Hiv Vaccines Overview


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  • Hello everyone and welcome! My name is Shaleena Theophilus and today I am fortunate enough to be able to give you an overview of HIV vaccines. CAS is the Canadian community partner for the International AIDS Vaccine Initiative and we have been involved in the community response to vaccines with IAVI since 2002. Now the first thing that you need to know is that I’m not a researcher or scientist. However, I love this stuff!! It won’t be too technical, and please if at any time you need me to clarify anything or have questions, just let me know.
  • Hiv Vaccines Overview

    1. 1. HIV Vaccines Overview Shaleena Theophilus
    2. 2. Definitions <ul><li>vaccine: A vaccine is a substance stimulates an immune response that can either prevent an infection or create a resistance to an infection. </li></ul><ul><li>No vaccine is 100% effective! Most that are used in North America are between 70 and 95% effective </li></ul><ul><li>Vaccines provide both an individual benefit and a public health benefit . </li></ul><ul><li>“ herd immunity” </li></ul>
    3. 3. <ul><li>Estimated Herd Immunity thresholds for vaccine preventable diseases </li></ul><ul><li>Disease Transmission R0[N] Herd immunity threshold </li></ul><ul><li>Diphtheria Saliva 6-7 85% </li></ul><ul><li>Measles Airborne 12-18 83 - 94% </li></ul><ul><li>Mumps Airborne droplet 4-7 75 - 86% </li></ul><ul><li>Pertussis Airborne droplet 12-17 92 - 94% </li></ul><ul><li>Polio Fecal-oral route 5-7 80 - 86% </li></ul><ul><li>Rubella Airborne droplet 5-7 80 - 85% </li></ul><ul><li>Smallpox Social contact 6-7 83 - 85% </li></ul><ul><li>^   - R0 is the basic reproduction number , or the average number of secondary infectious cases that are produced by a single index case in completely susceptible population. </li></ul>
    4. 4. Vaccine Type Disease Live, attenuated vaccine Measles, mumps, rubella, polio (Sabin vaccine), yellow fever Inactivated or “killed” vaccine Cholera, flu, hepatitis A, Japanese encephalitis, plague, polio (Salk vaccine), rabies Toxoid vaccine Diphtheria, tetanus Subunit vaccines Hepatitis B, pertussis, pneumonia caused by Streptococcus pneumoniae Conjugate vaccines Haemophilus Influenza type B, pneumonia caused by Streptococcus pneumoniae DNA vaccines In clinical testing Recombinant vector vaccines In clinical testing
    5. 5. HIV/AIDS Vaccine Mechanisms HIV VACCINE Treatment Prevent Infection Lower Initial Peak Viremia Lower Set Point or Eliminate HIV Stop Progression
    6. 6. <ul><li>preventive HIV vaccine: a vaccine designed to prevent getting infected from HIV. </li></ul><ul><li>Humoral immune system </li></ul>
    7. 7. <ul><li>Cellular system </li></ul>
    8. 8. <ul><li>therapeutic HIV vaccine: a vaccine designed to boost the immune response to HIV in a person already infected with the virus (immune based therapy). Also referred to as an immunotherapeutic vaccine. </li></ul>
    9. 9. <ul><li>Preventive HIV Vaccines </li></ul>Beyond HIV 101
    10. 10. Attachment and Entry
    11. 12.
