Table. 1:
Recombinant BCG (rBCG) strains tested as TB vaccine candidates.
| Development of rBCG strains expressing bacterial antigens and immune mediators tested as TB vaccine candidates | |||
|---|---|---|---|
| Name | Foreign antigen | Immune response and safety | Therapeutic efficacy |
| rBCG30 | Mtb - 30kDa secretory protein | Cutaneous DTH response and increased antibody titer | Improved protective immunity (Guinea pig model of Mtb infection) |
| Horwitz et al., 2006 | |||
| Ref. 57. | |||
| PMID: 16257099 | |||
| rBCG (mbtB)30 | M. tb. - 30kDa secretory protein, deleted mbtB | More attenuated than BCG in SCID mice | Improved protective efficacy (Guinea pig model of Mtb infection) |
| Tullius et al., 2008 | |||
| Ref. 59. | |||
| PMID: 18725418 | |||
| rBCG (panCD)30 | M. tb. - 30kDa secretory protein and deleted panCD; pantothenate auxotroph | More attenuated than BCG in SCID mice | Improved protective efficacy (Guinea pig model of Mtb infection) |
| Tullius et al., 2008 | |||
| Ref. 59. | |||
| PMID: 18725418 | |||
| rBCG::Ag85A | Mtb-Ag85A antigen | Stronger antigen-specific IFN-γ responses and higher antibody titers | Improved protective efficacy in (C57BL/6 mouse model of Mtb infection) |
| Xu et al., 2016 | |||
| Ref. 60. | |||
| PMID: 26858942 | |||
| rBCG::AB | Mtb-Ag85A and Ag85B antigen | Increased antigen-specific IFN-γ response in vitro | Long-term protection (C57BL/6 mouse model of Mtb infection) |
| Wang et al., 2012 | |||
| Ref. 61 | |||
| PMID: 22570667 | |||
| rBCG::XB | Mtb-Ag85B and HspX latency antigen | Increased antigen specific CD4+ and CD8+ T cells. Increased CD4+ TEM and CD8+ TCM response | Long-term protection (C57BL/6 mouse model of Mtb infection) |
| Yuan et al., 2015 | |||
| Ref. 62. | |||
| PMID: 26363555 | |||
| BCG85B-ES | Mtb-Ag85B and ESAT-6 fusion protein | No evidence | Improved protective efficacy (Mouse model of Mtb infection) |
| Palendira et al., | |||
| PMID: 15705472 | |||
| rBCG-AE | Mtb-Ag85A-ESAT-6 fusion protein | No evidence | No improvement in protective efficacy (BALB/c mouse model of Mtb infection) |
| Deng et al., 2014 | |||
| Ref. 63. | |||
| PMID: 23357605 | |||
| rBCG::Ag85B-ESAT6-Rv2608 | Mtb-Ag85B-ESAT-6-Rv2608 fusion protein | Increased CD4+ and CD8+ T lymphocytes proliferative response, stronger TH1 cytokine response and stronger humoral response | No evidence of protective immunity |
| Lu et al., 2012 | |||
| Ref. 64. | |||
| PMID: 22671973 | |||
| rBCG::Ag85B-ESAT6-Rv3620c | Mtb-Ag85B-ESAT-6-Rv3620c fusion protein | Increased CD4+ and CD8+ T lymphocytes proliferative response, stronger TH1 cytokine response and stronger humoral response | No evidence of protective immunity |
| Yang et al., 2014 | |||
| Ref. 65. | |||
| PMID: 24726737 | |||
| rBCG-AEI | Mtb-Ag85B-ESAT-6 and murine IFN-γ fusion protein | Increased antibody titers and higher cellular immune response as compared to rBCG::AE and wild-type BCG | Improved or similar protective immune response as compared rBCG::AE |
| Xu et al., 2007 | |||
| Ref. 66. | |||
| PMID: 17919299 | |||
| rBCG-Ag85B-ESAT6-TNF- α | Mtb-Ag85B-ESAT-6 and murine TNF- α fusion protein | Stronger immune response (IFN-γ and TNF- α) as compared to rBCG-Ag85B-ESAT-6 or BCG | No evidence of protective immunity |
| Shen et al., 2010 | |||
| Ref. 67. | |||
| PMID: 20646207 | |||
| Ag85B-IL15 | Mtb-Ag85B and murine IL-15 fusion protein | Increased IFN-γ producing CD4+ T cells as compared to rBCG-AG85B or BCG | No evidence of protective immunity |
| Tang et al., 2008 | |||
| Ref. 68. | |||
