Induction of HIV-1 broad neutralizing antibodies in 2F5 knock-in mice: Selection against membrane proximal external region-associated autoreactivity limits T-dependent responses

Journal of Immunology

Volumn 191, Issue 5, 2013, Pages 2538-2550

  Verkoczy, Laurent ^a   Chen, Yao ^a   Zhang, Jinsong ^a   Bouton Verville, Hilary ^a   Newman, Amanda ^a   Lockwood, Bradley ^a   Scearce, Richard M ^a   Montefiori, David C ^a   Dennison, S Moses ^a   Xia, Shi Mao ^a   Hwang, Kwan Ki ^a   Liao, Hua Xin ^a   Alam, S Munir ^a   Haynes, Barton F ^a  

^a DUKE UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CD40 LIGAND; EPITOPE; HUMAN IMMUNODEFICIENCY VIRUS VACCINE; IMMUNOGLOBULIN G ANTIBODY; NEUTRALIZING ANTIBODY; PLACEBO;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ANTIBODY PRODUCTION; ANTIBODY RESPONSE; ANTIBODY TITER; ANTIGEN BINDING; ARTICLE; B LYMPHOCYTE; B LYMPHOCYTE ACTIVATION; CELL EXPANSION; CONTROLLED STUDY; HUMAN IMMUNODEFICIENCY VIRUS 1; IMMUNIZATION; IN VIVO STUDY; MOUSE; NONHUMAN; PRIORITY JOURNAL; T LYMPHOCYTE; VIRUS NEUTRALIZATION;

AIDS VACCINES; ANIMALS; ANTIBODIES, MONOCLONAL; ANTIBODIES, NEUTRALIZING; ANTIGENS, VIRAL; B-LYMPHOCYTES; ENZYME-LINKED IMMUNOSORBENT ASSAY; GENE KNOCK-IN TECHNIQUES; HIV ANTIBODIES; HIV ENVELOPE PROTEIN GP41; HIV-1; HUMANS; LYMPHOCYTE ACTIVATION; MICE; MICE, KNOCKOUT; NEUTRALIZATION TESTS; T-LYMPHOCYTES;

EID: 84883348588     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1300971     Document Type: Article

References (52)

