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kvlevebi axali TB vaqcinis Sesaqmnelad tfdec; samecniero seminari; “samSabaToba”; neli solomonia; 08.12.09 BCG vaqcina 88 wlis win Seiqmna Calmette & Guérin 1908-1921 XXI saukune 2006-2015 $3.641 billion TB pandemiis winaaRmdeg BCG araefeqturi aRmoCnda • farTo gamoyenebis miuxedavad BCG-bam TB SemTxvevebis globalur zrdaze mniSvnelovani zegavlena ver moaxdina; • BCG vercerT asakSi saimedod ver icavs organizms TB-is ganviTarebisagan; • BCG bavSvs mxolod TB diseminirebuli formebis da TB meningitis ganviTarebisagan icavs ; • BCG ver icavs organizms LTBI-isagan; aiv-inficirebuli bavSvebis BCG-ireba saxifaToa tubsawinaaRmdego vaqcinacia, romelic rutinulad utardeba msoflioSi dabadebul CvilTa 75%-s, aiv-inficirebuli CvilebisaTvis maRal risks warmoadgens (yovel 100 000 mosaxleze aivinficirebulTa 992 SemTxvevaSi BCG-irebam TB diseminirebuli formebis ganviTareba gamoiwvia (95% CI: 567– 1495)Hesseling et al Bulletin of the World Health Organization; Type: Research Article DOI: 10.2471/BLT.08.055657 2009), amitom janmo iZleva rekomendacias aiv testirebis gareSe Cvilebis BCG-ireba ar Catardes; - 02.07.09; WHO. axali TB vaqcinis aucilebloba TB globaluri miznis miRweva (>1 TB SemTx./milion mosaxleze) axali vaqcinis, anu daavadebis prevenciis gareSe SeuZlebelia; aucilebelia TB axali, ekonomiuri, efeqturi vaqcina, romelic saimedod daicavs: nebismieri asakis organizms; maT Soris HIV-inficirebulebs; da uzrunvelyofs: LTBI_is prevencias (preinfeqciuri vaqcinacia); LTBI-is reaqtivaciis prevencias (postinfeqciuri vaqcinacia); TB pirveladi da meoradi, maT Soris MDR/XDR formebis prevencias; TB mkurnalobis xangrZlivobis Semcirebas da TB mkurnalobis efeqturobis zrdas (imunoTerapia). Aeras Global Vaccine Development Partners Foundations/ Governments/ NGOs Bill & Melinda Gates Foundation, U.S. Ministry of Foreign Affairs of Denmark The Netherlands Ministry of Foreign Affairs, the Netherlands Centers for Disease Control and Prevention (CDC), U.S. Fogarty International Center and NIAID, National Institutes of Health, U.S. Research Council of Norway, Norway AIDS Fondet, Denmark Cambodian Health Committee, Cambodia European and Developing Countries Clinical Trials Partnership (EDCTP), European Commission LHL/ The Norwegian Association of Heart and Lung Patients, Norway Planeta Salud, Spain Manhiça Health Research Centre, Mozambique Medicine in Need (MEND), U.S. Stop TB Partnership, Switzerland TB-Alert, United Kingdom Tuberculosis Vaccine Initiative (TBVI), Europe Wellcome Trust, United Kingdom Academia Aeras Foundations/ Government/ NGOs Oxford University, United Kingdom South African TB Vaccine Initiative (SATVI), South Africa St. Johns Research Institute, India Makerere University, Uganda Kenya Medical Research Institute, Kenya Karolinska Institute, Sweden Wuhan University, China Albert Einstein College of Medicine, U.S. Arizona State University, U.S. Biomedical Primate Research Center, the Netherlands Case Western Reserve University, U.S. Central Institute for Tuberculosis, Russia Centre for International Health, University of Bergen, Norway Colorado State University, U.S. Emory University, U.S. Food and Drug Administration, U.S. Foundation for Innovative New Diagnostics (FIND), Switzerland Harvard University, U.S. International AIDS Vaccine Initiative (IAVI), U.S. Johns Hopkins University, U.S. KNCV Tuberculosis Foundation, the Netherlands Leiden University Medical Center, the Netherlands Life Science Research Israel (LSRI), Israel Max Planck Institute for Infection Biology, Germany McGill University, Canada National Cancer Institute (NKI), the Netherlands New York University, U.S. Oregon Health Sciences University, U.S. Public Health Research Institute, U.S. Stanford University, U.S. Saint Louis University., U.S. University of Bergen, Norway University of California-Davis, U.S. University of California-San Francisco, U.S. University of Maryland, College Park, U.S. University of Tampere, Finland University of Wales, United Kingdom Vanderbilt University., U.S. Walter Reed Army Institute of Research, U.S. Academia Industry Industry GlaxoSmithKline Biologicals, Belgium Crucell, the Netherlands Statens Serum Institute, Denmark ImmunoBiology, United Kingdom Wuhan Institute of Biological Products, China Serum Institute, India Thymed, Germany Alphalyse, Denmark Japan BCG Laboratory, Japan