IAVI’s Integrated R&D Program Accelerating AIDS vaccine development
Source: Joint United Nations Programme on HIV/AIDS <ul><ul><li>33 million people living with HIV worldwide </li></ul></ul>...
AIDS vaccines  are part of a sustainable, comprehensive response <ul><li>Deliver  for today—better use of tools </li></ul>...
Vaccines can take decades to develop Measles Hepatitis B Human papilloma virus (cervical cancer) Rotavirus (diarrheal dise...
<ul><li>The Thai trial demonstrates an AIDS vaccine is possible </li></ul><ul><ul><li>Correlates may be found </li></ul></...
RV144 trial: F irst HIV vaccine candidate to show efficacy <ul><li>A Phase IIb test-of-concept trial, based on the expecte...
Immune Mechanisms   for an AIDS Vaccine Cell Mediated  Immunity Neutralizing Antibodies
IAVI’s roles Mission To  ensure  the development of safe, effective, accessible, preventive HIV vaccines for use throughou...
An early model  for the field 1986 ’ 87 ’ 88 ’ 89 1990 ’ 91 ’ 92 ’ 93 ’ 94 ’ 95 ’ 96 ’ 97 ’ 98 ’ 99 2000 ’ 01 ’ 02 ’ 03 ’ ...
What is IAVI? Political will and finance Research and development Clinical trials Production Health and  other systems Acc...
Early positioning   in AIDS vaccine R&D Advocacy Clinical trial network in developing world Gap-filling science Basic rese...
Public sector, academia Pharmaceutical companies, product-development partnerships Filling the gap   in AIDS vaccine R&D B...
VACCINE DEVELOPMENT IAVI’s R&D  integrates each step Public sector, academia Pharmaceutical companies, product-development...
IAVI’s R&D  integrates each step Public sector, academia Pharmaceutical companies, product-development partnerships PRODUC...
IAVI Partners Around the Globe Neutralizing Antibody Consortium Vectors Consortium Live Attenuated Consortium Innovation F...
UVRI-IAVI  lab and clinic:  Entebbe, Uganda <ul><ul><li>Before  lab/clinic  constructed </li></ul></ul><ul><ul><li>After  ...
IAVI’s Clinical Work: A History 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 IAVI-sponsored clinical trials and HIV e...
IAVI’s Clinical Trials:  A history IAVI-sponsored AIDS vaccine clinical trials 2000 2001 2002 2003 2004 2005 2006 2007 200...
“ Insanity:  doing the same thing over and over again and expecting different results.” — Albert Einstein
IAVI’s Mechanisms of I nnovation <ul><li>Scientific Consortia directed at major scientific challenges </li></ul><ul><li>Va...
Mechanisms of Innovation are now more important than ever <ul><li>Pushing the envelope with a new model … </li></ul><ul><u...
The  neutralizing antibody  challenge <ul><ul><li>Most licensed vaccines elicit neutralizing antibodies </li></ul></ul><ul...
The IAVI  Neutralizing Antibody Consortium
1. More than 1,800 blood samples collected from HIV-positive individuals around the world IAVI Human Immunology Laboratory...
1. More than 1,800 blood samples collected from HIV-positive individuals around the world 2. Samples sent to Monogram Bios...
3. IAVI and the Neutralizing Antibody Consortium review data About 1% are  “elite neutralizers” Blood samples collected Ab...
Elite Neutralizers:  score  ≥ 2.5  (N=18) Note: Donor that yielded two bnAbs- Score =2.1 Clade A Clade B Clade C CRF01_AE ...
4. Request for new samples to be collected from donors of interest  IAVI IAVI NAC  at Scripps IAVI Human Immunology Labora...
6. IAVI and NAC request samples be sent to partner labs for antibody rescue Protocol G:  The IAVI network in action IAVI I...
IAVI AIDS Vaccine Design and Development Lab IAVI Neutralizing Antibody Center at the Scripps Research Institute IAVI Huma...
