AN  .END .  TO.AIDS Immune Based Therapy For The Treatment Of HIV Infection Past, Preset and Future Richard Trauger, PhD
Immune Based Therapy (IBT) <ul><li>Active IBT: Designed to turn on an immune response </li></ul><ul><ul><li>Vaccines </li>...
Evolution of an immune response Innate immunity is characterized by an Inflammatory response that precedes adaptive immunity
Adaptive Immunity Increase Titer Increase CD4 Effectors (helpers) Increase CD8 effectors (killers) Vaccines
In The Beginning… <ul><li>Anti-viral therapy </li></ul><ul><ul><li>Chemical disruption of the virus replication cycle </li...
Anti-viral drug Treatment <ul><li>Clear reduction of viral burden </li></ul><ul><li>Structure Treatment Interruptions show...
Immune based therapies  <ul><li>Evidence of activity by recovery of immune functions  </li></ul><ul><ul><li>Antibodies +++...
WTF?  <ul><li>ARV failure to restore immunity </li></ul><ul><ul><li>Infection wipes out the HIV immune cells first </li></...
Hyper-Activation and Immunological Exhaustion <ul><li>Increased T cell activation is now widely accepted as an important f...
Inflammation
Chronic inflammation as a barrier to IBT   <ul><li>HAART improves CD4 cells count  </li></ul><ul><li>Not all CD4 cells are...
Elite Controllers HIV/AIDS  •  CID 2005:41  Walker Topics in HIV Medicine 2007
Elite control and the Immune Response Elite controllers provide a unique opportunity to examine the relationship between v...
The correlates of protection are still to de defined <ul><li>Certain HLA class I alleles are enriched in HIV controllers a...
HIV Controller Consortium <ul><li>Extensive viral and host genetic analyses are currently underway through the HIV Control...
Lessons from Elite Controllers: HAART and IBT <ul><li>Studies of ES have shown that control of fully pathogenic HIV-1 is p...
ERAMUNE 01: Enrolling people with HIV who are on a fully suppressive ARV regimen and who are judged to have a very small r...
Current IBTs which could be used with HAART <ul><li>Active IBT </li></ul><ul><li>Autologous </li></ul><ul><ul><li>Dendriti...
Role for Passive immunotherapy <ul><li>Anti-LFA-1 antibody (Cytolin) </li></ul>AIDS Research and Therapy  2009,  6 :15
Summary <ul><li>A variety of data indicate that risk of transmission of HIV is markedly reduced at plasma HIV RNA levels b...
Upcoming SlideShare
Loading in …5
×

Immune Based Therapies for HIV Richard Trauger, phd

2,183 views

Published on

Presentation on Immune Based Therapies and their implications for HIV treatment presented at the Fenway Health Center, Boston, MA for the public education conference An End To AIDS - How A State Bill Can Change Everything conducted by SearchForACure.org, the Fenway Health
Center, and the MA Dept. of Public Health

Published in: Health & Medicine
0 Comments
3 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
2,183
On SlideShare
0
From Embeds
0
Number of Embeds
6
Actions
Shares
0
Downloads
26
Comments
0
Likes
3
Embeds 0
No embeds

