HIV-1 envelope glycoprotein immunogens to induce broadly neutralizing antibodies

Expert Review of Vaccines

Volumn 15, Issue 3, 2016, Pages 349-365

  Sliepen, Kwinten ^a   Sanders, Rogier W ^a,b  

^a UNIVERSITY OF AMSTERDAM   (Netherlands)

^b WEILL CORNELL MEDICAL COLLEGE   (United States)

Author keywords

broadly neutralizing antibodies; envelope glycoprotein; HIV 1; immunogen design; nanoparticle vaccines; sequential vaccination; vaccination strategies; vaccines

Indexed keywords

ANTIGEN; B LYMPHOCYTE RECEPTOR; CD4 ANTIGEN; CHEMOKINE RECEPTOR CCR5; CHEMOKINE RECEPTOR CXCR4; CORE PROTEIN; ENVELOPE PROTEIN; EPITOPE; GLYCOPROTEIN; GLYCOPROTEIN GP 120; GLYCOPROTEIN GP 140; HUMAN IMMUNODEFICIENCY VIRUS VACCINE; INFLUENZA VACCINE; MANNOSE OLIGOSACCHARIDE; NANOPARTICLE; NEUTRALIZING ANTIBODY; SCAFFOLD PROTEIN; VIRUS ENVELOPE PROTEIN; HUMAN IMMUNODEFICIENCY VIRUS ANTIBODY; SUBUNIT VACCINE;

AFFINITY CHROMATOGRAPHY; CELL MATURATION; CELL MEMBRANE; CONFORMATIONAL TRANSITION; DRUG DESIGN; DRUG STRUCTURE; ENVELOPE GENE; GLYCOSYLATION; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; HUMAN IMMUNODEFICIENCY VIRUS INFECTED PATIENT; HUMORAL IMMUNITY; IMMUNOGENICITY; INFLUENZA VACCINATION; NONHUMAN; PASSIVE IMMUNIZATION; PRIORITY JOURNAL; PROTEIN QUATERNARY STRUCTURE; REVIEW; VACCINATION; BLOOD; IMMUNOLOGY;

AIDS VACCINES; ANTIBODIES, NEUTRALIZING; ENV GENE PRODUCTS, HUMAN IMMUNODEFICIENCY VIRUS; HIV ANTIBODIES; HIV-1; HUMANS; VACCINES, SUBUNIT;

EID: 84959163231     PISSN: 14760584     EISSN: 17448395     Source Type: Journal    
DOI: 10.1586/14760584.2016.1129905     Document Type: Review

References (182)

1. Plotkin SA. Correlates of protection induced by vaccination. Clin Vaccine Immunol. 2010; 17 (7): 1055-1065.
2. Simek MD, Rida W, Priddy FH, et al. Human immunodeficiency virus type 1 elite neutralizers: individuals with broad and potent neutralizing activity identified by using a high-throughput neutralization assay together with an analytical selection algorithm. J Virol. 2009; 83 (14): 7337-7348.
3. van Gils MJ, Sanders RW. Broadly neutralizing antibodies against HIV-1: templates for a vaccine. Virology. 2013; 435 (1): 46-56.
4. Dalgleish AG, Beverley PC, Clapham PR, et al. The CD4 (T4) antigen is an essential component of the receptor for the AIDS retrovirus. Nature. 1984; 312 (5996): 763-767.
5. Sanders RW, Moore JP. HIV: a stamp on the envelope. Nature. 2014; 514 (7523): 437-438.
6. McCune JM, Rabin LB, Feinberg MB, et al. Endoproteolytic cleavage of gp160 is required for the activation of human immunodeficiency virus. Cell. 1988; 53 (1): 55-67.
7. Checkley MA, Luttge BG, Freed EO. HIV-1 envelope glycoprotein biosynthesis, trafficking, and incorporation. J Mol Biol. 2011; 410 (4): 582-608.
8. Guttman M, Garcia NK, Cupo A, et al. CD4-induced activation in a soluble HIV-1 Env trimer. Structure. 2014; 22 (7): 974-984.
9. The PyMOL molecular graphics system, version 1.3r1. Schrödinger, LLC; 2010.
10. Pancera M, Zhou T, Druz A, et al. Structure and immune recognition of trimeric pre-fusion HIV-1 Env. Nature. 2014; 514 (7523): 455-461.
11. West AP, Scharf L, Scheid JF, et al. Structural insights on the role of antibodies in HIV-1 vaccine and therapy. Cell. 2014; 156 (4): 633-648.
12. Weiss RA. HIV and AIDS: looking ahead. Nat Med. 2003; 9 (7): 887-891.
13. Kwong PD, Doyle ML, Casper DJ, et al. HIV-1 evades antibody-mediated neutralization through conformational masking of receptor-binding sites. Nature. 2002; 420 (6916): 678-682.
14. Munro JB, Gorman J, Ma X, et al. Conformational dynamics of single HIV-1 envelope trimers on the surface of native virions. Science. 2014; 346 (6210): 759-763.
15. Schiller J, Chackerian B. Why HIV virions have low numbers of envelope spikes: implications for vaccine development. PLoS Pathog. 2014; 10 (8): e1004254.
