Table 1.
List of TB vaccines currently in clinical trials.
| Vaccine | NCT Number |
Phase | Population | Sample Size | Arms and Interventions | Primary Outcome Measures | Results | Ref. |
|---|---|---|---|---|---|---|---|---|
| M72/AS01E | NCT01755598 | I | LTBI individuals | 3575 | Experiment: 2 doses of M72/AS01E (10 µg), spaced one month apart, i.m. in the arm triangle area. Placebo comparator: 2 doses of placebo with a 1-month interval, i.m. in the arm triangle area. |
Incident rates of definite PTB disease, not associated with HIV-infection, meeting the case definition | LTBI population vaccinated with M72/AS01E can prevent latent infections from developing into TB, the vaccine efficacy in the 36th month was 49.7% | [78,79] |
| NCT00950612 | II | Adolescents | 60 | Experiment: 2 doses of M72/AS01E (10 µg), with an interval of one month, i.m. in the arm triangle area. Placebo comparator: 2 doses of placebo with a one-month interval, i.m. in the arm triangle area. |
Number of subjects with solicited local symptoms and solicited general symptoms, unsolicited AEs and SAEs, different levels biochemical and hematological levels | M72/AS01E induced strong T cell and antibody responses, including NK cells and IFN- γ generation | [80] | |
| NCT04556981 | III | HIV-positive patients | 402 | Experiment: 2 doses of M72AS01E (10 µg), i.m., at days 1 and 29. Placebo comparator: control sodium chloride 0.9%, i.m., at days 1 and 29. |
Number of participants with solicited AEs, unsolicited AEs, and SAEs | NA | ||
| GamTBvac | NCT03255278 | I | Healthy adults | 60 | Placebo comparator: s.c. 0.5 mL placebo. Safety and portable study group: s.c. 0.25 mL GamTBvac. Experimental 1: s.c. 0.25 mL GamTBvac. Experimental 2: s.c. 0.5 mL GamTBvac. Experimental 3: s.c. 1 mL GamTBvac. |
The number of AEs | Different doses of vaccines were evaluated for immunogenicity, with half dose (0.5 mL) having the best effect | [81] |
| NCT03878004 | II | Healthy adults | 180 | Experiment: s.c. 2 doses of 0.5 mL GamTBvac, with an interval of 8 weeks. Placebo comparator: s.c. 2 doses of 0.5 mL placebo, with an interval of 8 weeks. |
1. Level of IFN-γ secretion in whole blood or PBMC fraction 2. Number of participants with AEs |
The vaccine is well tolerated and induces specific and persistent Th1 and Humoral immunity responses | [82] | |
| NCT04975737 | III | Healthy adults | 7180 | Experiment: s.c. 2 doses of 0.5 mL GamTBvac, with an interval of 8 weeks. Placebo comparator: s.c. 2 doses of 0.5 mL placebo, with an interval of 8 weeks. |
Preventive efficacy (Ep) | NA | ||
| H56:IC31 | NCT01967134 | I | LTBI/healthy adults | 25 | Experiment: LTBI negative, i.m. 3 doses of 15 µg/500 nmol H56:IC31 at days 0, 56 and 112. Experiment: LTBI positive, i.m., 3 doses of 50 µg/500 nmol H56:IC31, days 0, 56 and 112. |
Number of participants with at least 1 AE until day 210 | H56:IC31 vaccine induces antigen-specific IgG response and CD4+ T cells expressing Th1 cytokines | [83] |
| NCT02378207 | Ib | Adolescent | 84 | Experiment: i.m. 0.5 mL H4:IC31 or H56:IC31 at days 0 and 56. Active comparator: i.m. 0.1 mL BCG at day 0. Placebo comparator: i.m. 0.5 mL NaCI at days 0 and 56. |
1. Number of participants with AEs 2. Percentage of participants with response rates to TB antigens as compared to baseline |
Both H4: IC31 and H56: IC31 induce CD4+ T cell responses, and H4:IC31 and H56:IC31 induce serum IgG | [84] | |
| NCT01865487 | IIa | Healthy adults/LTBI | 98 | Placebo control: i.m. 2 doses of NaCl. Experimental groups: 5/500, 15/500, 50/500 H56ug/IC31nmol QFT-negative and/or -positive, 2 doses, days 0 and 56. |
Number and percentage of unsolicited and solicited AEs | H56:IC31 induces a persistent antigen-specific Th1 response without being affected by MTB infection | [85] | |
