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BCG and Other Candidate Vaccines for Tuberculosis RajKumar Kayal Guwahati.

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Presentation on theme: "BCG and Other Candidate Vaccines for Tuberculosis RajKumar Kayal Guwahati."— Presentation transcript:

1 BCG and Other Candidate Vaccines for Tuberculosis RajKumar Kayal Guwahati

2 Tuberculosis: Global Burden One third of world’s population infected with M. tuberculosis Every year, 8 million cases of infective disease 2 million die of tuberculosis every year Ranks among 10 top causes of death MDR tuberculosis XDR tuberculosis Declared as global emergency by WHO

3 BCG Vaccine: Attenuated M. bovis Albert Calmette & Camille Guerin 1921: 13 years & 231 generations of subcultures: launched in 1924 Pasteur, Tokyo, Danish, Russian, GSK, Tice etc. strains Freeze dried, reconstituted in N/S, 0.1 mg in 0.1ml, I/D over L shoulder

4 BCG Vaccine Over 100 m children vaccinated / year In India, Danish strain 1331 at Guindy Store with diluent in ‘Fridge, avoid exposure to sunlight Reconstituted vaccine to be used within 3 hours

5 Worldwide BCG coverage

6 BCG: Side Effects Local Abscess Regional Adenopathy +- Suppuration Osteitis Disseminated BCG Disease Hypersensitivity reactions Others: Otitis, cutaneous lesions, metastatic abscesses, renal lesions etc.

7 BCG Side Effects: Management Local Abscess: No treatment Lymphadenitis: ?Drugs, ?Surgery Disseminated : ATT- pyrazinamide Osteitis: Drugs + surgery Anaphylaxis: Standard treatment

8 BCG: Efficacy 80% protection against TBM & mTB Overall 0-80% protection Effect wanes over years Protection only in naïve subjects No booster effect Risk of Disease in Immunocompromised Subjects

9 Development of New Vaccines Preclinical: Lab studies, animal models Phase I: Small field study: Safety Phase II: Slightly larger study: Does it induce the “right” immune response Phase III: Does it protect against TB License, Launch & Distribute Phase IV: Post-marketing surveillance

10 Possible types of new vaccines Pre-exposure Post-exposure Boost : early or late Therapeutic

11 M. Tuberculosis Genome

12 Possible Candidate Vaccines Improved BCG Attenuated M. tuberculosis Adjuvanated Protein, Peptide. Or DNA subunit Vaccine Virus vectored Vaccine Other Approaches

13 Improved BCG Expression of cytokine genes Over expression of protective antigens e.g., AG85B Reconstitution of deleted gene segments To be used as pre-exposure vaccine rBCG30, BCG:RD1, rBCG:D ure C-llo+

14 Attenuated M. tuberculosis Targeted inactivation of metabolic genes/ virulence genes To be used as post-exposure vaccine

15 Adjuvanated Protein, Peptide, or DNA subunit Vaccine Hypothesis driven selection: secreted AG, O2 starving Empirical selection: T cell recognition, MHC binding, Combination of Antigens Early or late boost

16 Virus Vectored Vaccine Modified Vaccinia Ankara Adenovirus Early or late boost

17 Other Approaches Nucleocapsids Killed mycobacteria e.g., M. vaccae or RUTI: as therapeutic vaccine Bacteria vectored AG : Salmonella Non-protein AG Conjugate vaccine

18 Vaccines currently under trial CandidateVaccine typeStageDeveloped by MVA Ag85AVirus vectoredPhase II ‘05Oxford Univ. BCG Ag85ArBCGPhase I ‘03UCLA/ AERAS 72f fusion protein SU+ Adj.Phase I ’03Crixa / GSK/ AERAS ESAT 6/85BSU + Adj.Phase I ‘05SSI/ TBVAC Adenovirus 85A Virus vectoredPhase I ’06Crucell / AERAS

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