the long road to an hiv vaccine el largo camino hacia una vacuna contra el vih n.
Download
Skip this Video
Loading SlideShow in 5 Seconds..
THE LONG ROAD TO AN HIV VACCINE (El largo camino hacia una vacuna contra el VIH) PowerPoint Presentation
Download Presentation
THE LONG ROAD TO AN HIV VACCINE (El largo camino hacia una vacuna contra el VIH)

Loading in 2 Seconds...

play fullscreen
1 / 36

THE LONG ROAD TO AN HIV VACCINE (El largo camino hacia una vacuna contra el VIH) - PowerPoint PPT Presentation


  • 75 Views
  • Uploaded on

A Multicultural Caribbean United Against HIV/AIDS Santo Domingo, 5-7 March 2004. THE LONG ROAD TO AN HIV VACCINE (El largo camino hacia una vacuna contra el VIH). j. j. José Esparza, MD, PhD WHO-UNAIDS HIV Vaccine Initiative Geneva, Switzerland.

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'THE LONG ROAD TO AN HIV VACCINE (El largo camino hacia una vacuna contra el VIH)' - uta


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
the long road to an hiv vaccine el largo camino hacia una vacuna contra el vih

A Multicultural Caribbean United Against HIV/AIDS

Santo Domingo, 5-7 March 2004

THE LONG ROAD TO AN HIV VACCINE(El largo camino hacia una vacuna contra el VIH)

j

j

José Esparza, MD, PhD

WHO-UNAIDS HIV Vaccine Initiative

Geneva, Switzerland

frequently asked questions about hiv vaccines
Frequently asked questions about HIV vaccines
  • How urgently a preventive HIV vaccine is needed?
  • Why an HIV vaccine has not been developed?
    • How vaccines are developed?
    • Where are we with HIV vaccines?
    • Scientific challenges in the development of an HIV vaccine.
  • Non-scientific issues on HIV vaccine development
    • Political support.
    • Community participation.
    • Ethical issues.
    • Future access.
slide3
An estimated 34-46 million people were living with HIV/AIDS by the end of 2003, 95% of them in developing countries (70% in Africa)

Eastern Europe & Central Asia

1.2-1.8 million

North America

790.000-1.2

million

Western Europe

520-680.000

East Asia & Pacific

7000.000-1.3

million

North Africa

& Middle East

470-730.000

Caribbean

350-590.000

South

& South-East Asia4.6-8.2 million

Sub-Saharan Africa

25-28.2 million

Latin America

1.3 - 1.9 million

Australia

& New Zealand

12-18.000

A safe, effective, affordable and available preventive HIV vaccine is the best long term hope for the control of the HIV/AIDS epidemic, especially in developing countries (complementing other preventive and therapeutic interventions)

hiv vaccines
HIV Vaccines
  • The development of an HIV vaccine is one of the most formidable challenges that modern biomedical science is confronting.
  • Intense international coordination and collaboration will be needed to develop such vaccine, including the conduct of multiple human trials in industrialized and developing countries.
  • And, when an HIV vaccine is finally developed, international solidarity will be essential to make it available to all populations in need.
a short history of hiv vaccines
A short history of HIV vaccines
  • 1981: AIDS was described as a new disease.
  • 1983-1984: HIV discovered as the cause of AIDS.
  • 1987: First small-scale HIV vaccine trial.
    • Since then, more than 30 candidate vaccines have been tested in industrialized and developing countries, involving over 10.000 healthy human volunteers.
  • 1998-2003: First two efficacy trials of HIV vaccines.
    • gp120 BB in the US, 5400 volunteers.
    • gp120 BE in Thailand, 2500 volunteers.
    • Failed to confer protection to the overall population.
  • 2003: Next phase III trial started in Thailand
    • 16.000 volunteers
how vaccines are developed
How vaccines are developed?

