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T B Vaccine Development in Indonesia

T B Vaccine Development in Indonesia. Francisca S Tanoerahardjo. SEA-EU NET , 2 1-22 January 2014. NATIONAL INSTITUTE OF Health research AND DEVELOPMENT. OUTLINE. TB Situation in Indonesia On Going TB Vaccine research consortium Challenges (Resources and Management). Indonesia .

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T B Vaccine Development in Indonesia

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  1. TB Vaccine Development in Indonesia

    Francisca S Tanoerahardjo SEA-EU NET, 21-22 January 2014 NATIONAL INSTITUTE OF Health research AND DEVELOPMENT
  2. OUTLINE TB Situation in Indonesia On Going TB Vaccine research consortium Challenges (Resources and Management)
  3. Indonesia Indonesia is an archipelago-17,508 islands Population over238 million people The 4thmost populouscountry
  4. TB Situation in Indonesia 22 TB High Burden Countries TB Prevalence (estimated) WHO – NTP : 124/100.000 population DOTS implementation Distric Health Clinic (Goverment) - 90% Hospital - 30-40% Private Clinic – Public Private Mixed Program
  5. TB Prevalence Survey 2013-2014
  6. Result Dec 2014
  7. Program 2011-2020 Ministry of Health National Institute of Health Research and Development Ministry of Research and Technology National Incentive Program Collaborative Research
  8. Goal of the Collaborative Research Focus on product : Health and Drug Vaccine development Drug discovery Improvement of Health Technology Assesment Saintifikasijamu (Herbal)– Natural Product Priority : Infectious diseases (Malaria, TB, HIV, Dengue, Influenza) No infectious diseases (Cardiovascular& cancer)
  9. On going TB Research TB Vaccine Research:Collaborative Research, Academicy (13 University ) – Goverment (Ministry of Health, Ministry of Research & Technology)– Industry (PT. Bio Farma Tbk) TB Prevalence Survey TB Operational Research Individual Research
  10. History <2011 2011 2012 2013 2014 Individual Research Working Group Research Consortium (8 Institutes) Research Consortium (12 Institutes) Research Consortium (12 Institutes)
  11. Sinergy Effeciency No duplication NIHRD TB Vaccine Research Consortium Ministry of Research & Technology Ministry of Health UI UNPAD ITB UGM UNAIR UNBRAW PT Bio Farma UNHAS UNEJ Protein Rekombinan, Immunonicity test Preparation forM.tbdorman islate 2012 UNRAM 2013 2012 + Sekuensing BCG, BCG effectivity study LIPI 2013+ SekuensingM.tb Beijing, proteomiksgranuloma, adjuvan, 2014 UNIKA AJ
  12. Protein Sub-Unit Secreted protein Esat6, Cfp10, Ag85, Ag38kD Protein PE & PPE PE17 PE41 Protein Rpf Lipoprotein LipY 5 Institution: University of Indonesia Institute of Technology Bandung University of Hasanuddin University of Mataram Center of Biomedic and Tecnology Developemny NIHRD
  13. Adjuvant LIPOTEK – Australia base on Liposome – Antigens Formulation & proof of concept
  14. Immunogeniety Study Subject TB patients Healthy but contact TB pos Healthy without contact Test TST CD4, CD8, IFNɣ, IL2 IL17
  15. Hasil pemeriksaan flowcytometry (SD) sitokin intraseluler IL-2 dan IFN-Ɣ in ach group
  16. IL-4 dan IL-10 Rerata limfosit (CD3) yang menghasilkan IL-4 pada masing-masing kelompok adalah sbb: Pasien: PK: 23,87%; PP: 25,50%; PA: 37,96%. Kontak: KK: 28,98%; KP: 16,80%; KA: 16,19%. Sehat: SK: 40,82%; SP: 22,71%; SA: 22,55%. Rerata limfosit (CD3) yang menghasilkan IL-10 pada masing-masing kelompok adalah sbb: Pasien: PK: 25,96%; PP: 18,73%; PA: 8,94%. Kontak: KK: 40,64%; KP: 34,48%; KA: 32,19%. Sehat: SK: 52,47%; SP: 37,58%; SA: 33,49%.
