Dose-response curve slope helps predict therapeutic potency and breadth of HIV broadly neutralizing antibodies

Nature Communications

Volumn 6, Issue , 2015, Pages

  Webb, Nicholas E ^a   Montefiori, David C ^b   Lee, Benhur ^a,c  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b DUKE UNIVERSITY MEDICAL CENTER   (United States)

^c MOUNT SINAI SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIRETROVIRUS AGENT; BROADLY NEUTRALIZING ANTIBODY; CD4 IMMUNOGLOBULIN; EPITOPE; GLYCAN DERIVATIVE; GLYCOPROTEIN GP 41; NEUTRALIZING ANTIBODY; SOLUBLE CD4 ANTIGEN; UNCLASSIFIED DRUG; V2 GLYCAN; V3 GLYCAN;

ANTIBODY; CONCENTRATION (COMPOSITION); DIAGRAM; DISEASE TREATMENT; DOSE-RESPONSE RELATIONSHIP; HUMAN IMMUNODEFICIENCY VIRUS; PROTEIN;

ARTICLE; BINDING SITE; CONTROLLED STUDY; DOSE RESPONSE; DRUG POTENCY; HUMAN IMMUNODEFICIENCY VIRUS 1; IC50; IMMUNOTHERAPY; IN VITRO STUDY; VIREMIA; ANTIBODY SPECIFICITY; HUMAN IMMUNODEFICIENCY VIRUS; IMMUNOLOGY;

ANTIBODIES, NEUTRALIZING; ANTIBODY SPECIFICITY; CD4 IMMUNOADHESINS; DOSE-RESPONSE RELATIONSHIP, DRUG; HIV;

EID: 84942927293     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms9443     Document Type: Article

References (54)

