• Vaccine Ontology ID: VO_0000536
• Type: Conjugate vaccine
• Antigen: Two immunodominant antigens, Ag85B and ESAT-6, were used in the analysis. ESAT-6 is a 6-kDA early secretory antigenic target. The two antigens are combined as a fusion protein in the vaccine (Olsen et al., 2001).
• EsxA (ESAT-6) gene engineering:
  • Type: Fusion protein ESAT6-Ag85B
  • Description: Fusion protein created in E. coli using His-tag cloning system pMCT6. Proteins were affinity purified, separated via ion exchange chromatography, and analyzed with SDS-PAGE and Western blots (Olsen et al., 2001).
  • Detailed Gene Information: Click Here.
• Ag85B from M. tuberculosis H37Rv gene engineering:
  • Type: Fusion protein Ag85B-ESAT6
  • Detailed Gene Information: Click Here.
• Adjuvant:
  • VO ID: VO_0001250
  • Description: 1 25 μg amount of monoposphoryl lipid A (MPL) adjuvant was added to 250μg dimethyl dioctadecylammonium bromide (DDA) emulsifier per 0.01-50μg of vaccine.
• Adjuvant:
  • VO ID: VO_0001261
• Preparation: M tuberculosis Erdamn and H37Rv were grown in media, while BCG Danish 1331 was acquired as a freeze dried-vaccine and replenished (Olsen et al., 2001). Recombinant ESAT-6 was obtained along with short-term culture filtrate. Esat6 and ag85B coding regions were obtained by PCR amplification from M. tuberculosis H37Rv chromosomal DNA using selected primers. PCR products were digested by two restriction endonucleases and cloned into pMCT6 prior to sequencing. The E. coli XL-1 Blue was used to express the His-tagged protein prior to purification, protein anion-exchange chromatography, and dialysis. PCR fragments per gene were joined at a HindIII site, cloned into pMCT6, expressed, and later purified to create a fusion protein and a chimeric plasmid.
  
  

• Vaccine Ontology ID: VO_0000528
• Type: Conjugate vaccine
• Antigen: Arabinomannan (AM) oligosaccharides. They are derived from Lipoarabinomannan (LAM), a carbohydrate antigen expressed on the surface of mycobacteria which contains a manna polysaccharide core attached to a phosphatidyl inositol lipid moiety (Hamasur et al., 2003). The surface carbohydrate was hypothesized to yield CD1-specific immune responses, promote mycobacterial clearance, downregulate T cell proliferation, and interfere with activation of macrophages through interferon gamma intervention (Hamasur et al., 2003).
• Ag85B from M. tuberculosis H37Rv gene engineering:
  • Type: Conjugate protein purified from LAM
  • Description: The 28-kDa AM oligos were pooled and linked to tetanus toxoid (TT) or other M. tuberculosis proteins (Ag85B, 75-kDa protein) with thioether linkage generated by conjugation method. Conjugation consisted of amination of AMO with ammonium chloride and sodium cyanoborohydride, deasalting and treatment with 2-imminothiolane, and end conjugation between thiolated oligsaccharide derivatives with bromoacetylated proteins and tributyl phosphine (Hamasur et al., 2003).
  • Detailed Gene Information: Click Here.
• Adjuvant:
  • VO ID: VO_0000127
  • Description: Alum (aluminum hydroxide gel) adjuvant was used initially. Eurocine L3 suspension adjuvant was prepared using 1:1 ratio solid monooleate and oleic acid, Tris buffer with pH adjustment including NaOH, and subsequent sonification. Eurocine L3 emulsion was prepared using 1:1 ratio solid monooleate and oleic acid which were liquified prior to addition of soy bean oil (Hamasur et al., 2003).
• Preparation: Arabinomannan (AM) oligosaccharides derived from LAM of Mycobacterium tuberculosis H37Rv were isolated and covalently conjugated to tetanus toxoid (TT) or to short-term culture filtrate proteins (antigen 85B (Ag85B) or a 75kDa protein) from M. tuberculosis strain Harlingen (Hamasur et al., 2003).

• Tradename: BCG
• Vaccine Ontology ID: VO_0000771
• CDC CVX code: 19
• Type: Attenuated live vaccine
• Preparation: The evaluation of BCG lacks comparability among the vaccination studies due to the use of six different BCG sub-strains [Copenhagen-1331, Pasteur-1173P, Glaxo-1077, Tokyo-172, Russian, Moreau]. The comparative genomic analysis of different BCG strains has shown that there is no uniformity among all presently used vaccines and this genetic variability may contribute to the variation in protective efficacy seen in different geographic regions of the world (Gupta et al., 2007).
  
  In one case, Calmette et al. (1923) used decreasing doses (1 mg, .01 mg, and .002 mg) of tubercle bacilli to infect guinea pigs s.c. Bacterial loads increased in response to decreasing dose sizes. Similar results were acquired for later intramuscular and intracerebral infection procedures by other groups (SWEDBERG, 1951)
• Virulence: The original BCG strain lost its virulence after 39 passages by Albert Calmette and Camille Guerin, and was administered to humans i.d. on the 231st passage. The BCG bacteria showed altered colony morphologies and no virulence in experimental animals. BCG has shown a high degree of safety over the years (Ducati et al., 2006).
  
  --Calmette et al. used length of survival as a metric for virulence in their 1923 study (Agger et al., 2002).
  --The increased ability for M. bovis strains to retain virulence was noted by Lange in 1922 (SWEDBERG, 1951).
• Description: Albert Calmette and Camille Guerin, two French scientists, made an attenuated strain from another mycobacterium (M. bovis) by growing it for 13 years on culture. They observed a reduction in the virulence in animals through this period. When infants were given this vaccine, it provided a reduction in mortality by 90%. Since then, Bacille Calmette Guerin [BCG] has become the most widely used vaccine throughout the world. It is estimated that more than 3 billion people have received BCG. The protective efficacy of BCG vaccine against adult pulmonary TB has varied dramatically from 80 to 0% (Gupta et al., 2007).
  
  Development of the BCG strain was predated by numerous M. tuberculosis studies from the 1890s-1920s, including (Lote 1889, Strauss 1895, Moriya 1909, Romer 1903, Weber 1912, Binder 1915, and Browning and Gulbransen 1926) in a diverse set of hosts (including mouse, avian, human, bovine, and guinea pig hosts) (SWEDBERG, 1951).
  
  Several new subunit booster vaccinations are under development, including Ag85, Mtb72F, HspX and other DosR-controlled gene products, Rv3407 and other Rpf-controlled gene products, and heparin-binding hemagglutinin (HBHA) (Kaufmann, 2005).

• Vaccine Ontology ID: VO_0004122
• Type: Live, attenuated vaccine
• Antigen: HIVA, an African HIV-1-derived immunogen, was identified as stable and inductive of HIV-1-specific CD4+ and CD8+ T cell responses. HIVA in this study contained an immunodominant H-2D^d restricted epitope P18-I10 (Im et al., 2007).
• Preparation: HIVA gene with mAb tag Pk was fused to M. tuberculosis 19-kDa lipoprotein signal sequence via PCR to improve foreign protein immunogenicity. HIVA was cloned into two plasmids, pJH222 and pJH223, as HindIII-HindIII fragment and used to transform a lysine auxotroph of BCG (BCG Pasteur lysA5::res). Additional preparations included MVA.HIVA and BCG.p. BCG cultures were grown in presence of kanamycin. HIVA immunogenicity was assessed using H-2D^d-restricted epitope P18-I10 and subdominant H-2K^d-restricted P epitope. MHC class II-restricted responses were tested using three epitope peptides derived from p24 (Im et al., 2007).
• Description: Goal of study was to develop a vaccine to minimize the risk of mother-to-child transmission (MTCT) of M. tuberculosis and HIV-1, and to protect against both pathogens in newborns. BCG was selected as a vaccine vector due to its long efficacy as a vaccine (10-15 years), frequent use in infant and newborn vaccination, and induction of humoral and cellular responses (Im et al., 2007).

• Vaccine Ontology ID: VO_0004618
• Type: Recombinant vector vaccine
• Status: Research
• Antigen: BCG vaccine with deficient urease; a fusion protein composed of Mycobacterium tuberculosis-derived major membrane protein II (MMP-II) and heat shock protein 70 (HSP70) of BCG (Mukai et al., 2014).
• DnaK gene engineering:
  • Type: Recombinant vector construction
  • Description: The M. tuberculosis gene dnaK, also known as hsp70, is a part of a fusion gene composed of the M. tuberculosis-derived MMP-II gene and the hsp70 gene of M. tuberculosis (locus tag: Rv0350). This fusion gene is introduced into the urease-deficient BCG-deltaUT-11-3 strain (Mukai et al., 2014).
  • Detailed Gene Information: Click Here.
• bfrA gene engineering:
  • Type: Recombinant vector construction
  • Description: The M. tuberculosis gene bfrA (also known as MMP-II) is a part of a fusion gene composed of the M. tuberculosis-derived MMP-II gene and the hsp70 gene of M. tuberculosis (locus tag: Rv0350). This fusion gene is introduced into the urease-deficient BCG-deltaUT-11-3 strain (Mukai et al., 2014).
  • Detailed Gene Information: Click Here.
• Immunization Route: subcutaneous injection

• Vaccine Ontology ID: VO_0004148
• Type: DNA vaccine
• Antigen: The antigens for this vaccine were wild-type or mutated caspase-3 inserted into a plasmid that encodes mycolyl transferase antigen 85A (Ag85A) (Gartner et al., 2008).
• FbpA (Ag85A) gene engineering:
  • Type: DNA vaccine construction
  • Detailed Gene Information: Click Here.
• Vector: pBudCE4.1 (Gartner et al., 2008)
• Preparation: Native Ag85A was purified from BCG culure and recombinant his-tagged Ag85A was purified by affinity chromatography. Dual expression-vectors were created encoding mature or secreted Ag85A and either mutant or wild-type caspase-3 (Gartner et al., 2008).

• Vaccine Ontology ID: VO_0004626
• Type: Recombinant vector vaccine
• Status: Research
• Host Species for Licensed Use: Baboon
• Ag85B from M. tuberculosis H37Rv gene engineering:
  • Type: Recombinant vector construction
  • Description: DNA-, protein- and lentiviral vector-based vaccines that express the antigens Ag85B and Rv3425 (Xu et al., 2014).
  • Detailed Gene Information: Click Here.
• Vector: (Xu et al., 2014)
• Preparation: DNA-, protein- and lentiviral vector-based vaccines that express the antigens Ag85B and Rv3425 (Xu et al., 2014).
• Immunization Route: Intramuscular injection (i.m.)

• Vaccine Ontology ID: VO_0004363
• Type: DNA vaccine
• Status: Research
• Host Species as Laboratory Animal Model: Mouse
• MPT64 gene engineering:
  • Type: DNA vaccine construction
  • Description: Vector pJW4303 encoded MPT-64 (Morris et al., 2000).
  • Detailed Gene Information: Click Here.
• MPT83 gene engineering:
  • Type: DNA vaccine construction
  • Description: Vector pJW4303 encoded MPT-83 (Morris et al., 2000).
  • Detailed Gene Information: Click Here.
• KatG gene engineering:
  • Type: DNA vaccine construction
  • Description: Vector pJW4303 encoded KatG (Morris et al., 2000).
  • Detailed Gene Information: Click Here.
• Vector: pJW4303 (Morris et al., 2000)
• Immunization Route: Intramuscular injection (i.m.)

• Vaccine Ontology ID: VO_0004364
• Type: DNA vaccine
• Status: Research
• Host Species as Laboratory Animal Model: Mouse
• FbpA (Ag85A) gene engineering:
  • Type: DNA vaccine construction
  • Description: Vector pcDNA3.1 expressed a single immunogenic M.tb Ag (Ag85A) (Wang et al., 2004).
  • Detailed Gene Information: Click Here.
• Vector: pCDNA3.1 (Wang et al., 2004)
• Immunization Route: intranasal immunization

• Vaccine Ontology ID: VO_0011410
• Type: DNA vaccine
• Status: Research
• Ag85B from M. tuberculosis H37Rv gene engineering:
  • Type: DNA vaccine construction
  • Detailed Gene Information: Click Here.
• Vector: pRC (Palma et al., 2007)
• Immunization Route: Intramuscular injection (i.m.)

