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. 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. 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.