Improving the safety of a conditional-live human immunodeficiency virus type 1 vaccine by controlling both gene expression and cell entry.
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.
Das
Atze T
AT
Department of Human Retrovirology, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
Baldwin
Chris E
CE
Vink
Monique
M
Berkhout
Ben
B
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
D016915:AIDS Vaccines; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; D011991:Receptors, Virus; D014613:Vaccines, Attenuated; D000077560:Enfuvirtide; D004318:Doxycycline
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