Characterization of VRC01, a potent and broadly neutralizing anti-HIV mAb, produced in transiently and stably transformed tobacco

Plant Biotechnology Journal

Volumn 12, Issue 3, 2014, Pages 300-311

  Teh, Audrey Y H ^a   Maresch, Daniel ^b   Klein, Katja ^c   Ma, Julian K C ^a  

^a ST GEORGE'S UNIVERSITY OF LONDON   (United Kingdom)

^b UNIVERSITY OF NATURAL RESOURCES AND LIFE SCIENCES   (Austria)

^c IMPERIAL COLLEGE LONDON   (United Kingdom)

Author keywords

HIV 1 broadly neutralizing antibody; PTRAk.2; Stable transgenics; Transient expression; VRC01

Indexed keywords

HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS 1; MAMMALIA; NICOTIANA BENTHAMIANA; NICOTIANA TABACUM;

HUMAN IMMUNODEFICIENCY VIRUS ANTIBODY; MONOCLONAL ANTIBODY; NEUTRALIZING ANTIBODY; VRC01 MONOCLONAL ANTIBODY;

AMINO ACID SEQUENCE; ARTICLE; BIOSYNTHESIS; GENE EXPRESSION; GENETICS; GLYCOSYLATION; HIV-1 BROADLY NEUTRALIZING ANTIBODY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; IMMUNOLOGY; ISOLATION AND PURIFICATION; METABOLISM; MOLECULAR GENETICS; PROTEIN BINDING; PTRAK.2; STABLE TRANSGENICS; TOBACCO; TRANSFORMED CELL LINE; TRANSGENIC PLANT; TRANSIENT EXPRESSION; VRC01;

HIV-1 BROADLY NEUTRALIZING ANTIBODY; PTRAK.2; STABLE TRANSGENICS; TRANSIENT EXPRESSION; VRC01;

AMINO ACID SEQUENCE; ANTIBODIES, MONOCLONAL; ANTIBODIES, NEUTRALIZING; CELL LINE, TRANSFORMED; GENE EXPRESSION; GLYCOSYLATION; HIV ANTIBODIES; HIV-1; HUMANS; MOLECULAR SEQUENCE DATA; PLANTS, GENETICALLY MODIFIED; PROTEIN BINDING; TOBACCO;

EID: 84896545772     PISSN: 14677644     EISSN: 14677652     Source Type: Journal    
DOI: 10.1111/pbi.12137     Document Type: Article

References (66)