Chennai Pune Kilifi Rustenburg Cape Town Lusaka Copperbelt Kigali Masaka Entebbe Nairobi 8. Ultimately, the process comes ...
Replication of the vaccine may be required for virus control  No Vaccine Vaccine  = Single-Cycle SIV Vaccine  = Live atten...
Balancing  safety and efficacy  in AIDS vaccine design
Cytomegalovirus controls SIV to levels only previously achieved with live attenuated SIV 54% of CMV vector-vaccinated monk...
IAVI is an essential component in the search for an AIDS vaccine <ul><li>IAVI’s mission has never changed but its programs...
A preventive vaccine  is the only way to end the AIDS epidemic
Imagine a world without   AIDS
 
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IAVI's Integrated R&D Program: Accelerating AIDS vaccine development

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the International AIDS Vaccine Initiative's presents its R&D strategies and approaches at the Partnering for Cures 2009 conference in New York.

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  • Most non clade B infected Score over 2.5 Top 1% 30% have some breadth
  • IAVI's Integrated R&D Program: Accelerating AIDS vaccine development

    1. 1. IAVI’s Integrated R&D Program Accelerating AIDS vaccine development
    2. 2. Source: Joint United Nations Programme on HIV/AIDS <ul><ul><li>33 million people living with HIV worldwide </li></ul></ul><ul><ul><li>7,400 new HIV infections daily </li></ul></ul><ul><ul><li>25 million AIDS-related deaths to date </li></ul></ul><ul><ul><li>2.7 million people a year become infected, including 370,000 children </li></ul></ul><ul><ul><li>270,000 children die of AIDS every year </li></ul></ul><ul><ul><li>Women bear the brunt of the epidemic, representing almost 60 percent of HIV-infected adults in Africa and half of adults worldwide </li></ul></ul>HIV continues to devastate 33 million 2007 7.5 million people living with HIV 1990 18.5 million 1995 28.5 million 2000 32 million 2005
    3. 3. AIDS vaccines are part of a sustainable, comprehensive response <ul><li>Deliver for today—better use of tools </li></ul><ul><ul><li>Prevent further spread of the virus </li></ul></ul><ul><ul><li>Treat those already infected </li></ul></ul><ul><ul><li>Mitigate societal impacts </li></ul></ul><ul><li>Develop better tools for the future </li></ul><ul><ul><li>Invest in innovation for new technologies (better drugs, diagnostics, barrier methods, microbicides, vaccines) </li></ul></ul><ul><ul><li>Better prevention —particularly AIDS vaccines—is critical for the affordability and sustainability of our commitments to universal access </li></ul></ul>
    4. 4. Vaccines can take decades to develop Measles Hepatitis B Human papilloma virus (cervical cancer) Rotavirus (diarrheal disease) Varicella zoster (chickenpox) Pertussis (whooping cough) Polio Haemophilus influenza Typhoid Malaria Human immunodeficiency virus (HIV/AIDS) INFECTIOUS AGENT (Disease) AGENT LINKED TO DISEASE IN … VACCINE LICENSED IN U.S. IN … 1953 1965 1884 1973 1953 1906 1908 1889 Early ’80s to mid-’90s 1893 1983 1963 1981 2006 2006 1995 1948 1955 1981 1989 — — YEARS ELAPSED 10 16 12-25 33 42 42 47 92 105 116 26
    5. 5. <ul><li>The Thai trial demonstrates an AIDS vaccine is possible </li></ul><ul><ul><li>Correlates may be found </li></ul></ul><ul><li>Two very potent and broadly neutralizing antibodies discovered; more coming </li></ul><ul><ul><li>New targets for Immunogen design </li></ul></ul><ul><ul><li>Passive immunity data from IAVI’s Neutralizing Antibody Consortium suggests that less antibody than previously thought may be required </li></ul></ul><ul><ul><li>Proof of principle possible </li></ul></ul><ul><li>CMI Vectors show significant promise </li></ul><ul><ul><li>Six vaccine concepts confer >2 logs suppression of viral load in pathogenic SIV- rhesus macaque model </li></ul></ul><ul><ul><li>CMV completely controls SIV infection in ~50% of monkeys </li></ul></ul>Recent Advances offer the most promise for AIDS vaccines since the discovery of HIV as the causal agent