• Vaccine Ontology ID: VO_0004362
• Type: DNA vaccine
• Status: Research
• Host Species as Laboratory Animal Model: Mouse
• Ag85B from M. tuberculosis H37Rv gene engineering:
  • Type: DNA vaccine construction
  • Description: Vector pJW4303 expressed Ag85B of H37Rv (Cai et al., 2005).
  • Detailed Gene Information: Click Here.
• MPT64 gene engineering:
  • Type: DNA vaccine construction
  • Description: Vector pJW4303 expressed MPT64 of H37Rv (Cai et al., 2005)
  • Detailed Gene Information: Click Here.
• MPT83 gene engineering:
  • Type: DNA vaccine construction
  • Description: Vector pJW4303 expressed MPT83 of H37Rv (Cai et al., 2005).
  • Detailed Gene Information: Click Here.
• Vector: pJW4303 (Cai et al., 2005)
• Immunization Route: Intramuscular injection (i.m.)

• Vaccine Ontology ID: VO_0004058
• Type: DNA vaccine
• Status: Research
• KatG gene engineering:
  • Type: DNA vaccine construction
  • Description: KatG protein was amplified from M. tuberculosis H37Rv chromosomal DNA by PCR, and then cloned into the eukaryotic expression vector pJW4303 (Li et al., 1999).
  • Detailed Gene Information: Click Here.
• Vector: The eukaryotic expression vector pJW4303
• Immunization Route: Intramuscular injection (i.m.)

• Vaccine Ontology ID: VO_0004035
• Type: DNA vaccine
• Status: Research
• Host Species as Laboratory Animal Model: Mouse
• Vector: pJW4303 (Morris et al., 2000)
• Immunization Route: Intramuscular injection (i.m.)

• Vaccine Ontology ID: VO_0004123
• Type: DNA vaccine
• Antigen: mycobacterial antigen superoxide dismutase A (Rv3846).
• SodA gene engineering:
  • Type: DNA vaccine preparation
  • Description: The gene sodA was subcloned into the expression vectors pAK3 and pAK4 (Khera et al., 2005).
  • Detailed Gene Information: Click Here.
• Vector: pAK4 (Khera et al., 2005)
• Preparation: PCR amplified using gene specific primers containing Bgl II overhangs and M. tuberculosis genomic DNA as template. The blunt end PCR amplicon was cloned into EcoR V digested pLitmus-38, and then subcloned into plasmids pAK3 and pAK4 resulting in pAK3-sod and pAK4-sod. While both pAK3 and pAK4 are the eukaryotic expression vectors, pAK4 contains more CpG motifs. pAK4 also carries the ampicillin resistance gene carrying two immunostimulatory sequences. pAK3 is devoid of this ampicillin gene (Khera et al., 2005).
• Virulence: None
• Description: A study compared DNA vaccines expressing mycobacterial antigens ESAT-6 (Rv3875), α-crystallin (Rv2031c) and superoxide dismutase A (Rv3846) in Balb/c mice and guinea pigs. The DNA vaccine expression sodA was found to offer maximum protection (Khera et al., 2005).

• Vaccine Ontology ID: VO_0004356
• Type: DNA vaccine
• Status: Research
• Host Species as Laboratory Animal Model: Mouse
• FbpA (Ag85A) gene engineering:
  • Type: DNA vaccine construction
  • Description: Vector pcDNA3.1 expressed Mycobacterium antigen 85A (Ag85A) (Wang et al., 2010).
  • Detailed Gene Information: Click Here.
• Vector: pcDNA3.1 (Wang et al., 2010)
• Immunization Route: Intramuscular injection (i.m.)

• Vaccine Ontology ID: VO_0004059
• Type: Subunit vaccine
• Status: Research
• Antigen: HBHA
• HBHA gene engineering:
  • Type: Recombinant protein preparation
  • Detailed Gene Information: Click Here.
• Adjuvant:
  • VO ID: VO_0001250
  • Description: DDA-MPL
• Adjuvant:
  • VO ID: VO_0001261
• Immunization Route: subcutaneous injection

• Vaccine Ontology ID: VO_0011412
• Type: Subunit vaccine
• Status: Research
• Mtb72F gene engineering:
  • Type: Recombinant protein preparation
  • Detailed Gene Information: Click Here.
• Adjuvant:
  • VO ID: VO_0001264
  • Description: AS02A (Skeiky et al., 2004).
• Immunization Route: Intramuscular injection (i.m.)

• Tradename: M. tuberculosis phoP mutant strain
• Vaccine Ontology ID: VO_0000588
• Type: Live attenuated vaccine
• PhoP gene engineering:
  • Type: Gene mutation
  • Description: The mutant strain was constructed by a single gene (phoP) disruption of the parental M. tuberculosis MT103 strain. PhoP has shown involvement in the regulation of complex mycobacterial lipids implicated in the virulence of M. tuberculosis (Martin et al., 2006).
  • Detailed Gene Information: Click Here.
• Preparation: Rabbits were treated with four doses of phoP prior to isolating polyclonal antibodies against phoP. Anti-phoP and monoclonal antibodies against ESAT-6 were obtained. Horseradish peroxidase-labelled goat anti-rabbit antibodies served as secondary antibodies (Martin et al., 2006). Mycobacterial cell-free protein extracts from M. tuberculosis were prepared, filtered, and precipitated with 45% (w/v) ammonium sulphate (Martin et al., 2006).
• Description: The phoP transcription factor is part of the two-component regulatory signal transduction system component which recently was linked to regulation of complex mycobacterial lipids implicated in the virulence of M. tuberculosis, as well as to multidrug resistance occurrences in a clinical isolate (Martin et al., 2006; Perez et al., 2001) established the selection of phoP as a vaccine candidate by showing that the mutant SO2 strain shows impaired multiplication within cultured macrophages and in vivo infection models (Martin et al., 2006).

• Vaccine Ontology ID: VO_0000564
• Type: Live, attenuated vaccine
• SecA2 gene engineering:
  • Type: secA2 transformation into M. tuberculosis
  • Description: The secA2 gene was amplified by PCR from virulent H37Rv genomic DNA, cloned into a pGEM vector, and later excised as a fragment and cloned into pMV361 (Hinchey et al., 2007).
  • Detailed Gene Information: Click Here.
• Preparation: Three virulent strains (M. tuberculosis H37Rv, HN878, and ΔsecA2 mutants) were obtained and grown on Middlebrook 7H9 broth or 7H10 agar containing 10% (vol/vol) oleic acid-albumin-dextrose-catalase, 0.5% glycerol, and 0.05% (vol/vol) Tween-80. Recombinant strains were selected using ampicillin, hygromycin, and kanamycin.
• Description: The secA2 gene encodes a component of a virulence-associated bacterial protein secretion system and is required for prevention of apoptosis in macrophages infected with M. tuberculosis. The apoptotic response is related to secA2-dependent secretion of mycobacterial superoxide dismutase A (SodA). M. tuberculosis H37Rv with deleted secA2 induces apoptosis, as indicated by TUNEL and polycaspase activation in mouse and human macrophages (Hinchey et al., 2007). Extrinsic and intrinsic caspase pathways were linked to initiation of apoptosis in the secA2-deleted mutants via caspase 8 and 9 activity. The secretion of SodA appears to be important for the inhibition of apoptosis by secA2-dependent mechanisms. Furthermore,
  

• Vaccine Ontology ID: VO_0004108
• Type: Fusion protein with adjuvant
• PepA gene engineering:
  • Type: Fusion protein from co-expressed ORFs
  • Description: Two open reading frames for M. tuberculosis antigenic proteins Mtb32 and Mtb39 (Rv0125 and Rv1196, respectively) were combined and expressed as a single recombinant polyprotein of size 72kDa. Each ORF was PCR amplified and subcloned into plasmids prior to transformation into E. coli. Correct inserts and orientation were identified by restriction digests and DNA sequencing. The final Mtb72f fusion protein acts as an activator of IFN-gamma in CD4 and CD8 T cells (Skeiky et al., 2004).
  • Detailed Gene Information: Click Here.
• PPE18 gene engineering:
  • Type: Fusion protein from co-expressed ORFs
  • Description: Two open reading frames for M. tuberculosis antigenic proteins Mtb32 and Mtb39 (Rv0125 and Rv1196, respectively) were combined and expressed as a single recombinant polyprotein of size 72kDa. Each ORF was PCR amplified and subcloned into plasmids prior to transformation into E. coli. Correct inserts and orientation were identified by restriction digests and DNA sequencing. The final Mtb72f fusion protein acts as an activator of IFN-gamma in CD4 and CD8 T cells (Skeiky et al., 2004).
  • Detailed Gene Information: Click Here.
• Adjuvant:
  • VO ID: VO_0001264
  • Description: Adjuvants included AS02A or AS01B (Skeiky et al., 2004).
• Preparation: See genetic engineering section for details regarding construction of rMtb72F. Vaccines included rMtb72F combined with either of two adjuvants, or Mtb72F alone (Skeiky et al., 2004). Immunization dose was either 50 or 43 μl with 1x PBS (pH 6.8) mixed with 50 μl of AS01B or 57 μl of AS02A, respectively (Skeiky et al., 2004).
  
• Description: Mice were immunized three times (at 3 week intervals) with 8μg of recombinant Mtb72F (rMtb72F) (Skeiky et al., 2004).

• Vaccine Ontology ID: VO_0004263
• Type: Recombinant vector vaccine
• Status: Research
• Antigen: A recombinant modified vaccinia Ankara (MVA) construct (MVA/IL-15/5Mtb) which overexpresses five Mycobacterium tuberculosis antigens (antigen 85A, antigen 85B, ESAT6, HSP60, and Mtb39) (Kolibab et al., 2010).
• FbpA (Ag85A) gene engineering:
  • Type: Recombinant vector construction
  • Detailed Gene Information: Click Here.
• Ag85B from M. tuberculosis H37Rv gene engineering:
  • Type: Recombinant vector construction
  • Detailed Gene Information: Click Here.
• EsxA (ESAT-6) gene engineering:
  • Type: Recombinant vector construction
  • Detailed Gene Information: Click Here.
• Adjuvant:
  • VO ID: VO_0001342
• Immunization Route: subcutaneous injection

• Vaccine Ontology ID: VO_0002780
• Type: Live, attenuated vaccine
• Status: Research
• Host Species as Laboratory Animal Model: Mouse
• drrC gene engineering:
  • Type: Gene mutation
  • Description: This drrC mutant is from Mycobacterium tuberculosis (Pinto et al., 2004).
  • Detailed Gene Information: Click Here.
• Immunization Route: Intravenous injection (i.v.)

• Vaccine Ontology ID: VO_0002781
• Type: Live, attenuated vaccine
• Status: Research
• Host Species as Laboratory Animal Model: Mouse
• fadD26 gene engineering:
  • Type: Gene mutation
  • Description: This fadD26 mutant is from Mycobacterium tuberculosis (Infante et al., 2005).
  • Detailed Gene Information: Click Here.
• Immunization Route: Intratracheal immunization

• Vaccine Ontology ID: VO_0002782
• Type: Live, attenuated vaccine
• Status: Research
• Host Species as Laboratory Animal Model: Mouse
• leuD gene engineering:
  • Type: Gene mutation
  • Description: This leuD mutant is from Mycobacterium tuberculosis (Hondalus et al., 2000).
  • Detailed Gene Information: Click Here.
• Immunization Route: Intravenous injection (i.v.)