16. Klein JS, Bjorkman PJ. Few and far between: how HIV may be evading antibody avidity. PLoS Pathog. 2010; 6 (5): e1000908.
17. Moore PL, Crooks ET, Porter L, et al. Nature of nonfunctional envelope proteins on the surface of human immunodeficiency virus type 1. J Virol. 2006; 80 (5): 2515-2528.
18. Burton DR, Mascola JR. Antibody responses to envelope glycoproteins in HIV-1 infection. Nat Immunol. 2015; 16 (6): 571-576.
19. McGuire AT, Dreyer AM, Carbonetti S, et al. Antigen modification regulates competition of broad and narrow neutralizing HIV antibodies. Science. 2014; 346 (6215): 1380-1383.
20. Doria-Rose NA, Schramm CA, Gorman J, et al. Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies. Nature. 2014; 509 (7498): 55-62.
21. Liao H-X, Lynch R, Zhou T, et al. Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus. Nature. 2013; 496 (7446): 469-476.
22. Gao F, Bonsignori M, H-X L, et al. Cooperation of B cell lineages in induction of HIV-1-broadly neutralizing antibodies. Cell. 2014;158(3);481-491.
23. Euler Z, van Gils MJ, Bunnik EM, et al. Cross-reactive neutralizing humoral immunity does not protect from HIV type 1 disease progression. J Infect Dis. 2010; 201 (7): 1045-1053.
24. Pegu A, Yang Z-Y, Boyington JC, et al. Neutralizing antibodies to HIV-1 envelope protect more effectively in vivo than those to the CD4 receptor. Sci Transl Med. 2014; 6 (243): 243ra88.
25. Shingai M, Donau OK, Plishka RJ, et al. Passive transfer of modest titers of potent and broadly neutralizing anti-HIV monoclonal antibodies block SHIV infection in macaques. J Exp Med. 2014; 211 (10): 2061-2074.
26. van Gils MJ, Sanders RW. In vivo protection by broadly neutralizing HIV antibodies. Trends Microbiol. 2014; 22 (10): 550-551.
27. Briney BS, Willis JR, Hicar MD, et al. Frequency and genetic characterization of V(DD)J recombinants in the human peripheral blood antibody repertoire. Immunology. 2012; 137 (1): 56-64.
28. Liu M, Yang G, Wiehe K, et al. Polyreactivity and autoreactivity among HIV-1 antibodies. J Virol. 2015; 89 (1): 784-798.
29. Haynes BF, Fleming J, St Clair EW, et al. Cardiolipin polyspecific autoreactivity in two broadly neutralizing HIV-1 antibodies. Science. 2005; 308 (5730): 1906-1908.
30. Hraber P, Seaman MS, Bailer RT, et al. Prevalence of broadly neutralizing antibody responses during chronic HIV-1 infection. AIDS. 2014; 28 (2): 163-169.
31. Mascola JR, Haynes BF. HIV-1 neutralizing antibodies: understanding natures pathways. Immunol Rev. 2013; 254 (1): 225-244.
32. Haynes BF, Kelsoe G, Harrison SC, et al. B-cell-lineage immunogen design in vaccine development with HIV-1 as a case study. Nat Biotechnol. 2012; 30 (5): 423-433.
33. Wu X, Zhang Z, Schramm CA, et al. Maturation and diversity of the VRC01-antibody lineage over 15 years of chronic HIV-1 infection. Cell. 2015; 161 (3): 470-485.
34. Kong L, Lee JH, Doores KJ, et al. Supersite of immune vulnerability on the glycosylated face of HIV-1 envelope glycoprotein gp120. Nat Struct Mol Biol. 2013; 20 (7): 796-803.
35. Huang J, Kang BH, 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.
36. Blattner C, Lee JH, Sliepen K, et al. Structural delineation of a quaternary, cleavage-dependent epitope at the gp41-gp120 Interface on intact HIV-1 Env trimers. Immunity. 2014; 40 (5): 669-680.
37. Walker LM, Phogat SK, 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.
38. Walker LM, Huber M, Doores KJ, et al. Broad neutralization coverage of HIV by multiple highly potent antibodies. Nature. 2011; 477 (7365): 466-470.
39. McLellan JS, Pancera M, Carrico C, et al. Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9. Nature. 2011; 480 (7377): 336-343.
40. Pejchal R, Doores KJ, Walker LM, et al. A potent and broad neutralizing antibody recognizes and penetrates the HIV glycan shield. Science. 2011; 334 (6059): 1097-1103.
41. Scharf L, Scheid JF, Lee JH, et al. Antibody 8ANC195 reveals a site of broad vulnerability on the HIV-1 envelope spike. Cell Rep. 2014;7(3);785-795.
42. Sanders RW, Venturi M, Schiffner L, et al. The mannose-dependent epitope for neutralizing antibody 2G12 on human immunodeficiency virus type 1 the mannose-dependent epitope for neutralizing sntibody 2G12 on human immunodeficiency virus type 1 glycoprotein gp120. J Virol. 2002; 76 (14): 7293-7305.
