Skip to main content
. 2021 Mar 26;17(8):2454–2470. doi: 10.1080/21645515.2021.1885280

Table 1.

Summary of current anti-TB vaccine candidates according to tuberculosis vaccine initiative

Vaccine Components Development Status Studies
Novel anti-TB vaccine      
Mycobacterium incidus
pranii (MIP) 		A nonpathogenic atypical mycobacterium Phase III

  • Safe and induced prominent Th1 responses with heat-killed MIP in mice and guinea pigs45

  • Enhanced bacterial clearance and improved lung pathology in guinea pig model46 and advanced pulmonary TB patients46
Mycobacterium vaccae (M. vaccae) Heat-killed M. vaccae, a nonpathogenic mycobacterial species Phase III

  • Effectively control M. tb infection in animal models47,48

  • Failed to provide protective benefits as a single-dose regimen in human trials49,50

  • Well-tolerated and immunogenic in three-dose and five-dose regimen in healthy51 and HIV-infected human52,53
RhMCV/TB Recombinant rhesus macaques Cytomegalovirus vectors expressing M. tb antigens Preclinical

  • Effective in TB prevention in rhesus macaque model54
ChadOx1/PPE15 Recombinant chimpanzee Adenoviral vector expressing M. tb antigens Preclinical

  • Intranasal administration induced differentiation of lung parenchymal naïve CD4+ and CD8 + T cells to protective phenotype CXCR3+ KLRG1- in mice55
AEC/BC02 Fusion of Ag85B and ESAT-6/CFP-10 antigens in CpG/aluminum salt-based adjuvant Phase I

  • Reduced bacterial load in guinea pig model56

  • Dose-dependent potency in stimulation of IFN-y response and effective in latent or active disease57
H1:IC31 Fusion of ESAT6 and Ag85B antigens in IC31 adjuvant system Phase I

  • Safe and immunogenic in murine models58

  • Safe in human adults59,60 and HIV-infected individuals61

  • Two low-dose regimens optimally induced polyfunctional CD4 + T cells in healthy adolescents62
M72/AS01E Fusion of M. tb32A and M. tb39A antigens in AS01 adjuvant system Phase II

  • Safe and immunogenic in BCG-vaccinated infants,63 healthy HIV-infected64 and M. tb-infected adults65

  • Render 54% protection against reactivation in TB-latent adults66
RUTI Polyantigenic liposomal expressing mycobacterial latent antigens Phase II

  • Reduce bacterial burden and macrophage infiltration in granulomas, promote strong IFN-y secretion in Th1 immune responses in murine models, and produce a balanced Th1/Th2 response in addition to M. tb antigen-specific IgG antibodies67–70

  • Safe and immunogenic in healthy adults71

  • Safe and immunogenic with a low dose vaccine in latent TB adults72
Recombinant BCG strain      
BCG-Zmp1 Deletion of zmp1 gene in M. bovis BCG strain Preclinical

  • More intense immune responses against M. tb compared to wild-type BCG in mice73

  • Safe and immunogenic in guinea pig model74
SapM:TnBCG Deletion of SapM gene from parental M. bovis BCG strain Preclinical

  • Robust Th1 immune response, decline in bacterial load, and improve long-term survival compared to parental BCG in mice75
CysVac2 Recombinant BCG expressing Ag85B-CysD fusion protein Preclinical

  • Steady reduction in bacterial load in heterologous prime-boost with BCG-CysVac276

  • Robust immunity prior to and after M. Tb exposure with induction of polyfunctional CD4 + T cells77

  • Profound Th1 response when CysVac2 formulated with Advax adjuvant78
VPM1002 Recombinant BCG replacing urease C gene with listeriolysin O Phase III

  • Acceptable safety profile in animal models and SCID mice79,80

  • Highly efficacious induction of Th1 responses and bacterial burden reduction compared to BCG-control80–83

  • Safe and efficacious in prevention of TB in newborns84
BCG Booster Vaccines      
BCG revaccination Wild-type M. bovis BCG strain Phase II