1. Arts, E.J. and Hazuda, D.J. (2012) HIV-1 Antiretroviral Drug Therapy. Cold Spring Harb. Perspect. Med. 2, a007161.
2. Barbaro, G. (2006) Metabolic and cardiovascular complications of highly active antiretroviral therapy for HIV infection. Curr. HIV Res. 4, 79-85.
3. Barbaro, G., Scozzafava, A., Mastrolorenzo, A. and Supuran, C.T. (2005) Highly active antiretroviral therapy: current state of the art, new agents and their pharmacological interactions useful for improving therapeutic outcome. Curr. Pharm. Des. 11, 1805-1843.
4. Bartlett, J.G. (2006) Ten Years of HAART: Foundation for the Future. http://www.medscape.org/viewarticle/523119. (accessed 03 April 2013).
5. Batard, Y., Hehn, A., Nedelkina, S., Schalk, M., Pallett, K., Schaller, H. and Werck-Reichhart, D. (2000) Increasing expression of P450 and P450-reductase proteins from monocots in heterologous systems. Arch. Biochem. Biophys. 379, 161-169.
6. Beck, A., Wurch, T., Bailly, C. and Corvaia, N. (2010) Strategies and challenges for the next generation of therapeutic antibodies. Nat. Rev. Immunol. 10, 345-352.
7. Caragea, C., Sinapov, J., Silvescu, A., Dobbs, D. and Honavar, V. (2007) Glycosylation site prediction using ensembles of Support Vector Machine classifiers. BMC Bioinformatics, 8, 438.
8. Castilho, A. and Steinkellner, H. (2012) Glyco-engineering in plants to produce human-like N-glycan structures. Biotechnol. J. 7, 1088-1098.
9. Castilho, A., Neumann, L., Gattinger, P., Strasser, R., Vorauer-Uhl, K., Sterovsky, T., Altmann, F. and Steinkellner, H. (2013) Generation of biologically active multi-sialylated recombinant human EPOFc in plants. PLoS ONE, 8, e54836.
10. Chen, W., Ying, T. and Dimitrov, D.S. (2013) Antibody-based candidate therapeutics against HIV-1: implications for virus eradication and vaccine design. Expert Opin. Biol. Ther. 13, 1-15.
11. Colgan, R., Atkinson, C.J., Paul, M.J., Hassan, S., Drake, P.M., Sexton, A.L., Santa-Cruz, S., James, D., Hamp, K., Gutteridge, C. and Ma, J.K.C. (2010) Optimization of contained Nicotiana tabacum cultivation for the production of recombinant protein pharmaceuticals. Transgenic Res. 19, 241-256.
12. Desai, P.N., Shrivastava, N. and Padh, H. (2010) Production of heterologous proteins in plants: strategies for optimal expression. Biotechnol. Adv. 28, 427-435.
13. Doria-Rose, N.A., Klein, R.M., Daniels, M.G., O'Dell, S., Nason, M., Lapedes, A., Bhattacharya, T., Migueles, S.A., Wyatt, R.T., Korber, B.T., Mascola, J.R. and Connors, M. (2010) Breadth of human immunodeficiency virus-specific neutralizing activity in sera: clustering analysis and association with clinical variables. J. Virol. 84, 1631-1636.
14. Edney, A. (2013) Protalix Wins FDA Approval for Its First Drug on the Market. http://www.bloomberg.com/news/2012-05-01/protalix-wins-fda-approval-for- its-first-drug-on-the-market.html. (accessed 04 March 2013).
15. EMEA. (2008) Guideline on the Quality of Biological Active Substance Produced by Stable Transgene Expression in Higher Plants EMA. London, UK: EMEA Committee for Proprietary Medicinal Products (CPMP).
16. Fischer, R., Schillberg, S., Hellwig, S., Twyman, R.M. and Drossard, J. (2012) GMP issues for recombinant plant-derived pharmaceutical proteins. Biotechnol. Adv. 30, 434-439.
17. Floss, D.M., Sack, M., Arcalis, E., Stadlmann, J., Quendler, H., Rademacher, T., Stoger, E., Scheller, J., Fischer, R. and Conrad, U. (2009) Influence of elastin-like peptide fusions on the quantity and quality of a tobacco-derived human immunodeficiency virus-neutralizing antibody. Plant Biotechnol. J. 7, 899-913.