43. Pancera M, Shahzad-Ul-Hussan S, Doria-Rose NA, et al. Structural basis for diverse N-glycan recognition by HIV-1-neutralizing V1-V2-directed antibody PG16. Nat Struct Mol Biol. 2013; 20 (7): 804-813.
44. Bonomelli C, Doores KJ, Dunlop DC, et al. The glycan shield of HIV is predominantly oligomannose independently of production system or viral clade. PLoS One. 2011; 6 (8): 1-7.
45. Pritchard LK, Vasiljevic S, Ozorowski G, et al. Structural constraints determine the glycosylation of HIV-1 envelope trimers. Cell Rep. 2015; 11 (10): 1604-1613.
46. Doores KJ, Bonomelli C, Harvey DJ, et al. Envelope glycans of immunodeficiency virions are almost entirely oligomannose antigens. Proc Natl Acad Sci. 2010; 107 (31): 13800-13805.
47. Crispin M, Bowden TA. Antibodies expose multiple weaknesses in the glycan shield of HIV. Nat Struct Mol Biol. 2013; 20 (7): 771-772.
48. Doores KJ. The HIV glycan shield as a target for broadly neutralizing antibodies. FEBS J. 2015. DOI: 10.1111/febs.13530. [Epub ahead of print]
49. Javaherian K, Langlois A, LaRosa G, et al. Broadly neutralizing antibodies elicited by the hypervariable neutralizing determinant of HIV-1. Science. 1990; 250 (4987): 1590-1593.
50. Hart MK, Palker TJ, Matthews TJ, et al. Synthetic peptides containing T and B cell epitopes from human immunodeficiency virus envelope gp120 induce anti-HIV proliferative responses and high titers of neutralizing antibodies in rhesus monkeys. J Immunol. 1990; 145 (8): 2677-2685.
51. Letvin NL. Progress in the development of an HIV-1 vaccine. Science. 1998; 280 (5371): 1875-1880.
52. Moseri A, Tantry S, Sagi Y, et al. An optimally constrained V3 peptide is a better immunogen than its linear homolog or HIV-1 gp120. Virology. 2010; 401 (2): 293-304.
53. Melchers M, Bontjer I, Tong T, et al. Targeting HIV-1 envelope glycoprotein trimers to B cells by using APRIL improves antibody responses. J Virol. 2012; 86 (5): 2488-2500.
54. Sanders RW, van Gils MJ, Derking R, et al. HIV-1 neutralizing antibodies induced by native-like envelope trimers. Science. 2015; 349 (6244): aac4223.
55. Seaman MS, Janes H, Hawkins N, et al. Tiered categorization of a diverse panel of HIV-1 Env pseudoviruses for assessment of neutralizing antibodies. J Virol. 2010; 84 (3): 1439-1452.
56. Muster T, Steindl F, Purtscher M, et al. A conserved neutralizing epitope on gp41 of human immunodeficiency virus type 1. J Virol. 1993; 67 (11): 6642-6647.
57. Zwick MB, Labrijn AF, Wang M, et al. Broadly neutralizing antibodies targeted to the membrane-proximal external region of human immunodeficiency virus type 1. J Virol. 2001; 75 (22): 10892-10905.
58. Zwick MB. The membrane-proximal external region of HIV-1 gp41: a vaccine target worth exploring. AIDS. 2005; 19 (16): 1725-1737.
59. Watson DS, Szoka FC. Role of lipid structure in the humoral immune response in mice to covalent lipid-peptides from the membrane proximal region of HIV-1 gp41. Vaccine. 2009; 27 (34): 4672-4683.
60. Matyas GR, Wieczorek L, Beck Z, et al. Neutralizing antibodies induced by liposomal HIV-1 glycoprotein 41 peptide simultaneously bind to both the 2F5 or 4E10 epitope and lipid epitopes. AIDS. 2009; 23 (16): 2069-2077.
61. Dennison SM, Sutherland LL, Jaeger FH, et al. Induction of antibodies in rhesus macaques that recognize a fusion-intermediate conformation of HIV-1 gp41. PLoS One. 2011; 6 (11): e27824.
62. Azoitei ML, Correia BE, Ban Y-EA, et al. Computation-guided backbone grafting of a discontinuous motif onto a protein scaffold. Science. 2011; 334 (6054): 373-376.
63. Correia BE, Ban YEA, Holmes MA, et al. Computational design of epitope-scaffolds allows induction of antibodies specific for a poorly immunogenic HIV vaccine epitope. Structure. 2010; 18 (9): 1116-1126.
64. Ofek G, Guenaga FJ, Schief WR, et al. Elicitation of structure-specific antibodies by epitope scaffolds. Proc Natl Acad Sci. 2010; 107 (42): 17880-17887.
65. Stanfield RL, Julien JP, Pejchal R, et al. Structure-based design of a protein immunogen that displays an HIV-1 gp41 neutralizing epitope. J Mol Biol. 2011; 414 (3): 460-476.
66. Correia BE, Bates JT, Loomis RJ, et al. Proof of principle for epitope-focused vaccine design. Nature. 2014; 507 (7491): 201-206.