Preclinicaldevelopment

Basic research

Clinicaltrials

Laboratory

in vitro & animal studies

Human research

Safety,

Immunogenicity

Discovery

Exploration

Efficacy

Vaccine concepts

Human trials

Phase I/II Phase III

Experiments in primates

Safety, immunogenicity

1

2

3

4

5

Likelihood of protection in humans

6

1: Recombinant Protein – 2: Synthetic Peptides – 3: Naked DNA

4. Live-recombinant vectors- 5: Whole inactivated virus – 6: Live attenuated virus

hiv vaccine approaches
HIV vaccine approaches

recombinantprotein (gp120)

synthetic peptides (V3)

naked DNA

live-recombinant vectors

(viral, bacterial)

whole-inactivated virus

live-attenuated virus

slide8

HIV Vaccines: Pipeline Situation (2004)

Vaccine constructs

in concept stage

~80

# GMP

lots made

25

# Entered

Phase II

5

# Entered

Phase III

2

# entered

phase I trials

~25

# GMP

lots made

~25

# entered

phase II trials

~5

# entered

phase III trials

3

From Larry Corey

hiv candidate vaccines in preclinical development
HIV candidate vaccines in preclinical development
  • ALVAC A Aventis/WRAIR/NIAID
  • DNA+MVA A,D,E WRAIR/NIAID
  • Salmonella A,A/G IHV/IAVI/NIAID
  • DNA+Env B,C Chiron/NIAID/SAAVI
  • VSV B Wyeth-Lederle/NIAID
  • DNA+lipopetides B Wyeth-Lederle/NIAID
  • DNA+IL2-Ig B NIAID/VRC/Harvard
  • MVA B Therion/NIAID
  • DNA+MVA C SAAVI, NIAID
  • AAV C Targeted Genetics/CH/IAVI
  • gp120 C VaxGen/NIAID/WRAIR
  • VEE-gag C AlphaVax/NIAID/SAAVI
  • DNA+vaccinia B/C, C ADARC/IAVI/China, Germany
  • DNA+MVA B-A/G-C Emory/NIAID/CDC
  • DNA+Adeno A-B-C NIAID/VRC
  • DNA+fowlpox E UNSW (Australia)/NIAID
  • DNA+Env multi ABL/NIAID
  • DNA+protein multi Epimmune/NIAID
  • BCG +/- vaccinia B, E Japan, Thailand

DAIDS, Feb 2003

hiv vaccine concepts tested in clinical trials 1
HIV Vaccine “concepts”tested in clinical trials (1)
  • Envelope proteins
    • Recombinant gp 160 in baculovirus/insect cell systems
    • Recombinant gp160 in mammalian cells
    • Recombinant gp120 in mammalian cells (multiple products)
  • Non-envelope proteins
    • Matrix (p17) and core (p24) proteins in yeast transposons (Ty)
    • p24 GAG protein produced in mammaliancells
    • TAT protein produced in E. coli
  • Peptides
    • Matrix (p17) peptide (HGP-30)
    • GAG lipopetides
    • C4-V3 gp120 peptides
    • Lipopetides (multiple products)
  • DNA vaccines
    • env/rev in plasmid backbone
    • gag in plasmid backbone
    • Multiple CTL epitopes in plasmid backbone (several constructs)
    • Multiple genes in plasmid backbone (several constructs)

+

hiv vaccine concepts tested in clinical trials 2
HIV Vaccine “concepts”tested in clinical trials (2)
  • Poxvirus vectors
    • Recombinant Vaccinia-gp160
    • Recombinant Vaccinia-env/gag/pol
    • Recombinant Canarypox-HIV (multiple constructs, B, E)
    • Recombinant Modified Vaccinia Ankara (MVA)-HIV (several)
    • Recombinant Fowlpox-HVI (AE subtype)
  • Other viral vectors
    • Recombinant Adenovirus 5-HIV gag
    • Venezuelan Equine Encephalitis (VEE) replicon-HIVgagC
  • Bacterial vectors
    • Salmonella typhy-HIV
  • Combinations (prime-boost)
    • Recombinant gp160 produced in mammalian cells with V3 peptides
    • Recombinant vacinia-gp160 with rgp160 or rgp120
    • Recombinant canarypox-HIV (several) with different boosters (gp120)
    • DNA vaccines boosted with recombinant viral vectors