18. Forthal, D.N., Gach, J.S., Landucci, G., Jez, J., Strasser, R., Kunert, R. and Steinkellner, H. (2010) Fc-Glycosylation influences Fcγ receptor binding and cell-mediated anti-HIV activity of monoclonal antibody 2G12. J. Immunol. 185, 6876-6882.
19. Gleba, Y., Klimyuk, V. and Marillonnet, S. (2007) Viral vectors for the expression of proteins in plants. Curr. Opin. Biotechnol. 18, 134-141.
20. Hamorsky, K.T., Grooms-Williams, T.W., Husk, A.S., Bennett, L.J., Palmer, K.E. and Matoba, N. (2013) Efficient single tobamoviral vector-based bioproduction of broadly neutralizing anti-HIV-1 monoclonal antibody VRC01 in Nicotiana plants and its utility in combination microbicides. Antimicrob. Agents Chemother. 57, 2076-2086.
21. Hehle, V.K., Paul, M.J., Drake, P.M., Ma, J.K.C. and van Dolleweerd, C.J. (2011) Antibody degradation in tobacco plants: a predominantly apoplastic process. BMC Biotechnol. 11, 128.
22. Hiatt, A., Caffferkey, R. and Bowdish, K. (1989) Production of antibodies in plants. Nature, 342, 76-78.
23. Hood, E.E., Woodard, S.L. and Horn, M.E. (2002) Monoclonal antibody manufacturing in transgenic plants - myths and realities. Curr. Opin. Biotechnol. 13, 630-635.
24. Horsch, R.B., Fry, J.E., Hoffmann, N.L., Eichholtz, D., Rogers, S.G. and Fraley, R.T. (1985) A simple and general method for transferring genes into plants. Science, 227, 1229-1231.
25. Kapila, J., De Rycke, R., Van Montagu, M. and Angenon, G. (1997) An Agrobacterium-mediated transient gene expression system for intact leaves. Plant Sci. 122, 101-108.
26. Kelley, B. (2009) Industrialization of mAb production technology the bioprocessing industry at a crossroads. mAbs, 1, 443-452.
27. Klein, F., Halper-Stromberg, A., Horwitz, J.A., Halper-Stromberg, A., Scheid, J.F., Bournazos, S., Mouquet, H., Spatz, L.A., Diskin, R., Abadir, A., Zang, T., Dorner, M., Billerbeck, E., Labitt, R.N., Gaebler, C., Marcovecchio, P.M., Incesu, R.-B., Eisenreich, T.R., Bieniasz, P.D., Seaman, M.S., Bjorkman, P.J., Ravetch, J.V., Ploss, A. and Nussenzweig, M.C. (2012) HIV therapy by a combination of broadly neutralizing antibodies in humanized mice. Nature, 492, 118-122.
28. Li, M., Gao, F., Mascola, J.R., Stamatatos, L., Polonis, V.R., Koutsoukos, M., Voss, G., Goepfert, P., Gilbert, P., Greene, K.M., Bilska, M., Kothe, D.L., Salazar-Gonzalez, J.F., Wei, X., Decker, J.M., Hahn, B.H. and Montefiori, D.C. (2005) 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.
29. Li, Y., Migueles, S.A., Welcher, B., Svehla, K., Phogat, A., Louder, M.K., Wu, X., Shaw, G.M., Connors, M., Wyatt, R.T. and Mascola, J.R. (2007) Broad HIV-1 neutralization mediated by CD4-binding site antibodies. Nat. Med. 13, 1032-1034.
30. Li, Y., Svehla, K., Louder, M.K., Wycuff, D., Phogat, S., Min, T., Migueles, S.A., Wu, X., Phogat, A., Shaw, G.M., Connors, M., Hoxie, J., Mascola, J.R. and Wyatt, R.T. (2009) Analysis of neutralization specificities in polyclonal sera derived from HUMAN immunodeficiency virus type 1-infected individuals. J. Virol. 83, 1045-1059.
31. Lopez, J.C., Khamsi, R., Dolgin, E., Grigoryev, Y., Jiang, K., Pola, C., Swami, M., Aranda, V., Basson, M., Chmielnicki, E., Da Silva, K., Farrell, A., Levinson, R., Boettner, B. and Gershon, D. (eds). (2013) Prevention measures. Nat. Med. 19, 247.
32. Marillonnet, S., Giritch, A., Gils, M., Kandzia, R., Klimyuk, V. and Gleba, Y. (2005) In planta engineering of viral RNA replicons: efficient assembly by recombination of DNA modules delivered by Agrobacterium. Proc. Natl Acad. Sci. USA, 101, 6852-6857.
33. May, M.T. and Ingle, S.M. (2011) Life expectancy of HIV-positive adults: a review. Sex. Health, 8, 526-533.
