Newer tb vaccine full details for md exams
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newer tuberculosis TB vaccines development candidates clinical trials
Harrison's Principles of Internal Medicine, Twenty First Edition
Page 5188
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BCG vaccine limitations newer TB vaccine M72 M. vaccae VPM1002 DAR-901
Harrison's Principles of Internal Medicine, Twenty First Edition
Page 5186
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Here is a comprehensive breakdown of newer TB vaccines for MD exams:
Newer TB Vaccines — Complete MD Exam Guide
1. Background: Why a New TB Vaccine?
BCG (Bacillus Calmette-Guérin) — the current standard — was derived from an attenuated strain of M. bovis and first administered to humans in 1921.
Limitations of BCG:
| Issue | Detail |
|---|---|
| Variable efficacy | 0–80% in randomized trials |
| Protective in children | Good protection against disseminated TB (miliary, meningitis) in infants |
| Poor protection in adults | Does not reliably prevent pulmonary TB in adults — the most common and infectious form |
| Cannot be given to immunocompromised | Live vaccine — contraindicated in HIV-positive individuals |
| Does not prevent reactivation | No efficacy against latent TB reactivation |
(Harrison's Principles of Internal Medicine, 21st Ed., p. 5186)
2. Categories of Newer TB Vaccine Candidates
Newer TB vaccines fall into three broad categories:
| Category | Examples | Mechanism |
|---|---|---|
| Whole-cell / mycobacterial lysate | DAR-901, RUTI, M. vaccae | Killed or inactivated mycobacterial preparations |
| Viral vector vaccines | MVA85A (Modified Vaccinia Ankara) | Recombinant viral vectors expressing TB antigens |
| Adjuvanted recombinant protein (subunit) | M72/AS01E, H4:IC31, H56:IC31 | Mycobacterial protein antigens + adjuvant |
3. Key Vaccine Candidates (High-Yield for Exams)
🔬 M72/AS01E — Most Important Newer TB Vaccine
(Harrison's 21st Ed., p. 5188)
| Feature | Detail |
|---|---|
| Type | Subunit (adjuvanted recombinant protein) vaccine |
| Antigens | Two M. tuberculosis antigens: Mtb32A and Mtb39A |
| Adjuvant | AS01E (GSK's proprietary adjuvant system — same used in RTS,S malaria vaccine) |
| Target population | Adults with latent TB infection (LTBI) — to prevent progression to active disease |
| Trial design | Randomized controlled trial in 3575 patients with M. tuberculosis infection |
| Efficacy | ~49.7% efficacy at 36 months in preventing active TB |
| TB cases | 13/vaccine group vs 26/placebo group |
| Safety | Adverse events not significantly different from placebo |
| Status | Under further development (Phase 2b complete; Phase 3 planned) |
| Key point | First subunit vaccine to show significant protection against active TB in latent-infected adults |
MVA85A (Modified Vaccinia Ankara expressing Antigen 85A)
| Feature | Detail |
|---|---|
| Type | Viral vector vaccine |
| Target | Boost BCG-primed immunity |
| Trial | Large Phase 2b trial in South African infants (published 2013) |
| Result | Well tolerated and modestly immunogenic — did NOT confer significant protection against clinical TB or M. tuberculosis infection |
| Status | Development largely discontinued for this indication |
| Exam note | Important as a landmark negative trial — shows that immunogenicity ≠ efficacy |
VPM1002 (rBCG ΔureC::hly)
| Feature | Detail |
|---|---|
| Type | Recombinant, live attenuated — modified BCG |
| Modification | Deletion of ureC gene + insertion of hly (listeriolysin O gene from Listeria) |
| Mechanism | Allows phagosomal escape → better MHC class I antigen presentation → stronger CD8+ T-cell response |
| Advantage | Potentially more immunogenic than BCG; may be usable in HIV+ infants |
| Status | Phase 2/3 clinical trials |
| Exam note | Represents the concept of "recombinant BCG" — key vaccine biology concept |
MTBVAC
| Feature | Detail |
|---|---|
| Type | Live attenuated M. tuberculosis (first human-derived live attenuated TB vaccine) |
| Origin | Derived directly from M. tuberculosis (not M. bovis like BCG) |
| Deletions | phoP and fadD26 gene deletions |
| Rationale | Contains full M. tuberculosis antigen repertoire → potentially broader immunity than BCG |
| Status | Phase 2 trials in adults and newborns |
DAR-901
| Feature | Detail |
|---|---|
| Type | Whole-cell, inactivated mycobacterial lysate (from M. obuense) |
| Strategy | Booster vaccine in BCG-vaccinated adolescents |
| Status | Phase 2 trials |
M. vaccae (SRL172 / INMUNE-201)
| Feature | Detail |
|---|---|
| Type | Killed whole-cell Mycobacterium vaccae |
| Historical use | Tested as immunotherapy for active TB and HIV |
| Current use | Being explored as prophylactic vaccine in adults |
4. Vaccine Strategy: Prevention vs. Treatment
| Goal | Approach | Vaccines |
|---|---|---|
| Pre-exposure (prevent infection) | Replace/boost BCG at birth | MTBVAC, VPM1002 |
| Post-exposure (prevent active TB in LTBI) | Vaccinate LTBI+ adults | M72/AS01E, H56:IC31 |
| Therapeutic (adjunct in active TB) | Immunotherapy | RUTI, M. vaccae |
5. Exam High-Yield Points
- BCG efficacy: 0–80% (variable); best for childhood disseminated TB (meningitis, miliary); poor for adult pulmonary TB.
- M72/AS01E: ~50% efficacy for prevention of active TB in latently infected adults — the most promising newer vaccine.
- MVA85A: Failed Phase 2b trial in infants — immunogenicity did not translate to protection.
- VPM1002: Modified BCG with listeriolysin — improved phagosomal escape and CD8+ T cell response.
- As of 2020: 14 candidate vaccines in various stages of clinical trials (Harrison's, p. 5188).
- Adjuvant AS01E in M72/AS01E — same adjuvant platform as the RTS,S (malaria) and shingrix (herpes zoster) vaccines.
- BCG cannot be given to immunocompromised patients (live vaccine) — VPM1002 and M72/AS01E may fill this gap.
- No vaccine has yet replaced BCG globally; BCG remains on the WHO Essential Medicines List and the National Immunization Schedule in TB-endemic countries.
6. BCG on National Immunization Schedule (India)
- Given at birth (as early as possible)
- Route: Intradermal, left deltoid region
- Dose: 0.05 mL (< 1 month), 0.1 mL (> 1 month)
- A visible scar forms at 6 weeks — indicates successful vaccination
- No booster recommended
Sources: Harrison's Principles of Internal Medicine, 21st Edition, pp. 5186–5188
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