Volume 9 Issue 7
Jul.  2018
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Huan Liu, Xiaojie Su, Lulu Si, Lu Lu, Shibo Jiang. The development of HIV vaccines targeting gp41 membrane-proximal external region (MPER): challenges and prospects[J]. Protein&Cell, 2018, 9(7): 596-615. doi: 10.1007/s13238-018-0534-7
Citation: Huan Liu, Xiaojie Su, Lulu Si, Lu Lu, Shibo Jiang. The development of HIV vaccines targeting gp41 membrane-proximal external region (MPER): challenges and prospects[J]. Protein&Cell, 2018, 9(7): 596-615. doi: 10.1007/s13238-018-0534-7

The development of HIV vaccines targeting gp41 membrane-proximal external region (MPER): challenges and prospects

doi: 10.1007/s13238-018-0534-7
Funds:  This work was supported by the National Natural Science Foundation of China (Grant Nos. 81661128041 and 81672019 to L. Lu; 81630090 to S. Jiang), Shanghai Rising-Star Program (16QA1400300) and Wuhan Science and Technology Project (2016060101010066). We also thank Guangzhou SageneBiotech Co., LTD for helping us draw pictures.
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  • A human immunodeficiency virus type-1 (HIV-1) vaccine which is able to effectively prevent infection would be the most powerful method of extinguishing pandemic of the acquired immunodeficiency syndrome (AIDS). Yet, achieving such vaccine remains great challenges. The membrane-proximal external region (MPER) is a highly conserved region of the envelope glycoprotein (Env) gp41 subunit near the viral envelope surface, and it plays a key role in membrane fusion. It is also the target of some reported broadly neutralizing antibodies (bNAbs). Thus, MPER is deemed to be one of the most attractive vaccine targets. However, no one can induce these bNAbs by immunization with immunogens containing the MPER sequence(s). The few attempts at developing a vaccine have only resulted in the induction of neutralizing antibodies with quite low potency and limited breadth. Thus far, vaccine failure can be attributed to various characteristics of MPER, such as those involving structure and immunology; therefore, we will focus on these and review the recent progress in the field from the following perspectives:(1) MPER structure and its role in membrane fusion, (2) the epitopes and neutralization mechanisms of MPER-specific bNAbs, as well as the limitations in eliciting neutralizing antibodies, and (3) different strategies for MPER vaccine design and current harvests.
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  • [1]
    Alam SM, McAdams M, Boren D, Rak M, Scearce RM, Gao F, Camacho ZT, Gewirth D, Kelsoe G, Chen P et al (2007) The role of antibody polyspecificity and lipid reactivity in binding of broadly neutralizing anti-HIV-1 envelope human monoclonal antibodies 2F5 and 4E10 to glycoprotein 41 membrane proximal envelope epitopes. J Immunol 178:4424-4435
    [2]
    Alam SM, Morelli M, Dennison SM, Liao HX, Zhang R, Xia SM, RitsVolloch S, Sun L, Harrison SC, Haynes BF et al (2009) Role of HIV membrane in neutralization by two broadly neutralizing antibodies. Proc Natl Acad Sci USA 106:20234-20239
    [3]
    Alfsen A, Bomsel M (2002) HIV-1 gp41 envelope residues 650-685 exposed on native virus act as a lectin to bind epithelial cell galactosyl ceramide. J Biol Chem 277:25649-25659
    [4]
    Alfsen A, Iniguez P, Bouguyon E, Bomsel M (2001) Secretory IgA specific for a conserved epitope on gp41 envelope glycoprotein inhibits epithelial transcytosis of HIV-1. J Immunol 166:6257-6265
    [5]
    Banerjee S, Shi H, Habte HH, Qin Y, Cho MW (2016) Modulating immunogenic properties of HIV-1 gp41 membrane-proximal external region by destabilizing six-helix bundle structure. Virology 490:17-26
    [6]
    Barouch DH (2008) Challenges in the development of an HIV-1 vaccine. Nature 455:613-619
    [7]
    Bellamy-McIntyre AK, Lay CS, Baar S, Maerz AL, Talbo GH, Drummer HE, Poumbourios P (2007) Functional links between the fusion peptide-proximal polar segment and membraneproximal region of human immunodeficiency virus gp41 in distinct phases of membrane fusion. J Biol Chem 282:23104-23116
    [8]
    Benen TD, Tonks P, Kliche A, Kapzan R, Heeney JL, Wagner R (2014) Development and immunological assessment of VLPbased immunogens exposing the membrane-proximal region of the HIV-1 gp41 protein. J Biomed Sci 21:79
    [9]
    Binley JM, Wrin T, Korber B, Zwick MB, Wang M, Chappey C, Stiegler G, Kunert R, Zolla-Pazner S, Katinger H et al (2004) Comprehensive cross-clade neutralization analysis of a panel of anti-human immunodeficiency virus type 1 monoclonal antibodies. J Virol 78:13232-13252
