A central goal of HIV-1 vaccine research is the elicitation of antibodies capable of neutralizing diverse primary isolates of HIV-1. Here we show that focusing the immune response to exposed N-terminal residues of the fusion peptide, a critical component of the viral entry machinery and the epitope of antibodies elicited by HIV-1 infection, through immunization with fusion peptide-coupled carriers and prefusion stabilized envelope trimers, induces cross-clade neutralizing responses. In mice, these immunogens elicited monoclonal antibodies capable of neutralizing up to 31% of a cross-clade panel of 208 HIV-1 strains. Crystal and cryoelectron microscopy structures of these antibodies revealed fusion peptide conformational diversity as a molecular explanation for the cross-clade neutralization. Immunization of guinea pigs and rhesus macaques induced similarly broad fusion peptide-directed neutralizing responses, suggesting translatability. The N terminus of the HIV-1 fusion peptide is thus a promising target of vaccine efforts aimed at eliciting broadly neutralizing antibodies.

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  1. 1.

    Korber, B. et al. Timing the ancestor of the HIV-1 pandemic strains. Science 288, 1789–1796 (2000).

  2. 2.

    UNAIDS. Global AIDS Update 2016, UNAIDS http://www.unaids.org/en/resources/documents/2016/Global-AIDS-update-2016 (2016).

  3. 3.

    Hraber, P. et al. Prevalence of broadly neutralizing antibody responses during chronic HIV-1 infection. AIDS 28, 163–169 (2014).

  4. 4.

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

  5. 5.

    Seaman, M. S. et al. Tiered categorization of a diverse panel of HIV-1 Env pseudoviruses for assessment of neutralizing antibodies. J. Virol. 84, 1439–1452 (2010).

  6. 6.

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

  7. 7.

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

  8. 8.

    Chen, L. et al. Structural basis of immune evasion at the site of CD4 attachment on HIV-1gp120. Science 326, 1123–1127 (2009).

  9. 9.

    Zhou, T. et al. Structural Repertoire of HIV-1-neutralizing antibodies targeting the CD4 supersite in 14 donors. Cell 161, 1280–1292 (2015).

  10. 10.

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

  11. 11.

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

  12. 12.

    Wu, X. et al. Focused evolution of HIV-1 neutralizing antibodies revealed by structures and deep sequencing. Science 333, 1593–1602 (2011).

  13. 13.

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

  14. 14.

    Gorman, J. et al. Structures of HIV-1 Env V1V2 with broadly neutralizing antibodies reveal commonalities that enable vaccine design. Nat. Struct. Mol. Biol. 23, 81–90 (2016).

  15. 15.

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

  16. 16.

    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).

  17. 17.

    Andrabi, R. et al. Identification of common features in prototype broadly neutralizing antibodies to HIV envelope V2 apex to facilitate vaccine design. Immunity 43, 959–973 (2015).

  18. 18.

    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).

  19. 19.

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

  20. 20.

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

  21. 21.

    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).

  22. 22.

    Garces, F. et al. Affinity maturation of a potent family of HIV antibodies is primarily focused on accommodating or avoiding glycans. Immunity 43, 1053–1063 (2015).

  23. 23.

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

  24. 24.

    Stiegler, G. et al. A potent cross-clade neutralizing human monoclonal antibody against a novel epitope on gp41 of human immunodeficiency virus type 1. AIDS Res. Hum. Retroviruses 17, 1757–1765 (2001).

  25. 25.

    Muster, T. et al. Cross-neutralizing activity against divergent human immunodeficiency virus type 1 isolates induced by the gp41 sequence ELDKWAS. J. Virol. 68, 4031–4034 (1994).

  26. 26.

    Muster, T. et al. A conserved neutralizing epitope on gp41 of human immunodeficiency virus type 1. J. Virol. 67, 6642–6647 (1993).

  27. 27.

    Ofek, G. et al. 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 (2004).

  28. 28.

    Ofek, G. et al. Relationship between antibody 2F5 neutralization of HIV-1 and hydrophobicity of its heavy chain third complementarity-determining region. J. Virol. 84, 2955–2962 (2010).