• Vaccine Ontology ID: VO_0002783
• Type: Live, attenuated vaccine
• Status: Research
• Host Species as Laboratory Animal Model: Mouse
• lysA gene engineering:
  • Type: Gene mutation
  • Description: This lysA/secA2 mutant is from Mycobacterium tuberculosis (Hinchey et al., 2011).
  • Detailed Gene Information: Click Here.
• SecA2 gene engineering:
  • Type: Gene mutation
  • Description: This lysA/secA2 mutant is from Mycobacterium tuberculosis (Hinchey et al., 2011).
  • Detailed Gene Information: Click Here.
• Immunization Route: subcutaneous injection

• Vaccine Ontology ID: VO_0004279
• Type: Live, attenuated vaccine
• Status: Research
• Host Species as Laboratory Animal Model: Mouse
• mce-2 gene engineering:
  • Type: Gene mutation
  • Description: This mce-2 mutant is from Mycobacterium tuberculosis (Aguilar et al., 2006).
  • Detailed Gene Information: Click Here.
• mce-3 gene engineering:
  • Type: Gene mutation
  • Description: This mce-2/mce-3 mutant is from Mycobacterium tuberculosis (Aguilar et al., 2006).
  • Detailed Gene Information: Click Here.
• Immunization Route: subcutaneous injection

• Vaccine Ontology ID: VO_0004288
• Type: Live, attenuated vaccine
• Status: Research
• Host Species for Licensed Use: Mouse
• mce-3 gene engineering:
  • Type: Gene mutation
  • Description: This mce-3 mutant is from Mycobacterium tuberculosis (Aguilar et al., 2006).
  • Detailed Gene Information: Click Here.
• Immunization Route: subcutaneous injection

• Vaccine Ontology ID: VO_0002786
• Type: Live, attenuated vaccine
• Status: Research
• Host Species as Laboratory Animal Model: Mouse
• panC gene engineering:
  • Type: Gene mutation
  • Description: This panCD mutant is from Mycobacterium tuberculosis (Sambandamurthy et al., 2002).
  • Detailed Gene Information: Click Here.
• panD gene engineering:
  • Type: Gene mutation
  • Description: This panCD mutant is from Mycobacterium tuberculosis (Sambandamurthy et al., 2002).
  • Detailed Gene Information: Click Here.
• Immunization Route: subcutaneous injection

• Vaccine Ontology ID: VO_0002791
• Type: Live, attenuated vaccine
• Status: Research
• Host Species as Laboratory Animal Model: Mouse
• proC gene engineering:
  • Type: Gene mutation
  • Description: This proC mutant is from Mycobacterium tuberculosis (Smith et al., 2001).
  • Detailed Gene Information: Click Here.
• Immunization Route: Intravenous injection (i.v.)

• Vaccine Ontology ID: VO_0002787
• Type: Live, attenuated vaccine
• Status: Research
• Host Species as Laboratory Animal Model: Mouse
• RD1 gene engineering:
  • Type: Gene mutation
  • Description: This RD1/panCD mutant is from Mycobacterium tuberculosis (Sambandamurthy et al., 2006).
  • Detailed Gene Information: Click Here.
• panC gene engineering:
  • Type: Gene mutation
  • Description: This RD1/panCD mutant is from Mycobacterium tuberculosis (Sambandamurthy et al., 2006).
  • Detailed Gene Information: Click Here.
• panD gene engineering:
  • Type: Gene mutation
  • Description: This RD1/panCD mutant is from Mycobacterium tuberculosis (Sambandamurthy et al., 2006).
  • Detailed Gene Information: Click Here.
• Immunization Route: subcutaneous injection

• Vaccine Ontology ID: VO_0002795
• Type: Live, attenuated vaccine
• Status: Research
• Host Species as Laboratory Animal Model: Mouse
• sigE gene engineering:
  • Type: Gene mutation
  • Description: This sigE mutant is from Mycobacterium tuberculosis (Hernandez et al., 2010).
  • Detailed Gene Information: Click Here.
• Immunization Route: Intratracheal immunization

• Vaccine Ontology ID: VO_0002796
• Type: Live, attenuated vaccine
• Status: Research
• Host Species as Laboratory Animal Model: Mouse
• trpD gene engineering:
  • Type: Gene mutation
  • Description: This trpD mutant is from Mycobacterium tuberculosis (Smith et al., 2001).
  • Detailed Gene Information: Click Here.
• Immunization Route: Intravenous injection (i.v.)

• Vaccine Ontology ID: VO_0004757
• Type: Recombinant vector vaccine
• Status: Research
• Host Species for Licensed Use: Baboon
• FbpA (Ag85A) gene engineering:
  • Type: Recombinant vector construction
  • Description: rBCG strains overexpressing immunodominant antigens Ag85B (rBCG::85B), Ag85A (rBCG::85A), or both (rBCG::AB) of Mycobacterium tuberculosis were constructed (Wang et al., 2012).
  • Detailed Gene Information: Click Here.
• Ag85B from M. tuberculosis H37Rv gene engineering:
  • Type: Recombinant protein preparation
  • Description: rBCG strains overexpressing immunodominant antigens Ag85B (rBCG::85B), Ag85A (rBCG::85A), or both (rBCG::AB) of Mycobacterium tuberculosis were constructed (Wang et al., 2012).
  • Detailed Gene Information: Click Here.
• Preparation: Three rBCG strains overexpressing immunodominant antigens Ag85B (rBCG::85B), Ag85A (rBCG::85A), or both (rBCG::AB) of Mycobacterium tuberculosis (Wang et al., 2012).
• Immunization Route: Intramuscular injection (i.m.)

• Vaccine Ontology ID: VO_0000535
• Type: Live, attenuated vaccine
• Antigen: ESAT-6 of Mycobacterium tuberculosis (Mollenkopf et al., 2001). ESAT-6 can induce IFN-gamma production and activate T cells in human peripheral blood mononuclear cells in TB patients.
• EsxA (ESAT-6) gene engineering:
  • Type: Fusion protein with adjuvant
  • Detailed Gene Information: Click Here.
• Preparation: This vaccine utilizes an attenuated Salmonella typhimurium that secretes a T-cell antigen called ESAT-6 of Mycobacterium tuberculosis through the hemolysin secretion system of E. coli (Mollenkopf et al., 2001).
• Description: ESAT-6 has been tested as a skin-test reagent in cattle and guinea pigs. The subunit vaccine which combines ESAT-6 with monophosphoryl lipid A (MPL) and dimethyl dioctadecylammonium bromide (DDA) was developed and tested for use in BALB/c female mice (Mollenkopf et al., 2001).

Human Response

• Immune Response: TB Ag-specific mucosal, humoral and cellular immune response via T cell proliferation and production (Wang et al., 2009).
• Description: SL(E6-85B) vaccine, when combined with BCG vaccination, induced the strongest TB Ag-specific mucosal, humoral, and cellular immune responses comprised of increased proliferation of T cells, IFN-gamma expression, granzyme B production (Wang et al., 2009).
• Host Ifng (Interferon gamma) response
  • Description: The experimental data demonstrated that three time vaccinations with BCG in BALB/c mice induced significant TB Ag-specific IFN-gamma immune responses in splenocytes. Splenocytes were stimulated with the Ag85B protein 2 weeks after the final immunization (Wang et al., 2009).
  • Detailed Gene Information: Click Here.

Human Response

• Vaccination Protocol: DNA was obtained from the peripheral blood of 99 NMIBC patients who were prospectively randomized to receive postresection intravesical BCG or BCG with interferon alpha. (Chiong et al., 2011)
• Immune Response: Patients with the NRAMP1 D543N G:G genotype and allele 3 (GT)n polymorphism had decreased recurrence time after BCG therapy. (Chiong et al., 2011)
• Host GPX1 response
  • Description: Polymorphisms of the GPX1 gene may be associated with recurrence of BCa after BCG immunotherapy. (Chiong et al., 2011)
  • Detailed Gene Information: Click Here.
• Host SLC11A1 response
  • Description: Polymorphisms of the SLC11A1 genes may be associated with recurrence of BCa after BCG immunotherapy. (Chiong et al., 2011)
  • Detailed Gene Information: Click Here.

Human Response

• Vaccination Protocol: Intradermally vaccinated the infants within 48 hours of birth. Examination of whole blood stimulated ex vivo with 1.2×106 CFU BCG 10 weeks after newborn BCG vaccination of South African infants (Randhawa et al., 2011).
• Immune Response: Increased production of TH1-type T cell cytokines (Randhawa et al., 2011).
• Host GPX1 response
  • Description: After stimulation with TLR6 lipopeptide ligands, PBMCs from TLR6-deficient, BCG-vaccinated individuals secreted lower amounts of IL-6 and IL-10 compared to those with responsive TLR6 genotypes (Randhawa et al., 2011).
  • Detailed Gene Information: Click Here.
• Host human IFNG response
  • Description: Increased IFNG production associated with TLR1/6 presence 10 weeks post BCG vaccination (Randhawa et al., 2011).
  • Detailed Gene Information: Click Here.
• Host IL10 response
  • Description: IL10 expression post vaccination increased in presence of TLR1/6 (Randhawa et al., 2011).
  • Detailed Gene Information: Click Here.
• Host IL2 response
  • Description: Increased IL2 production associated with TLR1/6 presence 10 weeks post BCG vaccination (Randhawa et al., 2011).
  • Detailed Gene Information: Click Here.
• Host IL6 response
  • Description: IL6 expression post vaccination expressed in higher amounts in presence of TLR1/6 (Randhawa et al., 2011).
  • Detailed Gene Information: Click Here.
• Host TLR1 response
  • Description: After stimulation with TLR1 lipopeptide ligands, PBMCs from TLR1-deficient, BCG-vaccinated individuals secreted lower amounts of IL-6 and IL-10 compared to those with responsive TLR1 genotypes (Randhawa et al., 2011).
  • Detailed Gene Information: Click Here.

Human Response

• Description: The human monocytic cell line THP-1 was obtained from the ATCC, and cultures were grown (Fontán et al., 2008).
• Host APOBEC3B response
  • Description: A sigE mutant upregulates APOBEC3B in human THP-1 cells, which was not significantly upregulated after infection with the wild type pathogen (Fontán et al., 2008).
  • Detailed Gene Information: Click Here.
• Host C19orf66 response
  • Description: A sigE mutant upregulates C19orf66 in human THP-1 cells, which was not significantly upregulated after infection with the wild type pathogen (Fontán et al., 2008).
  • Detailed Gene Information: Click Here.
• Host CD70 response
  • Description: A sigE mutant upregulates CD70 in human THP-1 cells, which was not significantly upregulated after infection with the wild type pathogen (Fontán et al., 2008).
  • Detailed Gene Information: Click Here.
• Host GPR182 response
  • Description: A sigE mutant upregulates GPR182 in human THP-1 cells, which was not significantly upregulated after infection with the wild type pathogen (Fontán et al., 2008).
  • Detailed Gene Information: Click Here.
• Host HIST1H2BE response
  • Description: A sigE mutant upregulates HIST1H2BE in human THP-1 cells, which was not significantly upregulated after infection with the wild type pathogen (Fontán et al., 2008).
  • Detailed Gene Information: Click Here.
• Host HIST2H4A response
  • Description: A sigE mutant upregulates HIST2H4A in human THP-1 cells, which was not significantly upregulated after infection with the wild type pathogen (Fontán et al., 2008).
  • Detailed Gene Information: Click Here.
• Host PCDHB1 response
  • Description: A sigE mutant upregulates PCDHB1 in human THP-1 cells, which was not significantly upregulated after infection with the wild type pathogen (Fontán et al., 2008).
  • Detailed Gene Information: Click Here.
• Host PTCD1 response
  • Description: A sigE mutant upregulates PTCD1 in human THP-1 cells, which was not significantly upregulated after infection with the wild type pathogen (Fontán et al., 2008).
  • Detailed Gene Information: Click Here.
• Host STAG3 response
  • Description: A sigE mutant upregulates STAG3 in human THP-1 cells, which was not significantly upregulated after infection with the wild type pathogen (Fontán et al., 2008).
  • Detailed Gene Information: Click Here.
• Host TBX21 response
  • Description: A sigE mutant upregulates TBX21 in human THP-1 cells, which was not significantly upregulated after infection with the wild type pathogen (Fontán et al., 2008).
  • Detailed Gene Information: Click Here.
• Host TSC22D4 response
  • Description: A sigE mutant upregulates TSC22D4 in human THP-1 cells, which was not significantly upregulated after infection with the wild type pathogen (Fontán et al., 2008).
  • Detailed Gene Information: Click Here.

Mouse Response

• Host Strain: C57BL/6J (H-2^b), specific pathogen-free female; B6CBAF1
• Vaccination Protocol: Female mice 6-12 weeks old were housed within a BSL-3 enclosure. Mice were immunized with 0.01-50 μg vaccine emulsed in 250 μg dimethyl dioctadecylammonium bromide (DDA) and 25 μg of monophosphoryl lipid A (MPL) aduvant. Vaccines were injected 3 times subcutaneously on back at 2-week intervals (Olsen et al., 2001). BCG Danish 1331 dose (5x10^4 baccilli/mouse) was administered via subcutaneous injection at base of tail simultaneously with first subunit vaccination. No booster injections were included (Olsen et al., 2001).
• Persistence: Mice were sacrificed at either 2 or 6 weeks post-innoculation via i.v. or aerosol routes, respectively prior to organ removal and bacterial enumeration(Olsen et al., 2001).
• Challenge Protocol: Prechallenge immunity was assessed 5 weeks post-first vaccination (Olsen et al., 2001).
  Mice were challenged at either 10 or 30 weeks post-immunization via aerosol route (100 CFU of M. tuberculosis Erdman per lung) or intravenous route (0.2 ml volume containing 5x10^4 CFU M. tuberculosis H37Rv in PBS) (Olsen et al., 2001).
• Efficacy: A statistical reduction in the number of bacteria was observed for vaccine doses as low as .01μg. The 0.1-10μg dose range showed a higher level of protection versus the .01μg dose. 50 μg doses resulted in reduced protection in lung and spleen, whereas, 10 μg showed significant levels of protection in spleen. The fusion protein Ag85B-ESAT-6 showed a statistically significant improvement in reduction of bacteria versus the individual Ag85B and ESAT-6 components (Olsen et al., 2001). Both recombinant proteins induced long-lived memory immunity when challenged 10 or 30 weeks post-first vaccination, while BCG showed significantly lower protection levels at the later challenge points(Olsen et al., 2001).
• Description: Blood lymphocytes were purified and pooled from eight mice per group and cultured in triplicate as 2x10^5 cells in 200μl of RPMI 1640 with 2-mercaptoethanol, glutamine, penicillin-streptomycin, and 5% v/v fetal calf serum. Mycobacterial antigens administered as 5-1.3μg/ml. Interferon gamma amounts were determined using ELISA (Olsen et al., 2001).