+

slide12

CTL

Kill

Neutralization

HIV Infected Cell

The two arms of the immune system:types of vaccine-induced immune responses

Humoral immunity

(Neutralizing

antibodies)

Cell-mediated

immunity

(CTL)

(And prime-boost combinations)

From Larry Corey

three waves of hiv vaccine paradigms and clinical trials
Three “waves” of HIV vaccine paradigms and clinical trials
  • First “wave” (1987 - mid 1990s):
    • Induction of neutralizing antibodies
    • Envelope antigens
  • Second “wave” (mid 1990s - early 2000s)
    • Induction of cell-mediated immunity (CD 8 CTL)
    • Live vectors, DNA vaccines
    • Prime-boost combinations (pox-vectors + gp120)
  • Third “wave” (now)
    • Better/broader immune responses
    • Novel immunogens and combinations

+

vaccine research and trials in developing countries are necessary because
Vaccine research and trials in developing countries are necessary because:
  • The majority of HIV infections occurs in these countries (where a future vaccine would have the most benefit)
  • Phase III trials need to be conducted in populations with high HIV incidence.
  • Need to assess vaccine safety, immunogenicity and efficacy in different populations (Different routes of transmission, genetic background, health status).
  • Genetic and antigenic variability of HIV strains.

+

hiv particle and genome
HIV particle and genome

MHC

gp120

gp41

envelope

gp160

lipidbilayer

matrix

p17

core

p24

RT

RNA

geographical distribution of hiv 1 env genetic subtypes 2000

A

B

B

B

B

A

C

B

B

Other

Other

E

C

B

A

A

D

A

E 3.2%

Others 5%

(F, G, H, J, NT)

D

5.3%

A27%

C

C47.2%

B 12.3%

Geographical distribution of HIV-1env genetic subtypes (2000)

B

clinical trials in developing countries 1993 2002

February 2004

Clinical trials in developing countries(1993-2002)
  • 1993 China II V3 branched peptide 23
  • 1994 Thailand II V3 branched peptide 30
  • 1994 Brazil II V3 branched peptide 30
  • 1995 Thailand I/II rgp 120 B (MN) 30
  • 1995 Thailand I/II rgp 120 B (SF2) 54
  • 1996 Cuba I V3-multi-epitope peptide 30
  • 1997 Thailand II rgp 120 BE (SF2/CM235) 380
  • 1998 Thailand II rgp 120 BE (MN/A244)* 92
  • 1999 Uganda II ALVAC vcp205 40
  • 1999 Thailand III rgp 120 BE (MN/A244) 2 .545 ( Phase III)
  • 2000 Thailand I/II ALVAC vCP1521 + rgp 120 BE 60
  • 2000 Thailand I/II ALVAC vCP1521 + orgp 160 E 70
  • 2000 Thailand I/II ALVAC vCP1521 + rgp 120 BE* 125
  • 2001 Kenya I DNA-HIVA 18
  • 2001 Haiti II ALVAC vCP1452 + rgp120 BB 40
  • 2001 Trinidad II ALVAC vCP1452 + rgp 120 BB 40
  • 2001 Brazil II ALVAC vCP1452 + rgp 120 BB 40
  • 2002 Perú II ALVAC vCP1452 + rgp 120 BB 40
  • 2002 Kenya I MVA-HIVA 18
clinical trials in developing countries 2003 2004