  29. 29.

    Irimia, A., Sarkar, A., Stanfield, R. L. & Wilson, I. A. Crystallographic identification of lipid as an integral component of the epitope of hiv broadly neutralizing antibody 4E10. Immunity 44, 21–31 (2016).

  30. 30.

    Haynes, B. F., Moody, M. A., Verkoczy, L., Kelsoe, G. & Alam, S. M. Antibody polyspecificity and neutralization of HIV-1: a hypothesis. Hum. Antibodies 14, 59–67 (2005).

  31. 31.

    Kong, R. et al. Fusion peptide of HIV-1 as a site of vulnerability to neutralizing antibody. Science 352, 828–833 (2016).

  32. 32.

    Carr, C. M. & Kim, P. S. A spring-loaded mechanism for the conformational change of influenza hemagglutinin. Cell 73, 823–832 (1993).

  33. 33.

    van Gils, M. J. et al. An HIV-1 antibody from an elite neutralizer implicates the fusion peptide as a site of vulnerability. Nat. Microbiol. 2, 16199 (2016).

  34. 34.

    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).

  35. 35.

    Boudko, S. P. et al. Crystal structure of human collagen XVIII trimerization domain: A novel collagen trimerization Fold. J. Mol. Biol. 392, 787–802 (2009).

  36. 36.

    Tan, K. et al. Crystal structure of the TSP-1 type 1 repeats: a novel layered fold and its biological implication. J. Cell Biol. 159, 373–382 (2002).

  37. 37.

    Chu, R. et al. Redesign of a four-helix bundle protein by phage display coupled with proteolysis and structural characterization by NMR and X-ray crystallography. J. Mol. Biol. 323, 253–262 (2002).

  38. 38.

    Mougous, J. D. et al. A virulence locus of Pseudomonas aeruginosa encodes a protein secretion apparatus. Science 312, 1526–1530 (2006).

  39. 39.

    Harris, J. R. & Markl, J. Keyhole limpet hemocyanin (KLH): a biomedical review. Micron 30, 597–623 (1999).

  40. 40.

    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).

  41. 41.

    Kwon, Y. D. et al. Crystal structure, conformational fixation and entry-related interactions of mature ligand-free HIV-1 Env. Nat. Struct. Mol. Biol. 22, 522–531 (2015).

  42. 42.

    Trkola, A. et al. Human monoclonal antibody 2G12 defines a distinctive neutralization epitope on the gp120 glycoprotein of human immunodeficiency virus type 1. J. Virol. 70, 1100–1108 (1996).

  43. 43.

    Trkola, A. et al. Delay of HIV-1 rebound after cessation of antiretroviral therapy through passive transfer of human neutralizing antibodies. Nat. Med. 11, 615–622 (2005).

  44. 44.

    Trkola, A. et al. In vivo efficacy of human immunodeficiency virus neutralizing antibodies: estimates for protective titers. J. Virol. 82, 1591–1599 (2008).

  45. 45.

    Pauthner, M. et al. Elicitation of robust tier 2 neutralizing antibody responses in nonhuman primates by HIV envelope trimer immunization using optimized approaches. Immunity 46, 1073–1088.e6 (2017).

  46. 46.

    Sanders, R. W. et al. HIV-1 vaccines. HIV-1 neutralizing antibodies induced by native-like envelope trimers. Science 349, aac4223 (2015).

  47. 47.

    de Taeye, S. W. et al. Immunogenicity of stabilized HIV-1 envelope trimers with reduced exposure of non-neutralizing epitopes. Cell 163, 1702–1715 (2015).

  48. 48.

    Guenaga, J. et al. Structure-guided redesign increases the propensity of HIV Env to generate highly stable soluble trimers. J. Virol. 90, 2806–2817 (2015).

  49. 49.

    Kong, L. et al. Uncleaved prefusion-optimized gp140 trimers derived from analysis of HIV-1 envelope metastability. Nat. Commun. 7, 12040 (2016).

  50. 50.

