| 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] |