67. Chakraborty K, Durani V, Miranda ER, et al. Design of immunogens that present the crown of the HIV-1 V3 loop in a conformation competent to generate 447-52D-like antibodies. Biochem J. 2006; 399 (3): 483-491.
68. Totrov M, Jiang X, Kong XP, et al. Structure-guided design and immunological characterization of immunogens presenting the HIV-1 gp120 V3 loop on a CTB scaffold. Virology. 2010; 405 (2): 513-523.
69. Zhou T, Zhu J, Yang Y, et al. Transplanting supersites of HIV-1 vulnerability. PLoS One. 2014; 9 (7): e99881.
70. Verkoczy L, Chen Y, Zhang J, et al. 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. 2013; 191 (5): 2538-2550.
71. Doyle-Cooper C, Hudson KE, Cooper AB, et al. Immune tolerance negatively regulates B cells in knock-in mice expressing broadly neutralizing HIV antibody 4E10. J Immunol. 2013; 191 (6): 3186-3191.
72. Ingale J, Tran K, Kong L, et al. Hyperglycosylated stable core immunogens designed to present the CD4 binding site are preferentially recognized by broadly neutralizing antibodies. J Virol. 2014; 88 (24): 14002-14016.
73. Joyce JG, Krauss IJ, Song HC, et al. An oligosaccharide-based HIV-1 2G12 mimotope vaccine induces carbohydrate-specific antibodies that fail to neutralize HIV-1 virions. Proc Natl Acad Sci. 2008; 105 (41): 15684-15689.
74. Victora GD, Nussenzweig MC. Germinal centers. Annu Rev Immunol. 2012; 30: 429-457.
75. Kwong PD, Wyatt R, Robinson J, et al. Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature. 1998; 393 (June): 648-659.
76. Wyatt R, Kwong PD, Desjardins E, et al. The antigenic structure of the HIV gp120 envelope glycoprotein. Nature. 1998; 393 (6686): 705-711.
77. Yang X, Tomov V, Kurteva S, et al. Characterization of the outer domain of the gp120 glycoprotein from human immunodeficiency virus type 1. J Virol. 2004; 78 (23): 12975-12986.
78. Derking R, Ozorowski G, Sliepen K, et al. Comprehensive antigenic map of a cleaved soluble HIV-1 envelope trimer. PLOS Pathog. 2015; 11 (3): e1004767.
79. Pantophlet R, Burton DR. GP120: target for neutralizing HIV-1 antibodies. Annu Rev Immunol. 2006; 24: 739-769.
80. Bhattacharyya S, Rajan RE, Swarupa Y, et al. Design of a non-glycosylated outer domain-derived HIV-1 gp120 immunogen that binds to CD4 and induces neutralizing antibodies. J Biol Chem. 2010; 285 (35): 27100-27110.
81. Qin Y, Banasik M, Kim S, et al. Eliciting neutralizing antibodies with gp120 outer domain constructs based on M-group consensus sequence. Virology. 2014; 462-463 (2): 363-376.
82. Chen H, Xu X, Jones IM. Immunogenicity of the outer domain of a HIV-1 clade C gp120. Retrovirology. 2007; 4 (1): 33.
83. Joyce MG, Kanekiyo M, Xu L, et al. Outer domain of HIV-1 gp120: antigenic optimization, structural malleability, and crystal structure with antibody VRC-PG04. J Virol. 2013; 87 (4): 2294-2306.
84. Jardine J, Julien J-P, Menis S, et al. Rational HIV immunogen design to target specific germline B cell receptors. Science. 2013; 340 (6133): 711-716.
85. Dosenovic P, von Boehmer L, Escolano A, et al. Immunization for HIV-1 broadly neutralizing antibodies in human Ig knockin mice. Cell. 2015; 161 (7): 1505-1515.
86. Georgiev IS, Gordon Joyce M, Zhou T, et al. Elicitation of HIV-1-neutralizing antibodies against the CD4-binding site. Curr Opin HIV AIDS. 2013; 8 (5): 382-392.
87. Wu X, Yang Z-Y, Li Y, et al. Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science. 2010; 329 (5993): 856-861.
88. Dey B, Pancera M, Svehla K, et al. Characterization of human immunodeficiency virus type 1 monomeric and trimeric gp120 glycoproteins stabilized in the CD4-bound state: antigenicity, biophysics, and immunogenicity. J Virol. 2007; 81 (11): 5579-5593.
89. Dey B, Svehla K, Xu L, et al. Structure-based stabilization of HIV-1 gp120 enhances humoral immune responses to the induced co-receptor binding site. PLoS Pathog. 2009; 5 (5): e1000445.
90. Flynn NM, Forthal DN, Harro CD, et al. Placebo-controlled phase 3 trial of a recombinant glycoprotein 120 vaccine to prevent HIV-1 infection. J Infect Dis. 2005; 191 (5): 654-665.
91. Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, et al. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med. 2009; 361 (23): 2209-2220.
92. Mascola JR, Snyder SW, Weislow OS, et al. Immunization with envelope subunit vaccine products elicits neutralizing antibodies against laboratory-adapted but not primary isolates of human immunodeficiency virus type 1. The National Institute of Allergy and Infectious Diseases AIDS Vaccine Evaluati. J Infect Dis. 1996; 173 (2): 340-348.
