Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Antibody responses to envelope glycoproteins in HIV-1 infection

Abstract

Antibody responses to the HIV-1 envelope glycoproteins can be classified into three groups. Binding but non-neutralizing responses are directed to epitopes that are expressed on isolated envelope glycoproteins but not on the native envelope trimer found on the surface of virions and responsible for mediating the entry of virus into target cells. Strain-specific responses and broadly neutralizing responses, in contrast, target epitopes that are expressed on the native trimer, as revealed by recently resolved structures. The past few years have seen the isolation of many broadly neutralizing antibodies of remarkable potency that have shown prophylactic and therapeutic activities in animal models. These antibodies are helping to guide rational vaccine design and therapeutic strategies for HIV-1.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Schematic of some of the forms of Env protein that may be present on infectious HIV-1 and available to elicit Ab responses.
Figure 2: Structure of the HIV-1 Env trimer.
Figure 3: Broadly neutralizing Abs (antigen-binding (Fab) fragments) bound to the HIV-1 Env trimer.

Similar content being viewed by others

References

  1. Poignard, P. et al. Heterogeneity of envelope molecules expressed on primary human immunodeficiency virus type 1 particles as probed by the binding of neutralizing and nonneutralizing antibodies. J. Virol. 77, 353–365 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Moore, P.L. et al. Nature of nonfunctional envelope proteins on the surface of human immunodeficiency virus type 1. J. Virol. 80, 2515–2528 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Decker, J.M. et al. Antigenic conservation and immunogenicity of the HIV coreceptor binding site. J. Exp. Med. 201, 1407–1419 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Dey, B. et al. Structure-based stabilization of HIV-1 gp120 enhances humoral immune responses to the induced co-receptor binding site. PLoS Pathog. 5, e1000445 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Walker, L.M. et al. Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target. Science 326, 285–289 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Walker, L.M. et al. Broad neutralization coverage of HIV by multiple highly potent antibodies. Nature 477, 466–470 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Falkowska, E. et al. Broadly neutralizing HIV antibodies define a glycan-dependent epitope on the prefusion conformation of gp41 on cleaved envelope trimers. Immunity 40, 657–668 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Blattner, C. et al. Structural delineation of a quaternary, cleavage-dependent epitope at the gp41-gp120 interface on intact HIV-1 Env trimers. Immunity 40, 669–680 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Doria-Rose, N.A. et al. Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies. Nature 509, 55–62 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Huang, J. et al. Broad and potent HIV-1 neutralization by a human antibody that binds the gp41-gp120 interface. Nature 515, 138–142 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Klein, F. et al. Broad neutralization by a combination of antibodies recognizing the CD4 binding site and a new conformational epitope on the HIV-1 envelope protein. J. Exp. Med. 209, 1469–1479 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Wyatt, R. et al. The antigenic structure of the HIV gp120 envelope glycoprotein. Nature 393, 705–711 (1998).

    Article  CAS  PubMed  Google Scholar 

  13. Moore, J.P. & Sodroski, J. Antibody cross-competition analysis of the human immunodeficiency virus type 1 gp120 exterior envelope glycoprotein. J. Virol. 70, 1863–1872 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Mascola, J.R. & Montefiori, D.C. The role of antibodies in HIV vaccines. Annu. Rev. Immunol. 28, 413–444 (2010).

    Article  CAS  PubMed  Google Scholar 

  15. Sanders, R.W. 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. 9, e1003618 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Ringe, R.P. et al. Cleavage strongly influences whether soluble HIV-1 envelope glycoprotein trimers adopt a native-like conformation. Proc. Natl. Acad. Sci. USA 110, 18256–18261 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Yasmeen, A. 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 11, 41 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Julien, J.P. et al. Crystal structure of a soluble cleaved HIV-1 envelope trimer. Science 342, 1477–1483 (2013).

    Article  CAS  PubMed  Google Scholar 

  19. Lyumkis, D. et al. Cryo-EM structure of a fully glycosylated soluble cleaved HIV-1 envelope trimer. Science 342, 1484–1490 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Pancera, M. et al. Structure and immune recognition of trimeric pre-fusion HIV-1 Env. Nature 514, 455–461 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Tomaras, G.D. et al. Initial B-cell responses to transmitted human immunodeficiency virus type 1: virion-binding immunoglobulin M (IgM) and IgG antibodies followed by plasma anti-gp41 antibodies with ineffective control of initial viremia. J. Virol. 82, 12449–12463 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Keele, B.F. et al. Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection. Proc. Natl. Acad. Sci. USA 105, 7552–7557 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Overbaugh, J. & Morris, L. The antibody response against HIV-1. Cold Spring Harbor Perspect. Med. 2, a007039 (2012).