1. Mascola, J. R., and D. C. Montefiori. 2010. The role of antibodies in HIV vaccines. Annu. Rev. Immunol. 28: 413-444.
2. McElrath, M. J., and B. F. Haynes. 2010. Induction of immunity to human immunodeficiency virus type-1 by vaccination. Immunity 33: 542-554.
3. Haynes, B. F., M. A. Moody, L. Verkoczy, G. Kelsoe, and S. M. Alam. 2005. Antibody polyspecificity and neutralization of HIV-1: a hypothesis. Hum. Antibodies 14: 59-67.
4. Haynes, B. F., J. Fleming, E. W. St Clair, H. Katinger, G. Stiegler, R. Kunert, J. Robinson, R. M. Scearce, K. Plonk, H. F. Staats, et al. 2005. Cardiolipin polyspecific autoreactivity in two broadly neutralizing HIV-1 antibodies. Science 308: 1906-1908.
5. Verkoczy, L., G. Kelsoe, M. A. Moody, and B. F. Haynes. 2011. Role of immune mechanisms in induction of HIV-1 broadly neutralizing antibodies. Curr. Opin. Immunol. 23: 383-390.
6. Stiegler, G., R. Kunert, M. Purtscher, S. Wolbank, R. Voglauer, F. Steindl, and H. Katinger. 2001. A potent cross-clade neutralizing human monoclonal anti-body against a novel epitope on gp41 of human immunodeficiency virus type 1. AIDS Res. Hum. Retroviruses 17: 1757-1765.
7. Zwick, M. B., A. F. Labriijn, M. Wang, C. Spenlehauer, E. O. Sapphire, J. M. Binley, J. P. Moore, G. Stiegler, H. Katinger, D. R. Burton, and P. W. Parren. 2001. Broadly neutralizing antibodies targeted to the membraneproximal external region of human immunodeficiency virus type 1 glycoprotein gp41. J. Virol. 75: 10892-10905.
8. Muster, T., F. Steindl, M. Purtscher, A. Trkola, A. Klima, G. Himmler, F. Ruker, and H. Katinger. 1993. A conserved neutralizing epitope on gp41 of human immunodeficiency virus type 1. J. Virol. 67: 6642-6647.
9. Ofek, G., M. Tang, A. Sambor, H. Katinger, J. R. Mascola, R. Wyatt, and P. D. Kwong. 2004. Structure and mechanistic analysis of the anti-human immunodeficiency virus type 1 antibody 2F5 in complex with its gp41 epitope. J. Virol. 78: 10724-10737.
10. Cardoso, R. M., M. B. Zwick, R. L. Stanfield, R. Kunert, J. M. Binley, H. Katinger, D. R. Burton, and I. A.Wilson. 2005. Broadly neutralizing anti-HIV antibody 4E10 recognizes a helical conformation of a highly conserved fusionassociated motif in gp41. Immunity 22: 163-173.
11. Verkoczy, L., M. Diaz, T. M. Holl, Y. B. Ouyang, H. Bouton-Verville, S. M. Alam, H. X. Liao, G. Kelsoe, and B. F. Haynes. 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.
12. Verkoczy, L., Y. Chen, H. Bouton-Verville, J. Zhang, M. Diaz, J. Hutchinson, Y. B. Ouyang, S. M. Alam, T. M. Holl, K. K. Hwang, 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.
13. Chen, Y., J. Zhang, K.-K. Hwang, H. Bouton-Verville, S.-M. Xia, A. Newman, Y.-B. Ouyang, B. F. Haynes, and L. Verkoczy. 2013. Common tolerance mechanisms, but distinct cross-reactivities associated with gp41 and lipids, limit production of HIV-1 broad neutralizing antibodies 2F5 and 4E10. J. Immunol. 191: 1260-1275.
14. Goodnow, C. C. 1992. Transgenic mice and analysis of B-cell tolerance. Annu. Rev. Immunol. 10: 489-518.
15. Cambier, J. C., S. B. Gauld, K. T. Merrell, and B. J. Vilen. 2007. B-cell anergy: from transgenic models to naturally occurring anergic B cells? Nat. Rev. Immunol. 7: 633-643.
16. Viglianti, G. A., C. M. Lau, T. M. Hanley, B. A. Miko, M. J. Shlomchik, and A. Marshak-Rothstein. 2003. Activation of autoreactive B cells by CpG dsDNA. Immunity 19: 837-847.
17. Uccellini, M. B., L. Busconi, N. M. Green, P. Busto, S. R. Christensen, M. J. Shlomchik, A. Marshak-Rothstein, and G. A. Viglianti. 2009. Autoreactive B cells discriminate CpG-rich and CpG-poor DNA and this response is modulated by IFN-alpha. J. Immunol. 181: 5875-5884.
18. Shlomchik, M. J. 2008. Sites and stages of autoreactive B cell activation and regulation. Immunity 28: 18-28.
19. Shlomchik, M. J. 2009. Activating systemic autoimmunity: B's, T's, and tolls. Curr. Opin. Immunol. 21: 626-633.