February 2004

Clinical trials in developing countries(2003-2004)
  • 2003 Uganda II DNA-HIVA + MVA-HIVA 50
  • 2003 Botswana I DNA-multi-epitope B 12
  • 2003 Kenya II DNA-HIVA + MVA-HIVA 120
  • 2003 South Africa II MVA-HIVA 55
  • 2003 South Africa I VEE-vectored C gag 40
  • 2003 South Africa MRKAd-5 gag B
  • and Malawi I/II MRKAd-5 gag 87
  • 2003 Brazil
  • and Peru I/II MRKAd-5 gag B 87
  • 2003 Thailand I/II MRKAd-5 gag B 87
  • 2003 Haiti (+PR) I/II MRKAd-5 gag B 87
  • 2003 Thailand III ALVAC vCP1521 + rgp 120 BE 16.000 (Phase III)
  • 2004? Rwanda II DNA-HIVA+ MVA-HIVA ?
  • 2004? Thailand I DNA-AE+FPV-AE 14
  • 2004? Thailand II DNA-AE+FPV-AE 160
  • 2004? Uganda II DNA gag,pol,nefB/envABC+Adeno 30
what have we learned from the trials conducted thus far
What have we learned from the trials conducted thus far?
  • Trials can be conducted with high scientific and ethical standards (also in developing countries)
  • Candidate vaccines are safe (only minor side effects).
  • Candidate vaccines induce anti-HIV specific immune responses: Neutralizing antibodies and/or cell-mediated immunity (although, the quality and quantity of these immune responses may need to be improved).
  • The first generation of HIV vaccines (based on monomeric envelope gp120 protein) did not show significant protective efficacy in two phase III trials conducted in US and in Thailand.
  • More Phase I, II and III trials are need to obtain more information on the safety, immunogenicity and protective efficacy of new HIV candidate vaccines.
  • Efficacy trials can also provide important information on what type of immune response can protect against HIV/AIDS (immune correlates of protection) , and that information will help on the design of the next generation of vaccines.
important scientific questions
Important scientific questions
  • People infected with HIV develop strong immune responses against the virus, but that immunity can not control the replication of HIV or prevent progression to AIDS.
    • Question: What type of immune responses should be induced by vaccines to prevent HIV infection or AIDS? (Imune correlate of protection)
  • There are many genetic variants (subtypes) of HIV.
    • Question: Do we need specific vaccines for each subtype?
  • Monkeys can be (partially) protected with experimental vaccines.
    • Question: Can these vaccines also protect humans (need phase III trials)
  • Many types of candidate HIV vaccines (and combinations) are been developed and tested.
    • Question: Are these vaccines sufficient to protect humans (to be learned from phase III trials). If the answer is not: can we develop better vaccines?
multiple hiv vaccine trials are needed to test the safety immunogenicity and protective efficacy of
Multiple HIV vaccine trials are needed to test the safety, immunogenicity and protective efficacy of:
  • Different types of candidate vaccines (and prime-boost combinations).
  • Against different HIV subtypes.
  • In different populations (different routes of transmission, genetic background, health status).

These trials need to be conducted in both

industrialized and developing countries

different phases of international site development
Different phases of International Site Development
  • Before 1992: “Epidemiological” assessments:
    • Studies to obtain (epidemiological) baseline data for determining the feasibility of conducting trials in international settings.
    • NIH PAVEs (Preparation for AIDS Vaccine Evaluation)
  • From 1992: First “National AIDS Vaccine Plans”:
    • WHO sponsored plans in Brazil, Rwanda, Thailand, and Uganda.
    • Including: policies, mechanisms for approval and preparatory research.
  • From ~1998: More comprehensive National Vaccine Strategies:
    • More proactive role for “host” countries (Example: SAAVI)
    • Consideration of non-vaccine issues in site development (including other preventive and therapeutic interventions)
  • From ~2001: Regional Vaccine Strategies:
    • African AIDS Vaccine Programme (AAVP)
  • From 2004: A Caribbean HIV Vaccine Strategy?
development of who sponsored national aids vaccine plans 1990 1992
Development of WHO-sponsored National AIDS Vaccine Plans” (1990-1992)
  • Fifteen countries around the world assessed (1-2 weeks site visits of multi-institutional teams).
  • WHO AIDS Vaccine Advisory Committee recommended to initially focus on four countries (Brazil, Rwanda, Thailand and Uganda).
  • National Plans developed through a process of extensive consultation and consensus building among all stakeholders (national and international).
  • The outcomes of the process were a better understanding and buying-in of the process and a document that describes the “rules of the game”.