  17. M.tuberculosis dorman M.tuberculosis isolates Sauton medium Minimum Carbon source M.tuberculosis from granuloma lung resection Proteomics analysis Re-culture
  18. BCG Effectivity- baseline data (2014) Community Study (+200 houses @ 4 person) East Java (rural area) Jakarta (urban area) Quesionairre – BCG vaccination TB cases Environment TST & IGRA HLA
  19. Problem Data on BCG vaccination Facilities - Technology Standarization
  20. Thank you
  21. Roadmap International TB Research - 2011 Treatment Epidemiology Fundamental Research Diagnostics Vaccine Operational & PH Research Characterized Human TB Host-pathogen interaction identification of the causes of low rate case detection & cure transmission host–pathogen Interaction: mechanisms leading to persistence M. tb with the immune system host’s immune system identification of biomarkers of patients at each stage. evaluation of biomarkers identified in fundamental studies for use as diagnostic tools - validation of novel simple tools for diagnosis at points of care design target drug discovery for TB active & TB persistence identification of the mechanisms of action of current and newly developed anti-TB drugs immunodominant antigens protective immunity after vaccination preparation of clinical trial TB case-finding, in HIV-infected expanded access to treatment for Vulnerable diagnosis of & access to treatment for MDR-TB and XDRTB
  22. TB Research 2009 – 2009 – Non-pharmaceutical Preventions: 1. Behavior change studies Mapping the problem & Burden of diseases: Case Detection Rate / Cure Rate Retro study: hosp-basedDOT’s : related mortality & Morbidity Prescription Study Risk factors: Immunocellular host Environment 3. Co-infection 4. Biosafety & Biosecurity Health Economics: 1. Cost & benefits studies of TB Case management & prevention OBJECTIVES: 1. Epidemiology: Burden of disease, mapping & early detection system 2. Mtb characterization & Mapping 3. Human susceptibility & pathogenesis 4. Prevention of Risk factors, Therapy & Case management 5. BIO-banking 6. Selections of vaccine / new drugs / new diagnostic test for TB; Production of Vaccine, Diagnostic Tests, Drugs, etc. Early detection: 1. Rapid Diagnostic Test (RDT) (new tool / new method ) 2. Optimized DOT’s programs at peripheral lab. 3. Optimized Operational Research Outbreak Investigation: 1. Mapping genotype & strain 2. Environment investigation 3. Peripheral Lab. investigation Case Identification: 1. Diagnosis of new case 2. Diagnosis of MDR/XDR 3. Diagnosis of nonTB / MOTT 4. Diagnosis of co-infection Development of candidate vaccine/new drugs/new diagtoctic test: 1. Identification of major / specific Mtbin Indonesia; Mtbsequencing; selection of candidate vaccine (primer/ species specific); selection of drugs delivery system(DDS) or vaccine model; pharmacology / bioavailability-bioequivalence (BA/BE) 2. Identification of specific plant for TB in Indonesia; pre clinic study (phase I – III); BA/BE 3. Selection of RDT method Case diagnosis & management: 1. Case studies for MDR / XDR – MOTT; co-infection 2. Case management studies: DOT’s & other (Operational Research) 3. Development & testing of rapid D/& other D/methods 4. Development of new vaccine & new drugs GOALS: TB prevention Early detection system Disease reduction Production of vaccine, dew drugs, rapid diagnostic test, etc Genetics: 1. Human genetic immunocellular 2. Genotype & phenotype of Mtb (Mycobact. tuberculosis) : inventory strain 3. Rapid Diagnostic Test (tool & method) 4. DOT’s drugs resistant (susceptibility of Mtb / MODS – Mycobacterium Observation of Drugs Susceptibility) Clinicaltrials: Colab.w/existing vacc./ new drugs / new diagnostic kit procedures (Phase IV) Clinico-pathogenesis, Immunity: 1. TB related Immunity studies (incl. co-infection studies)
  23. DATA SURVEILANS EPIDEMIOLOGIMOLEKULAR HASIL PENELITIAN 2008-2010 MEDAN P.BARU PONTIANAK BANJARMASIN MANADO SORONG 49,8 PALEMBANG PADANG DKI SURABAYA AMBON TJ.KARANG MAKASSAR 52,7 SERANG BANDUNG MATARAM Sampel : 404 spesimendahak BTA positifpasien TB dari 16 ibukotaprovinsi di Indonesia.
