HIV Vaccine Development Strategies

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  • The goal is to develop a vaccine that is 100 percent effective and protects everyone from infection. However, even if a vaccine only protects some people, it could have a major impact on controlling the epidemic. A partially effective vaccine could decrease the number of people who get infected with HIV; those people, in turn, would not pass the virus on to others. Even when an HIV vaccine is developed, education and other prevention efforts will be needed so that people continue to practice safe behaviors
  • An ideal HIV vaccine should be able to elicit an immune response that recruits the appropriate effector mechanisms in order to render the organism resistant to infection. Cytotoxic T lymphocytes (CTLs), are an integral part of such a response, and thus, the development of vaccines capable of inducing strong, sustained, polyclonal, cross-reactive CTLs is a primary goal in HIV vaccine development.
  • Ebola DNA vaccine works in Monkeys DNA vaccination, perhaps more precisely called DNA-mediated immunization, refers to the direct introduction by needle injection or particle bombardment into host organism tissues of a plasmid DNA (or an RNA) which is able to cause expression of an antigenic protein directly within the transfected cells. In this sense, DNA vaccination resembles a viral infection, since the biosynthetic machinery of the host is used for protein synthesis. This may result in secondary modifications of the synthesized antigen
  • Harmless bacteria engineered to carry genes encoding HIV proteins
  • Non-HIV viruses engineered to carry genes encoding HIV proteins; do not replicate completely
  • HIV Vaccine Development Strategies