    Zhou, T. et al. Quantification of the impact of the HIV-1-glycan shield on antibody elicitation. Cell Rep. 19, 719–732 (2017).

  51. 51.

    Ekiert, D. C. et al. Antibody recognition of a highly conserved influenza virus epitope. Science 324, 246–251 (2009).

  52. 52.

    Joyce, M. G. et al. Vaccine-induced antibodies that neutralize group 1 and group 2 influenza A viruses. Cell 166, 609–623 (2016).

  53. 53.

    Furuyama, W. et al. Discovery of an antibody for pan-Ebolavirus therapy. Sci. Rep. 6, 20514 (2016).

  54. 54.

    Wec, A. Z. et al. Antibodies from a human survivor define sites of vulnerability for broad protection against Ebolaviruses. Cell 169, 878–890.e15 (2017).

  55. 55.

    Zhao, X. et al. Immunization-elicited broadly protective antibody reveals Ebolavirus fusion loop as a site of vulnerability. Cell 169, 891–904.e15 (2017).

  56. 56.

    Hastie, K. M. et al. Structural basis for antibody-mediated neutralization of Lassa virus. Science 356, 923–928 (2017).

  57. 57.

    Sok, D. et al. Rapid elicitation of broadly neutralizing antibodies to HIV by immunization in cows. Nature 548, 108–111 (2017).

  58. 58.

    McCoy, L. E. et al. Potent and broad neutralization of HIV-1 by a llama antibody elicited by immunization. J. Exp. Med. 209, 1091–1103 (2012).

  59. 59.

    Muyldermans, S. Nanobodies: natural single-domain antibodies. Annu. Rev. Biochem. 82, 775–797 (2013).

  60. 60.

    Wang, F. et al. Reshaping antibody diversity. Cell 153, 1379–1393 (2013).

  61. 61.

    Mastronarde, D. N. Automated electron microscope tomography using robust prediction of specimen movements. J. Struct. Biol. 152, 36–51 (2005).

  62. 62.

    Tang, G. et al. EMAN2: an extensible image processing suite for electron microscopy. J. Struct. Biol. 157, 38–46 (2007).

  63. 63.

    Frank, J. et al. SPIDER and WEB: processing and visualization of images in 3D electron microscopy and related fields. J. Struct. Biol. 116, 190–199 (1996).

  64. 64.

    Huson, D. H. et al. Dendroscope: an interactive viewer for large phylogenetic trees. BMC Bioinformatics 8, 460 (2007).

  65. 65.

    Hall, T. BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucleic Acids Symposium Series 41, 95–98 (1999).

  66. 66.

    Sarzotti-Kelsoe, M. et al. Optimization and validation of the TZM-bl assay for standardized assessments of neutralizing antibodies against HIV-1. J. Immunol. Methods 409, 131–146 (2014).

  67. 67.

    Otwinowski, Z. & Minor, W. Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol. 276, 307–326 (1997).

  68. 68.

    Emsley, P. & Cowtan, K. Coot: model-building tools for molecular graphics. Acta Crystallogr. D Biol. Crystallogr. 60, 2126–2132 (2004).

  69. 69.

    Adams, P. D. et al. Recent developments in the PHENIX software for automated crystallographic structure determination. J. Synchrotron Radiat. 11, 53–55 (2004).

  70. 70.

    Razinkov, I. et al. A new method for vitrifying samples for cryoEM. J. Struct. Biol. 195, 190–198 (2016).

  71. 71.

    Dandey, V. P. et al. Spotiton: New features and applications. J. Struct. Biol. 202, 161–169 (2018).

  72. 72.

    Wei, H. et al. Optimizing "self-wicking" nanowire grids. J. Struct. Biol. 202, 170–174 (2018).

  73. 73.

    Zheng, S.Q. et al. MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy. Nat. Methods 14, 331–332 (2017).

  74. 74.

    Zhang, K. Gctf: real-time CTF determination and correction. J. Struct. Biol. 193, 1–12 (2016).

  75. 75.

    Lander, G. C. et al. Appion: an integrated, database-driven pipeline to facilitate EM image processing. J. Struct. Biol. 166, 95–102 (2009).