| NCT02503839 | I/II | ATB patients | 51 | Experimental 1: 120 g of etoricoxib, po. at days 0 and 140. Experimental 2: 140 µg H56:IC31 and no etoricoxib i.m. at days 84 and 140. Placebo comparator: Standard TB treatment. Experimental 3: 120 g etoricoxib po. at days 0 and 140; 140 µg H56:IC31 i.m. at days 0 and 140. |
1. Participants with AEs 2. Immunogenicity of etoricoxib/H56:IC31 vaccine |
H56:IC31 vaccination is safe and immunogenic in ATB patients | [86] | |
| NCT03512249 | IIb | ATB patients | 900 | Experiment: i.m. 2 doses of 0.5 mL H56:IC31 at days 0 and 56. Placebo comparator: i.m. 2 doses of 0.5 mL NaCI at days 0 and 56. |
Rate of TB disease recurrence | NA | ||
| H4:IC31 |
NCT02074956 NCT02066428 |
I | Healthy adults | 60 | Experimental 1–4 groups: i.m. 5 µg, 15 µg, 50 µg, or 150 µg/500 nmol, H4:IC31 at days 0 and 56. Experimental 5: i.m. H4:IC31 (15 µg/100 nmol). Placebo: NaCl. |
Safety profile of two injections of H4:IC31 at different dose levels; evaluate the safety of one or two injections of two H4:IC31 antigen amounts administered with three different amounts of adjuvant | The evidence provided by the dose escalation test indicates that the optimal antigen adjuvant dose combination is H4, 5, 15, or 50 µg and IC31 500 nmol | [87] |
| NCT02075203 | II | Adolescents | 989 | Experiment: i.d. 2 doses of H4:IC31 (15 mcgH4/500 nmol IC31) at days 0 and 56. Active comparator: i.d. BCG at day 0. Control group: i.d. 2 doses of 0.9% NaCl (0.9%) at day 0. |
1. Safety profile of H4:IC31 and BCG revaccination 2. Number of participants testing positive for MTB at day 84 |
The immune efficacy of the H4: IC31 vaccine is 30.5% (p = 0.16). 44 (14.3%) H4:IC31 group experienced QFT conversion, 41 (13.1%) BCG group experienced QFT conversion, and 49 (15.8%) placebo group experienced QFT conversion | [88] | |
| ID93/GLA-SE | NCT01599897 | I | Healthy adults | 60 | Experimental 1–4: i.m. 2 µg ID93 + 2 µg GLA-SE, 10 µg ID93 + 2 µg GLA-SE, 2 µg ID93 + 5 µg GLA-SE, 10 µg ID93 + 5 µg GLA-SE at days 0, 28, and 56, respectively. Active comparator 1–2: i.m. 2 µg or 10 µg ID93 at days 0, 28, and 56. |
Number of patients experiencing AEs | Showing a satisfactory safety profile and eliciting a functional humoral and T-helper 1 type cellular response | [89] |
| NCT02465216 | IIa | Healthy adults | 60 | Experimental 1–3: i.m. 2 μg ID93 + 2 μg GLA-SE, 10 μg ID93 + 2 μg GLA-SE, 2 μg ID93 + 5 μg GLA-SE at days 0 and 56, respectively. Experimental 4: i.m. 3 doses of 2 µg ID93+ 5 µg GLA-SE at days 0, 28, and 56. Active comparator: i.m., NaCI at days 0, 28, and 112. |
Number of AEs | The antigen-specific IgG and CD4 T cell responses induced by a dose of 2 μg ID93 + 5 μg GLA-SE were significantly higher than those induced by placebo, and lasted for 6 months | [90] | |
| NCT03806686 | IIa | Healthy adults | 107 | Experimental 1–2: i.m. 2 μg ID93 + 5 µg GLA-SE, 5 μg ID93 +5 μg GLA-SE at days 0, 28, and 56, respectively. Active comparator: i.m. 0.5 mL NaCI at days 0, 28, and 56. |
AEs | NA | ||
| AEC/BC02 | NCT04239313 | I | Healthy adults | 30 | Experiment: i.m. low-dose AEC/BC02; Active comparison: i.m. low-dose adjuvant; active comparator: i.m. placebo. | The number of AEs after i.m. | NA | |
| NCT05284812 | II | LTBI individuals | 200 | Negative control group: not vaccinated. Sentinel group: 18–59-year-olds received low- or high-dose injections; ≥60 years old received low or high-dose injections, i.m. Experimental group 1: EC positive, i.m. low-dose AEC/BC02. Experimental group 2: EC positive, i.m. high-dose AEC/BC02. Experimental group 3: EC positive, i.m. high-dose AEC/BC02 into 1,3, and 6 doses; i.m. 2, 4, 5 doses of placebo. Placebo group: EC positive, i.m. placebo. Adjuvant group: high-dose adjuvant for AEC/BC02. | The number of AEs after i.m. injection | NA | ||