    1. 1. HIV Vaccine Development Strategies Brian Wells University of Florida October 15, 2003
    2. 2. What is a vaccine? <ul><li>Substance that teaches the body’s immune system to defend itself from a particular threat (virus, bacteria, etc.) </li></ul><ul><li>Could work in a few ways </li></ul><ul><ul><li>Prevent the virus in most people </li></ul></ul><ul><ul><li>Prevent the virus in some people </li></ul></ul><ul><ul><li>Prepare the immune system to block continued infection and eliminate the virus (measles, mumps, polio) </li></ul></ul><ul><ul><li>Delay or prevent the onset of illness or AIDS </li></ul></ul>Source: http://www.niaid.nih.gov/publications/pdf/HIVvaccinebrochure.pdf
    3. 3. Why a vaccine? <ul><li>Best long term hope for controlling the AIDS pandemic </li></ul><ul><li>800,000 – 900,000 infected in the U.S. </li></ul><ul><li>40,000 newly infected each year in U.S. </li></ul><ul><li>Globally, 14,000 infected every day </li></ul><ul><li>Each minute, 6 people under 25 are infected </li></ul><ul><li>Over 40,000,000 infected worldwide </li></ul><ul><li>Over 16,000,000 have already died from HIV-related illness </li></ul>Source: http://www.cdc.gov/nchstp/od/news/At-a-Glance.pdf
    4. 4. What type of vaccine? <ul><li>Preventative vs. Therapeutic </li></ul><ul><ul><li>Multiple vaccines may be needed </li></ul></ul><ul><ul><li>Preventative vaccine could stop the spread of HIV but can not cure someone who is already infected. </li></ul></ul><ul><ul><li>Therapeutic vaccine could be used to treat individuals with HIV </li></ul></ul><ul><ul><li>What works to prevent HIV infection may not necessarily work in individuals who are already infected </li></ul></ul>
    5. 5. Challenges in developing a vaccine <ul><li>HIV continually mutates and recombines </li></ul><ul><li>HIV infects helper T cells (difficult to design a vaccine that needs to stimulate the very cells that are targeted) </li></ul><ul><li>HIV can be transmitted as free virus and in infected cells </li></ul><ul><li>Do not know what constitutes an effective immune response </li></ul><ul><li>Lack a good animal model for vaccine testing (but several studies have provided useful results) </li></ul>
    6. 7. Types of Vaccines <ul><li>Peptide Epitopes </li></ul><ul><ul><li>Status: In Phase I trials </li></ul></ul><ul><ul><li>Advantages: Simple and inexpensive to prepare; probably safe </li></ul></ul><ul><ul><li>Disadvantages: Can accommodate limited amount of HIV genetic material; stability challenges </li></ul></ul><ul><ul><li>Ex: HIV peptides </li></ul></ul>
    7. 8. Types of Vaccines <ul><li>DNA </li></ul><ul><ul><li>Status: In Phase I trials </li></ul></ul><ul><ul><li>Advantages: Simple and inexpensive to prepare </li></ul></ul><ul><ul><li>Disadvantages: Some worry that integration of HIV genes into human cells could harm patients (no current evidence of this); current vaccines elicit modest immune responses </li></ul></ul><ul><ul><li>Ex: Naked DNA containing one or more HIV genes </li></ul></ul>
    8. 9. Types of Vaccines <ul><li>Live vectors </li></ul><ul><ul><li>Status: In Phase I trials </li></ul></ul><ul><ul><li>Advantages: Simple and inexpensive to prepare; probably safe </li></ul></ul><ul><ul><li>Disadvantages: Can accommodate limited amount of HIV genetic material; stability challenges </li></ul></ul><ul><ul><li>Ex: Live bacterial vectors (harmless bacteria with genes to produce HIV proteins) </li></ul></ul>
    9. 10. Types of Vaccines <ul><li>Combination of Elements </li></ul><ul><ul><li>Status: In Phase II Trials </li></ul></ul><ul><ul><li>Advantages: Should stimulate both arms of immune response </li></ul></ul><ul><ul><li>Disadvantages: Current combinations elicit modest immune responses </li></ul></ul><ul><ul><li>Ex: pure gp120 protein plus canarypox vector </li></ul></ul>
    10. 11. Types of Vaccines <ul><li>Recombinant Viral Proteins </li></ul><ul><ul><li>Status: In Phase II and Phase III trials </li></ul></ul><ul><ul><li>Advantages: Safe and simple to prepare </li></ul></ul><ul><ul><li>Disadvantages: Vaccine-elicited antibodies have failed to recognize HIV from patients </li></ul></ul><ul><ul><li>Ex: Viral surface proteins (i.e. gp120) </li></ul></ul>
    11. 12. Types of Vaccines <ul><li>Pseudovirions </li></ul><ul><ul><li>Status: Close to Phase I trials </li></ul></ul><ul><ul><li>Advantages: Present HIV surface and internal proteins in a relatively natural conformation </li></ul></ul><ul><ul><li>Disadvantages: Difficult to produce </li></ul></ul>
    12. 13. Types of Vaccines <ul><li>Replicons </li></ul><ul><ul><li>Status: Close to Phase I trials </li></ul></ul><ul><ul><li>Advantages: Probably safe; can accommodate several HIV genes </li></ul></ul><ul><ul><li>Disadvantages: Complicated to prepare </li></ul></ul>
    13. 14. Types of Vaccines <ul><li>Live-Attenuated </li></ul><ul><ul><li>Status: Not under study in humans; being assessed in nonhuman primates </li></ul></ul><ul><ul><li>Advantages: Most closely mimics HIV; gives excellent protection in animal models </li></ul></ul><ul><ul><li>Disadvantages: Virus could potentially cause disease </li></ul></ul>
    14. 15. Types of Vaccines <ul><li>Whole-Killed </li></ul><ul><ul><li>Status: Not under study in humans </li></ul></ul><ul><ul><li>Advantages: Might present HIV surface proteins in a relatively natural conformation depending on inactivation procedure </li></ul></ul><ul><ul><li>Disadvantages: Slight risk that preparations might include some active virus; difficult to produce in large amounts </li></ul></ul>
    15. 16. AIDSVAX Phase III Trial <ul><li>Produced by VaxGen </li></ul><ul><li>Phase III in U.S. and Thailand </li></ul><ul><li>Bivalent vaccine composed of gp120 proteins from HIV-1 subtypes B and E </li></ul><ul><li>Proven safe and effective for stimulating antibody production against B and E (most common in Thailand) </li></ul><ul><li>However, what constitutes an effective immune response to HIV? </li></ul>
    16. 17. Questions?

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