Vaccine Description Results (compared to BCG) Reference
Recombinant BCG overexpressing native MTB proteins
rBCG30 BCG over expressing the 30kDa protein (Ag85B) The first vaccine demonstrating more potency than BCG against TB [114]
rBCG/Ag85A BCG over expressing Ag85B Fewer CFU in lung and spleen in vaccinated guinea pigs; fewer CFU in lung but not in spleen in cynomolgus monkeys [115,116]
rBCG/Ag85C BCG over expressing Ag85C In guinea pigs, reduced CFU in lung and spleen; reduced pathology in lung, spleen and liver; reduced pulmonary fibrosis [117]
rBCG/ESAT-6 (±CFP10) BCG secretes both ESAT-6 and CFP10 Tested in mice and guinea pigs; same protection in lung but better in spleen; not good in immunocompromised mice [118]
rBCG/38 kDa protein BCG over expressing 38kDa glycoprotein Immunized mice survived longer [119]
Recombinant BCG expressing MTB fusion proteins
rBCG/72f BCG secreting a hybrid of proteins Mtb39 +Mtb32 (named 72f) In cynomolgus monkey induced immune and protective responses but not different than BCG controls [120]
rBCG/Ag85B-ESAT-6 BCG secreting fusion proteins of Ag85B and ESAT-6 Protective responses similar to BCG controls in mice [121]
rBCG/Ag85B-Mpt64190-198-Mtb8.4 BCG expressing a fusion protein of Ag85B with immunodominant peptide Mpt64 and Mpt8.4 Comparable or slightly better efficacy than BCG in mice [61]
Recombinant BCG overexpressing native proteins and additionally attenuated for safety in HIV-positive persons
rBCG(mbtB)30 Rendered sideropore dependent by deletion of the gene mbtB Safer than BCG in SCID mice and more potent than BCG in the guinea pig model of TB [44]
rBCG(panCD)30 Rendered pantotenate dependent by deletion of the panCD genes Can multiply in vitro, but multiplication is limited in vivo; safer than BCG in SCID mice in protection comparable to BCG in the guinea pig model of TB [44]
Recombinant BCG expressing immunomodulatory cytokines
rBCG/GM-CSF BCG secreting murine granulocyte macrophage colony stimulating factor Immunized mice had higher numbers of antigen presenting cells; IFN-gamma secreting cells, and ~1 log fewer CFU in spleen after virulent challenge [122]
rBCG/IL-2 BCG secreting murine IL-2 to counter a Type 2 immune response Immunized mice exhibited greater splenocyte proliferation and IFN-gamma production in response to PPD, comparable protection to BCG [123]
rBCG/IL-15 BCG secreting a fusion protein of Ag85B and murine IL-15 Immunized mice had greater absolute numbers of CD4+ and CD8+ T cells in lung and spleen; greater numbers of IFN-gamma secreting CD4+ cells and lower CFU in the lung but not in the spleen [124]
Recombinant BCG overexpressing native proteins and escaping the phagosome
rBCG-Aeras403 BCG  over expressing Ag85B and TB10.4 with endosome escape Safer than BCG in SCID mice; induced stronger responses in mice and guinea pigs compared to BCG; mice survived longer than with BCG [125]
rBCG ΔureC hly+ BCG that expresses membrane perforating listeriolysine and is devoid of urease Induced superior protection in mice than BCG. Proven to be safe and immunogenic in phase I clinical trial [126]
Modified or attenuated MTB
MTB phoP mutant SO2 SO2 strain engineered by a disruption in the phoP gene  of MTB Impaired multiplication in vitro in mouse macrophages and in vivo in infected mice; Enhanced ability to bind human macrophages [127]
MTB ΔRD1 ΔpanCD MTBH37Rv with deletion of the primary attenuating mutation of BCG (DeltaRD1) and two genes for the synthesis of pantothenate (DeltapanCD). long-lived protective immune responses and longer survival in wild type mice, and CD4-deficient mice against an aerosol challenge with virulent MTB. Safe in guinea pigs and SCID mice [128]
MTB Δ leuD Δpan MTB with two independent attenuating auxotrophic mutations in leucine
and pantothenate biosynthesis
Long-term protection and survival in guinea pigs against challenge with virulent MTB similar to BCG. No vaccine-associated adverse effects (clinical, hematological and bacteriological) in  SIV-positive or SIV-negative Rhesus macaques [129]
Table 1: Summary of new vaccine candidates against TB by modification of the whole bacterium (modified from [43,46]).