Mouse Response

• Host Strain: C57BL/6, 8-10 wk female
• Vaccination Protocol: Mice were injected subcutaneously in flanks with 100μL or intranasal with 5μL/nostril of antigen plus adjuvant. The control BCG vaccination involved subcutaneous injection of 5x10^5 CFU in 100μL PBS in hind flank. Two formulations of the adjuvant were used, such that mice were either treated at day 0 with AMOs-TT conjugate in Eurocine L3 emulsion or suspension, followed by nasal booster at day 21 (Hamasur et al., 2003).
• Immune Response: Immunization with AMO-TT, AMOs-Ag85B, or AMOs-75kDa conjugate resulted in increased lymphocyte proliferation in spleen when responding to PPD (Hamasur et al., 2003).
• Challenge Protocol: Mice were challenged intranasally with 10^5 M. tuberculosis Harlingen on day 24 (vaccination on day 0).
• Efficacy: All mice started to die after 17 weeks (median time = 36 weeks) (Hamasur et al., 2003). Considerable increases in weight were observed for mice immunized with AMOs-TT conjugate or BCG versus those not vaccinated (Hamasur et al., 2003). Mice immunized with AMOs-TT conjugate and either adjuvant showed longer survival than sham-immunized mice. The emulsion adjuvant showed increased protective efficacy versus the suspension version (Hamasur et al., 2003)

Mouse Response

• Host Strain: C57BL/6, 8-10 wk female
• Vaccination Protocol: Mice were immunized subcutaneously on days 0, 28 with 5 or 25 μg of AMO-Ag85B in 1% alum. Control mice were vaccinated s.c. with live BCG on day 0.
• Side Effects: Reduced weight loss observed for BCG and AMO-Ag85B immunized mice versus shams (Hamasur et al., 2003).
• Challenge Protocol: Mice were challenged intravenously with 10^5 CFU M. tuberculosis H37Rv on day 60(Hamasur et al., 2003).
• Efficacy: BCG-immunized mice exhibited best survival versus mice immunized with the AMO-Ag85B vaccine. However, AMO-Ag85B immunized mice also showed significant improvement in survival versus sham-immunized mice.

Mouse Response

• Host Ifng (Interferon gamma) response
  • Description: Immunization with BCG[pMV361] (BCG with empty pMV361) vaccine induced significant up regulation of IFN-gamma in mice 45 days after immunization as compared to non-immunized mice. Cytokines were measured in lymphocytes from the spleen (Singh et al., 2011).
  • Detailed Gene Information: Click Here.
• Host IL-6 response
  • Description: Immunization with BCG[pMV361] (BCG with empty pMV361) vaccine induced significant up regulation of IL-6 in mice 45 days after immunization as compared to non-immunized mice. Cytokines were measured in lymphocytes from the spleen (Singh et al., 2011).
  • Detailed Gene Information: Click Here.
• Host Il2 response
  • Description: Immunization with BCG[pMV361] (BCG with empty pMV361) vaccine induced significant up regulation of IL-2 in mice 45 days after immunization as compared to non-immunized mice. Cytokines were measured in lymphocytes from the spleen (Singh et al., 2011).
  • Detailed Gene Information: Click Here.
• Host TNF-alpha response
  • Description: Immunization with BCG[pMV361] (BCG with empty pMV361) vaccine induced significant up regulation of TNF-alpha in mice 45 days after immunization as compared to non-immunized mice. Cytokines were measured in lymphocytes from the spleen (Singh et al., 2011).
  • Detailed Gene Information: Click Here.

Mouse Response

• Host Strain: C57BL/6
• Vaccination Protocol: Ten to twelve female C57BL/6 mice were immunized per group with 100 μl of the formulation, once, subcutaneously (s.c.) at the base of the tail. BCG and Lactoferrin were emulsified with Freund's adjuvant in a 1:1 ratio (Hwang et al., 2005).
• Immune Response: A single immunization of mice with Lactoferrin as an adjunct adjuvant resulted in amplified splenocyte proliferative response to heat-killed BCG, and elevated IL-12(p40) production with increased relative ratios of IL-12/IL-10. Furthermore, splenocyte recall response to HK-BCG was augmented for proinflammatory mediators, TNF-alpha, IL-1beta, and IL-6, approaching responses generated to complete Freund's adjuvant (CFA) immunized controls (Hwang et al., 2005).
• Challenge Protocol: Fourteen days post-immunization, four mice from each group were aerosol challenged with Erdman MTB (Hwang et al., 2005).
• Efficacy: All immunization groups showed significant reduction in lung organism load, decreased bacterial load in the spleen (Hwang et al., 2005).
• Host Ifng (Interferon gamma) response
  • Description: Lactoferrin was able to significantly augment the production of IFN-γ compared to vaccine preparations in IFA alone (Hwang et al., 2005).
  • Detailed Gene Information: Click Here.
• Host IL-1b response
  • Description: In concert with the increased stimulation index, there was significant production of all three proinflammatory mediators (TNF-alpha, IL-1beta, and IL-6) in the Lactoferrin immunization group compared to both the non-immunized and IFA immunized groups (Hwang et al., 2005).
  • Detailed Gene Information: Click Here.
• Host IL-6 response
  • Description: In concert with the increased stimulation index, there was significant production of all three proinflammatory mediators (TNF-alpha, IL-1beta, and IL-6) in the Lactoferrin immunization group compared to both the non-immunized and IFA immunized groups (Hwang et al., 2005).
  • Detailed Gene Information: Click Here.
• Host Il12b response
  • Description: A single administration of BCG in IFA and Lactoferrin resulted in significantly increased production of IL-12 in the splenic recall assay (Hwang et al., 2005).
  • Detailed Gene Information: Click Here.
• Host Ltf response
  • Description: Lactoferrin can act as an adjunct adjuvant to augment cellular immunity and boost BCG efficacy for protection against subsequent challenge with virulent MTB. Augmented responses were found for IL-12, TNF-alpha, IL-1beta, and IL-6 (Hwang et al., 2005).
  • Detailed Gene Information: Click Here.
• Host TNF-alpha response
  • Description: In concert with the increased stimulation index, there was significant production of all three proinflammatory mediators (TNF-alpha, IL-1beta, and IL-6) in the Lactoferrin immunization group compared to both the non-immunized and IFA immunized groups (Hwang et al., 2005).
  • Detailed Gene Information: Click Here.

Mouse Response

• Host Strain: BALB/c
• Vaccination Protocol: Mice were immunized on day 0 with either BCG.HIVA (pJH222.HIVA) and episomal plasmid, parental BCG (BCG.p), or control (no immunization). Half of the animals were boosted with MVA.HIVA on day 102. Mice were sacrificed on day 151. T cells were stimulated with peptides in a multicolor flow cytometric analysis to elicite interferon gamma, tumor necrosis factor alpha, and degranulating responses (Im et al., 2007).
• Immune Response: HIVA-specific responses peaked after 12 weeks, most likely as a result of BCG-induced activation of T cells. Three major observations were observed:
  1) BCG.HIVA alone induces undetectable CD8+ HIV-1-specific T cell responses secreting tum, though priming with BCG.HIVA shows significant increases in elicited H and P-specific splenocytes producing IFN-gamma and degranulating. Hence, BCG.HIVA enhancement of MVA.HIVA responses is HIVA-specific.
  2) BCG.HIVA priming with MVA.HIVA boost elicits the highest proportion of HIV-1 specific bifunctional cells in all the studies.
  3) No HIVA-induced CD4+ T cell responses were detected (Im et al., 2007).

Mouse Response

• Host Strain: BALB/c
• Vaccination Protocol: Mice were primed with increasing doses (10^3-10^7 CFU/animal, day 0) of BCG.HIVA or not vaccinated, and boosted (day 102) with constant doses of MVA.HIVA.
• Immune Response: Bifunctional responses increased steadily with dose up to 0.7% CD8+ splenocytes with 10^6 CFU BCG.HIVA for epitope H , and increased up to 0.2% CD8+ with 10^7 CFU for P response (Im et al., 2007). Priming dose of BCG.HIVA affects strength and quality of CD8+ T cell responses induced by the recombinant BCG priming followed by recombinant MVA boosting, with high priming dose being most important for quality of response to P epitope (Im et al., 2007).

Mouse Response

• Host Strain: BALB/c, 6-8 wk old
• Vaccination Protocol: Pathogen free mice were vaccinated in groups of 7-9 animals with 3x10^5 CFU of BCG.HIVA, BCG.p, or BCG wild type 1173 p2 via s.c. injection into left hind foot.
• Challenge Protocol: Mice were challenged via aerosol (nasal) route 12 weeks post-vaccination with M. tuberculosis Erdman using a modified Henderson apparatus. Approximately 25 CFU/lung were estimated 24 hours post-challenge (Im et al., 2007).
• Efficacy: All three vaccines tested here showed an approximate 2-fold reduction in M. tuberculosis load in the lungs and spleen. Data suggest that the "safer" lysine auxotrophBCG.HIVA could replace BCG vaccine in neonatal uses and still show comparable efficacy (Im et al., 2007).

Mouse Response

• Host Strain: BALB/c, female
• Vaccination Protocol: Groups of 4-5 mice were naive or immunized with 100 μg pTHr.HIVA, 10^6 pfu MVA.HIVA, or 10^6 cfu of either BCG.p or BCG.HIVA. BCG.HIVA boosting commenced on day 33.
• Immune Response: No HIVA-specific responses were noticed during the 4-day WR.HIVA infection. Mice receiving the pTHr.HIVA-BCG.p, pTHr.HIVA-BCG.HIVA , or BCG.HIVA showed both H and P specific responses. Highest responses were seen in pTHr.HIVA-BCG.HIVA-WR.HIVA which showed interferon gamma and degranulated responses. CD4+IFN-gamma+TNF-alpha+IL-2+ splenocytes exhibited high quality characteristics in the BCG.HIVA and BCG.p boosts following pTHr.HIVA priming. HIVA non-specific mechanisms were suggested by a two-log10 decrease in WR.HIVA titre when BCG.HIVA or BCG.p alone were used in immunization (Im et al., 2007).
• Challenge Protocol: Mice were challenged i.p. using 4x10^6 pfu vaccinia virus WR.HIVA. Plaque counts were determined for sonicated and serially-diluted mouse ovaries four days post-challenge (Im et al., 2007).
• Description: Surrogate challenge with recombinant replication-competent vaccinia virus (strain Western Reserve) is a cost-effective murine alternative to HIV-1challenge in non-human primate models.

Mouse Response

• Host Strain: C57BL/6J
• Vaccination Protocol: Five mice per group were vaccinated with BCG-261H (control) or BCG-DHTM at 1000 CFU/mouse for 6 weeks (Mukai et al., 2014)
• Vaccine Immune Response Type: VO_0003057
• Challenge Protocol: Mice were challenged with H37RV at 100 CFU per lung by aerosol infection (Mukai et al., 2014)
• Efficacy: At 6 weeks post challenge, mice vaccinated with BCG-261H (control) or BCG-DHTM showed inhibited multiplication of M. tuberculosis in the lung, and BCG-DHTM inhibited M. tuberculosis multiplication more strongly than BCG-261H (Mukai et al., 2014).

