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AIDS Vaccines: The basics

AIDS Vaccines: The basics. May 2014. Presentation Overview. What is a vaccine? How would an AIDS vaccine work? Where are we in the search? What is needed now?. What is a vaccine?. A substance that teaches the immune system how to protect itself against a virus or bacteria

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AIDS Vaccines: The basics

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  1. AIDS Vaccines: The basics May 2014

  2. Presentation Overview • What is a vaccine? • How would an AIDS vaccine work? • Where are we in the search? • What is needed now?

  3. What is a vaccine? • A substance that teaches the immune system how to protect itself against a virus or bacteria • No effective AIDS vaccine available today • AIDS vaccines cannot cause HIV • No vaccine is 100% effective • Most vaccines licensed in the US 70%-95% effective

  4. Why the interest in AIDS vaccines? • Proven prevention options have slowed HIV’s spread but thousands of people continue to get infected daily • There is a need for a range of HIV prevention methods; there is no silver bullet • Vaccines are one of the world’s most effective public health tools • Cost-effective – single or several doses likely provide protection for years

  5. How vaccines are crucial to ending AIDS

  6. Types of AIDS vaccines • Preventive vaccines • Designed for people who are not infected with HIV • If effective, would reduce risk of infection • May also reduce viral load set point after infection • Therapeutic vaccines • Designed for people who are living with HIV • If effective, would use the body’s immune system to help control or clear HIV in the body

  7. How do preventive vaccines work? By teaching the body to recognize and fight a pathogen • Vaccine carries something that ‘looks and feels’ like the pathogen, but is not really the pathogen • Body reacts by creating antibodies or killer cells and a memory response • Upon exposure to the ‘real’ pathogen, antibodies and killer cell are waiting to respond and attack Note: This is a general definition, not specific to HIV vaccines

  8. How might a preventive HIV vaccine work? A preventive vaccine would teach the body to recognize and fight HIV, should it be exposed • Vaccine would carry a component that ‘looks and feels’ like HIV, but is not HIV and cannot cause HIV infection • Component might be a synthetic fragment of HIV known to generate an immune response • Body would react by creating antibodies and/or killer cells and a memory response • Upon possible exposure to HIV, antibodies and killer cells would be waiting to prevent and/or control infection

  9. Immune responses Preventive HIV vaccines are meant to elicit two arms of the immune system – humoral and cellular (1) Humoral immunity • Primary action of humoral arm is creating antibodies • Antibodies are Y-shaped proteins developed in response to a pathogen to prevent infection

  10. Immune responses Preventive HIV vaccines are meant to elicit two arms of the immune system – humoral and cellular (2) Cellular immunity • Cytotoxic T lymphocytes and T-helper cells • Cells recognize HIV-infected cells and kill them

  11. Preventing vs. controlling infection PREVENT ESTABLISHED INFECTION? ***** C A HAART B Vaccine Administered A. Lower Initial Peak of Viremia B. Lower Set Point C.Delay Progression HIV Courtesy of HIV Vaccine Trials Network

  12. How have most vaccines been made? • Live attenuated vaccines (examples: measles, mumps, and rubella) • Whole killed virus vaccines (example: influenza and rabies)

  13. How are AIDS vaccines made? Recombinant vaccines • DNA vaccines • Vector vaccines • Subunit vaccines Do not contain HIV – only synthetic copies of fragments of HIV that will create an immune response but do not cause HIV infection

  14. Developing an AIDS vaccine is difficult • Numerous modes of transmission • HIV kills the very immune cells used in defending the body against HIV • HIV makes many copies of itself and mutates, making itself unrecognizable to the immune system • Mutation leads to different subtypes of the virus throughout the world

  15. Vaccine research in history Duration between discovery of microbiologic cause of selected infectious diseases and development of a vaccine Source: AIDS Vaccine Handbook, AVAC, 2005

