RBCG30: Difference between revisions

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'''rBCG30''' ('''recombinant Bacillus Calmette-Guérin 30''') is a prospective [[Bacillus Calmette-Guérin]] vaccine against [[tuberculosis]]. It is a live vaccine, consisting of [[Bacillus Calmette-Guerin|BCG]], which has been evaluated as a tuberculosis vaccination. It is genetically modified to produce abundant amounts of mycolyl transferase, a 30[[wikt:kilodalton|kDa]] antigen (Antigen 85B)<ref name="Horwitz_2005">{{cite journal | vauthors = Horwitz MA | title = Recombinant BCG expressing Mycobacterium tuberculosis major extracellular proteins | journal = Microbes and Infection | volume = 7 | issue = 5-6 | pages = 947–54 | date = May 2005 | pmid = 15919223 | doi = 10.1016/j.micinf.2005.04.002 }}</ref> that has been shown to produce a strong immune response in animals<ref>{{cite journal | vauthors = Horwitz MA, Harth G, Dillon BJ, Maslesa-Galic' S | title = 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 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 25 | pages = 13853–13858 | date = December 2000 | pmid = 11095745 | pmc = 17665 | doi = 10.1073/pnas.250480397 | doi-access = free | bibcode = 2000PNAS...9713853H }}</ref><ref>{{cite journal | vauthors = Horwitz MA, Harth G | title = A new vaccine against tuberculosis affords greater survival after challenge than the current vaccine in the guinea pig model of pulmonary tuberculosis | journal = Infection and Immunity | volume = 71 | issue = 4 | pages = 1672–1679 | date = April 2003 | pmid = 12654780 | pmc = 152073 | doi = 10.1128/iai.71.4.1672-1679.2003 }}</ref><ref>{{cite journal | vauthors = Horwitz MA, Harth G, Dillon BJ, Maslesa-Galić S | title = Extraordinarily few organisms of a live recombinant BCG vaccine against tuberculosis induce maximal cell-mediated and protective immunity | journal = Vaccine | volume = 24 | issue = 4 | pages = 443–451 | date = January 2006 | pmid = 16125825 | doi = 10.1016/j.vaccine.2005.08.001 | s2cid = 8581702 | url = https://escholarship.org/uc/item/6xs622bp }}</ref><ref>{{cite journal | vauthors = Horwitz MA, Harth G, Dillon BJ, Maslesa-Galić S | title = A novel live recombinant mycobacterial vaccine against bovine tuberculosis more potent than BCG | journal = Vaccine | volume = 24 | issue = 10 | pages = 1593–1600 | date = March 2006 | pmid = 16257099 | doi = 10.1016/j.vaccine.2005.10.002 | s2cid = 11798572 | url = https://www.escholarship.org/uc/item/6p6663p1 }}</ref> and humans. rBCG30 had been in human clinical trials, <ref name = "Hoft_2008" /> but no clinical development has been reported since 2007.<ref>{{cite web | title = Recombinant BCG vaccine - Aeras Global TB Vaccine Foundation/ UCLA | work = AdisInsight | publisher = Springer Nature Switzerland AG | url = https://adisinsight.springer.com/drugs/800020342 }}</ref>

== History ==

Trials with rBCG30 were halted as the vaccine contained an antibiotic resistance gene.<ref>{{cite journal | vauthors = Gong W, Liang Y, Wu X | title = The current status, challenges, and future developments of new tuberculosis vaccines | journal = Human Vaccines & Immunotherapeutics | volume = 14 | issue = 7 | pages = 1697–1716 | date = July 2018 | pmid = 29601253 | pmc = 6067889 | doi = 10.1080/21645515.2018.1458806 }}</ref> A new version of the vaccine without the antibiotic resistance marker was created.<ref name="US8932846">{{cite patent | country = US | number = 8932846 | url = https://patents.google.com/patent/US8932846B2/en?oq=US8932846B2 | inventor = Horwitz MA, Tullius MV | title = Unmarked recombinant intracellular pathogen immunogenic compositions expressing high levels of recombinant proteins | assign = University of California | gdate = 13 January 2015 | postscript = . }}</ref> This new version of the vaccine, rBCG30-ARMF-II, often called rBCG30, also expresses 2.6 fold more Ag85B than the original vaccine.<ref name="US8932846" />