Mouse Response

• Host Strain: (C57BL/6 × DBA/2)F1 (H-2b/d) or BALB/c (H-2d)
• Vaccination Protocol: Mice were injected four times intramuscularly with 100 micrograms of pDNA with at least three weeks between injections. As negative controls, mice were injected with 100 micrograms of empty pBudCE4.1 vector or left untreated. As a positive control for the challenge experiments, mice were vaccinated intravenously with M. bovis BCG strain GL2 along with the first vaccination or 5 weeks pre-vaccination (Gartner et al., 2008).
• Immune Response: Ag85A specific antibody titers were very low in mice vaccinated with the wild-type p-sAg85A–csp, but antibody titers in mice vaccinated with mutant p-sAg85A–csp were of a greater magnitude. IFN-γ and IL-2 production in mice vaccinated with plasmids co-expressing mAg85A and a caspase gene were similar to or lower than production in mice vaccinated with p-sAg85A. Vaccination with the wild-type caspase-encoding plasmids was not effective in inducing Ag85A specific CTL activity (Gartner et al., 2008).
• Challenge Protocol: Mice were challenged five weeks after their final vaccination with 2 x 10^5 CFUof M. tuberculosis H37Rv. Results were measured using a luminescence assay with a count of relative light units (RLU) (Gartner et al., 2008).
• Efficacy: The challenge revealed that mice vaccinated with mutant p-sAg85A–csp showed higher secretion of IL-6, IL-10 and IL-17A in their lungs, spontaneously and/or after antigenic stimulation.However, spontaneous IFN-γ production was highest in mice vaccinated with wild-type p-sAg85A–csp. Ag85A specific IL-2 and IFN-γ responses were low in spleen of BCG vaccinated mice, but high Th1 responses could be could be seen after stimulation with whole BCG culture filtrate in these mice (Gartner et al., 2008).

Mouse Response

• Host Strain: C57BL/6
• Vaccination Protocol: Six mice per group were first immunized subcutaneously (s.c.) with 5×10^6 CFU of BCG in 100μl of PBS and subsequently boosted twice at 2-week intervals with PAR, DAR or LAR [12]. Meanwhile, the mice were boosted with the controls for these three types of vaccines, which were PNC (i.e., MPL + TDM), DNC (i.e., pVax) and LNC (i.e.,pLenti6.3). For DAR immunization, 50μg of the DAR DNA vaccine in 100μl of sterile PBS was administered to the mice intramuscularly (i.m.) in the right thigh. For LAR immunization, the mice were immunized with 5×10^6 pfu of LAR in the foot pad. For PAR immunization, the mice were immunized subcutaneously (s.c.) with 50 μg of PAR formulated with the adjuvants MPL and TDM (Xu et al., 2014).
• Vaccine Immune Response Type: VO_0003057
• Challenge Protocol: 2 weeks after the last vaccination, all mice were challenged intravenously via the lateral tail vein with 1.2 × 10^6 CFU of M. tuberculosis H37Rv (Xu et al., 2014).
• Efficacy: Prime-boost BCG vaccination with a lentiviral vector expressing the antigens Ag85B and Rv3425 significantly enhanced immune responses, including Th1 and CD8+ CTL responses, compared to DNA- and protein-based vaccines. However, lentivirus-vectored and DNA-based vaccines greatly improved the protective efficacy of BCG against M. tuberculosis (Xu et al., 2014).

Mouse Response

• Vaccine Immune Response Type: VO_0000286
• Efficacy: The relative protection in the lung induced by the combination vaccine approached the BCG response in these experiments (Morris et al., 2000).

Mouse Response

• Vaccine Immune Response Type: VO_0000286
• Efficacy: Systemic priming with two repeated DNAAg85A injections and respiratory mucosal boosting once with AdAg85A provided the most potent protection of all of the tested vaccines/regimens, including s.c. BCG vaccination both at 4 and 8 wk postchallenge, and this level of protection was also better than single i.n. AdAg85A vaccination at 8 wk postchallenge (Wang et al., 2004).

Mouse Response

• Host Strain: C57BL/6
• Vaccination Protocol: Mice at or between 7 and 8 weeks old were immunized. Fifty micrograms of plasmid, both DNA-85B or control vector, was injected intramuscularly (i.m.) in 50 μl PBS into the hind leg. Mice were immunized two or four times at 2 week intervals. As a positive control, a single dose of BCG (105 cfu) was injected s.c. (Palma et al., 2007).
• Challenge Protocol: Four weeks after the last boost, mice were challenged intravenously (i.v.) in a lateral tail vein with 10^5 cfu of MTB H37Rv (Palma et al., 2007).
• Efficacy: A significant reduction of the bacterial load was observed in mice receiving two administrations of the DNA-85B vaccine (DNAx2-immunized mice) with respect to unvaccinated naïve control or empty-plasmid DNA recipient mice, indicating protection by the vaccine. The degree of reduction of the mycobacterial burden was not significantly different from that conferred by BCG, although the immunization with BCG caused the highest nominal reduction of mycobacteria in the lungs (Palma et al., 2007).

Mouse Response

• Vaccine Immune Response Type: VO_0000286
• Efficacy: Combined DNA vaccines including Ag85B, MPT64, and MPT83 formulated in IL-2 provided an efficient method for generating strong and sustained protective immunity in the spleen and lungs of experimental mice following i.v. challenge with M. tuberculosis H37Rv (Cai et al., 2005).

Mouse Response

• Host Strain: C57BL/6
• Vaccination Protocol: The C57BL/6 mice (five mice per group) were vaccinated intramuscularly into the thigh three times at 3-week intervals, with 100 μg of plasmid DNA per injection. Control mice were vaccinated with 10^6 CFU of BCG Pasteur injected subcutaneously (Li et al., 1999).
• Challenge Protocol: The mice were challenged by the aerosol route about 17 to 21 days after receiving the final DNA vaccine inoculation and 6 weeks after receiving the BCG vaccination with M. tuberculosis Erdman (Li et al., 1999).
• Efficacy: Vaccination with the KatG resulted in a 75 to 85% drop in number of lung bacteria. Moreover, mice immunized with the KatG TPA-positive constructs showed significantly decreased dissemination of the lung infection to the spleen (Li et al., 1999).

Mouse Response

• Vaccine Immune Response Type: VO_0000286
• Immune Response: Immunization with a multivalent combination DNA vaccine (containing the ESAT-6, MPT-64, MPT-63, and KatG constructs) generated immune responses that indicated an absence of antigenic competition since antigen-specific cell-mediated and humoral responses were detected to each component of the mixture (Morris et al., 2000).
• Efficacy: Prior to vaccination, mice were challenged with M. tuberculosis. Among the single DNA vaccines that were tested, the ESAT-6 construct consistently evoked the best protective responses. Compared with BCG, which on a relative scale elicited a protective value of 1, ESAT-6 elicited a protective value of 0.61 (Morris et al., 2000).

Mouse Response

• Host Strain: Balb/c mice
• Vaccination Protocol: Mice (in groups of six each) were immunized with either the pAK3 or pAK4 vector controls or DNA vaccine candidates. Three doses of 100 μg of plasmid DNA were administered intramuscularly at 3-week intervals. Following a rest period of 3 weeks after the last dose, mice were euthanized, and antigen specific cell mediated and humoral immune responses were evaluated (Khera et al., 2005).
• Immune Response: Immunization of mice with the DNA vaccines expressing superoxide dismutase A resulted in markedly higher levels of IFN-γ as compared to the levels of IL-10. The levels of IFN-γ in supernatants from pAK3-sod and pAK4-sod immunized mice increased 2.9 and 9.1 folds compared to the levels of IFN-γ in culture supernatant of mice immunized with pAK-3 and pAK-4, respectively. Approximately 3-fold increase in IFN-γ levels in pAK4-sod immunized mice in comparison to pAK3-sod immunized mice showed that the extra CpG motif activated Th1 subtype of host immunity. Though expression of SOD antigen increases IL-10 levels, the extra CpG motifs in the vector backbone decreases the concentration of IL-10 in pAK4-sod immunized mice in comparison to pAK3-sod immunized mice (Khera et al., 2005).
  
• Challenge Protocol: No challenge experiment was performed in mice. Guinea pigs were used for protection assay for this vaccine.
• Host Ifng (Interferon gamma) response
  • Description: The levels of IFN-γ in supernatants from pAK3-sod and pAK4-sod immunized mice significantly increased compared to the plasmid vector control groups (Khera et al., 2005).
  • Detailed Gene Information: Click Here.
• Host Il10 (interleukin 10) response
  • Description: Compared to the plasmid pAK3 and pAK4 controls, expression of the SODA antigen increased IL-10 levels in DNA vaccine pAK3-sod and pAK4-sod immunized mice. The extra CpG motifs in the pAK4 plasmid decreases the IL-10 level in pAK4-sod immunized mice compared to pAK3-sod immunized mice (Khera et al., 2005).
  • Detailed Gene Information: Click Here.

Mouse Response

• Vaccine Immune Response Type: VO_0000286
• Immune Response: Orally administrated liposomal-pcDNA3.1+/Ag85A DNA was efficiently incorporated into mucosal epithelium of the small intestine, Peyer's patches (PP). This initiated a Ag85A-specific Th1 dominant immune response, as evidenced by increased secretion of IL-2, IFN-γ, and no change of IL-4 (Wang et al., 2010)
• Efficacy: Liposomal-pcDNA3.1+/Ag85A DNA significantly increased the protection by giving a markedly reduction of TB burden in the lung, demonstrating that the TB-specific immune responses elicited by oral administration of liposomal-pcDNA3.1+/Ag85A DNA led to an enhanced host defense against TB infection. (Wang et al., 2010)

Mouse Response

• Host Strain: C57BL/6
• Vaccination Protocol: were vaccinated subcutaneously three times with 5 μg of either HPLC-purified HBHA (nHBHA) or recombinant HBHA emulsified in 150 μg of dimethyldioctadecylammonium bromide (DDA) (Acros Organics, Morris Plains, N.J.)-monophosphoryl lipid A (MPL) adjuvant or with the adjuvant combination alone (Parra et al., 2004).
• Challenge Protocol: Mice were challenged with aerosolized M. tuberculosis Erdman (200 CFU) 4 weeks following the final immunization (Parra et al., 2004).
• Efficacy: The HBHA-containing vaccine gave a approximately 0.7-log reduction in CFU in both mouse lungs and spleens compared to adjuvant controls 28 days following challenge (Parra et al., 2004).
• Host Ifng (Interferon gamma) response
  • Description: There was a ~10-fold increase in the amount of IFN-γ released in the ex vivo assay by spleen cells from HBHA-immunized mice compared to cells from naïve mice or mice immunized with only adjuvant, which was a significantly higher amount. Splenocytes from immunized mice were incubated with murine BMMΦ infected with M. bovis BCG for 72 hours. Lymph node-derived lymphocytes from HBHA-vaccinated mice released approximately eightfold more IFN-γ in the presence of HBHA-stimulated macrophages than cells from naïve or adjuvant control mice released, which was also significant (Parra et al., 2004).
  • Detailed Gene Information: Click Here.

Mouse Response

• Host Strain: C57/BL6
• Vaccination Protocol: Mice were immunized three times (3 wk apart) with 8 µg of rMtb72F formulated with the adjuvants AS02A. For protein formulations, the required immunization dose of rMtb72F (typically 8 µg) was brought up to either 50 or 43 µl with 1x PBS (pH 6.8) and mixed with 57 µl of AS02A. Mice were injected with a total volume of 100 µl/mouse via the i.m. (tibialis) route with 50 µl/leg. Positive control mice were immunized with BCG (5 x 10^4 CFU) in the base of the tail (once), and negative control animals were injected with saline, adjuvant alone, or DNA vector (Skeiky et al., 2004).
• Challenge Protocol: Thirty days after the last immunization, mice were challenged by low dose aerosol exposure with M. tuberculosis H37Rv strain (Skeiky et al., 2004).
• Efficacy: Immunization of mice with Mtb72F protein formulated in the adjuvant AS02A resulted in the elicitation of a moderate IFN-gamma response and a weak CD8(+) T cell response to Mtb32c. Mtb72F immunization resulted in the protection of C57BL/6 mice against aerosol challenge with a virulent strain of M. tuberculosis(Skeiky et al., 2004).

Mouse Response

• Host Strain: Balb/C mice
• Vaccination Protocol: Groups of four Balb/C mice were vaccinated with either 2.5x10^3 CFUs of SO2 or 8x10^3 CFUs of M. bovis BCG and later sacrificed at 7, 14, 21, 28, 45, and 60 days post-vaccination (Martin et al., 2006).
• Challenge Protocol: To asses protective efficacy of SO2 in Balc/c mice, mice were challenged by intravenous route with 2.5x10^5 CFU M. tuberculosis H37Rv at week 8 and sacrificed four weeks later.
  
