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HIV preventive vaccine trials in developing countries (July 1998)

HIV preventive vaccine trials in developing countries (July 1998). Correlation between HIV load in plasma and progression to AIDS. Adapted from D. Ho. Potential end-points of HIV-vaccine efficacy trials. HIV preventive candidate vaccines in Phase I/II clinical trials. Vaccine developer.

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HIV preventive vaccine trials in developing countries (July 1998)

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  1. HIV preventive vaccine trials in developing countries(July 1998)

  2. Correlation between HIV load in plasma and progression to AIDS Adapted from D. Ho

  3. Potential end-points of HIV-vaccine efficacy trials

  4. HIV preventive candidate vaccines in Phase I/II clinical trials Vaccine developer Trial site Vaccine concept • Envelope subunit • rgp160 MicroGeneSys Immuno Ag Pasteur-Mérieux-Connaught University of Bruxelles USA USA France Belgium • rgp120 Biocine SmithKline Beecham Genentech/VaxGen Biocine/Chiron USA, Switzerland UK USA, Thailand USA, Thailand • Peptides • Particles • Live vectors • Naked DNA

  5. HIV preventive candidate vaccines in Phase I/II clinical trials (cont’d) Vaccine developer Trial site Vaccine concept • Envelope subunit • Peptides United Biomedical Inc. USA, Thailand, Brazil,Australia, China • V3-MAPS • V3PPD conjugate • HGP–30 (p17) • V3, V3–p24 • rV3 peptides • rp24 Biocine SmithKline Beecham Genentech/VaxGen Biocine/Chiron USA, Switzerland UK USA, Thailand USA, Thailand • Particles British Biotechnology UK • Ty–p24 VLP • Live vectors • Naked DNA

  6. HIV preventive candidate vaccines in Phase I/II clinical trials (cont’d) Vaccine developer Trial site Vaccine concept • Envelope subunit • Peptides • Particles • Live vectors • Vaccinia-gp160 • Vaccinia-env/gag/pol • Canarypox-gp160 • Canarypox-env/gag/pol • Canarypox-env/gag/prot. Bristol-Meyers-Squibb Therion Biologicals Pasteur-Mérieux-Connaught Pasteur-Mérieux-Connaught Pasteur-Mérieux-Connaught USA USA USA, France USA USA, France • Naked DNA Apollon USA • env/rev

  7. UNAIDS Vaccine strategy OBJECTIVE To promote the development, evaluation, and future availability of safe, effective and affordable HIV preventive vaccines, for worldwide use, especially in developing countries. ACTIONS • Collection, exchangeand analysis of information • Creation of collaborative networks • Assistance with capacity buildingin developing countries • Provision of independentand authoritative advice • Identification of ethical,regulatory and legal barriers • Advocate for HIV vaccines

  8. UNAIDS vaccine advisory committee (1997) Roy Anderson (UK) Françoise Barré-Sinoussi (France) Natth Bhamarapravati (Thailand) Gunnel Biberfeld (Sweden) Barry Bloom (USA, Chairman) Mario Bronfman (Mexico) Mary-Lou Clements-Mann (USA) Roel Coutinho (Netherlands) Patricia Fast (USA) David Ho (USA) Souleymane Mboup (Senegal) Ruranga Rubaramira (Uganda) Shudo Yamazaki (Japan)

  9. Clinical trials of HIV preventive vaccines (1998) Number of volunteers Number of trials conducted Phase Objective safety and immunogenicity 20–50/trial approx. 25 I additional safety and immunogenicity 100s/trial 4 II efficacy (against infection or disease) 2(USA and Thailand) 1000s/trial III

  10. HIV preventive vaccine trialsin developing countries (up to 1998) Number of volunteers Starting date Country Candidate vaccine Phase I synthetic peptide MN-V3 branched (United Biomedical Inc.) China (Yunan) Thailand (Bangkok) Brazil (Rio, B. Horiz.) Sept. 1993 June 1994 March 1994 23 24 30 envelope gp120-MN (Genentech/VaxGen) Thailand (Bangkok) Feb. 1995 30 envelope gp120-SF (Biocine-Chiron) Thailand (Bangkok, Chiang Mai) Aug. 1995 52 recombinant V3 protein (Ctr. Ing. Gen. Biotec.) Cuba (Habana) Dec. 1996 30 canarypox-env/gag/pol (Pasteur-Mérieux-Connaught) Uganda (Kampala) 1998 40

  11. HIV preventive vaccine trialsin developing countries (up to 1998) cont’d Starting date Number of volunteers Country Candidate vaccine Phase II envelope: gp120-SF2 (B-SI) gp120-CM235 (E-NSI) and combinations of both (Chiron Vaccines) Thailand (Bangkok, Chiang Mai) Nov. 1997 380 envelope bivalent (VaxGen) gp120-MN (B-SI) + gp120-CM244 (E-NSI) Thailand (Bangkok) March 1998 90 Phase III canarypox-env/gag/pol (Pasteur-Mérieux-Connaught) Uganda (Kampala) 1998 40 envelope bivalent (VaxGen) gp120-MN (B-SI) + gp120-CM244 (E-NSI) Thailand (Bangkok, Chiang Mai) Thailand (IDU in Bangkok) Aug. 1995 52 pending 1998 2 500

  12. Results from Phase I/II trialsof preventive HIV vaccines Recombinant envelope vaccines should be produced in mammalian cells gp120 is more immunogenic than gp160 Immunization with envelope vaccines require high doses and multiple injections Neutralizing antibodies induced by envelope vaccines do not neutralize clinical isolates Only “replicating” vaccines induce CD8 + CTLs Prime-boost regimes more efficient in inducing humoral and cell-mediated immunity Candidate vaccines appear to be safe

  13. Conduct of efficacy trials of HIV preventive vaccines • Safe and immunogenic in Phase I/II trials • Protection experiments in animals (?) • Logistically feasible (administration, shelf-life) • Regulatory approvals • Match with strains circulating in study population Appropriate candidate vaccine • High HIV incidence (2–5%) despite available interventions • Willingness to participate and to follow-up (3–5 years) • Adequate research and clinical infrastructures • Independent review bodies (scientific and ethical) • Strong political and community support Appropriate population

  14. Phases on the development and evaluation of HIV vaccines Preclinical phase • Laboratory • Animal protection experiments • 20–50 HIV-negative volunteers (lower risk) • safety and immunogenicity Phase I • 100s of HIV-negative volunteers (lower and higher risk) • safety and immunogenicity; and also • doses, routes of administration, different populations Phase II Clinical phases • 1000s of HIV-negative volunteers (higher risk) • efficacy (against infection or against disease) Phase III • effectiveness (how to use the vaccine for public health purposes) Phase IV

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