G Ozorowski, A Cupo, C Simonich, L Goo, H Arendt, HJ Kim, JH Lee, P Pugach, M Williams, G Debnath, B Moldt, MJ van Breemen, G Isik, M Medina-Ramírez, JW Back, WC Koff, JP Julien, EG Rakasz, MS Seaman, M Guttman, KK Lee, PJ Klasse, C LaBranche, WR Schief, IA Wilson, J Overbaugh, DR Burton, AB Ward, DC Montefiori, H Dean, JP Moore. HIV-1 VACCINES. HIV-1 neutralizing antibodies induced by native-like envelope trimers. Science 2015; 349(6244): aac4223 https://doi.org/10.1126/science.aac4223 pmid: 26089353
119	PJ Klasse, CC LaBranche, TJ Ketas, G Ozorowski, A Cupo, P Pugach, RP Ringe, M Golabek, MJ van Gils, M Guttman, KK Lee, IA Wilson, ST Butera, AB Ward, DC Montefiori, RW Sanders, JP Moore. Sequential and simultaneous immunization of rabbits with HIV-1 envelope glycoprotein SOSIP.664 trimers from clades A, B and C. PLoS Pathog 2016; 12(9): e1005864 https://doi.org/10.1371/journal.ppat.1005864 pmid: 27627672
120	SW de Taeye, G Ozorowski, A Torrents de la Peña, M Guttman, JP Julien, TL van den Kerkhof, JA Burger, LK Pritchard, P Pugach, A Yasmeen, J Crampton, J Hu, I Bontjer, JL Torres, H Arendt, J DeStefano, WC Koff, H Schuitemaker, D Eggink, B Berkhout, H Dean, C LaBranche, S Crotty, M Crispin, DC Montefiori, PJ Klasse, KK Lee, JP Moore, IA Wilson, AB Ward, RW Sanders. Immunogenicity of stabilized HIV-1 envelope trimers with reduced exposure of non-neutralizing epitopes. Cell 2015; 163(7): 1702–1715 https://doi.org/10.1016/j.cell.2015.11.056 pmid: 26687358
121	JK Hu, JC Crampton, A Cupo, T Ketas, MJ van Gils, K Sliepen, SW de Taeye, D Sok, G Ozorowski, I Deresa, R Stanfield, AB Ward, DR Burton, PJ Klasse, RW Sanders, JP Moore, S Crotty. Murine antibody responses to cleaved soluble HIV-1 envelope trimers are highly restricted in specificity. J Virol 2015; 89(20): 10383–10398 https://doi.org/10.1128/JVI.01653-15 pmid: 26246566
122	Y Feng, K Tran, S Bale, S Kumar, J Guenaga, R Wilson, N de Val, H Arendt, J DeStefano, AB Ward, RT Wyatt. Thermostability of well-ordered HIV spikes correlates with the elicitation of autologous Tier 2 neutralizing antibodies. PLoS Pathog 2016; 12(8): e1005767 https://doi.org/10.1371/journal.ppat.1005767 pmid: 27487086
123	K Koch, S Kalusche, JL Torres, RL Stanfield, W Danquah, K Khazanehdari, H von Briesen, ER Geertsma, IA Wilson, U Wernery, F Koch-Nolte, AB Ward, U Dietrich. Selection of nanobodies with broad neutralizing potential against primary HIV-1 strains using soluble subtype C gp140 envelope trimers. Sci Rep 2017; 7(1): 8390 https://doi.org/10.1038/s41598-017-08273-7 pmid: 28827559
124	D Sok, KM Le, M Vadnais, KL Saye-Francisco, JG Jardine, JL Torres, ZT Berndsen, L Kong, R Stanfield, J Ruiz, A Ramos, CH Liang, PL Chen, MF Criscitiello, W Mwangi, IA Wilson, AB Ward, VV Smider, DR Burton. Rapid elicitation of broadly neutralizing antibodies to HIV by immunization in cows. Nature 2017; 548(7665): 108–111 https://doi.org/10.1038/nature23301 pmid: 28726771

[1]	Jingjing Yan, Shuye Zhang, Jun Sun, Jianqing Xu, Xiaoyang Zhang. Irreversible phenotypic perturbation and functional impairment of B cells during HIV-1 infection[J]. Front. Med., 2017, 11(4): 536-547.

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