    [10]
    Blumenthal R, Durell S, Viard M (2012) HIV entry and envelope glycoprotein-mediated fusion. J Biol Chem 287:40841-40849
    [11]
    Boehme KW, Ikizler M, Iskarpatyoti JA, Wetzel JD, Willis J, Crowe JE Jr, LaBranche CC, Montefiori DC, Wilson GJ, Dermody TS (2016) Engineering recombinant reoviruses to display gp41 membrane-proximal external-region epitopes from HIV-1.mSphere. https://doi.org/10.1128/mSphere.00086-16
    [12]
    Bolhassani A, Kardani K, Vahabpour R, Habibzadeh N, Aghasadeghi MR, Sadat SM, Agi E (2015) Prime/boost immunization with HIV-1 MPER-V3 fusion construct enhances humoral and cellular immune responses. Immunology Letters 168:366-373
    [13]
    Bomsel M (1997) Transcytosis of infectious human immunodeficiency virus across a tight human epithelial cell line barrier. Nat Med 3:42-47
    [14]
    Bomsel M, Tudor D, Drillet AS, Alfsen A, Ganor Y, Roger MG, Mouz N, Amacker M, Chalifour A, Diomede L et al (2011) Immunization with HIV-1 gp41 subunit virosomes induces mucosal antibodies protecting nonhuman primates against vaginal SHIV challenges. Immunity 34:269-280
    [15]
    Bonsignori M, Liao HX, Gao F, Williams WB, Alam SM, Montefiori DC, Haynes BF (2017) Antibody-virus co-evolution in HIV infection:paths for HIV vaccine development. Immunol Rev 275:145-160
    [16]
    Bryson S, Cunningham A, Ho J, Hynes RC, Isenman DE, Barber BH, Kunert R, Katinger H, Klein M, Pai EF (2001) Crossneutralizing human monoclonal anti-HIV-1 antibody 2F5:preparation and crystallographic analysis of the free and epitopecomplexed forms of its F-ab' fragment. Protein and Peptide Letters 8:413-418
    [17]
    Bryson S, Julien JP, Isenman DE, Kunert R, Katinger H, Pai EF (2008) Crystal structure of the complex between the F(ab)' fragment of the cross-neutralizing anti-HIV-1 antibody 2F5 and the F(ab) fragment of its anti-idiotypic antibody 3H6. J Mol Biol 382:910-919
    [18]
    Buchacher A, Predl R, Strutzenberger K, Steinfellner W, Trkola A, Purtscher M, Gruber G, Tauer C, Steindl F, Jungbauer A et al (1994) Generation of human monoclonal antibodies against HIV-1 proteins; electrofusion and Epstein-Barr virus transformation for peripheral blood lymphocyte immortalization. AIDS Res Hum Retrovir 10:359-369
    [19]
    Bures R, Morris L, Williamson C, Ramjee G, Deers M, Fiscus SA, Abdool-Karim S, Montefiori DC (2002) Regional clustering of shared neutralization determinants on primary isolates of clade C human immunodeficiency virus type 1 from South Africa. J Virol 76:2233-2244
    [20]
    Buzon V, Natrajan G, Schibli D, Campelo F, Kozlov MM, Weissenhorn W (2010) Crystal structure of HIV-1 gp41 including both fusion peptide and membrane proximal external regions. PLoS Pathog 6:e1000880
    [21]
    Cardoso RM, Zwick MB, Stanfield RL, Kunert R, Binley JM, Katinger H, Burton DR, Wilson IA (2005) Broadly neutralizing anti-HIV antibody 4E10 recognizes a helical conformation of a highly conserved fusion-associated motif in gp41. Immunity 22:163-173
    [22]
    Cardoso RM, Brunel FM, Ferguson S, Zwick M, Burton DR, Dawson PE, Wilson IA (2007) Structural basis of enhanced binding of extended and helically constrained peptide epitopes of the broadly neutralizing HIV-1 antibody 4E10. J Mol Biol 365:1533-1544
    [23]
    Chan DC, Kim PS (1998) HIV entry and its inhibition. Cell 93:681-684
    [24]
    Chen J, Frey G, Peng H, Rits-Volloch S, Garrity J, Seaman MS, Chen B (2014) Mechanism of HIV-1 neutralization by antibodies targeting a membrane-proximal region of gp41. J Virol 88:1249-1258
    [25]
    Dennison SM, Stewart SM, Stempel KC, Liao HX, Haynes BF, Alam SM (2009) Stable docking of neutralizing human immunodeficiency virus type 1 gp41 membrane-proximal external region monoclonal antibodies 2F5 and 4E10 is dependent on the membrane immersion depth of their epitope regions. J Virol 83:10211-10223
    [26]
    Dennison SM, Sutherland LL, Jaeger FH, Anasti KM, Parks R, Stewart S, Bowman C, Xia SM, Zhang R, Shen X et al (2011) Induction of antibodies in rhesus macaques that recognize a fusion-intermediate conformation of HIV-1 gp41. PLoS ONE 6:e27824
    [27]
    Dev J, Park D, Fu Q, Chen J, Ha HJ, Ghantous F, Herrmann T, Chang W, Liu Z, Frey G et al (2016) Structural basis for membrane anchoring of HIV-1 envelope spike. Science 353:172-175
    [28]
    Dimitrov AS, Jacobs A, Finnegan CM, Stiegler G, Katinger H, Blumenthal R (2007) Exposure of the membrane-proximal external region of HIV-1 gp41 in the course of HIV-1 envelope glycoprotein-mediated fusion. Biochemistry 46:1398-1401
    [29]
