Transcript axali TB vaqcinis Sesaqmnelad mimarTuli kvlevebi

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