| VPM1002 | NCT00749034 | I | Healthy male | 80 | Experiment: i.d. 0.05 mL VPM1002 (5 × 103, 5 × 104, 5 × 105 CFUs). Active comparator: i.d. 0.05 mL BCG (2–8 × 105 CFUs). |
Physical examination, vital signs, ECG, liver sonography, chest X-ray, laboratory safety parameters, tolerability, recording of concomitant medication and AEs | VPM1002 has safety and immunogenicity in response to B and T cells | [91] |
| NCT01479972 | II | Newborn infants | 48 | Experiment: i.d. 0.05 mL VPM1002. Active comparator: i.d. 0.05 mL BCG. |
1. Safety 2. Immunogenicity |
Inoculation with VPM1002 can induce multifunctional CD+ 4 and CD8+ T cells | [92] | |
| NCT02391415 | II | Newborn infants | 416 | Experiment: HIV-unexposed infants, i.d. 0.05 mL VPM1002. Control group: HIV-unexposed infants, i.d. 0.05 mL BCG. Experiment: HIV-unexposed infants, i.d. 0.05 mL VPM1002 (Hyg+). Control group: HIV-exposed infants, i.d. 0.05 mL BCG. Experiment: HIV-exposed infants, i.d. 0.05 mL VPM1002. |
The difference between the VPM1002 and BCG vaccination groups in the incidence of grade 3 and 4 adverse drug reactions and IMP-related ipsilateral or generalized lymphadenopathy of 10 mm or greater (diameter) | VPM1002 is safe for both HIV-exposed and -unexposed infants; both VPM1002 and BCG have immunogenicity, and from the 6th week onwards, the immune response intensity induced by BCG is greater than that of VPM1002 | [93] | |
| NCT03152903 | III | Healthy adults | 2000 | Experiment: i.d. 0.05 mL VPM1002. Active comparator: i.d. 0.05 mL placebo. |
Percentage of bacteriologically confirmed TB recurrence cases | NA | ||
| NCT04351685 | III | Newborn infants | 6940 | Experimental group: i.d. 0.05 mL VPM1002. Active comparator: i.d. 0.05 mL BCG. |
Incident cases of QFT conversion | NA | ||
| MTBVAC | NCT02013245 | I | Healthy adults | 34 | Experimental 1: i.d. 0.1 mL MTBVAC (5 × 103 CFUs). Experimental 2: i.d. 0.1 mL MTBVAC (5 × 104 CFUs). Experimental 3: i.d. 0.1 mL MTBVAC (5 × 105 CFUs). Active comparator: i.d. 0.1 mL BCG (5 dose 5 × 105 CFU). |
Number of participants with AEs up to 210 days after vaccination | MTBVAC exhibits good safety in healthy adults, similar to BCG | [94] |
| NCT02729571 | Ib | Newborn infants | 54 | Experimental 1: i.d. 0.1 mL MTBVAC (5 × 105 CFUs)/0.1 mL BCG SII (5 × 105 CFUs) adults. Experimental 2: i.d. 0.05 mL MTBVAC (2.5 × 103 CFUs/2.5 × 104 CFUs/2.5 × 105 CFUs) infants. Experimental 3: i.d. 0.05 mL BCG (2.5 × 105 CFUs) infants. |
Safety and reactogenicity in infants and adults | MTBVAC has good safety and immunogenicity, and can induce long-lasting CD4 cell responses in infants | [95] | |
| NCT02933281 | Ib/IIa | Healthy adults | 144 | Experimental 1–4: QFT negative, i.d. MTBVAC 5 × 103, 5 × 104, 5 × 105, or 5 × 106 CFUs at day 0, respectively. Experimental 5–8: QFT positive, i.d. MTBVAC 5 × 103, 5 × 104, 5 × 105, or 5 × 106 CFUs at day 0, respectively. Active comparator: i.d. BCG 5 × 105 CFUs at day 0. |
Safety and reactogenicity of MTBVAC at escalating dose levels compared to BCG vaccine by assessing number of participants with AEs and SAEs | NA | ||
| NCT03536117 | IIa | Newborn infants | 99 | Experimental 1–3: i.d. 0.05 mL MTBVAC (2.5 × 104, 2.5 × 105, or 2.5 × 106 CFUs), respectively. Active comparator: i.d. 0.05 mL BCG (2.5 × 105 CFUs). |
1. Number of participants with treatment-related AEs as defined in protocol 2. Immunogenicity analysis in infants |
NA | ||
| NCT04975178 | III | Newborn infants | 6960 | Experiment: i.d. 0.05 mL MTBVAC. Active comparator: i.d. 0.05 mL BCG. |
Prevention of TB disease in healthy HIV-uninfected and HIV-exposed uninfected neonates | NA | ||