    Donius LR, Cheng Y, Choi J, Sun ZY, Hanson M, Zhang M, Gierahn TM, Marquez S, Uduman M, Kleinstein SH et al (2016) Generation of long-lived bone marrow plasma cells secreting antibodies specific for the HIV-1 gp41 membrane-proximal external region in the absence of polyreactivity. J Virol 90:8875-8890
    [30]
    Doria-Rose NA, Klein RM, Manion MM, O'Dell S, Phogat A, Chakrabarti B, Hallahan CW, Migueles SA, Wrammert J, Ahmed R et al (2009) Frequency and phenotype of human immunodeficiency virus envelope-specific B cells from patients with broadly cross-neutralizing antibodies. J Virol 83:188-199
    [31]
    Doyle-Cooper C, Hudson KE, Cooper AB, Ota T, Skog P, Dawson PE, Zwick MB, Schief WR, Burton DR, Nemazee D (2013) Immune tolerance negatively regulates B cells in knock-in mice expressing broadly neutralizing HIV antibody 4E10. J Immunol 191:3186-3191
    [32]
    Fauci AS, Johnston MI, Dieffenbach CW, Burton DR, Hammer SM et al (2008) HIV vaccine research:the way forward. Science 321:530-532
    [33]
    Frey G, Peng H, Rits-Volloch S, Morelli M, Cheng Y, Chen B (2008) A fusion-intermediate state of HIV-1 gp41 targeted by broadly neutralizing antibodies. Proc Natl Acad Sci USA 105:3739-3744
    [34]
    Gray ES, Meyers T, Gray G, Montefiori DC, Morris L (2006) Insensitivity of paediatric HIV-1 subtype C viruses to broadly neutralising monoclonal antibodies raised against subtype B. PLoS Med 3:e255
    [35]
    Gray ES, Taylor N, Wycuff D, Moore PL, Tomaras GD, Wibmer CK, Puren A, DeCamp A, Gilbert PB, Wood B et al (2009) Antibody specificities associated with neutralization breadth in plasma from human immunodeficiency virus type 1 subtype C-infected blood donors. J Virol 83:8925-8937
    [36]
    Gu R, Stagnar C, Zaichenko L, Ramsingh AI (2012) Induction of mucosal HIV-specific B and T cell responses after oral immunization with live coxsackievirus B4 recombinants. Vaccine 30:3666-3674
    [37]
    Habte HH, Banerjee S, Shi H, Qin Y, Cho MW (2015) Immunogenic properties of a trimeric gp41-based immunogen containing an exposed membrane-proximal external region. Virology 486:187-197
    [38]
    Hanson MC, Abraham W, Crespo MP, Chen SH, Liu H, Szeto GL, Kim M, Reinherz EL, Irvine DJ (2015) Liposomal vaccines incorporating molecular adjuvants and intrastructural T-cell help promote the immunogenicity of HIV membrane-proximal external region peptides. Vaccine 33:861-868
    [39]
    Haynes BF, Mascola JR (2017) The quest for an antibody-based HIV vaccine. Immunol Rev 275:5-10
    [40]
    Haynes BF, Fleming J, St Clair EW, Katinger H, Stiegler G, Kunert R, Robinson J, Scearce RM, Plonk K, Staats HF et al (2005a) Cardiolipin polyspecific autoreactivity in two broadly neutralizing HIV-1 antibodies. Science 308:1906-1908
    [41]
    Haynes BF, Moody MA, Verkoczy L, Kelsoe G, Alam SM (2005b) Antibody polyspecificity and neutralization of HIV-1:a hypothesis. Hum Antib 14:59-67
    [42]
    Hessell AJ, Rakasz EG, Tehrani DM, Huber M, Weisgrau KL, Landucci G, Forthal DN, Koff WC, Poignard P, Watkins DI et al (2010) 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 84:1302-1313
    [43]
    Huang J, Ofek G, Laub L, Louder MK, Doria-Rose NA, Longo NS, Imamichi H, Bailer RT, Chakrabarti B, Sharma SK et al (2012) Broad and potent neutralization of HIV-1 by a gp41-specific human antibody. Nature 491:406-412
    [44]
    Huarte N, Lorizate M, Maeso R, Kunert R, Arranz R, Valpuesta JM, Nieva JL (2008) The broadly neutralizing anti-human immunodeficiency virus type 1 4E10 monoclonal antibody is better adapted to membrane-bound epitope recognition and blocking than 2F5. J Virol 82:8986-8996
    [45]
    Irimia A, Sarkar A, Stanfield RL, Wilson IA (2016) Crystallographic identification of lipid as an integral component of the epitope of HIV broadly neutralizing antibody 4E10. Immunity 44:21-31
    [46]
    Irimia A, Serra AM, Sarkar A, Jacak R, Kalyuzhniy O, Sok D, SayeFrancisco KL, Schiffner T, Tingle R, Kubitz M et al (2017) Lipid interactions and angle of approach to the HIV-1 viral membrane of broadly neutralizing antibody 10E8:Insights for vaccine and therapeutic design. PLoS Pathog 13:e1006212
    [47]
    Jain S, Patrick AJ, Rosenthal KL (2010) Multiple tandem copies of conserved gp41 epitopes incorporated in gag virus-like particles elicit systemic and mucosal antibodies in an optimized heterologous vector delivery regimen. Vaccine 28:7070-7080
    [48]
    Julien JP, Bryson S, Nieva JL, Pai EF (2008) Structural details of HIV-1 recognition by the broadly neutralizing monoclonal antibody 2F5:epitope conformation, antigen-recognition loop mobility, and anion-binding site. J Mol Biol 384:377-392
