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What can we learn from diverse spectrum of HIV/SIV infections?

Lecture at Academia Sinica 06 th October 2010 - Taiwan. What can we learn from diverse spectrum of HIV/SIV infections?. Françoise BARR É-SINOUSSI Regulation of Retroviral Infections Unit Department of Virology. Main milestones in 27 years of research on HIV. HIV biology and pathogenesis.

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What can we learn from diverse spectrum of HIV/SIV infections?

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  1. Lecture at Academia Sinica 06th October 2010 - Taiwan What can we learn from diverse spectrum of HIV/SIV infections? Françoise BARRÉ-SINOUSSI Regulation of Retroviral Infections Unit Department of Virology

  2. Main milestones in 27 years of research on HIV HIV biology and pathogenesis Therapy and prevention research Prophylactic and therapeutic vaccine research M. Müller-Trutwin & F. Barré-Sinoussi 35 SIV Identification VIH-2 Co-receptors CD4 Depletion in gut 25 Origin of HIV Number of people living with HIV (million) HIV-1 Diversity HIV controllers Recombinants VIH-1 HIV-1 Sequence HIV Reservoirs 15 HIV-1 O HIV-1 P HIV Restriction factors CD4 Receptor HIV-1 N HIV-1 subtypes HIV-1 Identification Microbial Translocation Immune activation 5 1980 81 82 84 85 86 88 89 90 95 96 97 98 00 01 02 03 05 06 07 08 09 83 87 91 92 93 94 99 04 AIDS STEP Trial Circumcision (risk reduction) HIV testing Vaccine therapy « Thaï » trial HAART VaxGen Trial PMTCT 1st phase I trial AZT Therapy African epidemic HIV Quantification ARVResistance

  3. HIV Vaccine history August 1987 1st phase I trial > 110 trials (10 Phase II/III) with 67 products (27 500 volunteers) 1987-2007 Candidate vaccine are usually safe and showed some degree of immunogenicity 2003 Data of the 1st phase III efficacy trial VaxGen Lack of efficacy of rgp120 definitively proven STEP/Phambili phase IIb trial (HIV-1B gag, pol, nef / rAd5) Sept. 2007 Discontinued for lack of efficacy RV144 “Thaï”: ALVAC (gag/pol/env) + AidsVax (B/ErGp120) Oct. 2009 Modest Efficacy 31% Ongoing phase II trials (DNA+MVA, DNA+NYVAC, lipopeptides…)

  4. Défis scientifiques du vaccin (2) 27 years after the discovery of AIDS virus, urgent need for a new vaccine strategies… • Animal model limitations • Genetic Variability of HIV • Viral evasion of the immune system • Early establishment of viral reservoirs • Mechanisms of protection still undefined ??? • Cell to cell transmission of the virus • HIV infects and alters key players of the immune system • Very rapid induction of dysfunctions in both innate and adaptative immune responses Think differently according to the knowledge pathogenesis

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