20. Montero, M., N. E. van Houten, X. Wang, and J. K. Scott. 2008. The membraneproximal 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.
21. Montero, M., N. Gulzar, K. A. Klaric, J. E. Donald, C. Lepik, S. Wu, S. Tsai, J. P. Julien, A. J. Hessell, S. Wang, et al. 2012. Neutralizing epitopes in the membrane-proximal external region of HIV-1 gp41 are influenced by the transmembrane domain and the plasma membrane. J. Virol. 86: 2930-2941.
22. Alam, S. M., M. Morelli, S. M. Dennison, H. X. Liao, R. Zhang, S. M. Xia, S. Rits-Volloch, L. Sun, S. C. Harrison, B. F. Haynes, and B. Chen. 2009. Role of HIV membrane in neutralization by two broadly neutralizing antibodies. Proc. Natl. Acad. Sci. USA 106: 20234-20239.
23. Dennison, S. M., L. L. Sutherland, F. H. Jaeger, K. M. Anasti, R. Parks, S. Stewart, C. Bowman, S. M. Xia, R. Zhang, X. Shen, et al. 2011. Induction of antibodies in rhesus macaques that recognize a fusion-intermediate conformation of HIV-1 gp41. PLoS ONE 6: e27824.
24. Frey, G., H. Peng, S. Rits-Volloch, M. Morelli, Y. Cheng, and B. Chen. 2008. A fusion-intermediate state of HIV-1 gp41 targeted by broadly neutralizing antibodies. Proc. Natl. Acad. Sci. USA 105: 3739-3744.
25. Ofek, G., F. J. Guenaga, W. R. Schief, J. Skinner, D. Baker, R. Wyatt, and P. D. Kwong. 2010. Elicitation of structure-specific antibodies by epitope scaffolds. J. Virol. 107: 17880-17887.
26. Alam, S. M., M. McAdams, D. Boren, M. Rak, R. M. Scearce, F. Gao, Z. T. Camacho, D. Gerwith, G. Kelsoe, P. Chen, and B. F. Haynes. 2007. The role of antibody specificity and lipid reactivity in binding of broadly neutralizing anti-HIV envelope human monoclonal antibodies 2F5 and 4E10 to glycoprotein 41 membrane proximal epitopes. J. Immunol. 178: 4424-4435.
27. Dennison, S. M., S. M. Stewart, K. C. Stempel, H.-X. Liao, B. F. Haynes, and S. M. Alam. 2009. Stable docking of neutralizing human immunodeficiency virus type1 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.
28. Renshaw, B. R., W. C. Fanslow, 3rd, R. J. Armitage, K.A. Campbell, D. Liggitt, B. Wright, B. L. Davison, and C. R. Maliszewski. 1994. Humoral immune responses in CD40-ligand-deficient mice. J. Exp. Med. 180: 1889-1900.
29. Liao, H-X., L.L. Sutherland, S.M. Xia, M.E. Brock, R.M. Scearce, S. Vanleeuwen, S.M. Alam, M. McAdams, E.A. Weaver, Z. Camacho, et al. 2006. A group M consensus envelope glycoprotein induces antibodies that neutralize subsets of subtype B and C HIV-1 primary viruses. Virology 353: 268-282.
30. Verkoczy, L., M. A. Moody, T. M. Holl, H. Bouton-Verville, R. M. Scearce, J. Hutchinson, S. M. Alam, G. Kelsoe, and B. F. Haynes. 2009. Functional, nonclonal IgMa-restricted B cell receptor interactions with the HIV-1 envelope gp41 membrane proximal external region. PLoS ONE 4: e7215.
31. Seaman, M. S., H. Janes, N. Hawkins, L. E. Grandpre, C. Devoy, A. Giri, R. T. Coffey, L. Harris, B. Wood, M. G. Daniels, et al. 2010. Tiered categorization of a diverse panel of HIV-1 Env pseudovirus for assessment of neutralizing antibodies. J. Virol. 84: 1439-1452.
32. Montefiori, D. C. 2004. Evaluating neutralizing antibodies against HIV and SHIV in luciferase reporter gene assays. Curr. Protocol. Immunol. Chapter 12: Unit 12.11.
33. Mascola, J. R., P. D'Souza, P. Gilbert, B. H. Hahn, N. L. Haigwood, L. Morris, C. J. Petropoulos, V. R. Polonis, M. Sarzotti, and D. C. Montefiori. 2005. Recommendations for the design and use of standard virus panels to assess neutralizing antibody responses elicited by candidate human immunodeficiency virus type 1 vaccines. J. Virol. 79: 10103-10107.
34. Tiller, T., C. E. Busse, and H. Wardemann. 2009. Cloning and expression of murine Ig genes from single B cells. J. Immunol. Methods 350: 183-193.