== 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|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).<ref name = "Hoft_2008">{{cite journal | vauthors = Hoft DF, Blazevic A, Abate G, Hanekom WA, Kaplan G, Soler JH, Weichold F, Geiter L, Sadoff JC, Horwitz MA | title = A new recombinant bacille Calmette-Guérin vaccine safely induces significantly enhanced tuberculosis-specific immunity in human volunteers | journal = The Journal of Infectious Diseases | volume = 198 | issue = 10 | pages = 1491–1501 | date = November 2008 | pmid = 18808333 | pmc = 2670060 | doi = 10.1086/592450 }}</ref> An additional animal study found that rBCG30 also helps protect against ''[[Mycobacterium leprae]]'', the bacteria that causes leprosy.<ref>{{cite journal | vauthors = Gillis TP, Tullius MV, Horwitz MA | title = rBCG30-induced immunity and cross-protection against Mycobacterium leprae challenge are enhanced by boosting with the Mycobacterium tuberculosis 30-kilodalton antigen 85B | journal = Infection and Immunity | volume = 82 | issue = 9 | pages = 3900–3909 | date = September 2014 | pmid = 25001602 | pmc = 4187824 | doi = 10.1128/IAI.01499-13 | veditors = Flynn JL }}</ref> Disrupting [[Interleukin 10|IL10]]/[[STAT3]] signaling during vaccination through small molecules enhances vaccination efficacy.<ref>{{Cite journal | vauthors = Ahmad F, Umar MS, Zubair S, Khan N, Gupta P, Gupta UD, Owais M |date=2022-10-01 |title=Efficacy of IL10/STAT3 directed small molecule immunotherapy in augmenting the potential of rBCG30 vaccine against murine pulmonary tuberculosis |journal=Molecular Immunology |volume=150 |pages=14 |doi=10.1016/j.molimm.2022.05.053 |s2cid=252930472 |issn=0161-5890}}</ref><ref>{{Cite journal | vauthors = Ahmad F, Umar MS, Khan N, Gupta P, Gupta UD, Owais M|date= May 2020 |title=A small molecule based immunotherapy targeting IL-10/STAT3 praxis to augment the potential of rBCG30 vaccine against experimental tuberculosis |journal=The Journal of Immunology |volume=204 |issue=1_Supplement |pages=168.24 |doi=10.4049/jimmunol.204.supp.168.24 |s2cid= 255645861 |issn=0022-1767}}</ref><ref>{{Cite journal | vauthors = Ahmad F, Umar MS, Khan N, Gupta P, Gupta UD, Owais M |date=2021 |title=A Potent Inhibitor of IL-10/STAT3 Axis Signaling Modulates Anti-Inflammatory Responses and Boosts Anti-Tuberculosis Immunity in rBCG30 Immunized Mice |journal=International Journal of Mycobacteriology |language=en |volume=9 |issue=5 |pages=49 |doi=10.4103/2212-5531.307099 |doi-access=free |issn=2212-5531}}</ref><ref>{{cite journal | vauthors = Ahmad F, Umar MS, Khan N, Jamal F, Gupta P, Zubair S, Gupta UD, Owais M | title = Immunotherapy With 5, 15-DPP Mediates Macrophage M1 Polarization and Modulates Subsequent <i>Mycobacterium tuberculosis</i> Infectivity in rBCG30 Immunized Mice | journal = Frontiers in Immunology | volume = 12 | pages = 706727 | date = 2021 | pmid = 34777338 | pmc = 8586420 | doi = 10.3389/fimmu.2021.706727 | doi-access = free }}</ref>

== References ==