  16. AIDS vaccine efficacy trial results www.avac.org/presentations

  17. Preventive HIV Vaccine Clinical Trials: A Research Timeline April 2013 * HVTN 505, Phase IIb HVTN 094, Phase II EuroNeut-41, Phase I IPCAVD004/IAVIB003, Phase I HVTN 085, Phase Ib RV 305, Phase II ANRS 149 LIGHT, Phase II HVTN 073E/SAAVI102, Phase I HVTN 076, Phase Ib HVTN 092, Phase I HVTN 099, Phase I HVTN 098, Phase I TaMoVac II, Phase II ISS P-002, Phase I HVTN 097, Phase I TAMOVAC01-MZ, Phase I GV-TH-01, Phase I SSC-0710, Phase I HVTN 088, Phase I IAVI S001, Phase I RV262, Phase I NCAIDS X111012202, Phase II 2009 VACCINE STRATEGY Poxvirus (canarypox) Poxvirus (MVA) Poxvirus (NYVAC) HIV-1 2010 Recombinant Vaccinia Virus Tiantan Sendai virus 2010 DNA (alternative delivery) HVTN 086/SAAVI103, Phase I HVTN 096, Phase I IAVI B004, Phase I DNA (conventional delivery) HVTN 087, Phase II Lipopeptide Protein (gp120) 2010 Protein (gp140) Protein (other) Adenovirus (human) 2010 Replicating viral vaccine Vesicular stomatitis virus Poly-ICLC (adjuvant) MF59C.1 (adjuvant) * Trial end-dates are estimates; due to the nature of clinical trials the actual dates may change. For full trial details, see www.avac.org/pxrd

  18. April 2013 Update of Vaccine Pipeline Candidates Visit www.avac.org/pxrd for more information.

  19. Antibody research • Advanced screening techniques have identified 100s of broadly neutralizing antibodies (bNAbs) • Aim to induce bNAbs with a vaccine • Scientists understand shape and identified where they bind with HIV • Binding of antibody with virus will block infection • Some bNAbs being tested as passive vaccines • Some may be developed into active vaccine candidates

  20. Neutralizing Antibodies: Research pathways HIV-infected individual Broadly neutralizing antibodies Reverse Engineering Vaccines Passive Immunization Trials Development of clinical grade purified form of BNAbs A protein from HIV surface (envelope) interacting with an antibody. Phase I: Safety and pharmacokinetic evaluation Molecular characterization of the interaction between HIV envelope and BNAbs * Modified env Phase II/III: Efficacy trials Development of immunogens to mimic the portion of HIV envelope that connects with BNAbs * ? Combination of several immunogens = vaccine Source: Adapted from: Burton, “Antibodies, viruses and vaccines,” Nature Reviews Immunology (2002) 2: 706-713.

  21. HVTN 505 and Adenovirus • Phase IIb, in circumcised MSM across US • DNA prime/rAd5 boost (T cell-based) • Immunizations halted in April 2013 due to futility • No statistically significant difference between infections in vaccine vs. placebo arm; based on review, trial would never be able to find a difference • All participants received the best available prevention services, however a number still became infected • Ad5 vector candidates will not move forward any further; more attention/scrutiny around other adenovirus vectors  More information about HVTN 505: www.hopetakesaction.org Get involved: www.bethegeneration.org; www.hvtn.org/about/sites/html; www.vaccineforall.org

  22. The Thai prime boost trial: RV144 • First glimpse of evidence a vaccine has a protective effect • 31.2 % (modest effect) • Not for licensure • Sept 2011 – announcement of two immune responses potentially linked to risk of infection • Research ongoing More information about Rv144 and the follow-up at: http://hivresearch.org/research.php?ServiceID=13

  23. Future priorities • Continued clinical research • P5 strategy – large scale trials following RV 144 results in South Africa and Thailand • Advancement of candidates/strategies currently in smaller scale trials, depending on results • Continued preclinical work to discover bNAbs, new vectors, and other strategies and advance them to candidates and clinical trials

  24. What is needed now? • Monitor timelines of clinical trials, especially delays and the reasons for them • Ensure diversity of approaches beyond P5 strategy, exploring novel directions for vaccine design • More stakeholder involvement, e.g., on trial design, standard of prevention/care, decision-making on moving candidates through the clinical pipeline

  25. Key resources • AVAC: www.avac.org/vaccines • Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID) • At Duke: www.chavi-id-duke.org • At Scripps: www.cavi-id.org • Collaboration for AIDS Vaccine Discovery: www.cavd.org • Global HIV Vaccine Enterprise: www.vaccineenterprise.org • HIV Px R&D Database (PxRD): www.data.avac.org • HIV Vaccines & Microbicides Resource Tracking Working Group: www.hivresourcetracking.org • HIV Vaccine Trials Network (HVTN): www.hvtn.org • International AIDS Vaccine Initiative (IAVI): www.iavi.org • Military HIV Research Program (MHRP): www.hivresearch.org • NIAID: www.niaid.nih.gov/topics/hivaids/research/vaccines/Pages/default.aspx • NIH Vaccine Research Center (VRC): www.vrc.nih.gov • Pox-Protein Public-Private Partnership (P5): www.hivresearch.org/media/pnc/9/media.749.pdf

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