Korean Institute of TB, Korea Cyncron, Denmark Cellestis, Australia Immune Solutions, New Zealand Larimer, U.S. Sanofi Pasteur, France Smittskyddsinstitutet, Sweden BIOCON, U.S. Emergent BioSolutions, U.S. Intercell, Austria Spring Valley Laboratories, U.S. Aeras TB axali vaqcinis klinikuri kvlevebis partniorebi St John’s Research Institute India Cambodian Health Committee Cambodia KEMRI/CDC Kenya Makerere University Uganda Manhiça Health Research Center Mozambique SATVI/University of Cape Town South Africa TB axali vaqcinis Seqmnisken mimarTuli “Prime-Booster” strategiis Sedegad 2050 wlisaTvis TB avadoba da sikvdilianoba mxolod axali TB vaqcinebis xarjze 1/3-iT unda Semcirdes. axali TB vaqcinis Seqmnis Tanamedrove strategia principulad gansxvavebulia: I mimarTuleba gulisxmobs rekombinirebuli BCG vaqcinis Seqmnas Cvilebis preeqspozi-ciuri imunizaciasaTvis; II mimarTleba gulisxmobs virusiT veqtorire-buli, baqteriuli kapsidiT (nukleokapsiduri), an cilovani SenaerTebiT rekombinirebuli vaqcinebis Seqmnas Cvilebis, mozardebis, axalgazrdebis, maT Soris aivinficirebulebis posteqspoziciuri imunizaciasaTvis; postinfeqciuri vaqcinacia LTBI-is reaqtivaciis prevenciisken aris mimarTuli da aqtiuri TB-is ganviTarebas 30-40%-iT Seamcirebs. Block Initial Infection Prevent Early Disease Prevent Latent Infection Prevent Reactivation Disease pre - da post-eqspoziciuri(infeqciuri) vaqcinacia, imunoTerapia? Birth pre-exposure uninfected Transmission X primary TB ?X primary TB X post-exposure infected: latent X TB deaths X non-infectious TB infectious TB therapeutic? relapse? cure TB deaths imunizaciis Prime –Boost reJimebi CvilebisaTvis Recombinant BCG IM or as an aerosol Capsids in bacteria orally or as an aerosol 14- 24 Weeks 10 -14 Weeks warsulSi BCG-irebuli mozardebis da mozrdilebis imunizacia Viral Vector rProtein + Adjuvant Viral Vector IM or as Aerosol Viral Vector 1 Capsids in bacteria or as Aerosal rProtein + Adjuvant Viral Vector IM or as Aerosol ViralVector Vector2 2 Viral Capsids in bacteria or as Aerosal TB axali vaqcinis formebi • rBCGrekombinirebuli formebi BCG -sagan gansxvavdebian genebiT, romlebic ESAT-6 (early secretory antigen target 6) da CFP-10 (culture filtrate protein 10) antigenebis sekreciaze arian pasuxismgebelni. es antigenebi ujreduli imunitetis inducirebas axdenen da gaxangrZlivebuli moqmedebiT xasiaTdebian; ESAT-6 da CFP-10 rBCG preklinikurma imunizaciam Tagvebi da gvineis goWebi xangrZlivad daicva diseminirebuli formebis ganviTarebisagan; • AERAS-402/Crucell Ad35 busteria da adenovirus 35 veqtoriT iwvevs M. tuberculosis 85A, 85B, TB10.4 antigenebis eqspresias, rac TavisTavad CD+4 da CD+8 markeris mqone T limfocitebis inducirebas axdens; • AERAS-485/MVA85A busteria; virus ankara MVA 85 veqtoriT aRwevs makrofagis SigniT da iwvevs TCD+4 limfocitebis gaxangrZlivebul inducirebas; klinikuri kvlevebis I faza 2010 wlidan gaaqtiurdeba Seva (SATVI). • Ag85 rBCG30 TB-s winaaRmdeg mzardi imuno proteqciiT xasiaTdeba. iwvevs specifiuri CD+4 da CD+8 markeris mqone limfocitebis inducirebas da ujredSida mikobaqteriis inhibirebas. masze preklinikuri kvlevebi dasrulebulia, dawyebulia klinikuri kvlevebi arainficirebul voluntarebze; • VPM 1002 rBCG garda listeriolisinis eqspresiiT gamowveuli imunoproteqciisa (IFN-g) fagosomis mJava garemos neitralizacias axdens. is CarTulia klinikur kvlevebSi. cocxali peroraluri nukleokapsiduri TB vaqcina rdsRP Shigella veqtoriT Induction of TB-specific CD4+ and CD8+ T cells Shigella-rdsRP vector Presentation of TB antigens in the context of HLA class I&II Invasion Nucleus • Access cytoplasm • Lysis due to asd • Release of rdsRP EF2-independent translation of TB antigens Amplification of mRNA encoding TB antigens by alphavirus amplicon Synthesis of recombinant segment-S mRNA by RNA-dependent RNA polymerase activity of rdsRP TB vaqcinebi, romlebzec mimdinareobs kvlevebi Pre-clinical Other rBCG rMtb AERAS Other Virus AERAS rBCG AERAS 405 Capsid Phase I VPM 1002 Phase II Phase IIB rekombinantuli BCGs CvilebisaTvis AERAS 402/ Crucell AdAg85A Phase III virusiT veqtorirebuli vaqcinebi CvilebisTvis, mozardebisTvis da aivinficirebulebisaTvis. (2009) MVA85A/ AERAS 485 Other Protein PSS HyVac4/ AERAS 404 AERAS PSS Hybrid 1 SSI GSK M72 rekombinantuli cilovani SenaerTebi CvilebisTvis, mozardebisTvis, axalgazrdebisTvis da aivinficirebulebisaTvis. April 2009 gmadlobT yuradRebisaTvis