HIV Vaccine Research Up dates

Transcription

1 HIV Vaccine Research Up dates Prof. Omu Anzala KAVI Department of Medical Microbiology University of Nairobi

2 Vaccines Mechanism of Action Exposure Infection Disease Death Recovery

3 HIV Vaccine After about 28 years of HIV vaccine research. Why is there no HIV vaccine? 3

4 the challenges The virus impairs the immune systems Viral diversity The correlates of immunity or protection not fully known Funding Keeping communities interested

5 HIV replication

6 Heterogeneity of HIV

7 HIV-1 Subtypes And Distribution (Africa)

8 Is the discovery of an HIV vaccine possible? Basic and Epidemiology research in HIV/AIDS continuous to point to this fact. RV144 trial in Thailand(Canary-pox-vector prime plus protein-subunit boost) Discovery of potent and broadly neutralizing antibodies

9 Exposed Seronegative Cohorts Repeated unprotected sexual HIV exposure Sex workers Discordant couples Repeated intravenous HIV exposure IDU Continuous HIV exposure Fetal or perinatal exposure Single accidental exposure Health care workers 9

10 HIV Immune Responses in ESN Studies have been able to demonstrate T-Helper Cells (CD4) CTL Cells (CD8) HIV Specific mucosal immunoglobulin A Neonates of HIV infected mothers generate both (T Helper and cytotoxic T cells) 10

11 Natural History AIDS Incubation time to AIDS is ten years Slow progression Viral factors ( Nef deletion) Host factors ( HLA B57,APOBEC ), 11

12 Slow Progressors to AIDS Elite Controllers >50 copies/ml of RNA Not on ARVs Infrequent episodes of viremia Viremic controllers >2000 copies/ml of RNA Not on ARVs Occasional epidoes of viremia (Elite Neutralizers) 12

13 preventive technologies 13

14 Vaccines Male and female condoms PrEP PEP Prevention of vertical transmission Microbicides Comprehensive HIV prevention Treatment as prevention Cervical barriers: vaginal diaphragms ARV Male circumcision Clean injecting equipment Voluntary counselling and testing

15 HIV vaccine design & development 15

16 Vaccine Development From the Lab to the Clinic Concept Vaccine design Testing Political will and finance Research and development Clinical trials Production Health and other systems Access and uptake

17 HIV Vaccine development

18 Balancing safety and efficacy in HIV vaccine design

19 Clinical Trials Phase I ( safety) Phase II ( immune response) Phase III ( Efficacy) 19

20 HIV Vaccine Efficacy Trials 5 preventive HIV vaccine Efficacy trials conducted to date: - (Vax004,Vax003 and Step/HVTN 502) vaccine efficacy near 0 - RV 144 VE of 31% - Phambili/HVTN was halted. 20

21 Probability of HIV-1 Infection (%) Thailand RV144 HIV vaccine trial Placebo Vaccine YEARS Placebo Vaccine

22 The ADCC mechanism: bridging the gap between innate and adaptive immunity antibody antigen granules Fc receptors (CD16, C EFFECTOR CELL TARGET CELL

23 The hunt for correlates RV 144 Trial One antibody response was inversely correlated with HIV infection risk While another antibody response was directly correlated with infection risk 23

24 What kind of immune responses are the future vaccines targeting? 24

25 Targets for Vaccine Design Neutralizing Antibodies Cell Mediated Immunity

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28 Vaccine-induced CD8 T cells can affect disease expression Viral Load or Disease Severity Persistent infection, but no disease

29 Viral Load or Disease Severity Prevention of HIV-1 acquisition is the new standard No infection No persistent infection

30 Current HIV Vaccine trials at KAVI 30

31 Ongoing Phase 1 clinical trials PaedVac Funded by EDCTP MVA + EPI vaccination vs EPI vaccination (alone) Safety, immunogenicity & interference with EPI vaccines Infants vaccinated at 20 weeks - single IM injectio 31

32 Ongoing Phase 1 clinical trials Protocol B002 Recombinant Fusion protein (F4co) in adjuvant (ASO1B or ASO1E) + replication incompetent Ad35- GRIN F4co [p24-rt-nef-p17 of HIV-1clade B Gag, Pol, Nef)] Ad35-GRIN [with HIV-1 clade A gag, RT, integrase, nef) Phase 1, double blind, randomized placebo controlled 140 participants (112 vaccine/28 placebo) 32

33 Ongoing Phase 1 clinical trials Protocol B003 Different combinations of recombinant Ad26 vector & recombinant Ad35 (HIV-1 sub-type A env gene) Heterologous or homologous Multi-centre Boston (USA), Rwanda, S/Africa KAVI-Kangemi 33

34 Is there need for an HIV vaccine?? 34

35 The AIDS Epidemic in Kenya Kenya: 7.4% Epidemic characteristics Adult HIV prevalence (2009) Number of people living with HIV (2009) Number of deaths per year (2009) Number of new adult infections per year (2009) Adult ART coverage (2009)* Generalized Severe Mature 7.4% 1,600,000 90, ,000 (98,000) A (13,000) C 70.4% * Not adjusted to reflect changes in WHO treatment guidelines UNGASS Coutnry Progress Report, Kenya, UNAIDS, 2010

36 The Questions?? Would an HIV vaccine be useful if it was less than 100% effective? Would a vaccine still be needed if current prevention programs and antiretroviral therapy (ART) are significantly expanded while the vaccine is still being developed? Would a vaccine result in cost-savings?

37 Key Model Assumptions Key model assumptions appropriate for the Kenyan context were developed: Year of vaccine introduction Level of vaccine coverage decided based on several factors, including: Demand for high-efficacy vaccine; Healthcare infrastructure; Costs and resources Levels of vaccine efficacy Goals of national strategic plans achieved: Male circumcision 80% Condom use in high risk groups 80% ART coverage 75%

38 The Potential Impact of an AIDS Vaccine in Kenya Low Vaccine effectiveness and coverage New infections prevented Vaccine scenarios Medium LOW IMPACT MEDIUM IMPACT 30% effective, 30% coverage of adult population 50% effective, 50% coverage of adult population 1.4 Million ( 25%) 2.4 Million ( 65%) High HIGH IMPACT 70% effective, 70% coverage of adult population 3.5 Million ( 90%)

39 UNGASS Country Progress Report, Kenya, UNAIDS, 2010 Sustainability example of Kenya AIDS Financing in Kenya by Source, 2009 US$ 687 Million HIV/AIDS treatment and care spending Kenya, 2009 International Donors 86 % Other 45% Treatment and Care 55% Government of Kenya 14%

40 Cost-Savings of an AIDS Vaccine The average lifetime cost of ART for one person in Kenya: $8,700 One infection averted by a vaccine means one person who will not need ART Impact modeling estimates that in a medium-efficacy scenario approximately 26 vaccinations would be needed to avert 1 HIV infection In comparison to ART, this means that a vaccine costing less than $335 per vaccination would result in cost savings KAVI, 2009

41 An HIV vaccine is our best hope

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