93. Pitisuttithum P, Berman PW, Phonrat B, et al. Phase I/II study of a candidate vaccine designed against the B and E subtypes of HIV-1. J Acquir Immune Defic Syndr. 2004; 37 (1): 1160-1165.
94. Moore JP, Sattentau QJ, Cao Y, et al. Studies on the interactions of monoclonal antibodies with HIV-1 isolates from clades A-F. Proceedings of IX Colloque des Cent Gardes; 1994 Oct 24-26; Paris. p. 151-155.
95. Yasmeen A, Ringe R, Derking R, et al. Differential binding of neutralizing and non-neutralizing antibodies to native-like soluble HIV-1 Env trimers, uncleaved Env proteins, and monomeric subunits. Retrovirology. 2014; 11 (1): 41.
96. Selvarajah S, Puffer B, Pantophlet R, et al. Comparing antigenicity and immunogenicity of engineered gp120. J Virol. 2005; 79 (19): 12148-12163.
97. Kovacs JM, Nkolola JP, Peng H, et al. HIV-1 envelope trimer elicits more potent neutralizing antibody responses than monomeric gp120. Proc Natl Acad Sci. 2012; 109 (30): 12111-12116.
98. Kim M, Qiao Z-S, Montefiori DC, et al. Comparison of HIV Type 1 ADA gp120 monomers versus gp140 trimers as immunogens for the induction of neutralizing antibodies. AIDS Res Hum Retroviruses. 2005; 21 (1): 58-67.
99. Beddows S, Franti M, Dey AK, et al. A comparative immunogenicity study in rabbits of disulfide-stabilized, proteolytically cleaved, soluble trimeric human immunodeficiency virus type 1 gp140, trimeric cleavage-defective gp140 and monomeric gp120. Virology. 2007; 360 (2): 329-340.
100. Sanders RW, Derking R, Cupo A, et al. 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.
101. Tran K, Poulsen C, Guenaga J, et al. Vaccine-elicited primate antibodies use a distinct approach to the HIV-1 primary receptor binding site informing vaccine redesign. Proc Natl Acad Sci. 2014; 111 (7): E738-47.
102. Pantophlet R, Wilson IA, Burton DR. Hyperglycosylated mutants of human immunodeficiency virus (HIV) type 1 monomeric gp120 as novel antigens for HIV vaccine design. J Virol. 2003; 77 (10): 5889-5901.
103. Forsell MNE, Soldemo M, Dosenovic P, et al. Independent expansion of epitope-specific plasma cell responses upon HIV-1 envelope glycoprotein immunization. J Immunol. 2013; 191 (1): 44-51.
104. Garrity RR, Rimmelzwaan G, Minassian A, et al. Refocusing neutralizing antibody response by targeted dampening of an immunodominant epitope. J Immunol. 1997; 159 (1): 279-289.
105. Ahmed FK, Clark BE, Burton DR, et al. An engineered mutant of HIV-1 gp120 formulated with adjuvant Quil A promotes elicitation of antibody responses overlapping the CD4-binding site. Vaccine. 2012; 30 (5): 922-930.
106. Forsell MNE, Schief WR, Wyatt RT. Immunogenicity of HIV-1 envelope glycoprotein oligomers. Curr Opin HIV AIDS. 2009; 4 (5): 380-387.
107. Binley JM, Sanders RW, Clas B, et al. A recombinant human immunodeficiency virus type 1 envelope glycoprotein complex stabilized by an intermolecular disulfide bond between the gp120 and gp41 subunits is an antigenic mimic of the trimeric virion-associated structure. J Virol. 2000; 74 (2): 627-643.
108. Earl PL, Broder CC, Long D, et al. Native oligomeric human immunodeficiency virus type 1 envelope glycoprotein elicits diverse monoclonal antibody reactivities. J Virol. 1994; 68 (5): 3015-3026.
109. Gao F, Weaver EA, Lu Z, et al. Antigenicity and immunogenicity of a synthetic human immunodeficiency virus type 1 group m consensus envelope glycoprotein. J Virol. 2005; 79 (2): 1154-1163.
110. Spearman P, Lally MA, Elizaga M, et al. A trimeric, V2-deleted HIV-1 envelope glycoprotein vaccine elicits potent neutralizing antibodies but limited breadth of neutralization in human volunteers. J Infect Dis. 2011; 203 (8): 1165-1173.
111. Kovacs JM, Noeldeke E, Ha HJ, et al. Stable, uncleaved HIV-1 envelope glycoprotein gp140 forms a tightly folded trimer with a native-like structure. Proc Natl Acad Sci. 2014; 111 (52): 18542-18547.
112. Yang X, Florin L, Farzan M, et al. Modifications that stabilize human immunodeficiency virus envelope glycoprotein trimers in solution. J Virol. 2000; 74 (10): 4746-4754.
113. Yang X, Lee J, Mahony EM, et al. Highly stable trimers formed by human immunodeficiency virus type 1 envelope glycoproteins fused with the trimeric motif of T4 bacteriophage fibritin. J Virol. 2002; 76 (9): 4634-4642.