    Article  Google Scholar 

  24. Burton, D.R. Antibodies, viruses and vaccines. Nat. Rev. Immunol. 2, 706–713 (2002).

    Article  CAS  PubMed  Google Scholar 

  25. Alpert, M.D. et al. A novel assay for antibody-dependent cell-mediated cytotoxicity against HIV-1- or SIV-infected cells reveals incomplete overlap with antibodies measured by neutralization and binding assays. J. Virol. 86, 12039–12052 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Smalls-Mantey, A. et al. Antibody-dependent cellular cytotoxicity against primary HIV-infected CD4+ T cells is directly associated with the magnitude of surface IgG binding. J. Virol. 86, 8672–8680 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Smalls-Mantey, A., Connors, M. & Sattentau, Q.J. Comparative efficiency of HIV-1-infected T cell killing by NK cells, monocytes and neutrophils. PLoS ONE 8, e74858 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Pollara, J. et al. High-throughput quantitative analysis of HIV-1 and SIV-specific ADCC-mediating antibody responses. Cytometry 79, 603–612 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Forthal, D.N. & Moog, C. Fc receptor-mediated antiviral antibodies. Curr. Opin. HIV AIDS 4, 388–393 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  30. Nimmerjahn, F. & Ravetch, J.V. FcγRs in health and disease. Curr. Top. Microbiol. Immunol. 350, 105–125 (2011).

    CAS  PubMed  Google Scholar 

  31. Ackerman, M.E. et al. Natural variation in Fc glycosylation of HIV-specific antibodies impacts antiviral activity. J. Clin. Invest. 123, 2183–2192 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Hessell, A.J. et al. Fc receptor but not complement binding is important in antibody protection against HIV. Nature 449, 101–104 (2007).

    Article  CAS  PubMed  Google Scholar 

  33. Bournazos, S. et al. Broadly neutralizing anti-HIV-1 antibodies require Fc effector functions for in vivo activity. Cell 158, 1243–1253 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Rerks-Ngarm, S. et al. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N. Engl. J. Med. 361, 2209–2220 (2009).

    Article  CAS  PubMed  Google Scholar 

  35. Haynes, B.F. et al. Immune-correlates analysis of an HIV-1 vaccine efficacy trial. N. Engl. J. Med. 366, 1275–1286 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Liao, H.X. et al. Vaccine induction of antibodies against a structurally heterogeneous site of immune pressure within HIV-1 envelope protein variable regions 1 and 2. Immunity 38, 176–186 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Yates, N.L. et al. Vaccine-induced Env V1–V2 IgG3 correlates with lower HIV-1 infection risk and declines soon after vaccination. Sci. Transl. Med. 6, 228ra239 (2014).

    Article  CAS  Google Scholar 

  38. Shukair, S.A. et al. Human cervicovaginal mucus contains an activity that hinders HIV-1 movement. Mucosal Immunol. 6, 427–434 (2013).

    Article  CAS  PubMed  Google Scholar 

  39. Boeras, D.I. et al. Role of donor genital tract HIV-1 diversity in the transmission bottleneck. Proc. Natl. Acad. Sci. USA 108, E1156–E1163 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Fahrbach, K.M., Malykhina, O., Stieh, D.J. & Hope, T.J. Differential binding of IgG and IgA to mucus of the female reproductive tract. PLoS ONE 8, e76176 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Forthal, D., Hope, T.J. & Alter, G. New paradigms for functional HIV-specific nonneutralizing antibodies. Curr. Opin. HIV AIDS 8, 393–401 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Baum, L.L. et al. HIV-1 gp120-specific antibody-dependent cell-mediated cytotoxicity correlates with rate of disease progression. J. Immunol. 157, 2168–2173 (1996).