    12. 13. Prime Boost Strategy Immune Response Prime Boost
    13. 15. HIV Genes Code Vaccine Targets <ul><li>Env: gp120 and gp41 </li></ul><ul><li>Gag: internal structural and capsid proteins </li></ul><ul><li>Pol: three replication enzymes </li></ul><ul><li>Nef: interferes with host for survival of infected T-cells </li></ul><ul><li>Tat: transcription activator protein </li></ul>
    14. 16. HIV Vaccine Strategies <ul><li>DNA </li></ul><ul><li>Peptides </li></ul><ul><li>Subunits </li></ul><ul><li>Live Vectors </li></ul><ul><li>Dendritic Cells </li></ul>Virus-like Particles / Pseudovirions +/- Adjuvants Combinations Whole killed HIV Live attenuated HIV X X (therapeutic history)
    15. 17. DNA Vaccines <ul><li>Instead of using the whole organism or its parts, these vaccines uses the microbe’s genetic material! </li></ul><ul><li>The DNA is vaccinated and then the cells take up this material. The cells secrete the antigens (a molecule that stimulates an immune response) and display them on their surfaces. In other words, the body’s own cells become vaccine-making factories. </li></ul>
    16. 18. <ul><li>HIV genes are put in a non-disease causing viruses </li></ul><ul><li>Viral vectors “transfect” the cell. </li></ul><ul><li>The cell generates and presents proteins. </li></ul><ul><li>The body responds to this as it does any other foreign substance </li></ul><ul><li>The aim is to get the immune system to recognize the HIV proteins and prepare long-lived memory cells that will &quot;remember&quot; the HIV proteins and act against the whole virus if a person later becomes exposed naturally through high-risk behavior. </li></ul><ul><li>However, the body’s immune response to the viral vector, mutations of the virus in the body and toxicity issues could limit effectiveness. </li></ul>Viral Vector Vaccines Adenovirus
    17. 19. Step Study <ul><li>MRKAd5 HIV-1 gag/pol/nef, or trivalent, vaccine, is based on adenovirus, </li></ul><ul><li>a common cold virus that has been modified so that it cannot reproduce and cause a cold in humans. The adenovirus is used as a vector, or a delivery vehicle, to transport three synthetically produced HIV genes into cells. These genes stimulate the body to generate a potent cellular immune response to HIV, producing an army of killer T-cells programmed to recognize and kill HIV-infected cells </li></ul>
    18. 21. <ul><li>Therapeutic HIV Vaccines </li></ul>
    19. 22. HIV Vaccine Strategies <ul><li>DNA </li></ul><ul><li>Peptides </li></ul><ul><li>Subunits </li></ul><ul><li>Live Vectors </li></ul><ul><li>Dendritic Cells </li></ul>Virus-like Particles / Pseudovirions +/- Adjuvants Combinations Whole killed HIV Live attenuated HIV X X (therapeutic history) HIV Vaccine Strategies <ul><li>DNA </li></ul><ul><li>Peptides </li></ul><ul><li>Subunits </li></ul><ul><li>Live Vectors </li></ul><ul><li>Dendritic Cells </li></ul>Virus-like Particles / Pseudovirions +/- Adjuvants Combinations Whole killed HIV Live attenuated HIV X X (therapeutic history)
    20. 23. Dendritic Cell Vaccines <ul><li>Dendritic cells orchestrate the body’s immune response </li></ul><ul><li>They grab foreign bodies in the blood and present them to other immune cells to trigger powerful immune system responses to destroy the foreign invaders. </li></ul><ul><li>HIV infection normally hijacks these important immune system responses and uses the dendritic cells to cross the mucosa and get to the CD4 cells. </li></ul>T Breinig, 2005
    21. 24. Dendritic Cell Vaccine in HIV-1 Infection <ul><li>Study from Barcelona, started in November 2006 </li></ul><ul><li>Our group has reported recently the first human trial of 4 therapeutic immunizations at six-week intervals with autologous monocyte-derived dendritic cells (MD-DC) loaded with heat-inactivated autologous HIV in 12 HIV infected patients who had been receiving highly active antiretroviral therapy (HAART) since early chronic infection. </li></ul><ul><li> </li></ul>
    22. 25. Immune Response to a Therapeutic HIV Vaccine Followed by Treatment Interruption in Patients With Acute or Recent HIV Infection <ul><li>This study will determine whether MRKAd5 HIV-1 gag/pol/nef vaccine followed by treatment interruption can maintain viral suppression in patients with acute or recent HIV infection. </li></ul>
