title: Improving the safety of a conditional-live human immunodeficiency virus type 1 vaccine by controlling both gene expression and cell entry.
abstract: Live attenuated human immunodeficiency virus type 1 (HIV-1) vaccines are considered unsafe because faster-replicating pathogenic virus variants may evolve after vaccination. We previously presented a conditional-live HIV-1 variant of which replication can be switched off as an alternative vaccination strategy. To improve the safety of such a vaccine, we constructed a new HIV-1 variant that depends not only on doxycycline for gene expression but also on the T20 peptide for cell entry. Replication of this virus can be limited to the level required to induce the immune system by transient administration of doxycycline and T20. Subsequent withdrawal of these inducers efficiently blocks viral replication and evolution.
authors.affiliation: Department of Human Retrovirology, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
authors.forename: Atze T
authors.initials: AT
authors.lastname: Das
authors.forename: Chris E
authors.initials: CE
authors.lastname: Baldwin
authors.forename: Monique
authors.initials: M
authors.lastname: Vink
authors.forename: Ben
authors.initials: B
authors.lastname: Berkhout
mesh_terms: D016915:AIDS Vaccines / Q000009:adverse effects; D004318:Doxycycline / Q000494:pharmacology*; D000077560:Enfuvirtide; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D015700:HIV Envelope Protein gp41 / Q000494:pharmacology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000502:physiology*; D006801:Humans; D009154:Mutation; D010446:Peptide Fragments / Q000494:pharmacology*; D011991:Receptors, Virus / Q000187:drug effects; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000009:adverse effects; D014779:Virus Replication / Q000187:drug effects
chemical_list: D016915:AIDS Vaccines; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; D011991:Receptors, Virus; D014613:Vaccines, Attenuated; D000077560:Enfuvirtide; D004318:Doxycycline
references.citation: Methods Enzymol. 2000;327:401-21
references.pmid: 11044999
references.citation: AIDS Clin Care. 2003 Nov;15(11):95-6
references.pmid: 14682275
references.citation: J Virol. 2001 Jan;75(2):979-87
references.pmid: 11134311
references.citation: Proc Natl Acad Sci U S A. 2001 May 22;98(11):6342-7
references.pmid: 11353837
references.citation: J Biol Chem. 2001 Aug 24;276(34):32184-90
references.pmid: 11397795
references.citation: J Virol. 2001 Nov;75(21):10187-99
references.pmid: 11581387
references.citation: J Virol. 2004 Feb;78(3):1080-92
references.pmid: 14722263
references.citation: GMHC Treat Issues. 2003 Dec;17(12):6
references.pmid: 15011643
references.citation: J Infect Dis. 2004 Mar 15;189(6):1075-83
references.pmid: 14999611
references.citation: J Biol Chem. 2004 Apr 30;279(18):18776-82
references.pmid: 14761948
references.citation: AIDS Rev. 2004 Jan-Mar;6(1):61
references.pmid: 15168742
references.citation: Methods Enzymol. 2004;388:359-79
references.pmid: 15289083
references.citation: Virology. 2004 Oct 10;328(1):1-6
references.pmid: 15380352
references.citation: J Virol. 2004 Nov;78(22):12428-37
references.pmid: 15507629
references.citation: AIDS Res Hum Retroviruses. 1992 Mar;8(3):411-21
references.pmid: 1571200
references.citation: Science. 1995 Mar 24;267(5205):1820-5
references.pmid: 7892606
references.citation: Lancet. 1995 May 27;345(8961):1342-4
references.pmid: 7752758
references.citation: Nat Med. 1998 Sep;4(9):982
references.pmid: 9734368
references.citation: J Virol. 1999 Feb;73(2):1138-45
references.pmid: 9882315
references.citation: Nat Med. 1999 Feb;5(2):194-203
references.pmid: 9930868
references.citation: J Virol. 2002 Mar;76(6):3084-8
references.pmid: 11861878
references.citation: Virus Res. 2002 Jan 30;82(1-2):103-8
references.pmid: 11885936
references.citation: Antimicrob Agents Chemother. 2002 Jun;46(6):1896-905
references.pmid: 12019106
references.citation: Curr Med Chem. 2003 Sep;10(17):1633-42
references.pmid: 12871113
references.citation: Expert Rev Vaccines. 2002 Oct;1(3):293-301
references.pmid: 12901570
references.citation: AIDS Res Hum Retroviruses. 2000 Oct 10;16(15):1453-61
references.pmid: 11054258