    6. 6. RV144 trial: F irst HIV vaccine candidate to show efficacy <ul><li>A Phase IIb test-of-concept trial, based on the expected number of HIV infection endpoints, conducted by Thailand Ministry of Public Health </li></ul><ul><li>Co-primary endpoints: Prevention of HIV infection and ability to reduce viral load </li></ul><ul><li>Duration: Six years (2003-2009) </li></ul><ul><li>Sponsor: US Army, Surgeon General </li></ul><ul><li>Trial Cost/funders: US$ 105 million; US National Institute of Allergy and Infectious Diseases (75%), US Army (25%) </li></ul>THE TRIAL <ul><li>Vaccine candidate provided ~30% protection against acquisition of HIV; No effect on viral load or CD4 levels in the blood of volunteers who became HIV-infected during the study </li></ul><ul><li>Trend towards limited durability; vaccine effect appears short lived </li></ul><ul><li>Mode of transmission may be important factor; Vaccine possibly less efficacious in high-risk groups </li></ul><ul><li>Vaccine likely not applicable to diversity of strains prominent in sub-Saharan Africa </li></ul>THE RESULTS 26,675 Thai citizens screened; 16,402 Thai citizens (60% male, 40% female) enrolled; 16,395 received at least one dose of vaccine or placebo THE VOLUNTEERS
    7. 7. Immune Mechanisms for an AIDS Vaccine Cell Mediated Immunity Neutralizing Antibodies
    8. 8. IAVI’s roles Mission To ensure the development of safe, effective, accessible, preventive HIV vaccines for use throughout the world Political will and finance Research and development Clinical trials Production Health and other systems Access and uptake <ul><li>Focus </li></ul><ul><li>Speed </li></ul><ul><li>Flexibility </li></ul><ul><li>Willingness to take informed risk </li></ul><ul><li>Access is part of our mission </li></ul>Core principles
    9. 9. An early model for the field 1986 ’ 87 ’ 88 ’ 89 1990 ’ 91 ’ 92 ’ 93 ’ 94 ’ 95 ’ 96 ’ 97 ’ 98 ’ 99 2000 ’ 01 ’ 02 ’ 03 ’ 04 ’ 05 ’ 06 ’ 07 ’ 08 ’ 09 Product-development partnerships in global health Selected other public-private partnerships Working on health issues BY YEAR STARTED 1986 1989 1990 1996 1998 1999 2000 2001 2002 2003 2005 1977
    10. 10. What is IAVI? Political will and finance Research and development Clinical trials Production Health and other systems Access and uptake <ul><ul><ul><ul><li>Integrated R&D </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Professional project & Portfolio management </li></ul></ul></ul></ul><ul><li>Infrastructure and full staffing across vaccine disciplines </li></ul><ul><li>Validated laboratories </li></ul><ul><li>Applied research consortia </li></ul><ul><li>Vaccine preparedness </li></ul><ul><li>Epidemiological and social research </li></ul><ul><li>Policy studies </li></ul><ul><li>Communications and publications </li></ul><ul><li>Advocacy and training from community to international level </li></ul>