    [49]
    Kajikawa A, Zhang L, LaVoy A, Bumgardner S, Klaenhammer TR, Dean GA (2015) Mucosal immunogenicity of genetically modified lactobacillus acidophilus expressing an HIV-1 epitope within the surface layer protein. PLoS ONE 10:e0141713
    [50]
    Kelsoe G, Haynes BF (2017) Host controls of HIV broadly neutralizing antibody development. Immunol Rev 275:79-88
    [51]
    Kim M, Song L, Moon J, Sun ZY, Bershteyn A, Hanson M, Cain D, Goka S, Kelsoe G, Wagner G et al (2013) Immunogenicity of membrane-bound HIV-1 gp41 membrane-proximal external region (MPER) segments is dominated by residue accessibility and modulated by stereochemistry. J Biol Chem 288:31888-31901
    [52]
    Kim AS, Leaman DP, Zwick MB (2014) Antibody to gp41 MPER alters functional properties of HIV-1 Env without complete neutralization. PLoS Pathog 10:e1004271
    [53]
    Kim JH, Excler JL, Michael NL (2015) Lessons from the RV144 Thai phase â…¢ HIV-1 vaccine trial and the search for correlates of protection. Annu Rev Med 66:423-437
    [54]
    Klasse PJ (2012) The molecular basis of HIV entry. Cell Microbiol 14:1183-1192
    [55]
    Krebs SJ, McBurney SP, Kovarik DN, Waddell CD, Jaworski JP, Sutton WF, Gomes MM, Trovato M, Waagmeester G, Barnett SJ et al (2014) Multimeric scaffolds displaying the HIV-1 envelope MPER induce MPER-specific antibodies and cross-neutralizing antibodies when co-immunized with gp160 DNA. PLoS ONE 9:e113463
    [56]
    Landais E, Huang X, Havenar-Daughton C, Murrell B, Price MA, Wickramasinghe L, Ramos A, Bian CB, Simek M, Allen S et al (2016) Broadly neutralizing antibody responses in a large longitudinal sub-Saharan HIV primary infection cohort. PLoS Pathog 12:e1005369
    [57]
    Law M, Cardoso RM, Wilson IA, Burton DR (2007) Antigenic and immunogenic study of membrane-proximal external regiongrafted gp120 antigens by a DNA prime-protein boost immunization strategy. J Virol 81:4272-4285
    [58]
    Lee JH, Ozorowski G, Ward AB (2016) Cryo-EM structure of a native, fully glycosylated, cleaved HIV-1 envelope trimer. Science 351:1043-1048
    [59]
    Leroux-Roels G, Maes C, Clement F, van Engelenburg F, van den Dobbelsteen M, Adler M, Amacker M, Lopalco L, Bomsel M, Chalifour A et al (2013) Randomized phase I:safety, immunogenicity and mucosal antiviral activity in young healthy women vaccinated with HIV-1 Gp41 P1 peptide on virosomes. PLoS ONE 8:e55438
    [60]
    Li QH, Jin G, Wang JY, Li HN, Liu H, Chang XY, Wang FX, Liu SL (2016) Live attenuated Salmonella displaying HIV-1 10E8 epitope on fimbriae:systemic and mucosal immune responses in BALB/c mice by mucosal administration. Sci Rep 6:29556
    [61]
    Liu J, Bartesaghi A, Borgnia MJ, Sapiro G, Subramaniam S (2008) Molecular architecture of native HIV-1 gp120 trimers. Nature 455:109-113
    [62]
    Liu M, Yang G, Wiehe K, Nicely NI, Vandergrift NA, Rountree W, Bonsignori M, Alam SM, Gao J, Haynes BF et al (2015) Polyreactivity and autoreactivity among HIV-1 antibodies. J Virol 89:784-798
    [63]
    Lorenz IC, Nguyen HT, Kemelman M, Lindsay RW, Yuan M, Wright KJ, Arendt H, Back JW, DeStefano J, Hoffenberg S et al (2014) The stem of vesicular stomatitis virus G can be replaced with the HIV-1 Env membrane-proximal external region without loss of G function or membrane-proximal external region antigenic properties. AIDS Res Hum Retrovir 30:1130-1144
    [64]
    Louder MK, Sambor A, Chertova E, Hunte T, Barrett S, Ojong F, Sanders-Buell E, Zolla-Pazner S, McCutchan FE, Roser JD et al (2005) HIV-1 envelope pseudotyped viral vectors and infectious molecular clones expressing the same envelope glycoprotein have a similar neutralization phenotype, but culture in peripheral blood mononuclear cells is associated with decreased neutralization sensitivity. Virology 339:226-238
    [65]
    Luo M, Yuan F, Liu Y, Jiang S, Song X, Jiang P, Yin X, Ding M, Deng H (2006) Induction of neutralizing antibody against human immunodeficiency virus type 1 (HIV-1) by immunization with gp41 membrane-proximal external region (MPER) fused with porcine endogenous retrovirus (PERV) p15E fragment. Vaccine 24:435-442
    [66]
    Lutje Hulsik D, Liu YY, Strokappe NM, Battella S, El Khattabi M, McCoy LE, Sabin C, Hinz A, Hock M, Macheboeuf P et al (2013) A gp41 MPER-specific llama VHH requires a hydrophobic CDR3 for neutralization but not for antigen recognition. PLoS Pathog 9:e1003202
    [67]
    Maddon PJ, Dalgleish AG, McDougal JS, Clapham PR, Weiss RA, Axel R (1986) The T4 gene encodes the AIDS virus receptor and is expressed in the immune system and the brain. Cell 47:333-348