  
• Efficacy: Vaccination with M. tuberculosis SO2 induced a significantly higher proportion of CD4+/IFN-gamma+ producing cells after 45 days of vaccination when compared with BCG (Martin et al., 2006). The proportion of CD8+/IFN-gamma+ producing cells was consistently higher in the M. tuberculosis SO2group. SO2 strain and BCG both conferred significant levels of protection compared to saline controls, with reductions of 1.5 and 1.3 log10 reductions in cfu counts in lung and spleen (Martin et al., 2006). However,
• Host Ifng (Interferon gamma) response
  • Description: Vaccination with M. tuberculosis SO2 induced a significantly higher proportion of CD4+/IFN-γ+ producing cells in mice 45 days after vaccination when compared with BCG (Martin et al., 2006).
  • Detailed Gene Information: Click Here.

Mouse Response

• Host Strain: CB-17/lcr lco SCID specific pathogen free (spf)
• Vaccination Protocol: No vaccination was employed here. Purpose of experiment is to assess survival of SCID mice following infection with either SO2 or BCG (Martin et al., 2006).
• Persistence: All SCID mice infected with SO2 strain survived for >245 days, whereas those infected with M. tuberculosis MT103 and SO2-pSO5 died within 62 days of infection(Martin et al., 2006).
• Challenge Protocol: Ten mice per experimental group were infected with 200μl PBS containing 2x10^5, 2x10^4, or 2x10^3 viable BCG Pasteur, or 5.4x10^6, 5.4x10^5, or 5.4x10^4 viable SO2. Aerosol infection was also used to nebulize with 7 ml of M. tuberculosis suspension, providing 20 viable bacilli within the lungs. Survival times were determined using Mantel-Haenszel test (Martin et al., 2006).

Mouse Response

• Host Strain: B6.PL (Thy1.1+), SIINFEKL/H-2K^b-reactive TCR-transgenic OT-1
• Vaccination Protocol: Donor splenocytes from Rag1 deficient OT1 TCR-transgenic mice were isolated and labeled with 20 μg CFSE and washed. Aliquots containing either 3x10^5 or 1x10^7 labeled cells were injected into lateral tail vein prior to subcutaneous or i.v. infection with 1x10^8 CFU M. tuberculosis ΔsecA2-OVA or control bacteria strains. Splenocytes were harvested and stained 5-7 days post-infection and analyzed by flow cytometry to determine percentage of undivided (high-CFSE) cells in the Thy1.2+ population (Hinchey et al., 2007).
• Immune Response: OT-1 T cells infected with H37Rv, H37Rv-OVA, and ΔsecA2-OVA showed negligible, modest, and massive increases in proliferation of transferred T cells. SecA2 addition can restore OT-1 T cell priming activities in the mutants. Furthermore, SIINFEKL epitope is produced in all mutants in an immunogenic form. Additional evidence suggested that tight linkage exists among CD8+ T cell priming, loss of SodA secretion, and blocked apoptosis (Hinchey et al., 2007).
• Challenge Protocol: No challenge was implemented here.
• Description: Procedure was designed to visualize and better understand the priming of MHC class I restricted CD8+ T cells with SIINFEKL fusion protein, as well as understand the relationship between SodA secretion, apoptosis, and secA2 (Hinchey et al., 2007).

Mouse Response

• Host Strain: C57BL/6
• Vaccination Protocol: Mice received 5x10^5 OT-1 cells one day before infecting subcutaneously with either 1x10^6 CFU H37Rv-OVA or ΔsecA2-OVA. Animals were sacrificed at 2, 4, or 20 weeks prior to splenic isolation and antibody labeling. Lympocyte subpopulations (CD44high,CD62high; CD44highCD62low) were quantified and separated using flow cytometry (Hinchey et al., 2007).
• Immune Response: Infection with H37Rv, H37Rv-OVA or ΔRD1-OVA induced background levels of IFN-gamma spot-forming cells while the ΔsecA2-OVA infection induces a 10-fold increase of similar spots above the background levels. Additional evidence from an in vivo CTL assay for SIINFEKL -induced CD8+ T cell activity strengthened the claim that enhanced T cell priming in the sec2A deletion mutants is restricted to CD8+ T cell compartment (Hinchey et al., 2007).
• Challenge Protocol: No challenge was introduced in this protocol.
• Description: Purpose of this experiment was to analyze memory T cell populations and abundance within the native splenic environment, and to determine the extent of antigen transmission to dendritic cells and enhanced CD8+ T cell priming (Hinchey et al., 2007).

Mouse Response

• Host Strain: C57BL/6
• Vaccination Protocol: Mice were vaccinated subcutaneously with 1x10^6 CFUs of either M. tuberculosis ΔsecA2 or M. bovis BCG-Pasteur.
• Persistence: Substantial growth of HN878 observed in lungs and spleens within one month of challenge (Hinchey et al., 2007), whereas both M. tuberculosis ΔsecA2 or M. bovis BCG-Pasteur showed decreased loads at the same interval.
• Immune Response: Mild inflammation including small/compact granulomas containing lymphocytes were observed for animals vaccinated with BCG or ΔsecA2 (Hinchey et al., 2007).
• Challenge Protocol: Mice were challenged via aerosol route two months post-vaccination using GlasCol inhalation chamber. Approximately 50-100 CFUs of either M. tuberculosis Beijing/W (HN878) or Erdman strains were administered using this approach. Mice were sacrificed at 1, 3, and 5 months post-challenge prior to isolation of lung and spleen. Mice infected with the Erdman strain were observed daily until euthanization in a second survival study (Hinchey et al., 2007).
• Efficacy: Protection by ΔsecA2 was significantly greater than in animals infected with M. bovis BCG-Pasteur at one month post-challenge (Hinchey et al., 2007). Furthermore, the protection offered by ΔsecA2 was still significant after five months post-challenge despite non-significant BCG protection at the same interval.

Mouse Response

• Host Strain: Outbred Hartley guinea pigs
• Vaccination Protocol: Guinea pigs were vaccinated intradermally with 1x10^3 M. tuberculosis ΔsecA2 or BCG-Pasteur (Hinchey et al., 2007).
• Persistence: Lower CFUs observed in ΔsecA2-immunized animals versus BCG and control animals (Hinchey et al., 2007).
• Immune Response: Minor fibrosis observed for in ΔsecA2-immunized animals at 2 months post-challenge (Hinchey et al., 2007).
• Challenge Protocol: Animals were challenged six weeks post-vaccination via aerosol route with 10-30CFUs of M. tuberculosis H37Rv strains (Madison chamber). Spleen, lung, and lymph node tissues were isolated at either 1 or 2 months post-challenge. (Hinchey et al., 2007).
• Efficacy: The ΔsecA2-immunized animals exhibited significant decreases (p<.01) in lung, splenic, and mediastinal lymph node CFUs versus control animals. Notable differences in CFU counts and organ size in the mediastinal lymph nodes were observed in only the M. tuberculosis ΔsecA2-innoculated animals, including only minor fibrosis at two months post-challenge (Hinchey et al., 2007).
• Description: Guinea pigs were vaccinated and challenged for CFU determination and histopathology comparison between different attenuated strains of M. tuberculosis and M. bovis. The results from the guinea pig study suggest that the . M. tuberculosis ΔsecA2 exceeds the efficacy of BCG in several aspects and may be a viable vaccine candidate (Hinchey et al., 2007).

Mouse Response

• Host Strain: C57/BL6 female mice
• Vaccination Protocol: Mice were age-matched (4-6 weeks) per experiment, and immunized 3 times (2 wk apart) with 8μg of rMtb72f and selected adjuvants. Immunization dose was increased from 8μg using 50 or 43 μl of PBS with 50 or 57 μl of AS01B or AS02A adjuvants. In total, 100 μl of vaccine was injected via i.m. (tibialis) route with 50 μl/leg (Skeiky et al., 2004). Additional culturing protocols were included for mononuclear and splenic cells (see (Skeiky et al., 2004)). Mice immunized with 5x10^4BCG in base of tail served as positive controls. Negative controls were injected with saline, adjuvant alone, or DNA vector.
  
• Persistence: The extent of protection with Mtb72F represents the longest documented survival end point reported for any defined subunit vaccine (~40% survival after 80 weeks post-challenge) (Skeiky et al., 2004).
• Challenge Protocol: Thirty days after the last immunization, mice were challenged by low-dose aerosol exposure (50-100 bacteria in lungs) with M. tuberculosis H37Rv strain. Mice were euthanized four weeks later prior to lung and spleen homogenate preparation.
• Efficacy: Mice immunized with DNA developed an Mtb72f Ab response of the IgG2a but not IgG1 subclasses which was directed against N-terminal (Mtb32c) molecules. Strong IFN-gamma responses were elicited in response to rMtb72F, rMtb32c, Mtb39, and PPD treatments. Mice immunized with rMtb72f and either adjuvant mounted strong IgG1 and IgG2a responses against Mtb72F. The AS01B-Mtb72F formulation elicited robust CD8+ T cell responses (directed against Mtb32c), whereas the AS02A-Mtb72F formulation were weaker than the AS01B formulation. However, both adjuvants when combined with Mtb72f could elicit ~0.6 log reduction in bacteria burden of mouse lungs. The Mtb72F-DNA provided 0.7-1.0 log reduction in bacterial load, which is comparable to BCG results (Skeiky et al., 2004).

Mouse Response

• Host Strain: C57BL/6
• Vaccination Protocol: C57BL/6 female mice were vaccinated once subcutaneously with 10^6 CFU of BCG Pasteur 6 weeks before challenge. For the wild-type MVA vector (as a control) or the MVA/IL-15/5Mtb vaccine, mice were administered two doses of 5 × 10^7 PFU subcutaneously at 1 month apart (Kolibab et al., 2010).
• Challenge Protocol: Five mice from each group were aerogenically challenged with M. tuberculosis Erdman K1 (Trudeau Mycobacterial Culture Collection) suspended in phosphate-buffered saline (PBS) at a concentration known to deliver 200 CFU in the lungs over a 30-min exposure in a Middlebrook chamber (Kolibab et al., 2010).
• Efficacy: Mice vaccinated with the MVA/IL-15/5Mtb construct had significant protection at 2 and 12 months post challenge. At 12 months postvaccination, highly persistent protective responses were seen in the lungs of mice immunized with BCG vaccine or our MVA/IL-15/5Mtb construct (Kolibab et al., 2010).
• Host Cxcl10 response
  • Description: Two and sixteen months post vaccination with MVA/IL-15/5Mtb, Cxcl10 was significantly upregulated in mice lungs as compared to naive control mice. However, it was significantly down-regulated as compared to mice vaccinated with BCG 16 months post vaccination (Kolibab et al., 2010).
  • Detailed Gene Information: Click Here.
• Host Cxcl11 response
  • Description: Two months post vaccination with MVA/IL-15/5Mtb, Cxcl11 was significantly upregulated in mice lungs as compared to naive control mice. However, it was significantly down-regulated as compared to mice vaccinated with BCG 16 months post vaccination (Kolibab et al., 2010).
  • Detailed Gene Information: Click Here.
• Host Cxcl9 response
  • Description: Two and sixteen months post vaccination with MVA/IL-15/5Mtb, Cxcl9 was significantly upregulated in mice lungs as compared to naive control mice. However, it was significantly down-regulated as compared to mice vaccinated with BCG 16 months post vaccination (Kolibab et al., 2010).
  • Detailed Gene Information: Click Here.
• Host Ebi3 response
  • Description: Two months post vaccination with MVA/IL-15/5Mtb, IL-27 beta (Ebi3) was significantly upregulated in mice lungs as compared to naive control mice
  • Detailed Gene Information: Click Here.
• Host Ifng (Interferon gamma) response
  • Description: Two and sixteen months post vaccination with MVA/IL-15/5Mtb, IFN-gamma was significantly upregulated in mice as compared to naive control mice in lungs. However, it was significantly down-regulated as compared to mice vaccinated with BCG (Kolibab et al., 2010).
  • Detailed Gene Information: Click Here.
• Host Il12b response
  • Description: Two months post vaccination with MVA/IL-15/5Mtb, IL12b (IL12 p40 subunit) was significantly upregulated in mice lungs as compared to naive control mice (Kolibab et al., 2010).
  • Detailed Gene Information: Click Here.
• Host Il15 response
  • Description: IL-15 was used as an adjuvant for the modified vaccinia Ankara vaccine (MVA). Homologous prime/boost studies showed that the MVA/IL-15/5Mtb vaccine induced moderate but highly persistent protective immune responses for at least 16 months after the initial vaccination and that the interval between the prime and boost did not significantly alter vaccine-induced antituberculosis protective immunity. Organ (lung or spleen) bacterial burdens (CFU) in the MVA/IL-15/5Mtb vaccine-immunized mice were greater than those in BCG vaccinated animals, but less than those in mice vaccinated with MVA alone. MVA/IL-15/5Mtb also induced protection that was equivalent to BCG, whereas MVA alone did not induce protective immunity (Kolibab et al., 2010).
  • Detailed Gene Information: Click Here.
• Host Il17f response
  • Description: Two and sixteen months post vaccination with MVA/IL-15/5Mtb, IL-17F was significantly upregulated in mice lungs as compared to naive control mice. However, it was significantly down-regulated as compared to mice vaccinated with BCG (Kolibab et al., 2010).
  • Detailed Gene Information: Click Here.