  • Increase magnitude of a robust CD4 + T cells response with no significant affect to the response rate of CD4 + T cells in homologous BCG prime-boost regimen85

  • Confer 45.4% efficacy against M. tb infection in BCG-primed group86

  • No additional benefits upon homologous BCG prime boost in two large-scale randomized trials87,88
Ad5Ag85A Adenovirus type 5 expressing Ag85A antigen Phase I

  • Superior efficacy of heterologous BCG-prime Ad5Ag85A-boost regimen among mice,89 cattle,89 and goat90

  • Greater degree of protection against TB seen in bovine model91

  • Administered intranasally, elicited significant T cells responses in the lung with better protection following pulmonary challenge92
Ad5-CEAB Adenovirus type 5 expressing CFP10, ESAT6, Ag85A, and Ag85B antigen in a mixture rather a fusion protein Unknown

  • Antigen-specific T cell responses were significantly amplified in heterologous prime-boost regimen93
Ad35-TBS (AERAS-402) Adenovirus type 35 expressing Ag85A, Ag85B, and TB10.4 antigens Unknown

  • Strong CD8+ and CD4 + T-cell response in a dose-dependent manner in murine model94

  • Heterologous prime-boost regimen greatly induces multifunctional CD4+ and CD8 + T cells95
GaM. tbVac Fusion of Ag85A and ESAt6-CFp10 with dextran-binding domain fixated on dextran and mixed with a dextran core/CpG ODN adjuvant system Phase I

  • Heterologous prime-boost regimen considerably enhanced antigen-specific responses and reduced bacterial burden compared to BCG alone and homologous GaM. tbVac-GaM. tbvac regimen96

  • Safe and efficacious as a heterologous prime-boost regimen in human adults97
H4:IC31 (AERAS-404) Fusion of TB10.4 and Ag85B in IC31 adjuvant system Unknown

  • Safe and protective against M. tb challenge in murine model98

  • Safe and optimal responses at low dose in human model99,100
H56:IC31 Fusion of Ag85B, ESAT-6, and Rv2660c in IC31 adjuvant system Phase II

  • Safe and effectively reduce bacterial burden in BCG-primed mice101 and nonhuman primates102,103

  • Induce polyfunctional CD4 + T cell responses at low dose104

  • Induce robust immune responses with three doses of H56:IC31 in QFT-negative individuals whereas no additional benefits were seen from the third dose in QFT-positive individuals105
ID93/GLA-SE Fusion of Rv1813, Rv2608, Rv3619, and Rv3620, combined with glucopyranosyl lipid adjuvant in oil-in-water stable emulsion Phase I

  • Heterologous BCG-prime ID93/GLA-SE-boost regimen enhanced survival in guinea pig model106,107 and against a virulent MTb strain in the mouse model108

  • Induced polyfunctional CD4 + T cells double expressing either cytokines CD154+ IFN-y+ or CD154+ TNF-a+ in mice109 and TB naïve human110

  • Tuberculin Skin Test is not compromised in ID93/GLA-SE vaccinated animals111
DAR-901 Inactivated M. tb SRL172 strain Phase II

  • Safe and immunogenic with superior protection compared to BCG alone in BCG-DAR-901-vaccinated mice112 and human adults113,114
MTBVAC Live-attenuated M. tb with deletion of virulence factors, fadD26 and phoP Phase II

  • Safe in SCID mice and guinea pigs115

  • No effect on growth and development in newborn mice116

  • Similar safety profile to BCG in adults and infants117

  • Reduce bacterial burden and enhance survival in mice,118 goats,119 and nonhuman primate120

  • Greater multifunctional CD4 + T cell responses with acceptable safety profile in humans121

  • BCG-prime M. TBVAC-boost regimen confers greater protection in guinea pigs compared to BCG alone122

  • Intranasal administration of heat-killed M. TBVAC induce profound humoral and cellular responses systemically and locally in BCG-prime animals123