    [68]
    Mader A, Kunert R (2012) Evaluation of the potency of the antiidiotypic antibody Ab2/3H6 mimicking gp41 as an HIV-1 vaccine in a rabbit prime/boost study. PLoS ONE 7:e39063
    [69]
    Mascola JR, Stiegler G, VanCott TC, Katinger H, Carpenter CB, Hanson CE, Beary H, Hayes D, Frankel SS, Birx DL et al (2000) Protection of macaques against vaginal transmission of a pathogenic HIV-1/SIV chimeric virus by passive infusion of neutralizing antibodies. Nat Med 6:207-210
    [70]
    Matthews QL, Fatima A, Tang Y, Perry BA, Tsuruta Y, Komarova S, Timares L, Zhao C, Makarova N, Borovjagin AV et al (2010) HIV antigen incorporation within adenovirus hexon hypervariable 2 for a novel HIV vaccine approach. PLoS ONE 5:e11815
    [71]
    Matyas GR, Wieczorek L, Beck Z, Ochsenbauer-Jambor C, Kappes JC, Michael NL, Polonis VR, Alving CR (2009) Neutralizing antibodies induced by liposomal HIV-1 glycoprotein 41 peptide simultaneously bind to both the 2F5 or 4E10 epitope and lipid epitopes. AIDS 23:2069-2077
    [72]
    McDougal JS, Maddon PJ, Dalgleish AG, Clapham PR, Littman DR, Godfrey M, Maddon DE, Chess L, Weiss RA, Axel R (1986) The T4 glycoprotein is a cell-surface receptor for the AIDS virus. Cold Spring Harb Symp Quant Biol 51(Pt 2):703-711
    [73]
    Medlock J, Pandey A, Parpia AS, Tang A, Skrip LA, Galvani AP (2017) Effectiveness of UNAIDS targets and HIV vaccination across 127 countries. Proc Natl Acad Sci USA 114:4017-4022
    [74]
    Miedema F (2008) A brief history of HIV vaccine research:stepping back to the drawing board? AIDS 22:1699-1703
    [75]
    Miglietta R, Pastori C, Venuti A, Ochsenbauer C, Lopalco L (2014) Synergy in monoclonal antibody neutralization of HIV-1 pseudoviruses and infectious molecular clones. J Transl Med 12:346
    [76]
    Mohan T, Verma P, Rao DN (2014) Comparative mucosal immunogenicity of HIV gp41 membrane-proximal external region (MPER) containing single and multiple repeats of ELDKWA sequence with defensin peptides. Immunobiology 219:292-301
    [77]
    Molinos-Albert LM, Bilbao E, Agullo L, Marfil S, Garcia E, Rodriguez de la Concepcion ML, Izquierdo-Useros N, Vilaplana C, NietoGarai JA, Contreras FX et al (2017a) Proteoliposomal formulations of an HIV-1 gp41-based miniprotein elicit a lipid-dependent immunodominant response overlapping the 2F5 binding motif. Sci Rep 7:40800
    [78]
    Molinos-Albert LM, Clotet B, Blanco J, Carrillo J (2017b) Immunologic insights on the membrane proximal external region:a major human immunodeficiency virus type-1 vaccine target. Front Immunol 8:1154
    [79]
    Montero M, van Houten NE, Wang X, Scott JK (2008) The membrane-proximal external region of the human immunodeficiency virus type 1 envelope:dominant site of antibody neutralization and target for vaccine design. Microbiol Mol Biol Rev 72:54-84
    [80]
    Morris L, Chen X, Alam M, Tomaras G, Zhang R, Marshall DJ, Chen B, Parks R, Foulger A, Jaeger F et al (2011) Isolation of a human anti-HIV gp41 membrane proximal region neutralizing antibody by antigen-specific single B cell sorting. PLoS ONE 6:e23532
    [81]
    Muhle M, Hoffmann K, Lochelt M, Denner J (2013) Immunisation with foamy virus Bet fusion proteins as novel strategy for HIV-1 epitope delivery. Immunol Res 56:61-72
    [82]
    Munoz-Barroso I, Salzwedel K, Hunter E, Blumenthal R (1999) Role of the membrane-proximal domain in the initial stages of human immunodeficiency virus type 1 envelope glycoprotein-mediated membrane fusion. J Virol 73:6089-6092
    [83]
    Muster T, Steindl F, Purtscher M, Trkola A, Klima A, Himmler G, Ruker F, Katinger H (1993) A conserved neutralizing epitope on gp41 of human immunodeficiency virus type 1. J Virol 67:6642-6647
    [84]
    Muster T, Guinea R, Trkola A, Purtscher M, Klima A, Steindl F, Palese P, Katinger H (1994) Cross-neutralizing activity against divergent human immunodeficiency virus type 1 isolates induced by the gp41 sequence ELDKWAS. J Virol 68:4031-4034
    [85]
    Nelson JD, Brunel FM, Jensen R, Crooks ET, Cardoso RM, Wang M, Hessell A, Wilson IA, Binley JM, Dawson PE et al (2007) An affinity-enhanced neutralizing antibody against the membraneproximal external region of human immunodeficiency virus type 1 gp41 recognizes an epitope between those of 2F5 and 4E10. J Virol 81:4033-4043
    [86]
    Nemazee D (2017) Mechanisms of central tolerance for B cells. Nat Rev Immunol 17:281-294
    [87]
    Ofek G, Tang M, Sambor A, Katinger H, Mascola JR, Wyatt R, Kwong PD (2004) Structure and mechanistic analysis of the antihuman immunodeficiency virus type 1 antibody 2F5 in complex with its gp41 epitope. J Virol 78:10724-10737