Mouse Response

• Persistence: A drrC mutant is highly attenuated in mice (Pinto et al., 2004).
• Efficacy: A drrC mutant induces significant protection in mice from challenge with wild type M. tuberculosis (Pinto et al., 2004).
• Host Ifng (Interferon gamma) response
  • Description: The drrC− strain was able to induce splenic anti–M. tuberculosis IFN-γ–secreting T cells responsive to CFP in mice to a level equal to that induced by M. tuberculosis infection and much greater than the amount induced by BCG and control mice. The drrC− mutant was also able to generate high numbers of IFN-γ–secreting cells that recognize the M. tuberculosis ESAT-6 antigen, which BCG and control mice could not do. IFN-gamma levels in both cases were comparable to levels induced by the wild type. This effect began 4 weeks after infection and was sustained long-term (24 weeks after infection) (Pinto et al., 2004).
  • Detailed Gene Information: Click Here.

Mouse Response

• Persistence: A fadD26 mutant is attenuated in mice (Infante et al., 2005).
• Efficacy: A fadD26 mutant induces significant protection in mice from challenge with wild type M. tuberculosis (Infante et al., 2005).
• Host Ifng (Interferon gamma) response
  • Description: The fadD26 mutant induced a progressive increase in IFN-γ expression in lung homogenates of mice, peaking at day 60, and 2 months later it had decreased by only 20% from its maximal level. However, it induced significantly lower expression than that induced by the wild type pathogen (MT-103) from days 1-21 post infection (Infante et al., 2005).
  • Detailed Gene Information: Click Here.
• Host Il4 (interleukin 4) response
  • Description: A fadD26 mutant induced a significantly lower and stable IL-4 expression as compared to the wild type (MT103) during the first month of infection in mice, followed by an increase of 50% at days 60 and 120. IL-4 levels of a fadD26 mutant-vaccinated mice were significantly lower than those infected with the wild type on days 3, 7, 21, 28, and 60 post infection in lung homogenates (Infante et al., 2005).
  • Detailed Gene Information: Click Here.
• Host Nos2 response
  • Description: Mice infected with the fadD26 mutant showed significant higher iNOS expression than the parent strain in lung homogenates days 21, 28 and 60 post infection. Results showed that the fadD26 mutant is also more efficient than its parental strain at inducing iNOS expression (Infante et al., 2005).
  • Detailed Gene Information: Click Here.
• Host TNF-alpha response
  • Description: The fadD26 mutant induced stable TNF-α expression in mice, significantly lower than that induced by MT-103 (WT strain) after 1 week of infection. In lung homogenates, fadD26 mutant vaccination induced significantly lower TNF-alpha levels on days 7, 14, 28, and 60 as compared to mice vaccinated with the wild type (Infante et al., 2005).
  • Detailed Gene Information: Click Here.

Mouse Response

• Persistence: A leuD mutant is attenuated in mice (Hondalus et al., 2000).
• Efficacy: A leuD mutant induces significant protection in mice from challenge with wild type M. tuberculosis (Hondalus et al., 2000).

Mouse Response

• Persistence: A lysA/secA2 mutant is highly attenuated in mice (Hinchey et al., 2011).
• Efficacy: A lysA/secA2 mutant induces significant protection in mice from challenge with wild type M. tuberculosis (Hinchey et al., 2011).

Mouse Response

• Persistence: A mce-2 mutant is attenuated in mice (Aguilar et al., 2006).
• Efficacy: A mce-2 mutant induces significant protection in mice from challenge with wild type M. tuberculosis (Aguilar et al., 2006).
• Host Ifng (Interferon gamma) response
  • Description: Mutant mce-2 induced a lower but progressive expression of IFN-γ than the parent strain in mice, peaking at day 120 post-infection. The IFN-gamma response in lungs was significantly lower in mice immunized with mce-2 mutants on days 1, 3, 7, 14, and 21 days post infection as compared to mice infected with the wild type (Aguilar et al., 2006).
  • Detailed Gene Information: Click Here.
• Host Il4 (interleukin 4) response
  • Description: The mce-2 mutant maintained low IL-4 expression until day 60 post-infection, showing slight increase at day 120. The expression of IL-4 was higher in the lungs of mice infected with the parental strain. Infection with the wild type strain induced significantly more IL-4 than that induced by immunization with the mutant on days 21, 28, and 60 post infection (Aguilar et al., 2006).
  • Detailed Gene Information: Click Here.

Mouse Response

• Persistence: A mce-3 mutant is attenuated in mice (Aguilar et al., 2006).
• Efficacy: A mce-3 mutant induces significant protection in mice from challenge with wild type M. tuberculosis (Aguilar et al., 2006).
• Host Ifng (Interferon gamma) response
  • Description: The mce-3 mutant induced a lower but progressive expression of IFN-γ than the parent strain in mice, peaking at day 120 post-infection. The IFN-gamma response in lungs was significantly lower in mice immunized with mce-3 mutants on days 1, 3, 7, 14, and 21 days post infection as compared to mice infected with the wild type (Aguilar et al., 2006).
  • Detailed Gene Information: Click Here.
• Host Il4 (interleukin 4) response
  • Description: The mce-3 mutant maintained low IL-4 expression until day 60 post-infection, showing slight increase at day 120. The expression of IL-4 was higher in the lungs of mice infected with the parental strain. Infection with the wild type strain induced significantly more IL-4 than that induced by immunization with the mutant on days 21, 28, and 60 post infection (Aguilar et al., 2006).
  • Detailed Gene Information: Click Here.

Mouse Response

• Persistence: A panCD mutant is attenuated in mice (Sambandamurthy et al., 2002).
• Efficacy: A panCD mutant induces significant protection in mice from challenge with wild type M. tuberculosis (Sambandamurthy et al., 2002).

Mouse Response

• Persistence: A proC mutant is attenuated in mice (Smith et al., 2001).
• Efficacy: A proC mutant induces significant protection in mice from challenge with wild type M. tuberculosis (Smith et al., 2001).

Mouse Response

• Persistence: An RD1/panCD mutant is attenuated in mice (Sambandamurthy et al., 2006).
• Efficacy: An RD1/panCD mutant induces significant protection in mice from challenge with wild type M. tuberculosis (Sambandamurthy et al., 2006).
• Host Ifng (Interferon gamma) response
  • Description: At the 10-day time point, substantial increases (relative to naive mice) were detected in IFN-γ positive CD4 and CD8 lung cells taken from the vaccinated mice (Sambandamurthy et al., 2006).
  • Detailed Gene Information: Click Here.

Mouse Response

• Persistence: A sigE mutant is attenuated in mice (Hernandez et al., 2010).
• Efficacy: A sigE mutant induces significant protection in mice from challenge with wild type M. tuberculosis (Hernandez et al., 2010).
• Host Defb3 response
  • Description: A sigE mutant showed a significantly higher and constant expression of the gene encoding β-defensin 3 in the lungs beginning the 7th day post vaccination until the 28th day as compared to mice infected with the parental strain (Hernandez et al., 2010).
  • Detailed Gene Information: Click Here.
• Host Ifng (Interferon gamma) response
  • Description: A sigE mutant showed a significantly higher and constant expression of the gene encoding IFN-γ as compared to mice infected with the parental strain. IFN-gamma was significantly upregulated in mice lungs after vaccination with the mutant as compared to infection with the wild type beginning day 1 post-infection and continuing throughout the duration of the experiment (Hernandez et al., 2010).
  • Detailed Gene Information: Click Here.
• Host Il10 (interleukin 10) response
  • Description: The expression of IL-10 was higher in sigE mutant-infected mice lungs as compared to infection with the parental strain, but it was significant only 21 and 28 days after the infection (Hernandez et al., 2010).
  • Detailed Gene Information: Click Here.
• Host Il4 (interleukin 4) response
  • Description: IL-4 was expressed at a significantly lower level in the sigE mutant-infected mice as compared to mice infected with the wild type pathogen. Significant down regulation of IL-4 by the mutant in mouse lungs was seen days 1-28 post infection as compared to infection with the wild type (Hernandez et al., 2010).
  • Detailed Gene Information: Click Here.
• Host TNF-alpha response
  • Description: A sigE mutant showed a significantly higher and constant expression of the gene encoding TNF-alpha as compared to mice infected with the parental strain. Vaccination with the mutant significantly up-regulated TNF-alpha in mice lungs on days 1, 21, and 28 post-infection as compared to infection with the wild type (Hernandez et al., 2010).
  • Detailed Gene Information: Click Here.

Mouse Response

• Persistence: A trpD mutant is attenuated in mice (Smith et al., 2001).
• Efficacy: A trpD mutant induces significant protection in mice from challenge with wild type M. tuberculosis (Smith et al., 2001).

Mouse Response

• Vaccination Protocol: Mice in each group were immunized s.c. once at the base of the tail with 1 × 106 CFU of either rBCG::85A, rBCG::85B, or rBCG::AB in a final volume of 100 μL of PBS (Wang et al., 2012).
• Vaccine Immune Response Type: VO_0003057
• Challenge Protocol: mice were challenged with virulent M. tuberculosis strain 6 weeks after immunization (Wang et al., 2012).
• Efficacy: rBCG::AB strain could provide the strongest short-term and long-term protection in the lung against intravenous infection with virulent M. tuberculosis than rBCG::261 control and other two rBCG strains overexpressing single antigen. The stronger and longer-lasting protection provided by rBCG::AB than rBCG::261 was correlated with systemic in vitro antigen-specific IFN-γ responses (Wang et al., 2012).

Mouse Response

• Host Strain: BALB/c, female
• Vaccination Protocol: Recombinant S. typhimurium was injected into tail vein of each mouse and cured with10 mg ampicillin injected intraperitoneally (i.p.). Five mice used per group. Group A received high-dose vaccine 90 days pre-challenge and was cured twice with ampicillin. Group B received low-dose recombinant vaccine 60 days pre-challenge. Group C was vaccinated at 90, 60, and 30 days pre-challenge. Group D received s.i. prime with bacteria and naked DNA 90 days pre-challenge, two DNA boosts at 60 and 30 days pre-challenge, and curing twice. Group E received the same vaccinations and challenges as in D, though in a different order. GeneGun and pcDNAesat or PIRESesat were used during vaccination (Mollenkopf et al., 2001).
• Persistence:
• Side Effects: Spleens were enlarged after procedure, though CFU analysis revealed that the mice were free of Salmonella bacteria (Mollenkopf et al., 2001).
• Challenge Protocol: Challenge route was same as in vaccination (tail vein injection), though employed 5x10^5 CFUs of the virulent M. tuberculosis H37Rv i.v. (Mollenkopf et al., 2001)
• Efficacy: A significant difference in colony-forming units was seen at 10 versus 60 days post challenge (Mollenkopf et al., 2001). S. typhimurium induced a small but signifcant degree of protection in lungs, though only small degree of protection in the liver at day 60 (Mollenkopf et al., 2001).

Rat Response

• Host Strain: Wistar rat
• Vaccination Protocol: Wistar rats were vaccinated with 10^6 BCG subcutaneously 6-8 weeks prior to challenge (Singhal et al., 2011).
• Vaccine Immune Response Type: VO_0000286
• Immune Response: A significantly greater number of total cells and CD8 T cells was observed in BCG vaccinated animals at day 60 post-challenge compared with unvaccinated animals. Immunohistochemistry revealed substantial higher number of CB8 cells in the lung lesions of vaccinated rats at day 30. Finally, a high number of mycobacteria-specific CD4 and CD8 T cells producing IFN-gamma was detected in BCG vaccinated rats (Singhal et al., 2011).
• Challenge Protocol: The rats were challenged with a low dose of Mtb W4 strain 6 weeks after vaccination (Singhal et al., 2011).
• Efficacy: A significantly reduced bacillary load was observed in the lungs of BCG vaccinated rats over the entire course of infection. About a 1 log(10) reduced bacillary load was observed in the lungs of vaccinated rats compared to unvaccinated animals (Singhal et al., 2011).
• Description: The study showed that BCG vaccinated Wistar rats efficiently control early bacillary growth and pathology related to Mtb infection (Singhal et al., 2011).