114. Yang X, Wyatt R, Sodroski J. Improved elicitation of neutralizing antibodies against primary human immunodeficiency viruses by soluble stabilized envelope glycoprotein trimers. J Virol. 2001; 75 (3): 1165-1171.
115. Ringe RP, Yasmeen A, Ozorowski G, et al. Influences on the design and purification of soluble, recombinant native-like HIV-1 envelope glycoprotein trimers. J Virol. 2015; 89 (23): 12189-12210.
116. Ringe RP, Sanders RW, Yasmeen A, et al. Cleavage strongly influences whether soluble HIV-1 envelope glycoprotein trimers adopt a native-like conformation. Proc Natl Acad Sci. 2013; 110 (45): 18256-18261.
117. Liu J, Bartesaghi A, Borgnia MJ, et al. Molecular architecture of native HIV-1 gp120 trimers. Nature. 2008; 455 (7209): 109-113.
118. Sliepen K, van Montfort T, Melchers M, et al. Immunosilencing a highly immunogenic protein trimerization domain. J Biol Chem. 2015; 290 (12): 7436-7442.
119. Go EP, Zhang Y, Menon S, et al. Analysis of the disulfide bond arrangement of the HIV-1 envelope protein CON-S gp140 ΔCFI shows variability in the V1 and V2 regions. J Proteome Res. 2011; 10 (2): 578-591.
120. Go EP, Hua D, Desaire H. Glycosylation and disulfide bond analysis of transiently and stably expressed clade C HIV-1 gp140 trimers in 293T cells identifies disulfide heterogeneity present in both proteins and differences in O-linked glycosylation. J Proteome Res. 2014; 13 (9): 4012-4027.
121. Li Y, Svehla K, Mathy NL, et al. Characterization of antibody responses elicited by human immunodeficiency virus type 1 primary isolate trimeric and monomeric envelope glycoproteins in selected adjuvants. J Virol. 2006; 80 (3): 1414-1426.
122. Sanders RW. Clinical evaluation of a soluble trimeric HIV-1 envelope glycoprotein vaccine. Expert Rev Vaccines. 2011; 10 (8): 1117-1122.
123. Pugach P, Ozorowski G, Cupo A, et al. A native-like SOSIP.664 trimer based on an HIV-1 subtype B env gene. J Virol. 2015; 89 (6): 3380-3395.
124. Julien J-P, Lee JH, Ozorowski G, et al. Design and structure of two HIV-1 clade C SOSIP.664 trimers that increase the arsenal of native-like Env immunogens. Proc Natl Acad Sci. 2015; 112 (38): 11947-11952.
125. Guenaga J, de Val N, Tran K, et al. Well-ordered trimeric HIV-1 subtype B and C soluble spike mimetics generated by negative selection display native-like properties. PLoS Pathog. 2015; 11 (1): e1004570.
126. Sanders RW, Vesanen M, Schuelke N, et al. Stabilization of the soluble, cleaved, trimeric form of the envelope glycoprotein complex of human immunodeficiency virus type 1. J Virol. 2002; 76 (17): 8875-8889.
127. Binley JM, Sanders RW, Master A, et al. Enhancing the proteolytic maturation of human immunodeficiency virus type 1 envelope glycoproteins. J Virol. 2002; 76 (6): 2606-2616.
128. Kang YK, Andjelic S, Binley JM, et al. Structural and immunogenicity studies of a cleaved, stabilized envelope trimer derived from subtype A HIV-1. Vaccine. 2009; 27 (37): 5120-5132.
129. Bartesaghi A, Merk A, Borgnia MJ, et al. Prefusion structure of trimeric HIV-1 envelope glycoprotein determined by cryo-electron microscopy. Nat Struct Mol Biol. 2013; 20 (12): 1352-1357.
130. Harris A, Borgnia MJ, Shi D, et al. Trimeric HIV-1 glycoprotein gp140 immunogens and native HIV-1 envelope glycoproteins display the same closed and open quaternary molecular architectures. Proc Natl Acad Sci. 2011; 108 (28): 11440-11445.
131. Iyer SPN, Franti M, Krauchuk AA, et al. Purified, proteolytically mature HIV type 1 SOSIP gp140 envelope trimers. AIDS Res Hum Retroviruses. 2007; 23 (6): 817-828.
132. Klasse PJ, Depetris RS, Pejchal R, et al. Influences on trimerization and aggregation of soluble, cleaved HIV-1 SOSIP envelope glycoprotein. J Virol. 2013; 87 (17): 9873-9885.
133. Khayat R, Lee JH, Julien J-P, et al. Structural characterization of cleaved, soluble HIV-1 envelope glycoprotein trimers. J Virol. 2013; 87 (17): 9865-9872.
134. Wu X, Parast AB, Richardson BA, et al. Neutralization escape variants of human immunodeficiency virus type 1 are transmitted from mother to infant. J Virol. 2006; 80 (2): 835-844.
135. Hoffenberg S, Powell R, Carpov A, et al. Identification of an HIV-1 clade A envelope that exhibits broad antigenicity and neutralization sensitivity and elicits antibodies targeting three distinct epitopes. J Virol. 2013; 87 (10): 5372-5383.