    CAS  PubMed  Google Scholar 

  43. Forthal, D.N. et al. Antibody-dependent cellular cytotoxicity independently predicts survival in severely immunocompromised human immunodeficiency virus-infected patients. J. Infect. Dis. 180, 1338–1341 (1999).

    Article  CAS  PubMed  Google Scholar 

  44. Dugast, A.S. et al. Lack of protection following passive transfer of polyclonal highly functional low-dose non-neutralizing antibodies. PLoS ONE 9, e97229 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Mascola, J.R. Defining the protective antibody response for HIV-1. Curr. Mol. Med. 3, 209–216 (2003).

    Article  CAS  PubMed  Google Scholar 

  46. Moldt, B. et al. Highly potent HIV-specific antibody neutralization in vitro translates into effective protection against mucosal SHIV challenge in vivo. Proc. Natl. Acad. Sci. USA 109, 18921–18925 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Shingai, M. et al. Passive transfer of modest titers of potent and broadly neutralizing anti-HIV monoclonal antibodies block SHIV infection in macaques. J. Exp. Med. 211, 2061–2074 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Pegu, A. et al. Neutralizing antibodies to HIV-1 envelope protect more effectively in vivo than those to the CD4 receptor. Sci. Transl. Med. 6, 243ra288 (2014).

    Article  CAS  Google Scholar 

  49. Burton, D.R. et al. Limited or no protection by weakly or nonneutralizing antibodies against vaginal SHIV challenge of macaques compared with a strongly neutralizing antibody. Proc. Natl. Acad. Sci. USA 108, 11181–11186 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Barouch, D.H. et al. Therapeutic efficacy of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys. Nature 503, 224–228 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Florese, R.H. et al. Evaluation of passively transferred, nonneutralizing antibody-dependent cellular cytotoxicity-mediating IgG in protection of neonatal rhesus macaques against oral SIVmac251 challenge. J. Immunol. 177, 4028–4036 (2006).

    Article  CAS  PubMed  Google Scholar 

  52. Shingai, M. et al. Antibody-mediated immunotherapy of macaques chronically infected with SHIV suppresses viraemia. Nature 503, 277–280 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Binley, J.M. et al. Comprehensive cross-clade neutralization analysis of a panel of anti-human immunodeficiency virus type 1 monoclonal antibodies. J. Virol. 78, 13232–13252 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Montefiori, D. Evaluating Neutralizing Antibodies Against HIV, SIV and SHIV in Luciferase Reporter Gene Assays (John Wiley & Sons, 2004).

  55. Wei, X. et al. Antibody neutralization and escape by HIV-1. Nature 422, 307–312 (2003).

    Article  CAS  PubMed  Google Scholar 

  56. Richman, D.D., Wrin, T., Little, S.J. & Petropoulos, C.J. Rapid evolution of the neutralizing antibody response to HIV type 1 infection. Proc. Natl. Acad. Sci. USA 100, 4144–4149 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Albert, J. et al. Rapid development of isolate-specific neutralizing antibodies after primary HIV-1 infection and consequent emergence of virus variants which resist neutralization by autologous sera. AIDS 4, 107–112 (1990).

    Article  CAS  PubMed  Google Scholar 

  58. Montefiori, D.C. et al. Homotypic antibody responses to fresh clinical isolates of human immunodeficiency virus. Virology 182, 635–643 (1991).

    Article  CAS  PubMed  Google Scholar 

  59. Derdeyn, C.A., Moore, P.L. & Morris, L. Development of broadly neutralizing antibodies from autologous neutralizing antibody responses in HIV infection. Curr. Opin. HIV AIDS 9, 210–216 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Rong, R. et al. Escape from autologous neutralizing antibodies in acute/early subtype C HIV-1 infection requires multiple pathways. PLoS Pathog. 5, e1000594 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Moore, P.L. et al. Limited neutralizing antibody specificities drive neutralization escape in early HIV-1 subtype C infection. PLoS Pathog. 5, e1000598 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Rong, R. et al. Role of V1V2 and other human immunodeficiency virus type 1 envelope domains in resistance to autologous neutralization during clade C infection. J. Virol. 81, 1350–1359 (2007).

    Article  CAS  PubMed  Google Scholar 

  63. Walker, L.M. et al. A limited number of antibody specificities mediate broad and potent serum neutralization in selected HIV-1 infected individuals. PLoS Pathog. 6, e1001028 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Li, Y. et al. Analysis of the neutralization specificities in polyclonal sera derived from human immunodeficiency virus type-1 infected individuals. J. Virol. 83, 1045–1059 (2009).

