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1 UNAIDS–97100 1 August 1998 HIV preventive vaccine trials in developing countries (July 1998)

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Presentation on theme: "1 UNAIDS–97100 1 August 1998 HIV preventive vaccine trials in developing countries (July 1998)"— Presentation transcript:

1 1 UNAIDS–97100 1 August 1998 HIV preventive vaccine trials in developing countries (July 1998)

2 2 UNAIDS–97100 1 August 1998 Correlation between HIV load in plasma and progression to AIDS Adapted from D. Ho

3 3 UNAIDS–97100 1 August 1998 Potential end-points of HIV-vaccine efficacy trials

4 4 UNAIDS–97100 1 August 1998 HIV preventive candidate vaccines in Phase I/II clinical trials Vaccine developer Vaccine concept Trial site l Envelope subunit MicroGeneSys Immuno Ag Pasteur-Mérieux-Connaught University of Bruxelles USA France Belgium – rgp160 Biocine SmithKline Beecham Genentech/VaxGen Biocine/Chiron USA, Switzerland UK USA, Thailand – rgp120 l Peptides l Particles l Live vectors l Naked DNA

5 5 UNAIDS–97100 1 August 1998 HIV preventive candidate vaccines in Phase I/II clinical trials (contd) Vaccine developer Vaccine concept Trial site l Envelope subunit United Biomedical Inc.USA, Thailand, Brazil, Australia, China – V3-MAPS Biocine SmithKline Beecham Genentech/VaxGen Biocine/Chiron USA, Switzerland UK USA, Thailand – V3PPD conjugate – HGP–30 (p17) – V3, V3–p24 – rV3 peptides – rp24 l Live vectors l Naked DNA l Peptides British BiotechnologyUK – Ty–p24 VLP l Particles

6 6 UNAIDS–97100 1 August 1998 HIV preventive candidate vaccines in Phase I/II clinical trials (contd) Vaccine developer Vaccine concept Trial site l Envelope subunit l Peptides l Particles Bristol-Meyers-Squibb Therion Biologicals Pasteur-Mérieux-Connaught USA USA, France USA USA, France – Vaccinia-gp160 – Vaccinia-env/gag/pol – Canarypox-gp160 – Canarypox- env/gag/pol – Canarypox- env/gag/prot. l Live vectors ApollonUSA – env /rev l Naked DNA

7 7 UNAIDS–97100 1 August 1998 UNAIDS Vaccine strategy To promote the development, evaluation, and future availability of safe, effective and affordable HIV preventive vaccines, for worldwide use, especially in developing countries. l Collection, exchange and analysis of information l Creation of collaborative networks l Assistance with capacity building in developing countries l Provision of independent and authoritative advice l Identification of ethical, regulatory and legal barriers l Advocate for HIV vaccines OBJECTIVE ACTIONS

8 8 UNAIDS–97100 1 August 1998 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 9 UNAIDS–97100 1 August 1998 Clinical trials of HIV preventive vaccines (1998) Phase I Objective Number of volunteers Number of trials conducted safety and immunogenicity 20–50/trialapprox. 25 additional safety and immunogenicity 100s/trial4 efficacy (against infection or disease) 1000s/trial 2 (USA and Thailand) II III

10 10 UNAIDS–97100 1 August 1998 Country Starting date Starting date Number of volunteers Candidate vaccine HIV preventive vaccine trials in developing countries (up to 1998) Phase I synthetic peptide MN-V3 branched (United Biomedical Inc.) envelope gp120-MN (Genentech/VaxGen) envelope gp120-SF (Biocine-Chiron) recombinant V3 protein (Ctr. Ing. Gen. Biotec.) canarypox-env/gag/pol (Pasteur-Mérieux-Connaught) China (Yunan) Thailand (Bangkok) Brazil (Rio, B. Horiz.) Thailand (Bangkok) Thailand (Bangkok, Chiang Mai) Cuba (Habana) Uganda (Kampala) Sept. 1993 June 1994 March 1994 Feb. 1995 Aug. 1995 Dec. 1996 1998 23 24 30 52 30 40

11 11 UNAIDS–97100 1 August 1998 HIV preventive vaccine trials in developing countries (up to 1998) contd Phase II Country Starting date Starting date Number of volunteers envelope:gp120-SF2 (B-SI) gp120-CM235 (E-NSI) and combinations of both (Chiron Vaccines) Candidate vaccine canarypox-env/gag/pol (Pasteur-Mérieux-Connaught) Thailand (Bangkok, Chiang Mai) Thailand (Bangkok) Thailand (Bangkok, Chiang Mai) Uganda (Kampala) Nov. 1997 March 1998 Aug. 1995 1998 380 90 52 40 Phase III envelope bivalent (VaxGen) gp120-MN (B-SI) +gp120-CM244 (E-NSI) envelope bivalent (VaxGen) gp120-MN (B-SI) +gp120-CM244 (E-NSI) Thailand (IDU in Bangkok) pending 19982 500

12 12 UNAIDS–97100 1 August 1998 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 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 Results from Phase I/II trials of preventive HIV vaccines

13 13 UNAIDS–97100 1 August 1998 Conduct of efficacy trials of HIV preventive vaccines Appropriate candidate vaccine Appropriate candidate vaccine l Safe and immunogenic in Phase I/II trials l Protection experiments in animals (?) l Logistically feasible (administration, shelf-life) l Regulatory approvals l Match with strains circulating in study population Appropriate population Appropriate population l High HIV incidence (2–5%) despite available interventions l Willingness to participate and to follow-up (3–5 years) l Adequate research and clinical infrastructures l Independent review bodies (scientific and ethical) l Strong political and community support

14 14 UNAIDS–97100 1 August 1998 Phases on the development and evaluation of HIV vaccines Preclinical phase l Laboratory l Animal protection experiments Clinical phases Clinical phases l 20–50 HIV-negative volunteers (lower risk) l safety and immunogenicity Phase I Phase II Phase III Phase IV l 100s of HIV-negative volunteers (lower and higher risk) l safety and immunogenicity; and also l doses, routes of administration, different populations l 1000s of HIV-negative volunteers (higher risk) l efficacy (against infection or against disease) l effectiveness (how to use the vaccine for public health purposes)


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