34. Montefiori, D.C. (2004) Evaluating neutralizing antibodies against HIV, SIV and SHIV in luciferase reporter gene assays. In: Current Protocols in Immunology, (Coligan, J.E., Kruisbeek, A.M., Margulies, D.H., Shevach, E.M., Strober, W. and Coico, R., eds), pp. 12.11.1-12.11.15. New York, NY: John Wiley & Sons.
35. Murashige, T. and Skoog, F. (1962) A revised medium for rapid growth and bioassays with tobacco culture. Physiol. Plant. 15, 473-497.
36. Nuttall, J., Vine, N., Hadlington, J.L., Drake, P., Frigerio, L. and Ma, J.K.C. (2002) ER-resident chaperone interactions with recombinant antibodies in transgenic plants. Eur. J. Biochem. 269, 6042-6051.
37. Overbaugh, J. and Morris, L. (2012) The antibody response against HIV-1. Cold Spring Harb. Perspec. Med. 2, a007039.
38. Pabst, M., Chang, M., Stadlmann, J. and Altmann, F. (2012) Glycan profiles of the 27 N-glycosylation sites of the HIV envelope protein CN54gp140. J. Biol. Chem. 393, 719-730.
39. Pachl, J., Svoboda, P., Jacobs, F., Vandewoude, K., van der Hoven, B., Spronk, P., Masterson, G., Malbrain, M., Aoun, M., Garbino, J., Takala, J., Drgona, L., Burnie, J., Matthews, R. and Group, M.I.C.S. (2006) A Randomized, Blinded, Multicenter Trial of Lipid-Associated Amphotericin B Alone versus in Combination with an Antibody-Based Inhibitor of Heat Shock Protein 90 in Patients with Invasive Candidiasis. Clin. Infect. Dis. 42, 1404-1413.
40. Pegu, A., Yang, Z.-Y., Chen, X., Todd, J.-P., McKee, K., Rao, S., Mascola, J.R. and Nabel, G. (2011) VRC01 provides sterilizing protection to non human primates from mucosal SHIV challenges. J. Immunol. 186, 155.111.
41. Pirrone, V., Thakkar, N., Jacobson, J.M., Wigdahl, B. and Krebs, F.C. (2011) Combinatorial approaches to the prevention and treatment of HIV-1 infection. Antimicrob. Agents Chemother. 55, 1831-1842.
42. Rosenberg, Y., Sack, M., Montefiori, D., Forthal, D., Mao, L., Hernandez-Abanto, S., Urban, L., Landucci, G., Fischer, R. and Jiang, X. (2013) Rapid high-level production of functional HIV broadly neutralizing monoclonal Antibodies in transient plant expression systems. PLoS ONE, 8, e58724.
43. Rouwendal, G.J.A., Mendes, O., Wolbert, E.J.H. and de Boer, D. (1997) Enhanced expression in tobacco of the gene encoding green fluorescent protein by modification of its codon usage. Plant Mol. Biol. 33, 989-999.
44. Rusconi, S., Scozzafava, A., Mastrolorenzo, A. and Supuran, C.T. (2007) An update in the development of HIV entry inhibitors. Curr. Top. Med. Chem. 7, 1273-1289.
45. Sack, M., Paetz, A., Kunert, R., Bomble, M., Hesse, F., Stiegler, G., Fischer, R., Katinger, H., Stoeger, E. and Rademacher, T. (2007) Functional analysis of the broadly neutralizing human anti-HIV-1 antibody 2F5 produced in transgenic BY-2 suspension cultures. FASEB J. 21, 1655-1664.
46. Sainsbury, F. and Lomonossoff, G. (2008) Extremely high-level and rapid transient protein production in plants without the use of viral replication. Plant Physiol. 148, 1212-1218.
47. Sainsbury, F., Thuenemann, E.C. and Lomonossoff, G.P. (2009) pEAQ: versatile expression vectors for easy and quick transient expression of heterologous proteins in plants. Plant Biotechnol. J. 7, 682-693.
48. Sainsbury, F., Sack, M., Stadlmann, J., Quendler, H., Fischer, R. and Lomonossoff, G.P. (2010) Rapid transient production in plants by replicating and non-replicating vectors yields high quality functional anti-HIV antibody. PLoS ONE, 5, e13976.
49. Scott, A.M., Wolchok, J.D. and Old, L.J. (2012) Antibody therapy of cancer. Nat. Rev. Cancer, 12, 278-287.
50. Shattock, R.J. and Rosenberg, Z. (2012) Microbicides: topical prevention against HIV. Cold Spring Harb. Perspect. Med. 2, a007385.