    Article  CAS  PubMed  Google Scholar 

  65. Binley, J.M. et al. Profiling the specificity of neutralizing antibodies in a large panel of plasmas from patients chronically infected with human immunodeficiency virus type 1 subtypes B and C. J. Virol. 82, 11651–11668 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Tomaras, G.D. et al. Polyclonal B cell responses to conserved neutralization epitopes in a subset of HIV-1-infected individuals. J. Virol. 85, 11502–11519 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Bonsignori, M. et al. Two distinct broadly neutralizing antibody specificities of different clonal lineages in a single HIV-1-infected donor: implications for vaccine design. J. Virol. 86, 4688–4692 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Stamatatos, L., Morris, L., Burton, D.R. & Mascola, J.R. Neutralizing antibodies generated during natural HIV-1 infection: good news for an HIV-1 vaccine? Nat. Med. 15, 866–870 (2009).

    Article  CAS  PubMed  Google Scholar 

  69. Dhillon, A.K. et al. Dissecting the neutralizing antibody specificities of broadly neutralizing sera from HIV-1 infected donors. J. Virol. 81, 6548–6562 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Simek, M.D. 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. 83, 7337–7348 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Gray, E.S. et al. 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. 85, 4828–4840 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Huang, J. et al. Broad and potent neutralization of HIV-1 by a gp41-specific human antibody. Nature 491, 406–412 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Scheid, J.F. et al. Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals. Nature 458, 636–640 (2009).

    Article  CAS  PubMed  Google Scholar 

  74. Wu, X. et al. Rational design of envelope surface identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science 329, 856–861 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Sok, D. et al. Recombinant HIV envelope trimer selects for quaternary-dependent antibodies targeting the trimer apex. Proc. Natl. Acad. Sci. USA 111, 17624–17629 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Burton, D.R., Poignard, P., Stanfield, R.L. & Wilson, I.A. Broadly neutralizing antibodies: new prospects to counter highly antigenically diverse viruses. Science 337, 183–186 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. West, A.P. Jr. et al. Structural insights on the role of antibodies in HIV-1 vaccine and therapy. Cell 156, 633–648 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Kwong, P.D. & Mascola, J.R. Human antibodies that neutralize HIV-1: identification, structures, and B cell ontogenies. Immunity 37, 412–425 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Ward, A.B. & Wilson, I.A. Insights into the trimeric HIV-1 envelope glycoprotein structure. Trends Biochem. Sci. 40, 101–107 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Stamatatos, L. HIV vaccine design: the neutralizing antibody conundrum. Curr. Opin. Immunol. 24, 316–323 (2012).

    Article  CAS  PubMed  Google Scholar 

  81. Moore, P.L., Williamson, C. & Morris, L. Virological features associated with the development of broadly neutralizing antibodies to HIV-1. Trends Microbiol. doi:10.1016/j.tim.2014.12.007 (5 January 2015).

  82. Mascola, J.R. & Haynes, B.F. HIV-1 neutralizing antibodies: understanding nature's pathways. Immunol. Rev. 254, 225–244 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Burton, D.R. et al. A blueprint for HIV vaccine discovery. Cell Host Microbe 12, 396–407 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Klein, F. et al. Somatic mutations of the immunoglobulin framework are generally required for broad and potent HIV-1 neutralization. Cell 153, 126–138 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Corti, D. & Lanzavecchia, A. Broadly neutralizing antiviral antibodies. Annu. Rev. Immunol. 31, 705–742 (2013).

