Evolution of Live-Attenuated HIV Vaccines - Safety concerns remain for developing replicating vectors based on the pathogen human immunodeficiency virus type 1. - BioPharm International

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Evolution of Live-Attenuated HIV Vaccines
Safety concerns remain for developing replicating vectors based on the pathogen human immunodeficiency virus type 1.


BioPharm International Supplements
Volume 24, pp. s4-s8

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24. Das AT, Zhou X, Vink M, Klaver B, Berkhout B. Conditional live virus as a novel approach towards a safe live attenuated HIV vaccine. Expert Rev Vaccines. 2002;1(3):293–301.

25. Das AT, Verhoef K, Berkhout B. A conditionally replicating virus as a novel approach toward an HIV vaccine. Methods Enzymol. 2004;388:359–79.

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28. Marzio G, Verhoef K, Vink M, Berkhout B. In vitro evolution of a highly replicating, doxycycline-dependent HIV for applications in vaccine studies. Proc Natl Acad Sci USA. 2001;98(11):6342–7.

29. Marzio G, Vink M, Verhoef K, de Ronde A, Berkhout B. Efficient human immunodeficiency virus replication requires a fine-tuned level of transcription. J Virol. 2002;76(6):3084–8.

30. Das AT, Zhou X, Vink M, Klaver B, Verhoef K, Marzio G, Berkhout B. Viral evolution as a tool to improve the tetracycline-regulated gene expression system. J Biol Chem. 2004;279(18):18776–82.

31. Zhou X, Vink M, Klaver B, Verhoef K, Marzio G, Das AT, Berkhout B. The genetic stability of a conditional-live HIV-1 variant can be improved by mutations in the Tet-On regulatory system that restrain evolution. J Biol Chem. 2006;281(25):17084–91.

32. Zhou X, Vink M, Klaver B, Berkhout B, Das AT. Optimization of the Tet-On system for regulated gene expression through viral evolution. Gene Ther. 2006;13(19):1382–90.

33. Zhou X, Vink M, Berkhout B, Das AT. Modification of the Tet-On regulatory system prevents the conditional-live HIV-1 variant from losing doxycycline-control. Retrovirol. 2006;3(1):82.

34. Das AT, Harwig A, Vrolijk MM, Berkhout B. The TAR hairpin of human immunodeficiency virus type-1 can be deleted when not required for Tat-mediated activation of transcription. J Virol. 2007;81(14):7742–8.

35. Kiselyeva Y, Ito Y, Lima RG, Grivel JC, Das AT, Berkhout B, Margolis LB. Depletion of CD4 T lymphocytes in human lymphoid tissue infected ex vivo with doxycycline-dependent HIV-1. Virol. 2004;10;328(1):1–6.

36. Das AT, Baldwin CE, Vink M, Berkhout B. Improving the safety of a conditional-live human immunodeficiency virus type 1 vaccine by controlling both gene expression and cell entry. J Virol. 2005;79(6):3855–8.

37. Baldwin CE, Sanders RW, Berkhout B. Inhibiting HIV-1 entry with fusion inhibitors. Curr Med Chem. 2003;10(17):1633–42.

38. Baldwin CE, Sanders RW, Deng Y, Jurriaans S, Lange JM, Lu M, Berkhout B. Emergence of a drug-dependent human immunodeficiency virus type 1 variant during therapy with the T20 fusion inhibitor. J Virol. 2004;78(22):12428–37.

39. Baldwin C, Berkhout B. Mechanistic studies on a T20-dependent HIV-1 variant. J Virol. 2008;82:7735–40.

40. Jeeninga RE, Jan B, Van der Linden B, Van den Berg H, Berkhout B. Construction of a minimal HIV-1 variant that selectively replicates in leukemic derived T-cell lines: towards a new virotherapy approach. Cancer Res. 2005;65(8):3347–55.

41. Jeeninga RE, Jan B, Van den Berg H, Berkhout B. Construction of doxycyline-dependent mini-HIV-1 variants for the development of a virotherapy against leukemias. Retrovirol. 2006;3:64.

42. Westerhout EM, Vink M, Haasnoot PC, Das AT, Berkhout B. A conditionally replicating HIV-based vector that stably expresses an antiviral shRNA against HIV-1 replication. Mol Ther. 2006;14(2):268–75.

43. Hacein-Bey-Abina S, Garrigue A, Wang GP, Soulier J, Lim A, Morillon E, et al. Insertional oncogenesis in 4 patients after retrovirus-mediated gene therapy of SCID-X1. J Clin Invest. 2008;118(9):3132–42.

44. Howe SJ, Mansour MR, Schwarzwaelder K, Bartholomae C, Hubank M, Kempski H, Brugman MH, Pike-Overzet K, Chatters SJ, de RD, et al. Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patients. J Clin Invest. 2008;118(9):3143–50.

45. Levine BL, Humeau LM, Boyer J, MacGregor RR, Rebello T, Lu X, et al. Gene transfer in humans using a conditionally replicating lentiviral vector. Proc Natl Acad Sci USA. 2006;103(46):17372–7.

46. Cartier N, Hacein-Bey-Abina S, Bartholomae CC, Veres G, Schmidt M, Kutschera I, et al. Hematopoietic stem cell gene therapy with a lentiviral vector in X-linked adrenoleukodystrophy. Science. 2009;326(5954):818–23.

47. Das AT, Klaver B, Harwig A, Vink M, Ooms M, Centlivre M, Berkhout B. Construction of a doxycycline-dependent simian immunodeficiency virus reveals a non-transcriptional function of Tat in viral replication. J Virol. 2007;81(20):11159–69.

48. An DS, Poon B, Ho Tsong FR, Weijer K, Blom B, Spits H, Chen IS, Uittenbogaart CH. Use of a novel chimeric mouse model with a functionally active human immune system to study human immunodeficiency virus type 1 infection. Clin Vaccine Immunol. 2007;14(4):391–6.

49. Ter Brake O, Legrand N, von Eije KJ, Centlivre M, Spits H, Weijer K, Blom B, Berkhout B. Evaluation of safety and efficacy of RNAi against HIV-1 in the human immune system (Rag-2(-/-)(c)(-/-)) mouse model. Gene Ther. 2009;16(1):148–53.


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