    11. 11. Early positioning in AIDS vaccine R&D Advocacy Clinical trial network in developing world Gap-filling science Basic research Applied research Preclinical development Clinical development Advanced development Large-scale Efficacy trials Public sector, academia Biotech companies Pharmaceutical companies A well-established continuum of players moves new drugs to market Basic research Applied research Preclinical development Clinical development Advanced development Large-scale Efficacy trials Public sector, academia IAVI initially worked to ensure a vaccine for the developing world by focusing on product development Biotech companies, pharmaceutical companies
    12. 12. Public sector, academia Pharmaceutical companies, product-development partnerships Filling the gap in AIDS vaccine R&D Basic research Applied research Preclinical development Clinical development Advanced development Large-scale Efficacy trials But as product failures forced big players out or moved them downstream, a development gap grew … … and IAVI moved to fill the void, creating new programs as needs arose Human Immunology Lab (2001) Neutralizing Antibody Consortium (2002) Live Attenuated Consortium (2006) AIDS Vaccine Design and Development Lab (2008) IAVI Neutralizing Antibody Center at The Scripps Research Institute (2009) Vectors Consortium (2007)
    13. 13. VACCINE DEVELOPMENT IAVI’s R&D integrates each step Public sector, academia Pharmaceutical companies, product-development partnerships RESEARCH CONSORTIA DESIGN & DEVELOPMENT LAB (Brooklyn) CLINICAL TRIALS NETWORK PRODUCT-DEVELOPMENT PARTNERSHIPS (EXTERNAL) INNOVATION FUND HUMAN IMMUNOLOGY LAB (London) NEW ALLIANCES Preclinical development Clinical development Applied research
    14. 14. IAVI’s R&D integrates each step Public sector, academia Pharmaceutical companies, product-development partnerships PRODUCT-DEVELOPMENT PARTNERSHIPS (EXTERNAL) INNOVATION FUND NEW ALLIANCES Preclinical development Clinical development Applied research <ul><li>CLINICAL TRIALS NETWORK </li></ul><ul><li>Clinical research (e.g., Protocol G) </li></ul><ul><li>Phase I trials </li></ul><ul><li>Feasibility studies </li></ul><ul><li>Small-scale efficacy trials </li></ul><ul><li>RESEARCH CONSORTIA </li></ul><ul><li>Neutralizing antibodies </li></ul><ul><li>Vectors </li></ul><ul><li>Live attenuated </li></ul><ul><li>DESIGN & DEVELOPMENT LAB </li></ul><ul><li>Antigen design </li></ul><ul><li>Vector design </li></ul><ul><li>Non-human primate prioritization </li></ul><ul><li>Process Development </li></ul><ul><li>Non-human primate studies </li></ul><ul><li>VACCINE DEVELOPMENT </li></ul><ul><li>Toxicology studies </li></ul><ul><li>Pilot manufacturing </li></ul><ul><li>Regulatory affairs </li></ul><ul><li>Manufacturing </li></ul><ul><li>HUMAN IMMUNOLOGY LAB </li></ul><ul><li>Assay development </li></ul><ul><li>Sample testing </li></ul>
    15. 15. IAVI Partners Around the Globe Neutralizing Antibody Consortium Vectors Consortium Live Attenuated Consortium Innovation Fund grant recipients IAVI-supported clinical research centers Other scientific and civil-society partners IAVI facilities
    16. 16. UVRI-IAVI lab and clinic: Entebbe, Uganda <ul><ul><li>Before lab/clinic constructed </li></ul></ul><ul><ul><li>After lab/clinic constructed </li></ul></ul><ul><ul><li>Clinic: Multiple Phase I AIDS vaccine trials, accelerated approval and enrollment vs. historical controls </li></ul></ul><ul><ul><li>Expansion: Field sites doing clinical studies in preparation for future efficacy trials </li></ul></ul><ul><ul><li>Laboratory: Validated assays,Good Laboratory Practices training </li></ul></ul><ul><ul><li>Accredited and now Gates Foundation/CAVD reference lab </li></ul></ul>
    17. 17. IAVI’s Clinical Work: A History 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 IAVI-sponsored clinical trials and HIV epidemiology studies, by year started 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 Australia