    Article  CAS  PubMed  Google Scholar 

  86. Kepler, T.B. et al. Immunoglobulin gene insertions and deletions in the affinity maturation of HIV-1 broadly reactive neutralizing antibodies. Cell Host Microbe 16, 304–313 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Sok, D. et al. The effects of somatic hypermutation on neutralization and binding in the PGT121 family of broadly neutralizing HIV antibodies. PLoS Pathog. 9, e1003754 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Liao, H.X. et al. Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus. Nature 496, 469–476 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Briney, B.S., Willis, J.R. & Crowe, J.E. Jr. Human peripheral blood antibodies with long HCDR3s are established primarily at original recombination using a limited subset of germline genes. PLoS ONE 7, e36750 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Pietzsch, J. et al. A mouse model for HIV-1 entry. Proc. Natl. Acad. Sci. USA 109, 15859–15864 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Parren, P.W. et al. Antibody protects macaques against vaginal challenge with a pathogenic R5 simian/human immunodeficiency virus at serum levels giving complete neutralization in vitro. J. Virol. 75, 8340–8347 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Nishimura, Y. et al. Determination of a statistically valid neutralization titer in plasma that confers protection against simian-human immunodeficiency virus challenge following passive transfer of high-titered neutralizing antibodies. J. Virol. 76, 2123–2130 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Rudicell, R.S. et al. Enhanced potency of a broadly neutralizing HIV-1 antibody in vitro improves protection against lentiviral infection in vivo. J. Virol. 88, 12669–12682 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Hessell, A.J. et al. Effective, low-titer antibody protection against low-dose repeated mucosal SHIV challenge in macaques. Nat. Med. 15, 951–954 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Klein, F. et al. HIV therapy by a combination of broadly neutralizing antibodies in humanized mice. Nature 492, 118–122 (2012).

    Article  CAS  PubMed  Google Scholar 

  96. Klein, F. et al. Enhanced HIV-1 immunotherapy by commonly arising antibodies that target virus escape variants. J. Exp. Med. 211, 2361–2372 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Gao, F. et al. Cooperation of B cell lineages in induction of HIV-1-broadly neutralizing antibodies. Cell 158, 481–491 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Crooks, E.T., Tong, T., Osawa, K. & Binley, J.M. Enzyme digests eliminate nonfunctional Env from HIV-1 particle surfaces, leaving native Env trimers intact and viral infectivity unaffected. J. Virol. 85, 5825–5839 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Scharf, L. et al. Antibody 8ANC195 reveals a site of broad vulnerability on the HIV-1 envelope spike. Cell Reports 7, 785–795 (2014).

    Article  CAS  PubMed  Google Scholar 

  100. Kong, L. et al. Supersite of immune vulnerability on the glycosylated face of HIV-1 envelope glycoprotein gp120. Nat. Struct. Mol. Biol. 20, 796–803 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Pejchal, R. et al. A potent and broad neutralizing antibody recognizes and penetrates the HIV glycan shield. Science 334, 1097–1103 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Julien, J.P. et al. Broadly neutralizing antibody PGT121 allosterically modulates CD4 binding via recognition of the HIV-1 gp120 V3 base and multiple surrounding glycans. PLoS Pathog. 9, e1003342 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. McLellan, J.S. et al. Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9. Nature 480, 336–343 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Buchacher, A. et al. in Vaccines '92: Modern Approaches to New Vaccines Including Prevention of AIDS (eds. Brown, F., Chanock, R., Ginsberg, H.S. & Lerner, R.) 191–194 (Cold Spring Harbor Laboratory Press, 1992).

  105. Zwick, M.B. et al. Broadly neutralizing antibodies targeted to the membrane-proximal external region of human immunodeficiency virus type 1 glycoprotein gp41. J. Virol. 75, 10892–10905 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Barbas, C.F. III et al. Recombinant human Fab fragments neutralize human type 1 immunodeficiency virus in vitro. Proc. Natl. Acad. Sci. USA 89, 9339–9343 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Scheid, J.F. et al. Sequence and structural convergence of broad and potent HIV antibodies that mimic CD4 binding. Science 333, 1633–1637 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Mouquet, H. et al. Complex-type N-glycan recognition by potent broadly neutralizing HIV antibodies. Proc. Natl. Acad. Sci. USA 109, E3268–E3277 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Supported by the National Institute of Allergy and Infectious Diseases (D.R.B.), the Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (D.R.B.), the International AIDS Vaccine Initiative (D.R.B.), the Bill and Melinda Gates Foundation (D.R.B.), the Ragon Institute of MGH, MIT and Harvard (D.R.B.) and the intramural research program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases (J.R.M.).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Dennis R Burton or John R Mascola.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Burton, D., Mascola, J. Antibody responses to envelope glycoproteins in HIV-1 infection. Nat Immunol 16, 571–576 (2015). https://doi.org/10.1038/ni.3158

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ni.3158

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing