1. AIDS Vaccines: the basics CindraFeuer AVAC: Global Advocacy for HIV Prevention 20 April 2010 The HIV Research Catalyst Forum Baltimore, Maryland April 2010www.avac.org/presentations

2. AIDS Vaccine Presentation Overview April 2010www.avac.org/presentations What is a vaccine? How would an AIDS vaccine work? Where are we in the search? How to get involved?

3. April 2010www.avac.org/presentations 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. What is a vaccine?

4. Why the interest in an AIDS vaccine? April 2010www.avac.org/presentations Need for a range of HIV prevention methods (There’s no silver bullet) Proven prevention options have slowedHIV’s spread but thousands of people continue to get infected daily Vaccines are one of the world’s most effective public health tools Cost-effective (administered once)

5. Types of AIDS vaccines April 2010www.avac.org/presentations Preventive Vaccines: – Designed for people who are not infected with HIV – Reduces risk of infection or viral load set point after infection Therapeutic Vaccines: – Designed for people who are living with HIV – Uses the body’s immune system to control HIV in the body

6. How does a vaccine work? April 2010www.avac.org/presentations By teaching the body to recognize and fight invaders – Subunit—small amount of virus or copy of virus in the form of vaccine – Body reacts by creating antibodies or killer cells – Upon viral infection, antibodies and killer cells are there waiting to attack

7. How a preventive AIDS vaccine would work April 2010www.avac.org/presentations Humoral – Antibodies – Y-shaped proteins that look for HIV to stop it from infecting cells – Adaptive immune system

8. How preventive vaccines would work (con’t) April 2010www.avac.org/presentations Cellular immunity – White blood cells or CTL – White blood cells that look for HIV-infected cells and kill them

9. How an HIV vaccine might work April 2010www.avac.org/presentations HIV PREVENT ESTABLISHED INFECTION? ***** Vaccine Administered A A. Lower Initial Peak of Viremia A B B. Lower Set Point B C. C.Delay Progression C HAART

10. How are most vaccines made? April 2010www.avac.org/presentations Live attenuated vaccines(examples: measles, mumps, and rubella) Whole killed virus vaccines (example: influenza and rabies)

11. How are AIDS vaccines made? April 2010www.avac.org/presentations Recombinant vaccines Do not contain HIV DNA vaccines Vector vaccines

12. Developing an AIDS vaccine is difficult April 2010www.avac.org/presentations Numerous modes of transmission HIV kills the very immune cells uses 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 through out the world

13. Vaccine research in perspective www.avac.org/presentations Virus or bacteriaYear cause discovered Year vaccine licensed Years elapsed Typhoid18841989105 HaemophilusInfluenzae1889198192 Malaria1893None– Pertussis1906199589 Polio1908195547 Measles1953199542 Hepatitis B1965198116 Rotavirus1973199825 HPV1974200733 HIV1983None– Duration between discovery of microbiologic cause of selected infectious diseases and development of a vaccine Source: AIDS Vaccine Handbook, AVAC, 2005

14. Timeline of results from AIDS vaccine efficacy trials April 2010www.avac.org/presentations

15. Thai prime-boost AIDS vaccine trial April 2010www.avac.org/presentations

16. The Thai trial: RV144 April 2010www.avac.org/presentations First glimpse of evidence a vaccine has a protective effect 31.2 % (modest effect) Not for licensure Research ongoing

17. Ongoing vaccine trials April 2010www.avac.org/presentations About two dozen safety and immunogenicity studies HIV Vaccine Trials Network (HVTN 505)

18. HVTN 505 April 2010www.avac.org/presentations Phase II, uses a DNA prime/rAd5 boost (T cell- based) Currently recruiting circumcised MSM at sites across the US Parts of this vaccine regimen are similar to the vaccine used in Step and Phambili Reduce viral load in individuals who receive the vaccine and go on to become infected with HIV

19. HVTN 505 continued April 2010www.avac.org/presentations Not expected to prevent HIV infection Not on the path to licensure Better understand and develop T cell-based vaccines Like in all prevention research studies, all participants will receive the best available prevention services Results expected 2013 More information about HVTN 505: www.hopetakeaction.orgwww.hopetakeaction.org Get involved: www.bethegeneration.org; www.hvtn.org/about/sites/html; www.vaccineforall.orgwww.bethegeneration.orgwww.hvtn.org/about/sites/htmlwww.vaccineforall.org

20. What is needed now? April 2010www.avac.org/presentations Vaccination to protect against infection, mitigate infection and prevent transmission to others Focus investigation to better understand the Thai trial result Ensure diversity of approaches beyond the Thai trial, exploring novel directions for vaccine design More community involvement

21. What can you do? April 2010www.avac.org/presentations Join a Community Advisory Board Ask your local AIDS organizations if they are aware of or involved in vaccine research Support trial volunteers and recognize their contribution to the fight against HIV/AIDS Volunteer to be in a clinical trial

22. Stay informed April 2010www.avac.org/presentations Join the Advocates Network AVAC publications: Px Wire, Anticipating and Understanding Results series, AVAC Report Attend events (AVAC calendar) AVAC: Global Advocacy for HIV Prevention www.avac.org www.avac.org International AIDS Vaccine Initiative www.iavi.org www.iavi.org HIV Vaccine Trials Network www.hvtn.org www.hvtn.org Global HIV Vaccine Enterprise www.hivvaccineenterprise.orgwww.hivvaccineenterprise.org

23. The search must go on April 2010www.avac.org/presentations “... they are ill discoverers that think there is no land when they can see nothing but sea.” — Francis Bacon (1561-1626)