| BCG (revaccination) | NCT02378207 | IIb | Adolescents | 84 | Active comparator: BCG (2–8 × 105 CFUS), i.m. as 0.1 mL in either deltoid muscle at day 0. Placebo comparator: control sodium chloride 0.9%, i.m. as 0.5 mL in alternating deltoid muscle at days 0 and 56. |
Number of participants with AEs; percentage of participants with response rates to TB antigens as compared to baseline | BCG revaccination had acceptable safety and induced robust, multifunctional BCG-specific CD4+ T cells | [84] |
| NCT02075203 | II | Adolescents | 989 | Active comparator: BCG SSI vaccine, 1 dose on day 0; placebo comparator: placebo, 2 doses on days 0 and 56. | Safety profile of BCG revaccination; number of participants testing positive for MTB at day 84 | BCG revaccination was immunogenic and reduced the rate of sustained QFT conversion, with an efficacy of 45.4% (p = 0.03) | [88] | |
| NCT04152161 | IIb | Children and adolescents | 1820 | Experiment: a single 0.1 mL of BCG vaccine SSI, i.d. in deltoid region of the upper arm. Placebo: a single 0.1 mL of normal saline, i.d. in deltoid region of the upper arm. |
Number of participants with sustained QFT conversion | NA | ||
| MIP | NCT00341328 | III | Category-I PTB patients | 300 | Experimental group: i.d., 6 doses MIP vaccine given 0.2 mL at baseline, then 0.1 mL every 2 weeks for 8 weeks. Control group: i.d., 6 doses placebo given 0.2 mL at baseline, then 0.1 mL every 2 weeks for 8 weeks. |
The time of sputum conversion, the cure rate; the relapse in patients of category-I pulmonary TB, and any clinical adverse reactions | NA | |
| NCT00265226 | III | Category-II PTB patients | 1020 | Experimental group: intradermal administration of mycobacterium W vaccine and category II ATT as per RNTCP guidelines. Control group: placebo administration and category II ATT drugs as per RNTCP guidelines. |
1. Sputum conversion time 2. Cure rate 3. Clinical adverse reactions |
At the 39th week follow-up, sputum culture conversion rate was 94.2% (309/328) in the MIP group and 89.17% (280/314) in the placebo group | [96] | |
| RUTI | NCT00546273 | I | Healthy adults | 24 | Experimental groups 1–4: RUTI (5 µg, 25 µg, 100 µg, or 200 µg) i.d., at days 0 and 28. Placebo comparator: placebo i.d. at days 0 and 28. |
1. VAS Pain Score 2. Local and systemic events occurrence, intensity, and relationship to vaccination 3. Number of clinically relevant abnormalities detected |
RUTI has been proven to trigger specific reactions against MTB | [97] |
| NCT01136161 | IIa | LTBI individuals | 95 | Experimental groups 1–5: HIV-negative, 5 µg, 25 µg, 100 µg, 200 µg RUTI or placebo i.d. at days 28 and 56, respectively. Experimental groups 6–10: HIV-positive, 5 µg, 25 µg, 100 µg, 200 µg RUTI or Placebo i.d. at days 28 and 56, respectively. |
1. Local tolerability, focal tolerability 2. Systemic tolerability, vital signs and physical examination, ECG, and laboratory tests |
The best cellular multi-antigen response was achieved when administered at 25 µg RUTI | [98] | |
| NCT04919239 | IIb | ATB patients | 140 | Experiment: 25 µg RUTI, i.d. Placebo comparator: 25 µg placebo, i.d. |
Percentage of patients with sputum culture negative | NA | ||
| NCT05455112 | IIb | ATB patients | 44 | Experiment: 25 µg RUTI, i.d. Placebo comparator: 25 µg NaCI, i.d. |
1. Early bactericidal activity (EBA) 0–14 2. AEs and grade 3–4 AEs |
NA | ||
| DAR-901 | NCT02063555 | I | Healthy adults | 59 | Experiment: 0.1 mL DAR-901 i.d., at 0, 2 and 4 months. Active comparator: 0.1 mL NaCI i.d., at 2 and 4 months; 0.1 mL BCG i.d., at 4 months. Placebo comparator: 0.1 mL NaCI, i.d. at 0, 2, and 4 months. |
Safety | DAR-901 induces low-intensity multifunctional memory CD4+ T cell response and reaching peak in 7 days | [99] |