1. Wu, X. et al. Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science 329, 856-861 (2010).
2. Balla-Jhagjhoorsingh, S. S. et al. The N276 glycosylation site is required for HIV-1 neutralization by the CD4 binding site specific HJ16 monoclonal antibody. PLoS ONE 8, e68863 (2013).
3. Scheid, J. F. et al. Sequence and structural convergence of broad and potent HIV antibodies that mimic CD4 binding. Science 333, 1633-1637 (2011).
4. Wu, X. et al. Focused evolution of HIV-1 neutralizing antibodies revealed by structures and deep sequencing. Science 333, 1593-1602 (2011).
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).
6. Walker, L. M. et al. Broad neutralization coverage of HIV by multiple highly potent antibodies. Nature 477, 466-470 (2011).
7. Mouquet, H. et al. Complex-type N-glycan recognition by potent broadly neutralizing HIV antibodies. Proc. Natl Acad. Sci. USA 109, E3268-E3277 (2012).
8. Bonsignori, M. et al. Analysis of a clonal lineage of HIV-1 envelope V2/V3 conformational epitope-specific broadly neutralizing antibodies and their inferred unmutated common ancestors. J. Virol. 85, 9998-10009 (2011).
9. Huang, J. et al. Broad and potent neutralization of HIV-1 by a gp41-specific human antibody. Nature 491, 406-412 (2012).
10. Muster, T. et al. A conserved neutralizing epitope on gp41 of human immunodeficiency virus type 1. J. Virol. 67, 6642-6647 (1993).
11. Zwick, M. B. et al. Broadly neutralizing antibodies targeted to the membraneproximal external region of human immunodeficiency virus type 1 glycoprotein gp41. J. Virol. 75, 10892-10905 (2001).
12. Scharf, L. et al. Antibody 8ANC195 reveals a site of broad vulnerability on the HIV-1 envelope spike. Cell Rep. 7, 785-795 (2014).
13. Falkowska, E. et al. Broadly neutralizing HIV antibodies define a glycandependent epitope on the prefusion conformation of gp41 on cleaved envelope trimers. Immunity 40, 657-668 (2014).
14. 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).
15. 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).
16. Kong, R. et al. improving neutralization potency and breadth by combining broadly reactive HIV-1 antibodies targeting major neutralization epitopes. J. Virol. 89, 2659-2671 (2015).
17. Burton, D. R. et al. A blueprint for HIV vaccine discovery. Cell Host Microbe 12, 396-407 (2012).
18. Mascola, J. R., Haynes, B. F. HIV-1 neutralizing antibodies: understanding nature's pathways. Immunol. Rev. 254, 225-244 (2013).
19. Klein, F. et al. HIV therapy by a combination of broadly neutralizing antibodies in humanized mice. Nature 492, 118-122 (2012).
20. Horwitz, J. A. et al. HIV-1 suppression and durable control by combining single broadly neutralizing antibodies and antiretroviral drugs in humanized mice. Proc. Natl Acad. Sci. USA 110, 16538-16543 (2013).
21. Klein, F. et al. Enhanced HIV-1 immunotherapy by commonly arising antibodies that target virus escape variants. J. Exp. Med. 211, 2361-2372 (2014).
22. Shingai, M. et al. Antibody-mediated immunotherapy of macaques chronically infected with SHIV suppresses viraemia. Nature 503, 277-280 (2013).
23. 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).
24. Caskey, M. et al. Viraemia suppressed in HIV-1-infected humans by broadly neutralizing antibody 3BNC117. Nature 522, 487-91 (2015).
25. Haaland, R. E. et al. Inflammatory genital infections mitigate a severe genetic bottleneck in heterosexual transmission of subtype A and C HIV-1. PLoS Pathog. 5, e1000274 (2009).
26. Abrahams, M.-R. et al. Quantitating the multiplicity of infection with human immunodeficiency virus type 1 subtype C reveals a non-poisson distribution of transmitted variants. J. Virol. 83, 3556-3567 (2009).
27. Li, H. et al. High multiplicity infection by HIV-1 in men who have sex with men. PLoS Pathog. 6, e1000890 (2010).
28. Shen, L. et al. Dose-response curve slope sets class-specific limits on inhibitory potential of anti-HIV drugs. Nat. Med. 14, 762-766 (2008).
29. Shen, L., Rabi, S. A., Siliciano, R. F. A novel method for determining the inhibitory potential of anti-HIV drugs. Trends Pharmacol. Sci. 30, 610-616 (2009).
30. Sampah, M. E. S., Shen, L., Jilek, B. L., Siliciano, R. F. Dose-response curve slope is a missing dimension in the analysis of HIV-1 drug resistance. Proc. Natl Acad. Sci. USA 108, 7613-7618 (2011).
31. Jilek, B. L. et al. A quantitative basis for antiretroviral therapy for HIV-1 infection. Nat. Med. 18, 446-451 (2012).
32. Laskey, S. B., Siliciano, R. F. A mechanistic theory to explain the efficacy of antiretroviral therapy. Nat. Rev. Microbiol. 12, 772-780 (2014).
33. Ketas, T. J., Holuigue, S., Matthews, K., Moore, J. P., Klasse, P. J. Envglycoprotein heterogeneity as a source of apparent synergy and enhanced cooperativity in inhibition of HIV-1 infection by neutralizing antibodies and entry inhibitors. Virology 422, 22-36 (2012).
34. deCamp, A. et al. Global panel of HIV-1 Env reference strains for standardized assessments of vaccine-elicited neutralizing antibodies. J. Virol. 88, 2489-2507 (2014).
35. Li, M. et al. Human immunodeficiency virus type 1 env clones from acute and early subtype B infections for standardized assessments of vaccine-elicited neutralizing antibodies. J. Virol. 79, 10108-10125 (2005).
36. Scanlan, C. N. et al. The broadly neutralizing anti-human immunodeficiency virus type 1 antibody 2G12 recognizes a cluster of alpha1-42 mannose residues on the outer face of gp120. J. Virol. 76, 7306-7321 (2002).
37. Chou, T. C., Talalay, P. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv. Enzyme Regul. 22, 27-55 (1984).
38. Doores, K. J., Burton, D. R. Variable loop glycan dependency of the broad and potent HIV-1-neutralizing antibodies PG9 and PG16. J. Virol. 84, 10510-10521 (2010).
39. Sok, D. et al. Promiscuous glycan site recognition by antibodies to the highmannose patch of gp120 broadens neutralization of HIV. Sci. Transl. Med. 6, 236-263 (2014).
40. Go, E. P. et al. Glycosylation site-specific analysis of HIV envelope proteins (JR-FL and CON-S) reveals major differences in glycosylation site occupancy, glycoform profiles, and antigenic epitopes' accessibility. J. Proteome Res. 7, 1660-1674 (2008).
41. Pritchard, L. K. et al. Glycan microheterogeneity at the PGT135 antibody recognition site on HIV-1 gp120 reveals a molecular mechanism for neutralization resistance. J. Virol. 89, 6952-6959 (2015).
42. Gardner, M. R. et al. AAV-expressed eCD4-Ig provides durable protection from multiple SHIV challenges. Nature 519, 87-91 (2015).
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. Mehandru, S. et al. Adjunctive passive immunotherapy in human immunodeficiency virus type 1-infected individuals treated with antiviral therapy during acute and early infection. J. Virol. 81, 11016-11031 (2007).
45. Manrique, A. et al. In vivo and in vitro escape from neutralizing antibodies 2G12, 2F5, and 4E10. J. Virol. 81, 8793-8808 (2007).
46. Trkola, A. et al. In vivo efficacy of human immunodeficiency virus neutralizing antibodies: estimates for protective titers. J. Virol. 82, 1591-1599 (2008).
47. Hoffman, A., Goldberg, A. The relationship between receptor-effector unit heterogeneity and the shape of the concentration-effect profile: pharmacodynamic implications. J. Pharmacokinet. Biopharm. 22, 449-468 (1994).
48. Crooks, E. T. et al. Characterizing anti-HIV monoclonal antibodies and immune sera by defining the mechanism of neutralization. Hum. Antibodies 14, 101-113 (2005).
49. Binley, J. M. et al. Redox-triggered infection by disulfide-shackled human immunodeficiency virus type 1 pseudovirions. J. Virol. 77, 5678-5684 (2003).
50. Montefiori, D. C. Measuring HIV neutralization in a luciferase reporter gene assay. Methods Mol. Biol. 485, 395-405 (2009).
51. Platt, E. J., Wehrly, K., Kuhmann, S. E., Chesebro, B., Kabat, D. Effects of CCR5 and CD4 cell surface concentrations on infections by macrophagetropic isolates of human immunodeficiency virus type 1. J. Virol. 72, 2855-2864 (1998).
52. Wei, X. et al. Emergence of resistant human immunodeficiency virus type 1 in patients receiving fusion inhibitor (T-20) monotherapy. Antimicrob. Agents Chemother. 46, 1896-1905 (2002).
53. 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).
54. Todd, C. A. et al. Development and implementation of an international proficiency testing program for a neutralizing antibody assay for HIV-1 in TZM-bl cells. J. Immunol. Methods 375, 57-67 (2012).