35. Alam, S. M., R. M. Scearce, R. J. Parks, K. Plonk, S. G. Plonk, L. L. Sutherland, M. K. Gorny, S. Zolla-Pazner, S. Vanleeuwen, M. A. Moody, et al. 2008. Human immunodeficiency virus type 1 gp41 antibodies that mask membrane proximal region epitopes: antibody binding kinetics, induction, and potential for regulation in acute infection. J. Virol. 82: 115-125.
36. Nicely, N. I., S. M. Dennison, L. Spicer, R. M. Scearce, G. Kelsoe, Y. Ueda, H. Chen, H. X. Liao, S. M. Alam, and B. F. Haynes. 2010. Crystal structure of a non-neutralizing antibody to the HIV-1 gp41 membrane-proximal external region. Nat. Struct. Mol. Biol. 17: 1492-1498.
37. Tran, T. T., C. F. Reich, 3rd, M. Alam, and D.S. Pisetsky. 2003. Specificity and immunochemical properties of anti-DNA antibodies induced in normal mice by immunization with mammalian DNA with a CpG oligonucleotide as adjuvant. Clin. Immunol. 109: 278-287.
38. Strasser, A., S. Whittingham, D. L. Vaux, M. L. Bath, J. M. Adams, S. Cory, and A. W. Harris. 1991. Enforced BCL2 expression in B-lymphoid cells prolongs antibody responses and elicits autoimmune disease. Proc. Natl. Acad. Sci. USA 88: 8661-8665.
39. Hartley, S. B., M. P. Cooke, D. A. Fulcher, A. W. Harris, S. Cory, A. Basten, and C. C. Goodnow. 1993. Elimination of self-reactive B lymphocytes proceeds in two stages: arrested development and cell death. Cell 72: 325-335.
40. Mond, J. J., A. Lees, and C. M. Snapper. 1995. T cell-independent antigens typee. Annu. Rev. Immunol. 13: 655-692.
41. Pone, E. J., J. Zhang, T. Mai, C. A. White, G. Li, J. K. Sakakura, P. J. Patel, A. Al-Qahtani, H. Zan, and P. Casali. 2012. BCR signaling synergizes with TLR signaling for induction of AID and immunoglobulin class-switching through the non-canonical NF-κB pathway. Nat. Commun. 3: 767-773.
42. Cascalho, M., A. Ma, S. Lee, L. Masat, and M. Wabl. 1996. A quasi-monoclonal mouse. Science 272: 1649-1652.
43. Yang, G., T. M. Holl, Y. Liu, X. Li, N. Nicely, T. B. Kepler, S. M. Alam, H.-X. Liao, D. W. Cain, L. Spicer, et al. 2013. Identification of autoantigens recognized by the 2F5 and 4E10 broadly neutralizing HIV-1 antibodies. J. Exp. Med. 210: 241-256.
44. Diaz, M., and N. R. Klinman. 2000. Relative roles of somatic and Darwinian evolution in shaping the antibody response. Immunol. Res. 21: 89-102.
45. Haynes, B. F., M. A. Moody, H.-X. Liao, L. Verkoczy, and G. D. Tomaras. 2011. B cell responses to HIV-1 infection and vaccination: pathways to preventing infection. Trends Microbiol. 17: 108-116.
46. Haynes, B. F., G. Kelsoe, S. C. Harrison, and T. B. Kepler. 2012. B-cell-lineage immunogen design in vaccine development with HIV-1 as a case study. Nat. Biotechnol. 30: 423-433.
47. Bonsignori, M., S. M. Alam, H.-X. Liao, L. Verkoczy, G. D. Tomaras, B. F. Haynes, and M. A. Moody. 2012. HIV-1 antibodies from infection and vaccination: insights for guiding vaccine design. Trends Microbiol. 20: 532-539.
48. Mascola, J. R., and B. F. Haynes. 2013. HIV-1 neutralizing antibodies: understanding nature's pathways. Immunol. Rev. 254: 225-244.
49. Liao, H.-X., R. Lynch, T. Zhou, F. Gao, S. M. Alam, S. D. Boyd, A. Z. Fire, K. M. Roskin, C. A. Schramm, Z. Zhang, et al. 2013. Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus. Nature 496: 469-476.
50. Klein, F., R. Diskin, J.F. Scheid, C. Gaebler, H. Mouquet, I.S. Georgiev, M. Pancer, T. Zhou, R-H. Incesu, B.Z. Fu, et al. 2013. Somatic mutations of the immunoglobulin framework are generally required for broad and potent neutralization. Cell 153: 126-138.
51. Alam, S. M., H. X. Liao, S. M. Dennison, F. Jaeger, R. Parks, K. Anasti, A. Foulger, M. Donathan, J. Lucas, and L. Verkoczy, et al. 2011. Differential reactivity germ line allelic variants of a broadly neutralizing HIV-1 antibody to a gp41 fusion intermediate conformation. J. Virol. 85: 11725-11731.
52. Zwick, M. B., H. K. Komori, R. L. Stanfield, S. Church, M. Wang, P. W. Parren, R. Kunert, H. Katinger, I. A. Wilson, and D. R. Burton. 2004. The 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.