| PMID: 18422438 | |||
| BCG::ESAT-L28A/L29S | Mutated version (modifications at residue Lue28-Leu29 of ESAT-6 of Mtb | Attenuated for virulence in SCID mice as compared to BCG-ESAT6 and BCG | Improved protective efficacy (C57BL/6 mouse model of Mtb infection) |
| Bottai et al., 2015 | |||
| Ref. 70. | |||
| PMID: 25869896 | |||
| (H)PE-ΔMPT64-BCG | Mtb-MPT64 fused to the PE domain of the PE_PGRS33 protein | Induction of MPT64-specific cytokine producing CD4 and CD8 cells; multifunctional CD4 cells specific for MPT64 | Improved protective efficacy (C57BL/6 mouse model of Mtb infection) |
| Sali et al., 2010 | |||
| PMID: 20921146 | |||
| BCG: ESX-1Mmar | ESX-1 region of M. marinum | Increased Type 1 IFN and infiammasomes, increased antigen specific CD8+ and polyfunctional CD4+ TH1 cells. Reduced virulence in SCID mice | Improved protective efficacy in (C57BL/6 mouse model of Mtb infection) |
| Gröschd et al., 2017 | |||
| Ref. 71 | |||
| PMID: 28297677 | |||
| VPM1002 | N-terminal region of Ag85B of Mtb. listeriolysin O (LLO) of L. monocytogenes and deletion of ureC gene | Increased antigen specific CD4+ and CD8+ T cells, increased autophagy, infiammasome activation and macrophage apoptosis. Reduced virulence in different rodent and non-human primates, safer in humans as compared to BCG | Improved protective efficacy in different animal models |
| (BCG ΔureC::hly+) | |||
| Grode et al. 2005 | |||
| PMID: 16110326 | |||
| VPM1002 ΔnuoG | Genetic modification ofVPM1002 vaccine with deletion of nuoG | Increased autophagic targeting of intracellular BCG, increased CD4+ T response as compared to VPM1002. Excellent safety profile in animal models | Improved protective efficacy as compared to VPM1002 as well as BCG in different animal models |
| Gengenbacher et al., 2016 | |||
| Ref. 76. | |||
| PMID: 27222470 | |||
| VPM1002 Δpdx1 | VPM1002 modified for deletion of pdx-1 (Vitamin B6 auxotrophy) | Increased innate immune response, increased CD4+ T- and B cell response. Increased safety in SCID mice as compared to VPM1002 and BCG | Improved protective efficacy (prime-boost model of Mtb infection) |
| Gengenbacher et al., 2014 | |||
| Ref. 78. | |||
| PMID: 24895310 | |||
| AERAS-401 (BCG1331 ΔureC::ΩpfoAG137Q) | BCG1331 expressing a mutant form of perfringolysin O (PfoAG137Q) from Clostridium perfringens and deleted ureC gene | Excellent safety profile in SCID mice | Improved protective efficacy (mouse model of Mtb infection) |
| Sun et al., 2009 | |||
| Ref. 79. | |||
| PMID: 19500523 | |||
| AFRO-1 or AERAS-422 | AERAS-401 expressing Ag85A, Ag85B, and TB10.4 of Mtb | Enhanced immune response in mice and guinea pigs | Improved protective efficacy (mouse model of hypervirulent Mtb infection) |
| Sun et al., 2009 | |||
| Ref. 79. | |||
| PMID: 19500523 | |||
| rBCG Δzmp1 | BCG zmp1 mutant | Increased safety profile in SCID mice | Improved protective efficacy (guinea pig model of Mtb infection) |
| Sander et al., 2015 | |||
| Ref. 81 | |||
| PMID: 25657094 | |||
| BCG ΔleuD/Ag85B | Mtb-Ag85B antigen expressed in BCG ΔleuD strain | Increased tumor cytotoxicity, strong induction pro-apoptotic genes in cancer cells as compared to wild-type BCG | No efficacy data |
| Begnini et al., 2013 | |||
| PMID: 23053076 | |||
| BCG-disA-OE | Mtb disA diadenylate cyclase gene overexpressed in BCG with excess release of the STING agonist, c-di-AMP | Increased IRF3 activation | Improved protective efficacy (guinea pig model of Mtb infection) |
| Dey et al., 2020 | |||
| Ref. 83 | |||
| PMID: 30901058 | |||