1 unaids–97100 1 august 1998 hiv preventive vaccine trials in developing countries (july 1998)

1UNAIDS–97100 1 August 1998

HIV preventive vaccine trials in developing countries(July 1998)


Correlation between HIV load in plasma and progression to AIDS

Adapted from D. HoAdapted from D. Ho


Potential end-points of HIV-vaccine efficacy trials


HIV preventive candidate vaccines in Phase I/II clinical trials

Vaccine developerVaccine developerVaccine conceptVaccine concept Trial siteTrial site

Envelope subunitMicroGeneSysImmuno AgPasteur-Mérieux-ConnaughtUniversity of Bruxelles

USAUSAFranceBelgium

– rgp160

BiocineSmithKline BeechamGenentech/VaxGenBiocine/Chiron

USA, SwitzerlandUKUSA, ThailandUSA, Thailand

– rgp120

Peptides Particles Live vectors Naked DNA


HIV preventive candidate vaccines in Phase I/II clinical trials (cont’d)

Vaccine developerVaccine developerVaccine conceptVaccine concept Trial siteTrial site

Envelope subunit

United Biomedical Inc. USA, Thailand, Brazil,Australia, China

– V3-MAPS

BiocineSmithKline BeechamGenentech/VaxGenBiocine/Chiron

USA, SwitzerlandUKUSA, ThailandUSA, Thailand

– V3PPD conjugate– HGP–30 (p17)– V3, V3–p24– rV3 peptides– rp24

Live vectors Naked DNA

Peptides

British Biotechnology UK– Ty–p24 VLP

Particles


HIV preventive candidate vaccines in Phase I/II clinical trials (cont’d)

Vaccine developerVaccine developerVaccine conceptVaccine concept Trial siteTrial site Envelope subunit Peptides Particles

Bristol-Meyers-SquibbTherion BiologicalsPasteur-Mérieux-ConnaughtPasteur-Mérieux-Connaught

Pasteur-Mérieux-Connaught

USAUSAUSA, FranceUSA

USA, France

– Vaccinia-gp160– Vaccinia-env/gag/pol– Canarypox-gp160– Canarypox-env/gag/

pol– Canarypox-env/gag/

prot.

Live vectors

Apollon USA– env/rev

Naked DNA


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.

Collection, exchangeand analysis of information

Creation of collaborative networks Assistance with capacity building

in developing countries

Provision of independentand authoritative advice

Identification of ethical,regulatory and legal barriers

Advocate for HIV vaccines

OBJECTIVEOBJECTIVE

ACTIONSACTIONS


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)


Clinical trials of HIV preventive vaccines (1998)

PhasePhase

I

ObjectiveObjectiveNumber of volunteersNumber of volunteers

Number of trials conducted

Number of trials conducted

safety andimmunogenicity 20–50/trial approx. 25

additional safety andimmunogenicity 100s/trial 4

efficacy (against infection or disease) 1000s/trial

2(USA and Thailand)

II

III


CountryCountry Starting date

Starting date

Number of volunteersNumber of volunteersCandidate vaccineCandidate vaccine

HIV preventive vaccine trialsin developing countries (up to 1998)

Phase IPhase Isynthetic peptideMN-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. 1993June 1994

March 1994

Feb. 1995

Aug. 1995

Dec. 1996

1998

232430

30

52

30

40


HIV preventive vaccine trialsin developing countries (up to 1998) cont’d

Phase IIPhase II

CountryCountry Starting date

Starting date

Number of volunteersNumber of volunteers

envelope: gp120-SF2 (B-SI)gp120-CM235 (E-

NSI)and combinations of both(Chiron Vaccines)

Candidate vaccineCandidate vaccine

canarypox-env/gag/pol(Pasteur-Mérieux-Connaught)


Thailand (Bangkok)


Uganda (Kampala)

Nov. 1997

March 1998

Aug. 1995

1998

380

90

52

40Phase IIIPhase 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 1998 2 500


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 trialsof preventive HIV vaccines


Conduct of efficacy trials of HIV preventive vaccines

Appropriatecandidate

vaccine

Appropriatecandidate

vaccine

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

Appropriatepopulation

Appropriatepopulation

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


Phases on the development and evaluation of HIV vaccines

Preclinical phasePreclinical phase Laboratory Animal protection experiments

ClinicalphasesClinicalphases

20–50 HIV-negative volunteers (lower risk) safety and immunogenicityPhase IPhase I

Phase IIPhase II

Phase IIIPhase III

Phase IVPhase IV

100s of HIV-negative volunteers (lower and higher risk) safety and immunogenicity; and also doses, routes of administration, different populations

1000s of HIV-negative volunteers (higher risk) efficacy (against infection or against disease)

effectiveness(how to use the vaccine for public health purposes)

1 unaids–97100 1 august 1998 hiv preventive vaccine trials in developing countries (july 1998)

Documents

france usa usa

connaught usa usa

hivvaccine efficacy

hiv vaccines objective

connaught thailand bangkok

ho slide

thailand rgp120

hiv load