    23. 26. Safety and Tolerability of and Immune Response to LC002, an Experimental Therapeutic Vaccine, in Adults Receiving Anti-HIV Treatment <ul><li>LC002 is a novel HIV therapeutic vaccine containing a DNA plasmid that codes for most of HIV-1's proteins. LC002 is a unique vaccine in that it is given through topical administration; this allows for Langerhans cells (immune cells located under the surface of the skin) to pick up the vaccine and deliver it to the lymph nodes, causing an immune reaction. </li></ul>
    24. 27. Study of the HIV gp120/NefTat/AS02A Vaccine to Treat Individuals With Chronic HIV-1 Infection on Highly Active Antiretroviral Therapy (HAART) <ul><li>The adjuvanted protein vaccine candidate consists of three recombinant viral antigens: the envelope glycoprotein gp120 and two regulatory proteins, Nef and Tat. The latter are expressed as one recombinant fusion protein, NefTat. The antigens are formulated in the proprietary AS02A adjuvant . The goal of this trial is to assess the safety and immunogenicity of the gp120/NefTat/AS02A vaccine in HIV-1-infected individuals. </li></ul>
    25. 28. Canadian Trials <ul><li>Remune® is a therapeutic vaccine made from whole HIV particles stripped of the envelope layer and sterilized. It is used to mimic an infection to boost the immune system. The dead virus is emulsified in an adjuvant called &quot;incomplete Freund's Adjuvant&quot; (IFA), a water and mineral oil mixture that helps to stimulate the immune system. </li></ul><ul><li>CTN 208 HAART alone or with Remune Vaccine followed by structured treatment interruption in early HIV infection / observation of recent HIV infection </li></ul><ul><li>CTN 203 Phase I/II Study of Remune® plus Amplivax™ </li></ul><ul><li>CTN 173 Vaccination Before Treatment Interruption </li></ul><ul><li> </li></ul>
    26. 29. Canadian HIV Vaccines Plan
    27. 30. Canadian HIV Vaccines Initiative <ul><li>On February 20, 2007, Prime Minister Stephen Harper and Bill Gates announced a partnership to fund the Canadian HIV Vaccine Initiative. The project will encourage collaboration between Canadian and international researchers and institutions in the discovery, development, clinical trials and manufacturing of vaccines within Canada for use globally. The federal government is contributing up to $111 million to the project, while the Bill and Melinda Gates Foundation will provide additional funding in the amount of $28 million. </li></ul><ul><ul><ul><li>Canadian International Development Agency </li></ul></ul></ul><ul><ul><ul><li>Public Health Agency of Canada </li></ul></ul></ul><ul><ul><ul><li>Industry Canada </li></ul></ul></ul><ul><ul><ul><li>Canadian Institutes of Health Research </li></ul></ul></ul><ul><ul><ul><li>Health Canada </li></ul></ul></ul>
    28. 31. <ul><li>Discovery and research </li></ul><ul><li>Clinical trials (low & middle income countries) </li></ul><ul><li>Production facility </li></ul><ul><li>Policy and regulatory capacity of low & middle income countries </li></ul><ul><li>Community, legal, ethical and human rights issues in Canada and globally </li></ul>
    29. 32. Global Vaccines Enterprise <ul><li>The Global HIV Vaccine Enterprise is an alliance of independent organizations around the world dedicated to accelerating the development of a preventive HIV vaccine. The Enterprise was formed in 2003 to coordinate scientific research and leverage funding to speed the discovery of a safe and effective HIV vaccine. The Enterprise was formally endorsed by the Group of 8 industrialized countries (G8) in June 2004. </li></ul><ul><li>3 guiding principles: </li></ul><ul><li>1. Continue regular scientific assessments - to reflect lessons learned, new opportunities and the influence of new discoveries 2. Establish a global process - standardization of data sharing, communication, and convening must be established to optimize progress at the global level. 3. Shared accountability - a culture of mutual accountability among partners will be necessary for the effective implementation of the scientific strategic plan. </li></ul><ul><li> </li></ul>
    30. 33. <ul><li> Basics, advocacy updates </li></ul><ul><li> Discussion paper, info sheets, HIV Vaccines and Human Rights: Community Action Kit </li></ul><ul><li> Primers </li></ul><ul><li> Information on trials </li></ul>Useful websites
    31. 34. Other useful websites <ul><li> </li></ul><ul><li> </li></ul><ul><li> </li></ul>