  76. 76.

    Scheres, S. H. RELION: implementation of a Bayesian approach to cryo-EM structure determination. J. Struct. Biol. 180, 519–530 (2012).

  77. 77.

    Punjani, A., Rubinstein, J. L., Fleet, D. J. & Brubaker, M. A. cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination. Nat. Methods 14, 290–296 (2017).

  78. 78.

    Pettersen, E. F. et al. UCSF Chimera–a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605–1612 (2004).

  79. 79.

    Davis, I. W., Murray, L. W., Richardson, J. S. & Richardson, D. C. MOLPROBITY: structure validation and all-atom contact analysis for nucleic acids and their complexes. Nucleic Acids Res. 32, W615–W619 (2004).

  80. 80.

    Barad, B. A. et al. EMRinger: side chain-directed model and map validation for 3D cryo-electron microscopy. Nat. Methods 12, 943–946 (2015).

  81. 81.

    Jorgensen, W. L., Chandrasekhar, J., Madura, J. D., Impey, R. W. & Klein, M. L. Comparison of simple potential functions for simulating liquid water. J. Chem. Phys. 79, 926–935 (1983).

  82. 82.

    Georgiev, I. S. et al. Delineating antibody recognition in polyclonal sera from patterns of HIV-1 isolate neutralization. Science 340, 751–756 (2013).

  83. 83.

    Doria-Rose, N. A. et al. Mapping polyclonal HIV-1 antibody responses via next-generation neutralization fingerprinting. PLoS Pathog. 13, e1006148 (2017).

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We thank J. Chrzas, U. Chinte, Z. Jin, and staff at SER-CAT (Southeast Regional Collaborative Access Team) for help with X-ray diffraction data collection; B. DeKosky for suggestions on lineage discrimination, W. Rice and SEMC staff for assistance with cryo-EM data collection; and J. Stuckey for assistance with figures. We thank D. Burton and M. Fineberg (International AIDS Vaccine Initiative (IAVI), Neutralizing Antibody Consortium (NAC)) for antibodies, including PGT122 used in cryo-EM studies, B. Haynes (The Duke Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID)) for information on antibody CH07, R. Sanders (Academisch Medisch Centrum Universiteit van Amsterdam (AMC)) for information on antibody ACS202, B. Graham (Vaccine Research Center, NIAID, NIH) for murine antibody 5C4, and the WCMC/AMC/TSRI HIVRAD team for their contributions to the design and validation of near-native mimicry for soluble BG505 SOSIP.664 trimers. We thank members of the Structural Biology Section, Structural Bioinformatics Core Section, and Human Immunology Section of the Vaccine Research Center for helpful comments. Support for this work was provided by the Intramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health. This work was also supported in part by IAVI's NAC (J.R.M and P.D.K.) and with federal funds from the Frederick National Laboratory for Cancer Research, NIH, under contract HHSN261200800001E (Y.T.). I.S.G. received support from NIH grant R01 AI131722. Some of this work was performed at the Simons Electron Microscopy Center and National Resource for Automated Molecular Microscopy, located at the New York Structural Biology Center, supported by grants from the Simons Foundation (SF349247) NYSTAR, and the NIH National Institute of General Medical Sciences (GM103310), with additional support from Agouron Institute (F00316) and NIH (OD019994). Use of insertion device 22 (SER-CAT) at the Advanced Photon Source was supported by the US Department of Energy, Basic Energy Sciences, Office of Science, under contract W-31-109-Eng-38.