136. Goo L, Chohan V, Nduati R, et al. Early development of broadly neutralizing antibodies in HIV-1-infected infants. Nat Med. 2014; 20 (6): 655-658.
137. Sok D, van Gils MJ, Pauthner M, et al. Recombinant HIV envelope trimer selects for quaternary-dependent antibodies targeting the trimer apex. Proc Natl Acad Sci. 2014; 111 (49): 17624-17629.
138. Do Kwon Y, Pancera M, Acharya P, et al. Crystal structure, conformational fixation and entry-related interactions of mature ligand-free HIV-1 Env. Nat Struct Mol Biol. 2015; 22 (7): 522-531.
139. Scharf L, Wang H, Gao H, et al. Broadly neutralizing antibody 8ANC195 recognizes closed and open states of HIV-1 Env. Cell. 2015; 162 (6): 1379-1390.
140. Lyumkis D, Julien J-P, de Val N, et al. Cryo-EM structure of a fully glycosylated soluble cleaved HIV-1 envelope trimer. Science. 2013; 342 (6165): 1484-1490.
141. Julien J-P, Cupo A, Sok D, et al. Crystal structure of a soluble cleaved HIV-1 envelope trimer. Science. 2013; 342 (6165): 1477-1483.
142. de Taeye SW, Ozorowski G, de la Peña AT, et al. Immunogenicity of stabilized HIV-1 envelope trimers with reduced exposure of non-neutralizing epitopes. Cell. 2015;163(7):1702-1715.
143. Garces F, Lee JH, de Val N, et al. Affinity maturation of a potent family of HIV antibodies is primarily focused on accommodating or avoiding glycans. Immunity. 2015;43(6):1053-1063.
144. McLellan JS, Chen M, Joyce MG, et al. Structure-based design of a fusion glycoprotein vaccine for respiratory syncytial virus. Science. 2013; 342 (6158): 592-598.
145. Impagliazzo A, Milder F, Kuipers H, et al. A stable trimeric influenza hemagglutinin stem as a broadly protective immunogen. Science. 2015; 349 (6254): 1301-1306.
146. Yassine HM, Boyington JC, McTamney PM, et al. Hemagglutinin-stem nanoparticles generate heterosubtypic influenza protection. Nat Med. 2015; 21 (9): 1065-1070.
147. Hu JK, Crampton JC, Cupo A, et al. Murine antibody responses to cleaved soluble HIV-1 envelope trimers are highly restricted in specificity. J Virol. 2015; 89 (20): 10383-10398.
148. Dintzis HM, Dintzis RZ, Vogelstein B. Molecular determinants of immunogenicity: the immunon model of immune response. Proc Natl Acad Sci. 1976; 73 (10): 3671-3675.
149. Bachmann MF, Zinkernagel RM. Neutralizing antiviral B cell responses. Annu Rev Immunol. 1997; 15: 235-270.
150. Bachmann MF, Jennings GT. Vaccine delivery: a matter of size, geometry, kinetics and molecular patterns. Nat Rev Immunol. 2010; 10 (11): 787-796.
151. Zhao Q, Li S, Yu H, et al. Virus-like particle-based human vaccines: quality assessment based on structural and functional properties. Trends Biotechnol. 2013; 31 (11): 654-663.
152. Amanna IJ, Slifka MK. Mechanisms that determine plasma cell lifespan and the duration of humoral immunity. Immunol Rev. 2010; 236 (1): 125-138.
153. Moon JJ, Suh H, Li AV, et al. Enhancing humoral responses to a malaria antigen with nanoparticle vaccines that expand Tfh cells and promote germinal center induction. Proc Natl Acad Sci. 2012; 109 (4): 1080-1085.
154. Kanekiyo M, Wei C-J, Yassine HM, et al. Self-assembling influenza nanoparticle vaccines elicit broadly neutralizing H1N1 antibodies. Nature. 2013; 499 (7456): 102-106.
155. Pejawar-Gaddy S, Kovacs JM, Barouch DH, et al. Design of lipid nanocapsule delivery vehicles for multivalent display of recombinant Env trimers in HIV vaccination. Bioconjug Chem. 2014;25(8):1470-1478.
156. Anderson KP, Lucas C, Hanson CV, et al. Effect of dose and immunization schedule on immune response of baboons to recombinant glycoprotein 120 of HIV-1. J Infect Dis. 1989; 160 (6): 960-969.
157. Lewis GK, DeVico AL, Gallo RC. Antibody persistence and T-cell balance: two key factors confronting HIV vaccine development. Proc Natl Acad Sci. 2014; 111 (44): 15614-15621.
158. Zhao L, Seth A, Wibowo N, et al. Nanoparticle vaccines. Vaccine. 2014; 32 (3): 327-337.
159. Leaman DP, Lee JH, Ward AB, et al. Immunogenic display of purified chemically cross-linked HIV-1 spikes. J Virol. 2015; 89 (13): 6725-6745.