The WHO-UNAIDS sponsored National

AIDS Vaccine Plans greatly facilitated the

conduct of trials in developing countries

who sponsored national aids vaccine plans from 1992
WHO-SPONSORED “NATIONAL AIDS VACCINE PLANS” (from 1992)
  • Definition of national policy:
    • Including HIV vaccines as an integral part of the national response to HIV/AIDS.
  • Establishment of mechanisms for submission, review, approval and monitoring of research proposals:
    • Scientific
    • Ethical
  • Implementation of “preparatory” research:
    • Virus isolation and characterization
    • Epidemiology and cohort development
    • Socio-behavioural studies
    • Clinical trials capacity
    • Data- Management
    • Public Information
brazil from the guinea pigs syndrome 1991 to community engagement 2003
Brazil: From the “guinea pigs” syndrome (1991) to community engagement (2003)

Third world countries will test vaccines

against AIDS:“Oh Boy, what an honour!”

early media reaction to a proposed hiv vaccine trial in thailand 1991
Early media reaction to a proposed HIV vaccine trial in Thailand (1991)

The Nation (Bangkok), 2 November 1991

national aids vaccine plans1
“National AIDS Vaccine Plans”

NORMATIVE FRAMEWORK

Political

Legal

Regulatory

Ethical

Logistical

TECHNICAL COMPONENTS

Virology

Epidemiology

Socio/

behavioural

Clinical

trials

Media and

PR

Etc

SUPPORTING ENVIRONMENT

Community

support

HIV/AIDS

Prevention

Access to care,

including ART

Infrastructure and

human resources

Etc

the african aids vaccine programme aavp
The African AIDS Vaccine Programme (AAVP)
  • The AAVP is a network of African scientists and community, working together to promote and facilitate HIV vaccine research and evaluation in Africa, through capacity-building and regional and international collaboration (“the voice of Africa”).
  • Activities being developed and implemented through six thematic working groups:
    • Advocacy, information and resource mobilization.
    • Biomedical sciences (laboratory and clinical).
    • Population studies (Epidemiology and Socio-Behavioural issues).
    • Ethics, Law and Human Rights.
    • National Strategic Planning.
    • Community participation.

A model for a Caribbean Strategy?

future challenges on site development
Future challenges on site development
  • Need to increase clinical trial capacity worldwide (identified as a priority by the Gates Foundation-driven “Global HIV Vaccine Enterprise”).
  • Multiple sites needed to test different candidate vaccines, against different HIV subtypes, in populations with different transmission partners.
  • Comprehensively developed sites could be used for vaccines and other HIV preventive research (including microbicides).
  • Consider impact of scaling-up ART on vaccine trials: HIV incidence, level of care, etc.
  • Need to ensure that the “most appropriate” candidate vaccines are tested in the “most appropriate” sites, regardless of whom developed the product or strengthened the site. This will require intense international collaboration and coordination (a a great deal of good-will from all partners).
hiv vaccines the way forward
HIV vaccines: The way forward
  • More basic research is needed to obtain scientific knowledge required for rational vaccine development.
  • Additional clinical trials must be conducted to obtain information on:
    • Type of immune response(s) required for protection.
    • Type of protection conferred by different candidate vaccines (protection against infection or against disease).
    • Relevance of HIV genetic subtypes for vaccine induced protection.
  • Clinical trials and laboratory research should be part of an iterative process leading to incremental knowledge and better vaccines.
  • Urgent need to increase world-wide effort on HIV vaccine research and development, with better coordination and collaboration.
in conclusion
In conclusion
  • An HIV vaccine (complementing other interventions) remains the best long-term hope for the control of the AIDS pandemic, especially in developing countries.
  • Present activities to develop an HIV vaccine should increase significantly, to produce a vaccine with the required urgency.
  • For this, a better coordinated effort is needed to accelerate HIV vaccine development, and this effort should involve the full participation of developing countries.
  • And once a vaccine is developed, international solidarity will be essential to make it available to all countries and populations in need.