    [88]
    Ofek G, Zirkle B, Yang Y, Zhu Z, McKee K, Zhang B, Chuang GY, Georgiev IS, O'Dell S, Doria-Rose N et al (2014) Structural basis for HIV-1 neutralization by 2F5-like antibodies m66 and m66.6. J Virol 88:2426-2441
    [89]
    Pegu A, Yang ZY, Boyington JC, Wu L, Ko SY, Schmidt SD, McKee K, Kong WP, Shi W, Chen X et al (2014) Neutralizing antibodies to HIV-1 envelope protect more effectively in vivo than those to the CD4 receptor. Sci Transl Med. https://doi.org/10.1126/scitranslmed.3008992
    [90]
    Phogat S, Svehla K, Tang M, Spadaccini A, Muller J, Mascola J, Berkower I, Wyatt R (2008) Analysis of the human immunodeficiency virus type 1 gp41 membrane proximal external region arrayed on hepatitis B surface antigen particles. Virology 373:72-84
    [91]
    Provine NM, Puryear WB, Wu X, Overbaugh J, Haigwood NL (2009) The infectious molecular clone and pseudotyped virus models of human immunodeficiency virus type 1 exhibit significant differences in virion composition with only moderate differences in infectivity and inhibition sensitivity. J Virol 83:9002-9007
    [92]
    Provine NM, Cortez V, Chohan V, Overbaugh J (2012) The neutralization sensitivity of viruses representing human immunodeficiency virus type 1 variants of diverse subtypes from early in infection is dependent on producer cell, as well as characteristics of the specific antibody and envelope variant. Virology 427:25-33
    [93]
    Rizzuto CD, Wyatt R, Hernandez-Ramos N, Sun Y, Kwong PD, Hendrickson WA, Sodroski J (1998) A conserved HIV gp120 glycoprotein structure involved in chemokine receptor binding. Science 280:1949-1953
    [94]
    Salzwedel K, West JT, Hunter E (1999) A conserved tryptophan-rich motif in the membrane-proximal region of the human immunodeficiency virus type 1 gp41 ectodomain is important for Envmediated fusion and virus infectivity. J Virol 73:2469-2480
    [95]
    Scheid JF, Mouquet H, Feldhahn N, Seaman MS, Velinzon K, Pietzsch J, Ott RG, Anthony RM, Zebroski H, Hurley A et al (2009) Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals. Nature 458:636-640
    [96]
    Song L, Sun ZY, Coleman KE, Zwick MB, Gach JS, Wang JH, Reinherz EL, Wagner G, Kim M (2009) Broadly neutralizing antiHIV-1 antibodies disrupt a hinge-related function of gp41 at the membrane interface. Proc Natl Acad Sci USA 106:9057-9062
    [97]
    Soto C, Ofek G, Joyce MG, Zhang B, McKee K, Longo NS, Yang Y, Huang J, Parks R, Eudailey J et al (2016) Developmental pathway of the MPER-directed HIV-1-neutralizing antibody 10E8. PLoS ONE 11:e0157409
    [98]
    Stano P, Bufali S, Domazou AS, Luisi PL (2005) Effect of tryptophan oligopeptides on the size distribution of POPC liposomes:a dynamic light scattering and turbidimetric study. J Liposome Res 15:29-47
    [99]
    Stiegler G, Kunert R, Purtscher M, Wolbank S, Voglauer R, Steindl F, Katinger H (2001) A potent cross-clade neutralizing human monoclonal antibody against a novel epitope on gp41 of human immunodeficiency virus type 1. AIDS Res Hum Retrovir 17:1757-1765
    [100]
    Strasz N, Morozov VA, Kreutzberger J, Keller M, Eschricht M, Denner J (2014) Immunization with hybrid proteins containing the membrane proximal external region of HIV-1. AIDS Res Hum Retrovir 30:498-508
    [101]
    Su S, Wang Q, Xu W, Yu F, Hua C, Zhu Y, Jiang S, Lu L (2017a) A novel HIV-1 gp41 tripartite model for rational design of HIV-1 fusion inhibitors with improved antiviral activity. AIDS 31:885-894
    [102]
    Su S, Zhu Y, Ye S, Qi Q, Xia S, Ma Z, Yu F, Wang Q, Zhang R, Jiang S et al (2017b) Creating an artificial tail anchor as a novel strategy to enhance the potency of peptide-based HIV fusion inhibitors. J Virol. https://doi.org/10.1128/JVI.01445-16
    [103]
    Suarez T, Gallaher WR, Agirre A, Goni FM, Nieva JL (2000a) Membrane interface-interacting sequences within the ectodomain of the human immunodeficiency virus type 1 envelope glycoprotein:putative role during viral fusion. J Virol 74:8038-8047
    [104]
    Suarez T, Nir S, Goni FM, Saez-Cirion A, Nieva JL (2000b) The pretransmembrane region of the human immunodeficiency virus type-1 glycoprotein:a novel fusogenic sequence. FEBS Lett 477:145-149
    [105]
    Subramaniam S (2006) The SIV surface spike imaged by electron tomography:one leg or three? PLoS Pathog 2:e91
    [106]
    Sun ZY, Oh KJ, Kim M, Yu J, Brusic V, Song L, Qiao Z, Wang JH, Wagner G, Reinherz EL (2008) HIV-1 broadly neutralizing antibody extracts its epitope from a kinked gp41 ectodomain region on the viral membrane. Immunity 28:52-63
