Initiation of HIV neutralizing B cell lineages with sequential envelope immunizations

Nature Communications

Volumn 8, Issue 1, 2017, Pages

  Williams, Wilton B ^a   Zhang, Jinsong ^a   Jiang, Chuancang ^a   Nicely, Nathan I ^a   Fera, Daniela ^b   Luo, Kan ^a   Moody, M Anthony ^a   Liao, Hua Xin ^a,g   Alam, S Munir ^a   Kepler, Thomas B ^c   Ramesh, Akshaya ^c   Wiehe, Kevin ^a   Holland, James A ^a   Bradley, Todd ^a   Vandergrift, Nathan ^a   Saunders, Kevin O ^a   Parks, Robert ^a   Foulger, Andrew ^a   Xia, Shi Mao ^a   Bonsignori, Mattia ^a   Montefiori, David C ^a   Louder, Mark ^d   Eaton, Amanda ^a   Santra, Sampa ^b   Scearce, Richard ^a   Sutherland, Laura ^a   Newman, Amanda ^a   Bouton Verville, Hilary ^a   Bowman, Cindy ^a   Bomze, Howard ^a   Gao, Feng ^a   Marshall, Dawn J ^a   Whitesides, John F ^a,h   Nie, Xiaoyan ^a   Kelsoe, Garnett ^a   Reed, Steven G ^e   Fox, Christopher B ^e   Clary, Kim ^e   Koutsoukos, Marguerite ^f   Franco, David ^f   Mascola, John R ^d   Harrison, Stephen C ^b   Haynes, Barton F ^a   Verkoczy, Laurent ^a   more..

^a DUKE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b BOSTON CHILDREN S HOSPITAL   (United States)

^c BOSTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

^e INFECTIOUS DISEASE RESEARCH INSTITUTE   (United States)

^f GSK   (Belgium)

^g JINAN UNIVERSITY   (China)

^h WAKE FOREST SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 CYCLOHEXYLAMINO 1 (1 NAPHTHYLOXY) 2 BUTANOL; CD4 ANTIGEN; CH505 VACCINE; HUMAN IMMUNODEFICIENCY VIRUS VACCINE; UNCLASSIFIED DRUG; HUMAN IMMUNODEFICIENCY VIRUS ANTIBODY; NEUTRALIZING ANTIBODY; VIRUS ENVELOPE PROTEIN;

ANTIBODY; CELLS AND CELL COMPONENTS; COMMON ANCESTRY; HUMAN IMMUNODEFICIENCY VIRUS; IMMUNE RESPONSE; IMMUNIZATION; INFECTIOUS DISEASE; PROTEIN; VACCINATION; VACCINE;

ALLELE; ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; BINDING SITE; CELL LINEAGE; CELL MATURATION; CELL SELECTION; CONTROLLED STUDY; DEVELOPMENTAL STAGE; ENZYME LINKED IMMUNOSORBENT ASSAY; FEMALE; FLOW CYTOMETRY; HUMAN IMMUNODEFICIENCY VIRUS 1; IMMUNOGENETICS; IMMUNOGENICITY; IMMUNOLOGICAL TOLERANCE; LIGHT CHAIN; MALE; MEMORY CELL; MOUSE; NONHUMAN; PHENOTYPE; PRE B LYMPHOCYTE; RHESUS MONKEY; VACCINATION; ANIMAL; ANTIBODY COMBINING SITE; B LYMPHOCYTE; BIOSYNTHESIS; CHEMISTRY; CLONAL ANERGY; CYTOLOGY; GENE KNOCK-IN; GENETICS; HUMAN; IMMUNIZATION; IMMUNOLOGY; METABOLISM; MOLECULAR MODEL; PROCEDURES; TRANSGENIC MOUSE;

HUMAN IMMUNODEFICIENCY VIRUS 1; MUS;

AIDS VACCINES; ANIMALS; ANTIBODIES, NEUTRALIZING; B-LYMPHOCYTES; BINDING SITES, ANTIBODY; CD4 ANTIGENS; CELL LINEAGE; CLONAL ANERGY; ENV GENE PRODUCTS, HUMAN IMMUNODEFICIENCY VIRUS; FEMALE; GENE KNOCK-IN TECHNIQUES; HIV ANTIBODIES; HIV-1; HUMANS; IMMUNE TOLERANCE; IMMUNIZATION; MACACA MULATTA; MALE; MICE; MICE, TRANSGENIC; MODELS, MOLECULAR;