    18. 18. IAVI’s Clinical Trials: A history IAVI-sponsored AIDS vaccine clinical trials 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 Countries participating in IAVI trials DNA+Ad5—VRC Phase II First AIDS vaccine trial in Kenya DNA First AIDS vaccine trial in Zambia DNA candidates AAV candidates Adeno-based candidates ADARC DNA and MVA candidates All trials are Phase I, except where noted Belgium, Germany, India, Kenya, Rwanda, South Africa, Switzerland, Uganda, United Kingdom, United States, Zambia, Start date Final volunteer visit ADMVA ADMVA TBC-M4 ADVAX Phase IIa Ad35 First AIDS vaccine trial in India, Germany MVA candidates PreP 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 First AIDS vaccine trial in Rwanda DNA+MVA candidates ADVAX+TBC-M4
    19. 19. “ Insanity: doing the same thing over and over again and expecting different results.” — Albert Einstein
    20. 20. IAVI’s Mechanisms of I nnovation <ul><li>Scientific Consortia directed at major scientific challenges </li></ul><ul><li>Vaccine Development Laboratory </li></ul><ul><li>Innovation Fund </li></ul><ul><li>Incentives, Prizes, etc. </li></ul><ul><li>Accelerated Clinical Testing </li></ul>
    21. 21. Mechanisms of Innovation are now more important than ever <ul><li>Pushing the envelope with a new model … </li></ul><ul><ul><li>Partnership with BMGF </li></ul></ul><ul><ul><li>Move beyond mainstream HIV vaccine research; Venture capital approach </li></ul></ul><ul><ul><ul><li>‘ Seed capital’ grants for feasibility studies </li></ul></ul></ul><ul><ul><ul><li>Non-dilutive, minimal diligence, speed </li></ul></ul></ul><ul><ul><ul><li>Welcome creativity, ‘unproven’ ideas </li></ul></ul></ul><ul><ul><li>Draw from other disciplines </li></ul></ul><ul><ul><ul><li>Cross fertilization of ideas </li></ul></ul></ul><ul><ul><ul><li>Adopt advances, not trying to re-create the wheel </li></ul></ul></ul>Venture Advisory Committee Paul Klingenstein Aberdare Amir Nashat Polaris Mike Powell Sofinnova Bryan Roberts Venrock Otello Stampacchia Omega Funds Greg Weinhoff CHL Medical Brook Byers KPCB (founding member)
    22. 22. The neutralizing antibody challenge <ul><ul><li>Most licensed vaccines elicit neutralizing antibodies </li></ul></ul><ul><ul><li>Neutralizing antibodies protect against SIV/HIV challenge in animal models </li></ul></ul><ul><ul><li>Broadly neutralizing antibodies in humans against HIV exist, although they are weak. This is a solvable problem </li></ul></ul><ul><ul><li>But no candidate vaccine in the pipeline elicits broadly neutralizing antibodies against HIV </li></ul></ul>gp41 b12 2G12 2F5 4E10/Z13 CD4 gp120
    23. 23. The IAVI Neutralizing Antibody Consortium
    24. 24. 1. More than 1,800 blood samples collected from HIV-positive individuals around the world IAVI Human Immunology Laboratory, London 200 200 25 91 238 200 81 200 200 Number of donor samples from each site 200 215 Protocol G: An example of the IAVI network in action
    25. 25. 1. More than 1,800 blood samples collected from HIV-positive individuals around the world 2. Samples sent to Monogram Biosciences to screen for neutralization using IAVI algorithm IAVI Human Immunology Laboratory, London 200 200 25 91 238 200 81 200 200 Number of donor samples from each site 200 215 Protocol G: The IAVI network in action
    26. 26. 3. IAVI and the Neutralizing Antibody Consortium review data About 1% are “elite neutralizers” Blood samples collected About 10% are donors of interest Protocol G: The IAVI network in action Protocol G: The IAVI network in action