    [107]
    Sun Z, Zhu Y, Wang Q, Ye L, Dai Y, Su S, Yu F, Ying T, Yang C, Jiang S et al (2016) An immunogen containing four tandem 10E8 epitope repeats with exposed key residues induces antibodies that neutralize HIV-1 and activates an ADCC reporter gene. Emerg Microbes Infect 5:e65
    [108]
    Trkola A, Kuster H, Rusert P, Joos B, Fischer M, Leemann C, Manrique A, Huber M, Rehr M, Oxenius A et al (2005) Delay of HIV-1 rebound after cessation of antiretroviral therapy through passive transfer of human neutralizing antibodies. Nat Med 11:615-622
    [109]
    Ura T, Yoshida A, Xin KQ, Yoshizaki S, Yashima S, Abe S, Mizuguchi H, Okuda K (2009) Designed recombinant adenovirus type 5 vector induced envelope-specific CD8(+) cytotoxic T lymphocytes and cross-reactive neutralizing antibodies against human immunodeficiency virus type 1. J Gene Med 11:139-149
    [110]
    Vassell R, He Y, Vennakalanti P, Dey AK, Zhuang M, Wang W, Sun Y, Biron-Sorek Z, Srivastava IK, LaBranche CC et al (2015) Immunogens modeling a fusion-intermediate conformation of gp41 elicit antibodies to the membrane proximal external region of the HIV envelope glycoprotein. PLoS ONE 10:e0128562
    [111]
    Venditto VJ, Wieczorek L, Molnar S, Teque F, Landucci G, Watson DS, Forthal D, Polonis VR, Levy JA, Szoka FC Jr (2014) Chemically modified peptides based on the membrane-proximal external region of the HIV-1 envelope induce high-titer, epitopespecific nonneutralizing antibodies in rabbits. Clin Vaccine Immunol 21:1086-1093
    [112]
    Verkoczy L, Diaz M (2014) Autoreactivity in HIV-1 broadly neutralizing antibodies:implications for their function and induction by vaccination. Curr Opin HIV AIDS 9:224-234
    [113]
    Verkoczy L, Diaz M, Holl TM, Ouyang YB, Bouton-Verville H, Alam SM, Liao HX, Kelsoe G, Haynes BF (2010) Autoreactivity in an HIV-1 broadly reactive neutralizing antibody variable region heavy chain induces immunologic tolerance. Proc Natl Acad Sci USA 107:181-186
    [114]
    Verkoczy L, Chen Y, Bouton-Verville H, Zhang J, Diaz M, Hutchinson J, Ouyang YB, Alam SM, Holl TM, Hwang KK et al (2011) Rescue of HIV-1 broad neutralizing antibody-expressing B cells in 2F5 VH x VL knockin mice reveals multiple tolerance controls. J Immunol 187:3785-3797
    [115]
    Verkoczy L, Chen Y, Zhang J, Bouton-Verville H, Newman A, Lockwood B, Scearce RM, Montefiori DC, Dennison SM, Xia SM et al (2013) Induction of HIV-1 broad neutralizing antibodies in 2F5 knock-in mice:selection against membrane proximal external region-associated autoreactivity limits T-dependent responses. J Immunol 191:2538-2550
    [116]
    Verkoczy L, Kelsoe G, Haynes BF (2014) HIV-1 envelope gp41 broadly neutralizing antibodies:hurdles for vaccine development. PLoS Pathog 10:e1004073
    [117]
    Vishwanathan SA, Hunter E (2008) Importance of the membraneperturbing properties of the membrane-proximal external region of human immunodeficiency virus type 1 gp41 to viral fusion. J Virol 82:5118-5126
    [118]
    von Boehmer H, Melchers F (2010) Checkpoints in lymphocyte development and autoimmune disease. Nat Immunol 11:14-20
    [119]
    Walker BD, Burton DR (2008) Toward an AIDS vaccine. Science 320:760-764
    [120]
    Walker LM, Phogat SK, Chan-Hui PY, Wagner D, Phung P, Goss JL, Wrin T, Simek MD, Fling S, Mitcham JL et al (2009) Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target. Science 326:285-289
    [121]
    Wang J, Tong P, Lu L, Zhou L, Xu L, Jiang S, Chen YH (2011) HIV-1 gp41 core with exposed membrane-proximal external region inducing broad HIV-1 neutralizing antibodies. PLoS ONE 6:e18233
    [122]
    Wang Q, Dai Y, Sun Z, Su X, Yu Y, Hua C, Xu W, Jiang S, Lu L (2017) HIV-1 Env DNA prime plus gp120 and gp70-V1V2 boosts induce high level of V1V2-specific IgG and ADCC responses and low level of Env-specific IgA response:implication for improving RV144 vaccine regimen. Emerg Microbes Infect 6:e102
    [123]
    West AP Jr, Scharf L, Scheid JF, Klein F, Bjorkman PJ, Nussenzweig MC (2014) Structural insights on the role of antibodies in HIV-1 vaccine and therapy. Cell 156:633-648
    [124]
    Williams LD, Ofek G, Schatzle S, McDaniel JR, Lu X, Nicely NI, Wu L, Lougheed CS, Bradley T, Louder MK et al (2017) Potent and broad HIV-neutralizing antibodies in memory B cells and plasma. Sci Immunol. https://doi.org/10.1126/sciimmunol.aal2200
    [125]
    Wu L, Zhou T, Yang ZY, Svehla K, O'Dell S, Louder MK, Xu L, Mascola JR, Burton DR, Hoxie JA et al (2009) Enhanced exposure of the CD4-binding site to neutralizing antibodies by structural design of a membrane-anchored human immunodeficiency virus type 1 gp120 domain. J Virol 83:5077-5086
    [126]
    Wu X, Yang ZY, Li Y, Hogerkorp CM, Schief WR, Seaman MS, Zhou T, Schmidt SD, Wu L, Xu L et al (2010) Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science 329:856-861
    [127]
    Wyatt R, Kwong PD, Desjardins E, Sweet RW, Robinson J, Hendrickson WA, Sodroski JG (1998) The antigenic structure of the HIV gp120 envelope glycoprotein. Nature 393:705-711
    [128]
    Yang G, Holl TM, Liu Y, Li Y, Lu X, Nicely NI, Kepler TB, Alam SM, Liao HX, Cain DW et al (2013) Identification of autoantigens recognized by the 2F5 and 4E10 broadly neutralizing HIV-1 antibodies. J Exp Med 210:241-256
    [129]
    Ye L, Wen Z, Dong K, Wang X, Bu Z, Zhang H, Compans RW, Yang C (2011) Induction of HIV neutralizing antibodies against the MPER of the HIV envelope protein by HA/gp41 chimeric proteinbased DNA and VLP vaccines. PLoS ONE 6:e14813
    [130]
    Yi G, Lapelosa M, Bradley R, Mariano TM, Dietz DE, Hughes S, Wrin T, Petropoulos C, Gallicchio E, Levy RM et al (2013) Chimeric rhinoviruses displaying MPER epitopes elicit anti-HIV neutralizing responses. PLoS ONE 8:e72205
    [131]
    Yi G, Tu X, Bharaj P, Guo H, Zhang J, Shankar P, Manjunath N (2015) Human rhinovirus presenting 4E10 epitope of HIV-1 MPER elicits neutralizing antibodies in human ICAM-1 transgenic mice. Mol Ther 23:1663-1670
    [132]
    Yu Y, Tong P, Li Y, Lu Z, Chen Y (2014) 10E8-like neutralizing antibodies against HIV-1 induced using a precisely designed conformational peptide as a vaccine prime. Sci China Life Sci 57:117-127
    [133]
    Yu Y, Fu L, Shi Y, Guan S, Yang L, Gong X, Yin H, He X, Liu D, Kuai Z et al (2015) Elicitation of HIV-1 neutralizing antibodies by presentation of 4E10 and 10E8 epitopes on Norovirus P particles. Immunol Lett 168:271-278
    [134]
    Zanetti G, Briggs JA, Grunewald K, Sattentau QJ, Fuller SD (2006) Cryo-electron tomographic structure of an immunodeficiency virus envelope complex in situ. PLoS Pathog 2:e83
    [135]
    Zang Y, Du D, Li N, Su W, Liu X, Zhang Y, Nie J, Wang Y, Kong W, Jiang C (2015) Eliciting neutralizing antibodies against the membrane proximal external region of HIV-1 Env by chimeric live attenuated influenza A virus vaccines. Vaccine 33:3859-3864
    [136]
    Zhai Y, Zhong Z, Zariffard M, Spear GT, Qiao L (2013) Bovine papillomavirus-like particles presenting conserved epitopes from membrane-proximal external region of HIV-1 gp41 induced mucosal and systemic antibodies. Vaccine 31:5422-5429
    [137]
    Zhang R, Verkoczy L, Wiehe K, Munir Alam S, Nicely NI, Santra S, Bradley T, Pemble CW, Zhang J, Gao F et al (2016) Initiation of immune tolerance-controlled HIV gp41 neutralizing B cell lineages. Sci Transl Med. https://doi.org/10.1126/scitranslmed.aaf0618
    [138]
    Zhou MK, Kostoula I, Brill B, Panou E, Sakarellos-Daitsiotis M, Dietrich U (2012) Prime boost vaccination approaches with different conjugates of a new HIV-1 gp41 epitope encompassing the membrane proximal external region induce neutralizing antibodies in mice. Vaccine 30:1911-1916
    [139]
    Zhu P, Liu J, Bess J Jr, Chertova E, Lifson JD, Grise H, Ofek GA, Taylor KA, Roux KH (2006) Distribution and three-dimensional structure of AIDS virus envelope spikes. Nature 441:847-852
    [140]
    Zolla-Pazner S, Powell R, Yahyaei S, Williams C, Jiang X, Li W et al (2016) Rationally-designed vaccines targeting the V2 region of HIV-1 gp120 induce a focused, cross clade-reactive, biologically functional antibody response. J Virol 90:10993-11006
    [141]
    Zwick MB, Labrijn AF, Wang M, Spenlehauer C, Saphire EO, Binley JM, Moore JP, Stiegler G, Katinger H, Burton DR et al (2001) Broadly neutralizing antibodies targeted to the membrane-proximal external region of human immunodeficiency virus type 1 glycoprotein gp41. J Virol 75:10892-10905
    [142]
    Zwick MB, Komori HK, Stanfield RL, Church S, Wang M, Parren PW, Kunert R, Katinger H, Wilson IA, Burton DR (2004) The long third complementarity-determining region of the heavy chain is important in the activity of the broadly neutralizing anti-human immunodeficiency virus type 1 antibody 2F5. J Virol 78:3155-3161
    [143]
    Zwick MB, Jensen R, Church S, Wang M, Stiegler G, Kunert R, Katinger H, Burton DR (2005) Anti-human immunodeficiency virus type 1 (HIV-1) antibodies 2F5 and 4E10 require surprisingly few crucial residues in the membrane-proximal external region of glycoprotein gp41 to neutralize HIV-1. J Virol 79:1252-1261
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