Author information

Author notes

  1. These authors contributed equally: Kai Xu, Priyamvada Acharya, Rui Kong, Cheng Cheng.


  1. Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA

    • Kai Xu
    • , Priyamvada Acharya
    • , Rui Kong
    • , Cheng Cheng
    • , Gwo-Yu Chuang
    • , Kevin Liu
    • , Mark K. Louder
    • , Sijy O’Dell
    • , Reda Rawi
    • , Mallika Sastry
    • , Chen-Hsiang Shen
    • , Baoshan Zhang
    • , Tongqing Zhou
    • , Mangaiarkarasi Asokan
    • , Robert T. Bailer
    • , Michael Chambers
    • , Xuejun Chen
    • , Chang W. Choi
    • , Nicole A. Doria-Rose
    • , Aliaksandr Druz
    • , S. Katie Farney
    • , Kathryn E. Foulds
    • , Hui Geng
    • , Jason Gorman
    • , Kurt R. Hill
    • , Alexander J. Jafari
    • , Young D. Kwon
    • , Yen-Ting Lai
    • , Krisha McKee
    • , Tiffany Y. Ohr
    • , Li Ou
    • , Dongjun Peng
    • , Ariana P. Rowshan
    • , John-Paul Todd
    • , Elise G. Viox
    • , Yiran Wang
    • , Yongping Yang
    • , Amy F. Zhou
    • , Diana G. Scorpio
    • , Adrian B. McDermott
    • , Lawrence Shapiro
    • , John R. Mascola
    •  & Peter D. Kwong
  2. National Resource for Automated Molecular Microscopy, Simons Electron Microscopy Center, New York Structural Biology Center, New York, NY, USA

    • Priyamvada Acharya
    • , Venkata P. Dandey
    • , Edward T. Eng
    • , Hui Wei
    • , Bridget Carragher
    •  & Clinton S. Potter
  3. Vanderbilt Vaccine Center, Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, and Department of Electrical Engineering and Computer Science, Vanderbilt University, Nashville, TN, USA

    • Ivelin S. Georgiev
  4. Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, USA

    • Thomas Lemmin
  5. Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA

    • Zizhang Sheng
    • , Lawrence Shapiro
    •  & Peter D. Kwong
  6. Department of Systems Biology, Columbia University, New York, NY, USA

    • Zizhang Sheng
    •  & Lawrence Shapiro
  7. Electron Microscopy Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA

    • Yaroslav Tsybovsky
  8. GenScript USA, Piscataway, NJ, USA

    • Rui Chen
    •  & Lu Yang


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K.X. conceived and led the project and determined crystal structures; P.A. determined cryo-EM structures; R.K. and N.A.D.-R. coordinated neutralization assessments; C.C. coordinated guinea pig and NHP immunization; G.-Y.C. coordinated statistical and bioinformatical analyses; K.L. prepared proteins and co-determined crystal structures; M.K.L. and R.T.B. assessed antibody neutralization in the large panel; C.-H.S. performed antibody sequence analyses; M.S. performed all Alanine–Glycine scans; B.Z. prepared antibodies for the large panel and performed various binding analyses; T.Z. performed SPR analyses, calculated the antibody's approach angle to the trimer, and made antibody neutralization dendrograms; M.A. performed antibody autoreactivity tests; I.S.G. performed antibody neutralization fingerprint analyses; T.L. performed molecular dynamics analyses; S.O’D., K.M., C.W.C., E.G.V., and A.P.R. co-performed neutralization assays; A.D., D.P., B.Z., and Y.Y. helped with protein expression; E.T.E., V.P.D., and H.W. helped with cryo-EM structures; X.C., H.G., J.G., M.S., and Y.D.K. performed protein purification; K.R.H., A.J.J., K.E.F., D.G.S., and J.-P.T. assisted in the NHP study; Y.-T.L. and Y.W. assisted with X-ray crystal dataset processing; B.Z., L.O., and M.C. helped with immunogen preparation and characterization; R.R. and S.K.F. performed statistical and bioinformatical analyses; Z.S. performed antibody gene comparisons; Y.T. performed negative-stain EM; T.Y.O. participated in immunogen binding tests; A.F.Z. helped with SPR assays; R.C. and L.Y. supervised the research team in GenScript; A.B.M. supervised MSD-based immunogen antigenicity characterization; L.S. supervised antibody gene analyses and comparison; B.C. and C.S.P. supervised cryo-EM studies; K.X., L.S., J.R.M., and P.D.K. wrote the manuscript; and all authors read, edited, and approved the manuscript. J.R.M. and P.D.K. conceived and supervised the study.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to John R. Mascola or Peter D. Kwong.

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