EID: 85034965352     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/s41467-017-01336-3     Document Type: Article

References (79)

1. Mascola, J. R. & Haynes, B. F. HIV-1 neutralizing antibodies: understanding nature's pathways. Immunol. Rev. 254, 225-244 (2013).
2. Sanders, R. W. et al. HIV-1 vaccines. HIV-1 neutralizing antibodies induced by native-like envelope trimers. Science 349, aac4223 (2015).
3. Williams, W. B. et al. HIV-1 vaccines. Diversion of HIV-1 vaccine-induced immunity by gp41-microbiota cross-reactive antibodies. Science 349, aab1253 (2015).
4. Haynes, B. F. et al. Immune-correlates analysis of an HIV-1 vaccine efficacy trial. N. Engl. J. Med. 366, 1275-1286 (2012).
5. Havenar-Daughton, C. et al. Direct probing of germinal center responses reveals immunological features and bottlenecks for neutralizing antibody responses to HIV Env trimer. Cell Rep. 17, 2195-2209 (2016).
6. Liao, H. X. et al. Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus. Nature 496, 469-476 (2013).
7. Doria-Rose, N. A. et al. Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies. Nature 509, 55-62 (2014).
8. Gao, F. et al. Cooperation of B cell lineages in induction of HIV-1-broadly neutralizing antibodies. Cell 158, 481-491 (2014).
9. Tian, M. et al. Induction of HIV neutralizing antibody lineages in mice with diverse precursor repertoires. Cell 166, 1471-1484.e18 (2016).
10. Jardine, J. G. et al. HIV-1 vaccines. Priming a broadly neutralizing antibody response to HIV-1 using a germline-targeting immunogen. Science 349, 156-161 (2015).
11. Jardine, J. G. et al.HIV-1 broadly neutralizing antibody precursor B cells revealed by germline-targeting immunogen. Science 351, 1458-1463 (2016).
12. Escolano, A. et al. Sequential immunization elicits broadly neutralizing anti-HIV-1 antibodies in Ig knockin mice. Cell 166, 1445-1458.e12 (2016).
13. Briney, B. et al. Tailored immunogens direct affinity maturation toward HIV neutralizing antibodies. Cell 166, 1459-1470.e11 (2016).
14. Verkoczy, L. 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. 191, 2538-2550 (2013).
15. Dosenovic, P. et al. Immunization for HIV-1 broadly neutralizing antibodies in human Ig knockin mice. Cell 161, 1505-1515 (2015).
16. Verkoczy, L. et al.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 (2011).
17. McGuire, A. T. et al. Specifically modified Env immunogens activate B-cell precursors of broadly neutralizing HIV-1 antibodies in transgenic mice. Nat. Commun. 7, 10618 (2016).
18. Chen, Y. et al. 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 (2013).
19. Zhang, R. et al.Initiation of immune tolerance-controlled HIV gp41 neutralizing B cell lineages. Sci. Transl. Med. 8, 336ra62 (2016).
20. Bonsignori, M. et al. Maturation pathway from germline to broad HIV-1 neutralizer of a CD4-mimic antibody. Cell. https://doi.org/10.1016/j.cell.2016.02.022 (2016).
21. Stewart-Jones, G. B. et al. Trimeric HIV-1-Env structures define glycan shields from clades A, B, and G. Cell 165, 813-826, https://doi.org/10.1016/j.cell.2016.04.010 (2016).
22. Zhou, T. et al. Quantification of the impact of the HIV-1-glycan shield on antibody elicitation. Cell Rep. 19, 719-732, https://doi.org/10.1016/j.celrep.2017.04.013 (2017).
23. Huang, C. C. et al. Structural basis of tyrosine sulfation and VH-gene usage in antibodies that recognize the HIV type 1 coreceptor-binding site on gp120. Proc. Natl Acad. Sci. USA 101, 2706-2711, https://doi.org/10.1073/pnas.0308527100 (2004).
