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RBCG30

rBCG30 (recombinant Bacillus Calmette-Guérin 30) is a prospective Bacillus Calmette-Guérin vaccine against tuberculosis. It is a live vaccine, consisting of BCG, which has been evaluated as a tuberculosis vaccination. It is genetically modified to produce abundant amounts of mycolyl transferase, a 30kDa antigen (Antigen 85B)[1] that has been shown to produce a strong immune response in animals[2][3][4][5] and humans. rBCG30 had been in human clinical trials, [6] but no clinical development has been reported since 2007.[7]

History

Trials with rBCG30 were halted as the vaccine contained an antibiotic resistance gene.[8] A new version of the vaccine without the antibiotic resistance marker was created.[9] This new version of the vaccine, rBCG30-ARMF-II, often called rBCG30, also expresses 2.6 fold more Ag85B than the original vaccine.[9]

Research

The vaccine completed a Phase I double-blind randomized controlled clinical trial that demonstrated that rBCG30 was safe and immunogenic; during nine months of follow-up, rBCG30, but not BCG, induced significantly increased Antigen 85B-specific immune responses in eight immunological assays (blood lymphocyte proliferation, antibody responses by ELISA, interferon-gamma producing CD4+ and CD8+ T cells ex vivo, central memory CD4+ and CD8+ T cells, interferon-gamma ELISPOT responses, and the capacity of T cells to activate macrophages to inhibit mycobacterial intracellular multiplication).[6] An additional animal study found that rBCG30 also helps protect against Mycobacterium leprae, the bacteria that causes leprosy.[10] Disrupting IL10/STAT3 signaling during vaccination through small molecules enhances vaccination efficacy.[11][12][13][14]

References

  1. ^ Horwitz MA (May 2005). "Recombinant BCG expressing Mycobacterium tuberculosis major extracellular proteins". Microbes and Infection. 7 (5–6): 947–54. doi:10.1016/j.micinf.2005.04.002. PMID 15919223.
  2. ^ Horwitz MA, Harth G, Dillon BJ, Maslesa-Galic' S (December 2000). "Recombinant bacillus calmette-guerin (BCG) vaccines expressing the Mycobacterium tuberculosis 30-kDa major secretory protein induce greater protective immunity against tuberculosis than conventional BCG vaccines in a highly susceptible animal model". Proceedings of the National Academy of Sciences of the United States of America. 97 (25): 13853–13858. Bibcode:2000PNAS...9713853H. doi:10.1073/pnas.250480397. PMC 17665. PMID 11095745.
  3. ^ Horwitz MA, Harth G (April 2003). "A new vaccine against tuberculosis affords greater survival after challenge than the current vaccine in the guinea pig model of pulmonary tuberculosis". Infection and Immunity. 71 (4): 1672–1679. doi:10.1128/iai.71.4.1672-1679.2003. PMC 152073. PMID 12654780.
  4. ^ Horwitz MA, Harth G, Dillon BJ, Maslesa-Galić S (January 2006). "Extraordinarily few organisms of a live recombinant BCG vaccine against tuberculosis induce maximal cell-mediated and protective immunity". Vaccine. 24 (4): 443–451. doi:10.1016/j.vaccine.2005.08.001. PMID 16125825. S2CID 8581702.
  5. ^ Horwitz MA, Harth G, Dillon BJ, Maslesa-Galić S (March 2006). "A novel live recombinant mycobacterial vaccine against bovine tuberculosis more potent than BCG". Vaccine. 24 (10): 1593–1600. doi:10.1016/j.vaccine.2005.10.002. PMID 16257099. S2CID 11798572.
  6. ^ a b Hoft DF, Blazevic A, Abate G, Hanekom WA, Kaplan G, Soler JH, et al. (November 2008). "A new recombinant bacille Calmette-Guérin vaccine safely induces significantly enhanced tuberculosis-specific immunity in human volunteers". The Journal of Infectious Diseases. 198 (10): 1491–1501. doi:10.1086/592450. PMC 2670060. PMID 18808333.
  7. ^ "Recombinant BCG vaccine - Aeras Global TB Vaccine Foundation/ UCLA". AdisInsight. Springer Nature Switzerland AG.
  8. ^ Gong W, Liang Y, Wu X (July 2018). "The current status, challenges, and future developments of new tuberculosis vaccines". Human Vaccines & Immunotherapeutics. 14 (7): 1697–1716. doi:10.1080/21645515.2018.1458806. PMC 6067889. PMID 29601253.
  9. ^ a b US 8932846, Horwitz MA, Tullius MV, "Unmarked recombinant intracellular pathogen immunogenic compositions expressing high levels of recombinant proteins", issued 13 January 2015, assigned to University of California. 
  10. ^ Gillis TP, Tullius MV, Horwitz MA (September 2014). Flynn JL (ed.). "rBCG30-induced immunity and cross-protection against Mycobacterium leprae challenge are enhanced by boosting with the Mycobacterium tuberculosis 30-kilodalton antigen 85B". Infection and Immunity. 82 (9): 3900–3909. doi:10.1128/IAI.01499-13. PMC 4187824. PMID 25001602.
  11. ^ Ahmad F, Umar MS, Zubair S, Khan N, Gupta P, Gupta UD, et al. (2022-10-01). "Efficacy of IL10/STAT3 directed small molecule immunotherapy in augmenting the potential of rBCG30 vaccine against murine pulmonary tuberculosis". Molecular Immunology. 150: 14. doi:10.1016/j.molimm.2022.05.053. ISSN 0161-5890. S2CID 252930472.
  12. ^ Ahmad F, Umar MS, Khan N, Gupta P, Gupta UD, Owais M (May 2020). "A small molecule based immunotherapy targeting IL-10/STAT3 praxis to augment the potential of rBCG30 vaccine against experimental tuberculosis". The Journal of Immunology. 204 (1_Supplement): 168.24. doi:10.4049/jimmunol.204.supp.168.24. ISSN 0022-1767. S2CID 255645861.
  13. ^ Ahmad F, Umar MS, Khan N, Gupta P, Gupta UD, Owais M (2021). "A Potent Inhibitor of IL-10/STAT3 Axis Signaling Modulates Anti-Inflammatory Responses and Boosts Anti-Tuberculosis Immunity in rBCG30 Immunized Mice". International Journal of Mycobacteriology. 9 (5): 49. doi:10.4103/2212-5531.307099. ISSN 2212-5531.
  14. ^ Ahmad F, Umar MS, Khan N, Jamal F, Gupta P, Zubair S, et al. (2021). "Immunotherapy With 5, 15-DPP Mediates Macrophage M1 Polarization and Modulates Subsequent Mycobacterium tuberculosis Infectivity in rBCG30 Immunized Mice". Frontiers in Immunology. 12: 706727. doi:10.3389/fimmu.2021.706727. PMC 8586420. PMID 34777338.
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