  24. KeragamangenotipeMtb di Indonesia
  25. PetaawalfilogenetikMtbdi Indonesia: Menggambarkandiversitasbakteri yang bersirkulasi Sum - Kal Jawa Wil. Timur
  26. Hasil Pengembangan Kit Diagnostik Diagnostikmolekuler – deteksi DNA M.tb MetodeLoop-Mediated Isothermal Amplification (LAMP), yang dimodifikasimenggunakan primer sesuaiisolat Indonesia yang telahdilakukan genotyping Kit Diagnostik Sederhana MemungkinkanuntukdilaksanakanpadaLaboratorium RS Ujiklinikskalakeciltelahdilaksanakan In house
  27. Sinergi Efisiensi No duplikasi PBTDK KONSORSIUM RISET VAKSIN TB PBTDK-BALITBANGKES KEMENKES InsentifSINas KEMENRISTEK UI UNPAD ITB UGM UNAIR UNBRAW PT Bio Farma UNHAS Protein Rekombinan, UjiImunogenitas PenyiapanisolatM.tbdorman 2012 UNEJ 2013 2012 + Sekuensing BCG, efektivitas BCG UNRAM 2012 + SekuensingM.tb Beijing, proteomiksgranuloma, peranTreg, adjuvan 2014 LIPI
  28. ROADMAP VAKSIN TB SUB-UNIT Tahapanpembuatanvaksin Pre Development 2014 - 2017 Development 2017 - 2019 Production 2020 Basic Research 2012 - 2015 Tujuantahapanpembuatanvaksin PenyiapanKandidat antigen: Mencegah infeksi Mencegah TB primer Mencegah infeksi laten 4. Mencegah reaktivasi laten UjiImunogenisitas FormulasiKandidatVaksin Uji Preliminary padaHewanCoba Pembuatan experimental lot Pembuatan clinical lot Preclinical trial Clinical trial Launching Product Produksirutin Institusi BIO FARMA BIOFARMA, LITBANGKES, UNPAD, UGM, UNAIR LITBANGKES, ITB, UI, UGM, UNPAD, UNAIR, UNHAS BIO FARMA, LITBANGKES, UNPAD, UGM, UNAIR
  29. BASIC RESEARCH Tahapanpembuatanvaksin Antigen & Epitop Selection Protective Immunity Community Study Seed Vaccine Genomics Analysis Tujuantahapanpembuatanvaksin (Basic Research) Genome Sequence, Computer Analysis Antigen Selection/ Production, B&T Cell Epitope Animal Protective Immunity Epid Molecular & UjiDiagnostik Seed Vaccine FasilitasInstitusi Studilapangan & Laboratorium LaboratoriumHewanCoba Laboratorium Laboratorium
  30. TERIMA KASIH
  31. HASIL PENELITIAN
  32. HASIL PENELITIAN
  33. HASIL PENELITIAN
  34. RENCANA TINDAK LANJUT Keberlanjutan: (?) Jaminanpendanaan & program & institusi yang mengawalkegiatanKonsorsium BedahBukuKonsorsiumRisetVaksin: CeritakebutuhankeberlanjutanRisetVaksinsebagaisalahsaturiset yang berorientasipada PRODUK yang akandiproduksiolehIndustri. Merupakanrisetjangkapanjang yang merupakankebijakan TOPDOWN (tidakkompetitif)
  35. RENCANA TINDAK LANJUT SumberPendanaan: Kemenkes – DIPA (multi years sampai 2020) Kemenristek – INSINas (?) – dpt TOP DOWN? Kemendikbud – in kind Universitas (sarpras & SDM) Kemen BUMN – Industri Bappenas -- Kemenkeu – Sosialisasi - KolaborasiRisetdengan LN ASEAN-European Union Meeting, Bangkok Januari 2014 TBVI (TuBerculosis Vaccine Initiative) dengansumberpendanaan Bill Gate Foundation
  36. TERIMA KASIH
  37. Global TB Vaccine Pipeline Phase I Phase II Phase IIb Phase III M72+AS01GSK, Aeras VPM 1002Max Planck, Vakzine Projekt Mgmt, TBVI Hybrid-1+IC31SSI, TBVI, EDCTP, Intercell RUTIArchivel Farma, S.L. MVA85A/AERAS-485Oxford-Emergent Tuberculosis Consortium (OETC), Aeras, EDCTP, Wellcome Trust AERAS-402/ Crucell Ad35Crucell, Aeras, EDCTP, NIH Mw [M. indicus pranii (MIP)] Dept of Biotechnology (India), M/s. Cadila AdAg85AMcMaster University Hybrid-I+CAF01SSI, TBVI H56+IC31SSI, Aeras, Intercell Hyvac 4/ AERAS-404+IC31SSI, sanofi-pasteur, Aeras, Intercell ID93/GLA-SEIDRI, Aeras Prime Boost Post-infection Immunotherapy TB Vaccine Types Viral-vectored: MVA85A, AERAS-402, AdAg85A Protein/adjuvant: M72, Hybrid-1, Hyvac 4, H56 rBCG: VPM 1002, ID93/GLA-SE Killed WC or Extract: Mw, RUTI Source: Tuberculosis Vaccine Candidates – 2011
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