24. Huang, C. C. et al. Structures of the CCR5 N terminus and of a tyrosine-sulfated antibody with HIV-1 gp120 and CD4. Science 317, 1930-1934, https://doi.org/10.1126/science.1145373 (2007).
25. Kwong, P. D. et al. Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature 393, 648-659, https://doi.org/10.1038/31405 (1998).
26. Kwong, P. D. et al. Structures of HIV-1 gp120 envelope glycoproteins from laboratory-adapted and primary isolates. Structure 8, 1329-1339 (2000).
27. Chen L. et al. Structural basis of immune evasion at the site of CD4 attachment on HIV-1 gp120. Science 326, 1123-1127, https://doi.org/10.1126/science.1175868 (2009).
28. Kwon, Y. D. et al. Crystal structures of HIV-1 gp120 envelope glycoprotein in complex with NBD analogues that target the CD4-binding site. PLoS ONE 9, e85940, https://doi.org/10.1371/journal.pone.0085940 (2014).
29. Liu, M. et al. Polyreactivity and autoreactivity among HIV-1 antibodies. J. Virol. 89, 784-798, https://doi.org/10.1128/JVI.02378-14 (2015).
30. Gay, D., Saunders, T., Camper, S. & Weigert, M. Receptor editing: an approach by autoreactive B cells to escape tolerance. J. Exp. Med. 177, 999-1008 (1993).
31. Goodnow, C. C., Brink, R. & Adams, E. Breakdown of self-tolerance in anergic B lymphocytes. Nature 352, 532-536, https://doi.org/10.1038/352532a0 (1991).
32. Cambier, J. C., Gauld, S. B., Merrell, K. T. & Vilen, B. J. B-cell anergy: from transgenic models to naturally occurring anergic B cells? Nat. Rev. Immunol. 7, 633-643, https://doi.org/10.1038/nri2133 (2007).
33. Acevedo-Suárez, C. A., Kilkenny, D. M., Reich, M. B. & Thomas, J. W. Impaired intracellular calcium mobilization and NFATc1 availability in tolerant anti-insulin B cells. J. Immunol. 177, 2234-2241 (2006).
34. Sabouri, Z. et al. Redemption of autoantibodies on anergic B cells by variable-region glycosylation and mutation away from self-reactivity. Proc. Natl Acad. Sci. USA 111, E2567-E2575, https://doi.org/10.1073/pnas.1406974111 (2014).
35. Dal Porto, J. M., Haberman, A. M., Shlomchik, M. J. & Kelsoe, G. Antigen drives very low affinity B cells to become plasmacytes and enter germinal centers. J. Immunol. 161, 5373-5381 (1998).
36. Haynes, B. F. & Verkoczy, L. AIDS/HIV. Host controls of HIV neutralizing antibodies. Science 344, 588-589, https://doi.org/10.1126/science.1254990 (2014).
37. Haynes, B. F. et al. HIV-host interactions: implications for vaccine design. Cell Host Microbe 19, 292-303, https://doi.org/10.1016/j.chom.2016.02.002 (2016).
38. Ota, T. et al. B cells from knock-in mice expressing broadly neutralizing HIV antibody b12 carry an innocuous B cell receptor responsive to HIV vaccine candidates. J. Immunol. 191, 3179-3185, https://doi.org/10.4049/jimmunol.1301283 (2013).
39. Doyle-Cooper, C. et al. Immune tolerance negatively regulates B cells in knock-in mice expressing broadly neutralizing HIV antibody 4E10. J. Immunol. 191, 3186-3191, https://doi.org/10.4049/jimmunol.1301285 (2013).
40. McGuire, A. T. et al. HIV antibodies. Antigen modification regulates competition of broad and narrow neutralizing HIV antibodies. Science 346, 1380-1383, https://doi.org/10.1126/science.1259206 (2014).
41. Luzina, I. G. et al. Spontaneous formation of germinal centers in autoimmune mice. J. Leukoc. Biol. 70, 578-584 (2001).
42. Grimsholm, O. et al. Absence of surrogate light chain results in spontaneous autoreactive germinal centres expanding V(H)81X-expressing B cells. Nat. Commun. 6, 7077, https://doi.org/10.1038/ncomms8077 (2015).
43. Cappione, A. et al. Germinal center exclusion of autoreactive B cells is defective in human systemic lupus erythematosus. J. Clin. Invest. 115, 3205-3216, https://doi.org/10.1172/JCI24179 (2005).
