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AVAC Global Advocacy for HIV Prevention AIDS Vaccines: The basics May 2014.

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Presentation on theme: "AVAC Global Advocacy for HIV Prevention AIDS Vaccines: The basics May 2014."— Presentation transcript:

1 AVAC Global Advocacy for HIV Prevention 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 (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 Preventive HIV vaccines are meant to elicit two arms of the immune system – humoral and cellular

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

11 Preventing vs. controlling infection Courtesy of HIV Vaccine Trials Network 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

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 Virus or bacteriaYear cause discovered Year vaccine licensed Years elapsed Typhoid Haemophilus Influenzae Malaria1893None– Pertussis Polio Measles Hepatitis B Rotavirus HPV HIV1983None– 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 YEAR COMPLETED PRODUCT/ CLADE/ TRIAL NAME COUNTRIESNUMBER OF PARTICIPANTS RESULT 2003AIDSVAX B/B VAX003 Canada, Netherlands, Puerto Rico, US 5,417No effect 2003AIDSVAX B/E VAX004 Thailand2,546No effect 2007MRK-Ad5 B Step Australia, Brazil, Canada, Dominican Republic, Haiti, Jamaica, Peru, Puerto Rico, US 3,000Immunizations halted early for futility; subsequent data analysis found potential for increased risk of HIV infection among Ad5-seropositive, uncircumcised men. 2007MRK-Ad5 B Phambili South Africa801Immunizations halted based on Step result. 2009ALVAC-HIV (vCP1521) and AIDSVAX B/E Thai Prime-Boost/RV 144 Thailand16,402Modest effect (31.2%) 2013DNA and Ad5 A/B/C HVTN 505 US2,500Immunizations halted early for futility; vaccine regimen did not prevent HIV infection nor reduce viral load among vaccine recipients who became infected with HIV; follow- up continues.

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

18 StrategyPhase IPhase IbPhase IIPhase IIb Poxvirus MVA ( MHRP, EDCTP, SAAVI, GeoVax, HVTN, Oxford) MVA ( EDCTP, GeoVax) NYVAC ( HVTN ) Protein AIDSVAX ( HVTN )ALVACAIDSVAX (MHRP) gp140 ( Novartis, HVTN, SAAVI ) gp120 ( GSK ) gp41 ( EC ) mAb ( Rockefeller ) Tat Protein ( Istituto Superiore di Sanita, Novartis ) VICHERPOL ( Russian Federation ) DNA DNA plasmid ( HVTN, GeoVax, Oxford ) PENNVAX ( MHRP ) HIV-MAG ( HVTN, IAVI )HIVIS ( EDCTP ) GTU-Multi ( ANRS ) IL-12 pDNA ( HVTN ) SAAVI DNA-C2 ( SAAVI, HVTN ) Adenovirus rAd5 ( HVTN, Brigham) rAd35 ( HVTN, IAVI ) rAd26 ( Brigham ) ChAdV63.HIVconsv ( Oxford) LipopeptideHIV-LIPO-5 ( ANRS ) Sendai virusSendai SeV-G ( IAVI) Replicating viral vectorrTV ( NCAIDS/China) HIV-1HIV-1 delta ( Istituto Superiore di Sanita ) Vesicular Stomatitis virusVSV Indiana HIV gag ( HVTN) Visit for more information.www.avac.org/pxrd April 2013 Update of Vaccine Pipeline Candidates

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20 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

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

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24 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: Get involved:

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26 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:

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28 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

29 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

30 Key resources AVAC: Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID) o At Duke: o At Scripps: Collaboration for AIDS Vaccine Discovery: Global HIV Vaccine Enterprise: HIV Px R&D Database (PxRD): HIV Vaccines & Microbicides Resource Tracking Working Group: HIV Vaccine Trials Network (HVTN): International AIDS Vaccine Initiative (IAVI): Military HIV Research Program (MHRP): NIAID: NIH Vaccine Research Center (VRC): Pox-Protein Public-Private Partnership (P5):


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