160. Tong T, Crooks ET, Osawa K, et al. Multi-parameter exploration of HIV-1 virus-like particles as neutralizing antibody immunogens in guinea pigs, rabbits and macaques. Virology. 2014; 456-457 (1): 55-69.
161. Tong T, Crooks ET, Osawa K, et al. HIV-1 virus-like particles bearing pure Env trimers expose neutralizing epitopes but occlude nonneutralizing epitopes. J Virol. 2012; 86 (7): 3574-3587.
162. Crooks ET, Tong T, Chakrabarti B, et al. Vaccine-elicited tier 2 HIV-1 neutralizing antibodies bind to quaternary epitopes involving glycan-deficient patches proximal to the CD4 binding site. PLOS Pathog. 2015; 11 (5): e1004932.
163. Zingler K, Littman DR. Truncation of the cytoplasmic domain of the simian immunodeficiency virus envelope glycoprotein increases env incorporation into particles and fusogenicity and infectivity. J Virol. 1993; 67 (5): 2824-2831.
164. Ofek G, Zirkle B, Yang Y, et al. Structural basis for HIV-1 neutralization by 2F5-like antibodies m66 and m66.6. J Virol. 2014; 88 (5): 2426-2441.
165. Jardine JG, Ota T, Sok D, et al. Priming a broadly neutralizing antibody response to HIV-1 using a germline-targeting immunogen. Science. 2015; 349 (6244): 156-161.
166. Kanekiyo M, Bu W, Joyce MG, et al. Rational design of an epstein-barr virus vaccine targeting the receptor-binding site. Cell. 2015; 162 (5): 1090-1100.
167. Sliepen K, Ozorowski G, Burger JA, et al. Presenting native-like HIV-1 envelope trimers on ferritin nanoparticles improves their immunogenicity. Retrovirology. 2015; 12 (1): 82.
168. Pape KA, Catron DM, Itano AA, et al. The humoral immune response is initiated in lymph nodes by B cells that acquire soluble antigen directly in the follicles. Immunity. 2007; 26 (4): 491-502.
169. McLellan JS, Chen M, Leung S, et al. Structure of RSV fusion glycoprotein trimer bound to a prefusion-specific neutralizing antibody. Science. 2013; 340 (6136): 1113-1117.
170. Guttman M, Cupo A, Julien J, et al. Antibody potency relates to the ability to recognize the closed, pre-fusion form of HIV Env. Nat Commun. 2015; 6: 6144.
171. Sharma SK, de Val N, Bale S, et al. Cleavage-independent HIV-1 Env trimers engineered as soluble native spike mimetics for vaccine design. Cell Rep. 2015; 11 (4): 539-550.
172. Georgiev IS, Joyce MG, Yang Y, et al. Single-chain soluble BG505.SOSIP gp140 trimers as structural and antigenic mimics of mature closed HIV-1 Env. J Virol. 2015; 89 (10): 5318-5329.
173. Julien JP, Lee PS, Wilson IA. Structural insights into key sites of vulnerability on HIV-1 Env and influenza HA. Immunol Rev. 2012; 250 (1): 180-198.
174. Chaudhury S, Reifman J, Wallqvist A. Simulation of B cell affinity maturation explains enhanced antibody cross-reactivity induced by the polyvalent malaria vaccine AMA1. J Immunol. 2014; 193 (5): 2073-2086.
175. Wang S, Mata-Fink J, Kriegsman B, et al. Manipulating the selection forces during affinity maturation to generate cross-reactive HIV antibodies. Cell. 2015; 160 (4): 785-797.
176. Moore PL, Williamson C, Morris L. Virological features associated with the development of broadly neutralizing antibodies to HIV-1. Trends Microbiol. 2015; 23 (4): 1-8.
177. Hoot S, McGuire AT, Cohen KW, et al. Recombinant HIV envelope proteins fail to engage germline versions of anti-CD4bs bNAbs. PLoS Pathog. 2013; 9 (1): e1003106.
178. McGuire AT, Glenn JA, Lippy A, et al. Diverse recombinant HIV-1 Envs fail to activate B cells expressing the germline B cell receptors of the broadly neutralizing anti-HIV-1 antibodies PG9 and 447-52D. J Virol. 2013; 88 (5): 2645-2657.
179. McGuire AT, Hoot S, Dreyer AM, et al. Engineering HIV envelope protein to activate germline B cell receptors of broadly neutralizing anti-CD4 binding site antibodies. J Exp Med. 2013; 210 (4): 655-663.
180. Lee E-C, Liang Q, Ali H, et al. Complete humanization of the mouse immunoglobulin loci enables efficient therapeutic antibody discovery. Nat Biotechnol. 2014; 32 (4): 356-363.
181. Sliepen K, Medina-Ramírez M, Yasmeen A, et al. Binding of inferred germline precursors of broadly neutralizing HIV-1 antibodies to native-like envelope trimers. Virology. 2015; 486: 116-120.
182. Andrabi R, Voss JE, Liang C, et al. Identification of common features in prototype broadly neutralizing antibodies to HIV envelope V2 apex to facilitate vaccine design article identification of common features in prototype broadly neutralizing antibodies to HIV envelope V2 apex to facilitate vaccine design. Immunity. 2015; 43 (5): 959-973.