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Effective HIV vaccines are possible: update on the science for non-scientists

Effective HIV vaccines are possible: update on the science for non-scientists



The Power of Vaccines: ‘getting to zero’ for HIV and TB was an event hosted by the TB/HIV and Prevention Working Groups of the UK Consortium on AIDS and International Development. The meeting was ...

The Power of Vaccines: ‘getting to zero’ for HIV and TB was an event hosted by the TB/HIV and Prevention Working Groups of the UK Consortium on AIDS and International Development. The meeting was sponsored by Pamela Nash MP and held on Friday, 18th May 2012, in Portcullis House, Westminster. Read more at http://storify.com/PamojaUK/the-power-of-vaccines




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    Effective HIV vaccines are possible: update on the science for non-scientists Effective HIV vaccines are possible: update on the science for non-scientists Presentation Transcript

    • Effective HIV vaccines are possible: update on the science for non-scientists Robin Shattock Infectious Diseases, Medicine, St Mary’s, Imperial College, London, UK
    • •The total number living with HIV continues to rise •HIV prevalence (33 million) constant at 0.8% of global population since 2001 •6.6 million are now on antiretroviral treatment (ART) •9 million are waiting to receive it •For every person starting ART two people are newly infected“Successful provision of •20 million more people predicted touniversal treatment acquire HIV by 2031access may be critically •increasing potential treatment costs updependent on reducing to $35 billion a year2.the number of newinfections” 1. UNAIDS, AIDS at 30: Nations at the Crossroads (2011) 2. R. Hecht et al., Lancet 376, 1254 (2010).
    • Challenges in developing a vaccine against HIV?•Classic vaccines mimic natural immunity against re-infection : no one has recovered from HIV-1 infection.•Most vaccines protect against disease, not againstinfection; HIV infection may remain latent for longperiods before causing disease (provirus).•Protection against HIV infection may require sterilizingimmunity (preventing entry); no current vaccine is knowto do this.•Many vaccines use attenuated pathogens, this approachwould not be appropriate for HIV due to inherent safetyconcerns.•HIV has multiple mechanisms of immune evasionincluding: massive diversity, high mutation rate, virallatency (hiding) and antigen masking (cloaking)
    • Vaccine research in perspectiveDuration between discovery of microbiologic cause of selected infectious diseases and development of a vaccine Virus or bacteria Year cause Year vaccine Years elapsed discovered licensed Typhoid 1884 1989 105 Haemophilus Influenzae 1889 1981 92 Malaria 1893 None – Pertussis 1906 1995 89 Polio 1908 1955 47 Measles 1953 1995 42 Hepatitis B 1965 1981 16 Rotavirus 1973 1998 25 HPV 1974 2007 33 HIV 1983 None – Source: AIDS Vaccine Handbook, AVAC, 2005
    • What’s in the prevention tool box? 1 2 4 3 Coates et al., Lancet 2008
    • The HIV prevention revolution VACCINES •AIDS vaccine shows first efficacy in clinical trials •Replicating viral vector effective in controlling SIV in animal studies •Multiple new antibodies and targets on HIV discoveredMICROBICIDES •Microbicide gel (CAPRISA 004) reduces HIV infections in womenTREATMENT AS PREVENTION •Initiating ART earlier reduces HIV transmission among discordant couplesPRE-EXPOSURE PROPHYLAXIS •Oral drugs reduces HIV infections among MSM and transgendered women
    • New biomedical intervention strategiesStudy Effect size (CI)Prime-boost HIV 31% (1, 51)Vaccine (Thai RV144)1% tenofovir gel 39% (6, 60)(Caprisa 004, Karim et al.)TDF/FTC oral-PrEP in MSM 44% (15, 63)(iPrEx, Grant et al 2010)Medical male circumcision 57% (42, 68)(MMC) (Orange Farm, Rakai, Kisumu)TDF/FTC oral-PrEP in 63% (22, 83)*heterosexuals (TDF2, CDC)TDF oral-PrEP in serodiscordant 62% (34, 78)*Partner (Partners PrEP)TDF/FTC oral-PrEP in serodiscordant 73% (49, 85)*Partner (Partners PrEP)Immediate ART for positive 96% (82, 99)*Partners (HPTN052) 0% 10 20 30 40 50 60 70 80 90 100% Efficacy *Provisional