No notes for slide

Immune Based Therapies for HIV Richard Trauger, phd

  1. 1. AN .END . TO.AIDS Immune Based Therapy For The Treatment Of HIV Infection Past, Preset and Future Richard Trauger, PhD
  2. 2. Immune Based Therapy (IBT) <ul><li>Active IBT: Designed to turn on an immune response </li></ul><ul><ul><li>Vaccines </li></ul></ul><ul><ul><li>Ex vivo expansion of immune cells </li></ul></ul><ul><ul><li>Cytokines </li></ul></ul><ul><li>Passive IBT: Designed to deliver a specific type of immunity directly into the blood </li></ul><ul><ul><li>Antibodies </li></ul></ul>
  3. 3. Evolution of an immune response Innate immunity is characterized by an Inflammatory response that precedes adaptive immunity
  4. 4. Adaptive Immunity Increase Titer Increase CD4 Effectors (helpers) Increase CD8 effectors (killers) Vaccines
  5. 5. In The Beginning… <ul><li>Anti-viral therapy </li></ul><ul><ul><li>Chemical disruption of the virus replication cycle </li></ul></ul><ul><li>Immune based therapy </li></ul><ul><ul><li>Biological disruption of the virus replication cycle </li></ul></ul>TIME Viral Burden? HIV-specific Immunity TIME Viral Burden HIV-specific Immunity?
  6. 6. Anti-viral drug Treatment <ul><li>Clear reduction of viral burden </li></ul><ul><li>Structure Treatment Interruptions showed no recovery of HIV specific immunity </li></ul>
  7. 7. Immune based therapies <ul><li>Evidence of activity by recovery of immune functions </li></ul><ul><ul><li>Antibodies +++ </li></ul></ul><ul><ul><li>Cell Mediated Immunity +++ </li></ul></ul><ul><ul><li>CTL +/- </li></ul></ul><ul><li>Transient improvement in CD4 cell numbers </li></ul><ul><li>Marginal to no impact on viral burden </li></ul>
  8. 8. WTF? <ul><li>ARV failure to restore immunity </li></ul><ul><ul><li>Infection wipes out the HIV immune cells first </li></ul></ul><ul><ul><li>Immune exhaustion from prolonged viral infection </li></ul></ul><ul><li>IBT failure to lower viral burden </li></ul><ul><ul><li>Immune exhaustion from prolonged viral infection </li></ul></ul><ul><ul><li>No clear indication of the immunological function that could control vial burden </li></ul></ul>Why The Failures? “ If you don’t know where you’re going any road will get you there.” c.cat
  9. 9. Hyper-Activation and Immunological Exhaustion <ul><li>Increased T cell activation is now widely accepted as an important factor in the pathogenesis of HIV. </li></ul><ul><li>Widespread activation-induced death of effector T cells eventually drains the naive and resting memory T cell pools, which eventually leads to immunologic exhaustion </li></ul>
  10. 10. Inflammation
  11. 11. Chronic inflammation as a barrier to IBT <ul><li>HAART improves CD4 cells count </li></ul><ul><li>Not all CD4 cells are equal </li></ul><ul><ul><li>CD4 IL-17 producing cells are lost early </li></ul></ul><ul><ul><li>CD4 IL-17 producing cells control gut bacteria </li></ul></ul><ul><li>Delay in HAART may limit the response to immune based therapy </li></ul>
  12. 12. Elite Controllers HIV/AIDS • CID 2005:41 Walker Topics in HIV Medicine 2007
  13. 13. Elite control and the Immune Response Elite controllers provide a unique opportunity to examine the relationship between viral characteristics and host genetics/immune responses in a successful model of durable HIV control without the use of antiretroviral therapy. Insight gained from these individuals could be used as a platform for studies aimed at therapeutic vaccines and the eradication of HIV.
  14. 14. The correlates of protection are still to de defined <ul><li>Certain HLA class I alleles are enriched in HIV controllers and are associated with strong Gag-specific CD8IFN-IL-2 T cells. </li></ul><ul><li>However, the absence of evidence of T cell-mediated control in many controllers suggests the presence of alternative mechanisms for viral control in these individuals. </li></ul><ul><li>Defining mechanisms for virus control in “non-T-cell controllers” might lead to insights into preventing HIV transmission or preventing virus replication. </li></ul>
  15. 15. HIV Controller Consortium <ul><li>Extensive viral and host genetic analyses are currently underway through the HIV Controller Consortium, which seeks to enroll 1000 elite controllers and 1000 viremic controllers in order to perform a whole-genome association study to define the genetic basis for this remarkable phenotype. </li></ul><ul><li>This collaborative effort will extend the current study in the hope of defining disease pathways that not only predict durable control of infection but can also lead to new interventions to achieve this state in persons with otherwise-progressive HIV infection. </li></ul>
  16. 16. Lessons from Elite Controllers: HAART and IBT <ul><li>Studies of ES have shown that control of fully pathogenic HIV-1 is possible. </li></ul><ul><li>This control typically occurs shortly after primary infection </li></ul><ul><li>Thus one strategy for an effective therapeutic vaccine may be to initiate HAART in primary infection and then to immunize patients to build up an effective adaptive immune response. </li></ul>Control of HIV-1 Replication in Elite Suppressors . J. Blankson, Discovery Medicine March 24, 2010
  17. 17. ERAMUNE 01: Enrolling people with HIV who are on a fully suppressive ARV regimen and who are judged to have a very small reservoir of infected cells based on a measurement of HIV DNA in the blood. The study will enroll 28 people living with HIV in Paris, Milan, Barcelona and London. Katlama and her colleagues will add Isentress and Selzentry to everyones regimen, an approach known as treatment intensification, to help maximize control of HIV replication. Eight weeks after people add Isentress and Selzentry, the research team will give them two cycles of IL-7 injections . The primary aim is to simply decrease the size of the HIV reservoir. ERAMUNE 02: Overall, 28 HIV-positive patients will have their antiretroviral treatment intensified and will be randomly assigned to either a control or an experimental group. The experimental group will receive an additional vaccine treatment , in the hopes that this new combination will completely eradicate HIV from the infected individual’s body. HAART plus Treatment Intensification and IBT
  18. 18. Current IBTs which could be used with HAART <ul><li>Active IBT </li></ul><ul><li>Autologous </li></ul><ul><ul><li>Dendritic cell vaccines </li></ul></ul><ul><ul><li>Redirected Gag specific T Cell Vaccines </li></ul></ul><ul><li>Non-autologous </li></ul><ul><ul><li>Viral protein specific CTL inducing vaccines </li></ul></ul><ul><ul><li>Polyvalent CTL inducing Vaccines </li></ul></ul><ul><ul><li>Neutralizing antibodies </li></ul></ul><ul><ul><li>IL-7 stimulation </li></ul></ul>
  19. 19. Role for Passive immunotherapy <ul><li>Anti-LFA-1 antibody (Cytolin) </li></ul>AIDS Research and Therapy 2009, 6 :15
  20. 20. Summary <ul><li>A variety of data indicate that risk of transmission of HIV is markedly reduced at plasma HIV RNA levels below 2000 copies/mL, a level of viremia at which progression of disease is also slowed. (Walker, Topics in Med) </li></ul><ul><li>Elite controllers may provide a direction for the development of an effective immune based therapy </li></ul><ul><ul><li>First evidence of immunological control of viral burden </li></ul></ul><ul><ul><li>Probably not associated with one type of response </li></ul></ul><ul><li>Intensive HAART plus an effective immune based therapy may provide a therapeutic regimen that can result in long term immune control of the virus </li></ul>

×