51. Simek, M.D., Rida, W., Priddy, F.H., Pung, P., Carrow, E., Laufer, D.S., Lehrman, J.K., Boaz, M., Tarragona-Fiol, T., Miiro, G., Birungi, J., Pozniak, A., McPhee, D.A., Manigart, O., Karita, E., Inwoley, A., Jaoko, W., DeHovitz, J., Bekker, L.-G., Pitisuttithum, P., Paris, R., Walker, L.M., Poignard, P., Wrin, T., Fast, P.E., Burton, D.R. and Koff, W.C. (2009) 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.
52. Strasser, R., Stadlmann, J., Schahs, M., Stiegler, G., Quendler, H., Mach, L., Glossl, J., Weterings, K., Pabst, M. and Steinkellner, H. (2008) Generation of glyco-engineered Nicotiana benthamiana for the production of monoclonal antibodies with a homogeneous human-like N-glycan structure. Plant Biotechnol. J. 6, 392-402.
53. Strasser, R., Castilho, A., Stadlmann, J., Kunert, R., Quendler, H., Gattinger, P., Jez, J., Rademacher, T., Altmann, F. and Mach, L. (2009) Improved virus neutralization by plant-produced anti-HIV antibodies with a homogeneous β1, 4-galactosylated N-glycan profile. J. Biol. Chem. 284, 20479-20485.
54. UN. (2011) Political Declaration on HIV/AIDS: Intensifying our Efforts to Eliminate HIV/AIDS. http://daccess-dds-ny.un.org/doc/UNDOC/LTD/N11/367/84/PDF/N1136784.pdf?O penElement. (accessed 04 March 2012).
55. UNAIDS. (2012) Global Report: UNAIDS Report on the Global AIDS Epidemic 2012.
56. Veselinovic, M., Preston Neff, C., Mulder, L.R. and Akkina, R. (2012) Topical gel formulation of broadly neutralizing anti-HIV-1 monoclonal antibody VRC01 confers protection against HIV-1 vaginal challenge in a humanized mouse model. Virology, 432, 505-510.
57. Wadman, M. (2013) HIV trial under scrutiny. Nature, 493, 279-280.
58. Wei, X., Decker, J.M., Wang, S., Hui, H., Kappes, J.C., Wu, X., Salazar-Gonzalez, J.F., Salazar, M.G., Kilby, J.M., Saag, M.S., Komarova, N.L., Nowak, M.A., Hahn, B.H., Kwong, P.D. and Shaw, G.M. (2003) Antibody neutralization and escape by HIV-1. Nature, 422, 307-312.
59. WHO. (2006) Antiretroviral Therapy for HIV Infection in Adults and Adolescents: Recommendations for a Public Health Approach. (Gilks, C. and Vitoria, A., eds), 128 pp. http://www.who.int/hiv/pub/guidelines/artadultguidelines.pdf. (accessed 03 April 2013).
60. WHO. (2008) The Top 10 Causes of Death-WHO Fact Sheet No. 310. http://who.int/mediacentre/factsheets/fs310/en/. (accessed 03 April 2013).
61. WHO. (2012a) Antiretroviral Treatment as Prevention (TASP) of HIV and TB: Programmatic Update. http://whqlibdoc.who.int/hq/2012/WHO_HIV_2012.12_eng.pdf. (accessed 04 March 2013).
62. WHO (2012b) Guidance on Oral pre-Exposure prophylaxis (PrEP) for Serodiscordant Couples, Men and Transgender Women who have Sex with Men at High Risk of HIV.
63. WHO and ILO. (2007) Post-exposure Prophylaxis to Prevent HIV Infection: Joint WHO/ILO Guidelines on Post-exposure Prophylaxis (PEP) to Prevent HIV Infection.
64. WHO, UNAIDS and UNICEF. (2007) Towards Universal Access: Scaling up Priority HIV/AIDS Interventions in the Health Sector (progress report). http://www.who.int/hiv/mediacentre/universal_access_progress_report_en.p df. (accessed 04 March 2013).
65. Wu, X., Yang, Z.Y., Li, Y., Hogerkorp, C.M., Schief, W.R., Seaman, M.S., Zhou, T., Schmidt, S.D., Wu, L., Xu, L., Longo, N.S., McKee, K., O'Dell, S., Louder, M.K., Wycuff, D.L., Feng, Y., Nason, M., Doria-Rose, N., Connors, M., Kwong, P.D., Roederer, M., Wyatt, R.T., Nabel, G.J. and Mascola, J.R. (2010) Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science, 329, 856-861.
66. Zhou, T., Georgiev, I., Wu, X., Yang, Z.Y., Dai, K., Finzi, A., Kwon, Y.D., Scheid, J.F., Shi, W., Xu, L., Yang, Y., Zhu, J., Nussenzweig, M.C., Sodroski, J., Shapiro, L., Nabel, G.J., Mascola, J.R. and Kwong, P.D. (2010) Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01. Science, 329, 811-817.