Rabbit Response

• Host Strain: White New Zealand female rabbits (2.5-3kg)
• Vaccination Protocol: Rabbits were immunized with LAM (50 μg), AMO-TT (20 μg), AMO-Ag85B (20 μg), or AMO-75kDA (20 μg) conjugates via i.m. injection with 100 μl PBS and 100 μl FIA emulsifier, and later boosted (weeks 2, 4) with same dose of the previous vaccine.
• Immune Response: LAM alone did not induce LAM IgG antibodies, whereas the three conjugate vaccines induced high IgG antibody titers (Hamasur et al., 2003).
• Challenge Protocol: No challenge protocol implemented for rabbit immunogenicity study.
• Description: Purpose of the experiment with rabbits was to determine immunogenicity response to LAM and AMO-protein conjugates.

Rabbit Response

• Host Strain: New Zealand White Rabbits
• Vaccination Protocol: Rabbits were vaccinated three times at 3-week intervals intramuscularly with a total of 500 micro liters of BCG (Tsenova et al., 2006).
• Persistence: Rabbits were euthanized 8 weeks post-infection (Tsenova et al., 2006).
• Vaccine Immune Response Type: VO_0000134
• Immune Response: Significantly smaller amounts of CFU of the bacterium were observed in the brains of rabbits that were vaccinated with BCG. No granulomas were found in the lungs of mice vaccinated with BCG while they were found in the unvaccinated group. Vaccination with BCG induced a statistically significant increase in antigen-specific T-cell proliferation compared to that of non-vaccinated controls (Tsenova et al., 2006).
• Challenge Protocol: Ten weeks after immunization with BCG the rabbits were anesthetized and immobilized and a spinal needle was used to withdraw .3 mL of cerebrospinal fluid and .2 mL of 5X10^5 CFU of M. tuberculosis was injected intracisternally (Tsenova et al., 2006).
• Efficacy: This study showed that vaccination with BCG induced protection against M. tuberculosis because rabbits that were vaccinated showed increased T-cell proliferation and no granulomas in the lungs (Tsenova et al., 2006).

Guinea pig Response

• Host Strain: Dunkin Hartley, female (250-300g)
• Vaccination Protocol: Guinea pigs were immunized s.c. (day 0) and boosted nasally (day 24) with Eurocine L3 emulsion, AMO-TT conjugate, and variable antigen doses and adjuvant concentrations (Hamasur et al., 2003). A protection study included immunization with 15 μg AMO-Ag85B in 10% Eurocine L3 emulsion. Comparison BCG groups were injected s.c. with 5x10^4 CFU live BCG (Hamasur et al., 2003).
• Side Effects: Five of six animals non-vaccinated and two of six AMO-Ag85B vaccinated were killed before 120 days post-challenge if observed >20% loss of starting weight.
• Challenge Protocol: Guinea pigs were aerosol challenged with saline suspension containing 10^6 organisms per ml (~10 CFU/lung).
• Efficacy: BCG vaccinated animals showed reduced counts of M. tuberculosis bacilli in lung and spleen samples versus saline controls. The reduced CFUs in spleen samples along with histological sections analyzed with double blind analysis suggested an overall decrease in disease severity in lung and spleen (Hamasur et al., 2003).

Guinea pig Response

• Host Strain: Dunkin Hartley (Thom et al., 2012).
• Vaccination Protocol: Pathogen-free, female outbred Dunkin Hartley strain guinea pigs (weighing 500–550 g) were vaccinated subcutaneously with 5 × 104 colony forming units (CFU) of M. bovis BCG Pasteur (Thom et al., 2012).
• Immune Response: Significant down-regulation of both ferritin light- and heavy-chain (Thom et al., 2012).
• Description: PPD from M. tuberculosis was added to splenocytes from BCG-vaccinated guinea pigs at a final concentration of 30 μg/ml for 16 and 24 h at 37 °C in the presence of 5% CO2. The splenocyte cultures from naïve and BCG-vaccinated guinea pigs were infected with M. tuberculosis at an MOI of 0.2 and incubated for 4, 16 and 24 h at 37 °C in the presence of 5% CO2. The viability of uninfected and infected splenocytes from the same vaccination group was determined at 4, 16 and 24 h post-M. tuberculosis infection by trypan blue exclusion (Thom et al., 2012).
• Host Fth1 response
  • Description: Splenocytes from BCG-vaccinated guinea pigs were stimulated ex vivo with purified protein derivative from M. tuberculosis and a significant down-regulation of ferritin light- and heavy-chain was measured by reverse-transcription quantitative-PCR (Thom et al., 2012).
  • Detailed Gene Information: Click Here.
• Host Ftl response
  • Description: Splenocytes from BCG-vaccinated guinea pigs were stimulated ex vivo with purified protein derivative from M. tuberculosis and a significant down-regulation of ferritin light- and heavy-chain was measured by reverse-transcription quantitative-PCR (Thom et al., 2012).
  • Detailed Gene Information: Click Here.

Guinea pig Response

• Host Strain: Outbred guinea pigs of the Duncan Hartley strain
• Challenge Protocol: Guinea pigs (in groups of six) were immunized intramuscularly with three doses (of 100 μg each) of pAK4, pAK4-E6 expressing ESAT-6, pAK4-αcry expressing α-crystallin, or pAK4-sod at 3 weeks intervals. Four weeks after the last booster, guinea pigs were subcutaneously challenged with 1 × 10^5 CFU of M. tuberculosis H37Rv. Guinea pigs were euthanised 4 weeks after challenge (Khera et al., 2005).
• Efficacy: DNA vaccine expressing superoxide dismutase imparted the maximum protection as observed by a 50 and 10 folds reduction in bacillary load in spleens and lungs, respectively, in comparison to immunization with vector control. Among the animals vaccinated with various DNA vaccines, pAK4-sod immunized guinea pigs exhibited the minimal granuloma (Khera et al., 2005).

Guinea pig Response

• Vaccination Protocol: Groups of six guinea pigs were used in two procedures. Guinea pigs were vaccinated subcutaneously with 250μl of 5x10^4 CFU BCG (Pasteur) or SO2 in both the low-dose and high-dose challenge experiments. Saline was also used in the low-dose experiments.
• Side Effects: SO2-treated guinea pigs gained weight. No visible or clinical signs of disease after challenge.
• Challenge Protocol: In the low dose challenge, guinea pigs were aerosol challenged at 12 weeks using a Henderson apparatus and 2x10^6 CFU/ml M. tuberculosis water suspension to give estimated inhaled dose of 10-50 CFU/lung. In high dose challenge, guinea pigs were aerosol challenged at 10 weeks with 5x10^7 CFU/ml M.tuberculosis in water suspension to give approimately 500 CFUs to the lungs. Animals were killed by peritoneal overdose of sodium pentabarbitone (Chandra et al., 2006).
• Efficacy: A significant difference was observed between non-vaccinated and vaccinated (both BCG and SO2-recipient) groups receiving low-dose treatment, whereas no significant difference was evident between the BCG and SO2 groups. In high dose challenge, all non-vaccinated and BCG-vaccinated were euthanized according to set humane end-point, while all SO2-vaccinated groups showed significantly longer survival than BCG groups and saline-treated groups. Pulmonary disease most evident in non-vaccinated guinea pigs. Consolidation was significantly less in the SO2-vaccinated groups versus non-vaccinated and BCG-vaccinated groups. "M. tuberculosis SO2 strain was superior to BCG in conferring enhanced survival to infected guinea pigs, reduction in the severity of the disease in the lung, and dissemination of infection to the spleen" (Martin et al., 2006).

Guinea pig Response

• Vaccination Protocol: Similar to mouse protocol, the guinea pigs were immunized three times (3 weeks apart) with 200μg Mtb72F-DNA with 250μl of 1xPBS @ pH 7.0, 20-μg dose of rMtb72f, or a mixture of these components in a total 250uL dose containing AS02A. Guinea pigs were immunized with 125μl of final formula in the leg (Skeiky et al., 2004). BCG administered to some animals via intradermal route. ***
• Persistence: Evidence suggests that the protection can last for > 1 year (Skeiky et al., 2004).
• Challenge Protocol: Animals were challenged with virulent H37Rv strain via aerosol route after 13 weeks, with nebulizer providing 20-50 bacteria into the lungs (Skeiky et al., 2004).
• Efficacy: After 30 wk postchallenge, four of five guinea pigs immunized with rMtb72F and three of five immunized with Mtb72F-DNA were alive, whereas after 70 weeks, two of five in DNA-immunized groups were still alive.

Cattle Response

• Host Strain: Friesian Calves
• Vaccination Protocol: Vaccinated subcutaneously in the neck with 2 mL of 2X10^5 cfu BCG
• Persistence: Cattle were examined 154 to 164 days after they had been challenged.
• Vaccine Immune Response Type: VO_0000408
• Immune Response: The cattle that had been vaccinated with BCG showed significantly less numbers of lesions in the lungs and lymph nodes.
• Challenge Protocol: 54 days after vaccination the calves were challenged intratracheally with 2X10^3 cfu M. bovis strain 83/6235.
• Efficacy: Vaccination with BCG induced considerable protection against a challenge with M. bovis, there were significantly fewer animals with Tuberculosis lesions.
• Description: This study showed that killed M. vaccae did not protect against challenge by M. bovis, however, the vaccination of cattle with BCG by the respiratory route protected them against the development of tuberculous lung lesions.
• Host IFNG response
  • Description: In the vaccinated cattle group, increased IFN-gamma was released from the culture of peripheral blood lymphocytes from cattle after stimulation with bovine purified protein derivative (PPD) (Buddle et al., 1995).
  • Detailed Gene Information: Click Here.
• Host IL10 response
  • Description: In the vaccinated cattle group, increased IL-2 was released from the culture of peripheral blood lymphocytes from cattle after stimulation with bovine purified protein derivative (PPD) (Buddle et al., 1995).
  • Detailed Gene Information: Click Here.

Macaque Response

• Host Strain: cynomolgus monkey (M. fascicularis) and rhesus monkey (M. mulatta)
• Vaccination Protocol: The macaques were vaccinated intradermally with 1–4 X 10^5 cfu bacillus Calmette–Guerin
• Vaccine Immune Response Type: VO_0000859
• Immune Response: Showed specific cell-mediated immune responses after bacillus Calmette–Guerin vaccination as observed by skin test, lymphoproliferation, and IFN-gamma production (Langermans et al., 2001).
• Challenge Protocol: 17 weeks after vaccination the monkeys were challenged with 3,000 cfu M. tuberculosis by intratracheal installation of 3 ml of the bacterial suspension. Between 59 and 65 days after infection the animals were killed, and necropsies were undertaken for pathological examination (Langermans et al., 2001).
• Description: This study showed that cynomolgus monkey (M. fascicularis) is a better model than rhesus monkey (M. mulatta) for M. tuberculosis vaccination and infection studies. From a challenge with 3,000 cfu M. tuberculosis, BCG vaccination protects cynomolgus monkeys with >2-log reduction of the bacterial load and diminished pathology, whereas only a minimal BCG vaccination effect was observed in rhesus monkeys. These two species represent the two extremes of BCG-induced protection that is found in humans (Langermans et al., 2001).

Zebrafish Response

• Host Strain: Wildtype AB or adult rag hu1999 mutant fish
• Vaccination Protocol: Fish were vaccinated with ~8X10^3 CFU BCG intraperitoneally or intramuscularly (Oksanen et al., 2013).
• Vaccine Immune Response Type: VO_0003057
• Challenge Protocol: Fish were anesthetized and intraperitoneally injected 3-4 weeks after immunization with ~20-30 bacteria (Oksanen et al., 2013).
• Efficacy: BCG was unable to prevent infection with mycobacteria, however, it improved fish survival lowering the mortality rate from 84.2% to 45.0% (Oksanen et al., 2013).
• Description: BCG is unable to prevent infection in zebrafish, however, it is able to improve fish survival (Oksanen et al., 2013).