44. Yang, G. et al. Identification of autoantigens recognized by the 2F5 and 4E10 broadly neutralizing HIV-1 antibodies. J. Exp. Med. 210, 241-256, https://doi.org/10.1084/jem.20121977 (2013).
45. Chen, L. et al. Structural basis of immune evasion at the site of CD4 attachment on HIV-1 gp120. Science 326, 1123-1127, https://doi.org/10.1126/science.1175868 (2009).
46. Zhou, T. et al. Structural definition of a conserved neutralization epitope on HIV-1 gp120. Nature 445, 732-737, https://doi.org/10.1038/nature05580 (2007).
47. Doores, K. J. et al. Envelope glycans of immunodeficiency virions are almost entirely oligomannose antigens. Proc. Natl Acad. Sci. USA 107, 13800-13805, https://doi.org/10.1073/pnas.1006498107 (2010).
48. Li, J. et al. HIV/SIV DNA vaccine combined with protein in a co-immunization protocol elicits highest humoral responses to envelope in mice and macaques. Vaccine 31, 3747-3755, https://doi.org/10.1016/j.vaccine.2013.04.037 (2013).
49. Beck, Z. et al. Differential immune responses to HIV-1 envelope protein induced by liposomal adjuvant formulations containing monophosphoryl lipid A with or without QS21. Vaccine 33, 5578-5587, https://doi.org/10.1016/j.vaccine.2015.09.001 (2015).
50. Alam, S. M. et al. Antigenicity and immunogenicity of RV144 vaccine AIDSVAX clade E envelope immunogen is enhanced by a gp120 N-terminal deletion. J. Virol. 87, 1554-1568, https://doi.org/10.1128/JVI.00718-12 (2013).
51. Bradley, T. et al. Pentavalent HIV-1 vaccine protects against simian-human immunodeficiency virus challenge. Nat. Commun. 8, 15711, https://doi.org/10.1038/ncomms15711 (2017).
52. Liao, H. X. et al. High-throughput isolation of immunoglobulin genes from single human B cells and expression as monoclonal antibodies. J. Virol. Methods 158, 171-179, https://doi.org/10.1016/j.jviromet.2009.02.014 (2009).
53. Smith, K. et al. Rapid generation of fully human monoclonal antibodies specific to a vaccinating antigen. Nat. Protoc. 4, 372-384, https://doi.org/10.1038/nprot.2009.3 (2009).
54. Kepler, T. B. et al. Reconstructing a B-cell clonal lineage. II. Mutation, selection, and affinity maturation. Front. Immunol. 5, 170, https://doi.org/10.3389/fimmu.2014.00170 (2014).
55. Volpe, J. M., Cowell, L. G. & Kepler, T. B. SoDA: implementation of a 3D alignment algorithm for inference of antigen receptor recombinations. Bioinformatics 22, 438-444, https://doi.org/10.1093/bioinformatics/btk004 (2006).
56. Ewing, B., Hillier, L., Wendl, M. C. & Green, P. Base-calling of automated sequencer traces using phred. I. Accuracy assessment. Genome Res. 8, 175-185 (1998).
57. Tiller, T., Busse, C. E. & Wardemann, H. Cloning and expression of murine Ig genes from single B cells. J. Immunol. Methods 350, 183-193, https://doi.org/10.1016/j.jim.2009.08.009 (2009).
58. Wang, Z. et al. Universal PCR amplification of mouse immunoglobulin gene variable regions: the design of degenerate primers and an assessment of the effect of DNA polymerase 3′ to 5′ exonuclease activity. J. Immunol. Methods 233, 167-177 (2000).
59. Verkoczy, L. et al. Autoreactivity in an HIV-1 broadly reactive neutralizing antibody variable region heavy chain induces immunologic tolerance. Proc. Natl Acad. Sci. USA 107, 181-186, https://doi.org/10.1073/pnas.0912914107 (2010).
60. Liang, X., Jensen, K. & Frank-Kamenetskii, M. D. Very efficient template/primer-independent DNA synthesis by thermophilic DNA polymerase in the presence of a thermophilic restriction endonuclease. Biochemistry 43, 13459-13466, https://doi.org/10.1021/bi0489614 (2004).
