1 / 19

BCG and Other Candidate Vaccines for Tuberculosis

BCG and Other Candidate Vaccines for Tuberculosis. RajKumar Kayal Guwahati. 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

fisseha
Download Presentation

BCG and Other Candidate Vaccines for Tuberculosis

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. BCGand 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 10-20 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

  19. THANK YOU

More Related