| NCT02712424 | IIb | Adolescents | 625 | Experimental group: 0.1 mL DAR-901, i.d. Placebo comparator: 0.1 mL NaCI, i.d. |
New infection with MTB | The three-dose series of DAR-901 is safe and well tolerated, but cannot prevent initial or sustained IGRA conversion | [100] | |
| MVA85A | NCT00460590 | I | Healthy adults | 24 | Experimental groups 1–3: adults vaccinated with BCG, adults without BCG vaccination, or teenagers i.d. 5 × 107 pfu MVA85A, respectively. | The safety of a single injection of MVA85A in healthy subjects by collecting data on AEs | MVA85A vaccine induces the production of long-lasting, multifunctional, Ag85A specific CD4+ T cells | [101] |
| NCT01650389 | II | HIV-exposed infants | 248 | Experimental group: 1 × 108 pfu MVA85A vaccine within 96 h of birth, i.d. Placebo comparator: equal volume intradermal administration within 96 h of birth i.d. |
Safety | MVA85A immunization in newborns exposed to HIV is safe and induces a moderate antigen-specific immune response without affecting BCG vaccination | [102] | |
| NCT00953927 | II | Infants | 2797 | Experiment: 1 × 108 pfu MVA85A vaccine, i.d. Placebo comparator: 1 × 108 pfu candida skin test antigen, i.d. |
Safety profile of MVA85A in BCG-vaccinated, HIV-negative infants | 32 out of 1399 MVA85A subjects (2%) achieved the primary efficacy endpoint 39 out of 1395 controls (3%) achieved the primary efficacy endpoint |
[103] | |
| ChAdOx1.85A | NCT01829490 | I | Healthy adults | 42 | Experimental groups 1–2: 1 dose of 5 × 109 or 2.5 × 1010 vp of ChAdOx1.85A, i.m., respectively. Experimental group 3: 1 dose of 2.5 × 1010 vp of ChAdOx1.85A, followed by a boost dose of 1 × 108 pfu of MVA85A, at 56 days later, i.m. Experimental group 4: 2 doses of 2.5 × 1010 vp of ChAdOx1.85A i.m., at days 0 and 28, followed by a boost dose of 1 × 108 pfu of MVA85A, at day 119, i.m. |
Safety of ChAdOx1 85A vaccination with and without MVA85A boost vaccination in healthy, BCG-vaccinated adults | ChAdOx1.85A induces Ag85A specific CD4+ T and CD8+ T cell responses | [104] |
| NCT03681860 | IIa | Healthy adults | 72 | Experiment: i.m. 5 × 109 vp ChAdOx1.85A. Experimental 2: 3 adults i.m. 2.5 × 1010 vp ChAdOx1.85A. Experimental 3: 3 adolescents i.m. 5 × 109 vp ChAdOx1.85A. Experimental 4: 3 adolescents i.m. 2.5 × 1010 vpChAdOx1.85A. Placebo comparator: 30 EMaBS adolescents i.m. 2.5 × 1010 vp ChAdOx1.85A, further strengthened MVA85A, other adolescents BCG revaccinated. |
Safety and immunogenicity | NA | [104] | |
| AdHu5Ag85A | NCT02337270 | I | Healthy adults | 36 | Experiment: aerosol 106 Ad5Ag85A at day 0. Experiment: aerosol 2 × 106 Ad5Ag85A at day 0. Experiment: i.m. 108 Ad5Ag85A at day 0. |
Number of participants reporting AEs | Compared with i.m., aerosol delivered AdHu5Ag85A vaccine has advantages in inducing respiratory epithelium immunity | [105] |
| TB/FLU-01L | NCT03017378 | I | Healthy adults | 36 | Active comparator: TB/FLU-01L (intranasal application). Active comparator: TB/FLU-01L (sublingual application). |
AEs, solicited local and systemic reactions, unsolicited AEs, SAEs, including abnormal laboratory findings | NA | |
| TB/FLU-04L | NCT02501421 | I | Healthy adults | 44 | Experiment: TB/FLU-04L, at days 1 and 21. Placebo comparator: placebo, at days 1 and 21. |
Immediate reactions, solicited local and systemic reactions, unsolicited events and abnormal laboratory findings, SAEs | NA |
Abbreviations: i.m., intramuscular injection; s.c., subcutaneous injection; i.d., intradermal injection; po., oral administration; EC: recombinant mycobacterium tuberculosis fusion protein ESAT6-CFP10; AEs: adverse events; SAEs: serious adverse events; EMaBS: Entebbe mother and baby study; NA, not available.