61. 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, https://doi.org/10.1016/j.immuni.2012.11.011 (2013).
62. Lynch, R. M. et al. The development of CD4 binding site antibodies during HIV-1 infection. J. Virol. 86, 7588-7595, https://doi.org/10.1128/JVI.00734-12 (2012).
63. Montefiori, D. C. et al. Magnitude and breadth of the neutralizing antibody response in the RV144 and Vax003 HIV-1 vaccine efficacy trials. J. Infect. Dis. 206, 431-441, https://doi.org/10.1093/infdis/jis367 (2012).
64. 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, https://doi.org/10.1128/JVI.02108-09 (2010).
65. Nicely, N. I. et al. Crystal structure of a non-neutralizing antibody to the HIV-1 gp41 membrane-proximal external region. Nat. Struct. Mol. Biol. 17, 1492-1494, https://doi.org/10.1038/nsmb.1944 (2010).
66. Liao, H. X. et al. A group M consensus envelope glycoprotein induces antibodies that neutralize subsets of subtype B and C HIV-1 primary viruses. Virology 353, 268-282 (2006).
67. Kong, L., Wilson, I. A. & Kwong, P. D. Crystal structure of a fully glycosylated HIV-1 gp120 core reveals a stabilizing role for the glycan at Asn262. Proteins 83, 590-596, https://doi.org/10.1002/prot.24747 (2015).
68. Otwinowski, Z. & Minor, W. Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol. 276, 307-326 (1997).
69. Terwilliger, T. C. et al. Iterative model building, structure refinement and density modification with the PHENIX AutoBuild wizard. Acta Crystallogr. D Biol. Crystallogr. 64(Pt 1): 61-69, https://doi.org/10.1107/S090744490705024X (2008).
70. Fera, D. et al. Affinity maturation in an HIV broadly neutralizing B-cell lineage through reorientation of variable domains. Proc. Natl Acad. Sci. USA 111, 10275-10280, https://doi.org/10.1073/pnas.1409954111 (2014).
71. Guan, Y. et al. Diverse specificity and effector function among human antibodies to HIV-1 envelope glycoprotein epitopes exposed by CD4 binding. Proc. Natl Acad. Sci. USA 110, E69-E78, https://doi.org/10.1073/pnas.1217609110 (2013).
72. Acharya, P. et al. Structural definition of an antibody-dependent cellular cytotoxicity response implicated in reduced risk for HIV-1 infection. J. Virol. 88, 12895-12906, https://doi.org/10.1128/JVI.02194-14 (2014).
73. Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D Biol. Crystallogr. 66(Pt 4): 486-501, https://doi.org/10.1107/S0907444910007493 (2010).
74. Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D Biol. Crystallogr. 66(Pt 2): 213-221, https://doi.org/10.1107/S0907444909052925 (2010).
75. Lovell, S. C. et al. Structure validation by Calpha geometry: phi, psi and Cbeta deviation. Proteins 50, 437-450, https://doi.org/10.1002/prot.10286 (2003).
76. Sanders, R. W. et al. A next-generation cleaved, soluble HIV-1 Env trimer, BG505 SOSIP.664gp140, expresses multiple epitopes for broadly neutralizing but not non-neutralizing antibodies. PLoS Pathog. 9, e1003618, https://doi.org/10.1371/journal.ppat.1003618 (2013).
77. Tang, G. et al. EMAN2: an extensible image processing suite for electron microscopy. J. Struct. Biol. 157, 38-46, https://doi.org/10.1016/j.jsb.2006.05.009 (2007).
78. Liu, J., Bartesaghi, A., Borgnia, M. J., Sapiro, G. & Subramaniam, S. Molecular architecture of native HIV-1 gp120 trimers. Nature 455, 109-113, https://doi.org/10.1038/nature07159 (2008).
79. Pettersen, E. F. et al. UCSF Chimera-a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605-1612, https://doi.org/10.1002/jcc.20084 (2004).