    27. 27. Elite Neutralizers: score ≥ 2.5 (N=18) Note: Donor that yielded two bnAbs- Score =2.1 Clade A Clade B Clade C CRF01_AE Rank Score Country 94UG103 92BR020 JRCSF IAVI C22 93IN905 92TH021 1 3.67 Ivory Coast 900 900 2700 2700 2700 2700 2 3 Zambia 300 300 2700 300 2700 2700 5 2.83 Ivory Coast 300 300 900 300 2700 2700 5 2.83 Ivory Coast 300 900 2700 900 2700 100 5 2.83 Kenya 300 900 900 900 2700 300 5 2.83 South Africa 300 900 900 2700 2700 100 5 2.83 Rwanda 300 2700 900 2700 2700 <100 8 2.69 Zambia 345 345 1190 1190 1190 345 10 2.67 UK 300 900 900 2700 900 100 10 2.67 Zambia 900 900 900 300 2700 100 10 2.67 Uganda 900 900 900 2700 900 <100 15 2.5 Ivory Coast 300 900 300 900 900 300 15 2.5 South Africa 100 300 300 2700 900 900 15 2.5 South Africa 300 300 300 2700 2700 100 15 2.5 UK 300 900 300 900 900 300 15 2.5 South Africa 2700 100 300 2700 2700 <100 15 2.5 Uganda 900 900 900 900 900 <100 15 2.5 Zambia 300 <100 900 300 2700 2700
    28. 28. 4. Request for new samples to be collected from donors of interest IAVI IAVI NAC at Scripps IAVI Human Immunology Laboratory 5. New samples make their way to Monogram Biosciences for screening Protocol G: The IAVI network in action
    29. 29. 6. IAVI and NAC request samples be sent to partner labs for antibody rescue Protocol G: The IAVI network in action IAVI IAVI NAC at Scripps IAVI Human Immunology Laboratory Theraclone Rockefeller University IAVI NAC at Scripps HuMabs
    30. 30. IAVI AIDS Vaccine Design and Development Lab IAVI Neutralizing Antibody Center at the Scripps Research Institute IAVI Human Immunology Lab Neutralizing Antibody Consortium members 7. When antibodies are identified, IAVI’s immunogen design partners take over IAVI has submitted a proposal to build an applied research lab in India Strand Life Sciences Elevation Biotech Chembiotek IAVI Innovation Fund recipients Lipoxen Pepscan ProSci Avatar Protocol G: The IAVI network in action
    31. 31. Chennai Pune Kilifi Rustenburg Cape Town Lusaka Copperbelt Kigali Masaka Entebbe Nairobi 8. Ultimately, the process comes full circle with clinical testing of vaccine candidates IAVI’s Network of Clinical Research Centers
    32. 32. Replication of the vaccine may be required for virus control No Vaccine Vaccine = Single-Cycle SIV Vaccine = Live attenuated SIVmac239 Evans, DT. et al (2005)
    33. 33. Balancing safety and efficacy in AIDS vaccine design
    34. 34. Cytomegalovirus controls SIV to levels only previously achieved with live attenuated SIV 54% of CMV vector-vaccinated monkeys controlled viral load to undetectable levels . . . L Picker, OHSU n=1 n=26 n=6 n=6 n=7 n=5 Control of SIV No control of SIV Unvaccinated (n=27) 4% 96% CMV alone (n=12) 50% 50% CMV + Ad5 (n=12) 60% 40%
    35. 35. IAVI is an essential component in the search for an AIDS vaccine <ul><li>IAVI’s mission has never changed but its programs have evolved continuously over the years, driven by the scientific data and the need to bridge key gaps in the field </li></ul><ul><li>IAVI operates globally and in partnership with others, which means the organization can work with the most gifted researchers and advance the most promising approaches regardless of their origin </li></ul><ul><li>IAVI’s integrated R&D program quickly and seamlessly moves a vaccine approach through every step, from concept to design to development to manufacturing to regulatory approval to clinical trial and if necessary back again </li></ul>
    36. 36. A preventive vaccine is the only way to end the AIDS epidemic
    37. 37. Imagine a world without AIDS

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