    • The Thai trial (RV144): light in the tunnel?• 125 infections from17,115 participants• 74 out of 8,198 volunteers who received placebo• 51 out of 8,917 volunteers who received prime boost vaccine• Protective efficacy a little over 31% p=0.039
    • RV 144 Vaccination and Follow- up Schedule HIV test, risk assessment and counseling 0.5 1 2 3 (time in years)6-month vaccination schedule 3 years of follow-up (every 6 mo.) ALVAC®-HIV (vCP1521) priming at weeks 0, 4, 12, 24 AIDSVAX® B/E gp120 (alum adjuvant) boosting at weeks 12, 24
    • 1.0 .96 Placebo 0.9 .84 0.8Pr obability of HIV- 1 Infection ( %) 0.7 .64 .68 Vaccine 0.6 .58 Vaccine infections: 51 0.5 Placebo infections: 74 .41 p = 0.04 .38 0.4 Efficacy: 31.2% 95% CI (OBF): 1.1, 51.2 0.3 0.2 .15 RV144 Acquisition 0.1 Placebo Vaccine Endpoint: Modified 0.0 Intent-to-Treat (mITT) 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 YEARS month 6 12 18 24 30 Events 16 42 67 82 95 Efficacy 54% 60% 44% 36% 36%
    • Lessons from RV144– Protection from infection is possible • Highest protection in first 6-12 months (61%) • Antibody titers appear to wanes in line with protection • Follow up studies planned to determine if boosting can prolong protection • Ongoing work to improve both the priming (ALVAC) and boosting (AIDSVAX) components • Planned studies to assess similar approach in Sub-Saharan Africa
    • Unprecedented progress in the discovery ofneutralizing antibodies • Up to 25% of infected subjects found to have broadly neutralizing antibodies a year or more after infection • 1% (elite controllers) have potent activity against a majority of strains • Induction of responses to such regions could provide potent protection *Humans can make protective antibody responses – providingunique tools for development of new vaccine candidates
    • >50% of macaquesimmunized with areplicating CMVvector manifestedearly completecontrol of infection
    • Sustained funding to harnessing the product development cycle 10,000s, 1000s 100s 10s 1-2 Product Development Partnerships (PDPs) Multinational National laboratories and Biotech / Small Medium pharmaceutical and academic institutions Enterprises (SMEs) biotechnology HIV VaccineBasic Applied Product Early product Advanced Large-scale Deliveryresearch research design development development Efficacy trials & Access Clinical Trials Partnerships
    • NUMBER OF VACCINE TRIAL VOLUNTEERS: THEN AND NOW www.avac.org 1997 2012 TOTAL VOLUNTEERS 1997 TO 2012 1,350 6,590 69,042 250 VOLUNTEERSTotal volunteers for 2012 is only inclusive of biomedical preventive HIV vaccine trials. The total number of volunteers including observational and therapeutic HIV vaccine trials ismore than 23,000. The total number of volunteers from 1997 – 2012 was assessed using information available on www.clinicaltrials.gov and is an approximate number.
    • VACCINE CLINICAL TRIALS: TRIAL PARTICIPANTS IN 2012 www.avac.org SwedenTOTAL TRIAL PARTICIPANTS 6,590 Switzerland 24 105 United Kingdom 124 France 105 China Italy 48 50 United States Brazil 3,690 25 Kenya Thailand 157 782 Uganda 103 Tanzania Peru 170 174 Mozambique Rwanda 120 109 Zambia 46 South Africa 486When participants by country were not specified by trial sponsors, funders, and/or implementers, total trial participants are divided evenly among countries. Not all trials in 2012 areincluded, only those for which both estimated or actual participants and countries were available.
    • Pathway to reversing the epidemicSeeing prevention research/funding as a continuum Circumcision Treatment for prevention Prophylaxis (oral, topical, injectable) Partially effective vaccine HIV incidence highly effective vaccine Behavioral and structural interventions Science. 2011;333:42-3