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Vaccine Comparison

Arabinomannan-tetanus toxoid conjugate attenuated M. bovis strain WAg539 Bacille Calmette-Guérin (BCG) BCG expressing MSP DNA vaccine Rv1806-1807 M. bovis WAg520 strain M. bovis WAg522 strain M. tuberculosis DNA Vaccine APADNA priming and APAMVA boosting M. tuberculosis DNA vaccine pAK4-sod M. tuberculosis phoP mutant SO2 Mtb72f fusion protein rBCG-Ag85A[Tokyo]
Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information
  • 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: aluminum hydroxide vaccine 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).
  • Vaccine Ontology ID: VO_0000543
  • Type: Live, attenuated vaccine
  • Antigen: M. bovis with gene mutations due to signature-tagged mutigenesis to create attenuated mutants. Ten genes were found to be deleted or interrupted in the 10.1-kb deletion in WAg539, including mmpL4, mmpS4, ufaA1, and sigK, as well as unknown genes (Collins et al., 2005).
  • Preparation: M. bovis strain and its recombinants were cultured in Middlebrook 7H9 (Difco) liquid medium supplemented with albumin-dextrose complex (Difco), 0.05% Tween 80, and and 0.4% sodium pyruvate and on Middlebrook 7H11 (Difco) solid medium supplemented with albumin-dextrose complex and 0.4% sodium pyruvate. Recombinants were cultured on kanamycin-supplemented medium. M. bovis culture from pig spleens were homogenized, filtered, and further processed (Collins et al., 2005). Forty-five recombinants with unique tags were subcultured separately and pooled together. The forty-five M. bovis recombinants were subcultured separately, and 106 CFU of each pool was inoculated subcutaneously into the flank of each guinea pig. Splenic culture were extracted from sacrificed animals and used to isolate 500-2,000 colonies per spleen. Tags identified in both the inoculated and recovered pools were amplified by PCR and processed.
  • Description: Signature tag morphogenesis was used to generate illegitimate recombinants of M. bovis. Several of the recombinant strains produced protection that was "at least as good as that provided by M. bovis BCG" in guinea pig models (Collins et al., 2005).
  • 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_0004107
  • Type: Live, attenuated vaccine
  • Antigen: MSP, a 30-kDa major secretory protein or mycolyltransferase, is used as vaccine antigen (Horwitz et al., 2000).
  • Preparation: Recombinant BCG (rBCG30) was prepared using E.coli/mycobacteria shuttle plasmid pSMT3. Plasmid was electoporated into the wild-type M. bovis BCG Tice strain. The 30-kDa MSP was isolated from the subcultured strains and further processed prior to inclusion in the vaccine (Horwitz et al., 2000).
  • Vaccine Ontology ID: VO_0000567
  • Type: DNA vaccine
  • Antigen: Rv1806 and Rv1807 (Vipond et al., 2006).
  • PE20 gene engineering:
    • Type: DNA vaccine construction
    • Detailed Gene Information: Click Here.
  • PPE31 gene engineering:
    • Type: DNA vaccine construction
    • Detailed Gene Information: Click Here.
  • Adjuvant: DDA vaccine adjuvant
  • Vector: pET11d, modified to form pET3a (Vipond et al., 2006)
  • Preparation: Two bacterial strains, E. coli DH5α and Rosetta™ 2(DE3)pLysS, were propagated in Luria Bertani (LB) broth and solid medium at 37°C. An expression vector pET3a was created from pET11d expression vector (Novagen) by replacing an ampicillin cassette with kanamycin cassette, followed by restriction digestion of a HindIII site and linker insertion containing cloning sites and an N- and C-terminal 6* histidine tag. The vaccine candidate gene was amplified from M. tuberculosis using PCR and cloned into pVAX1tPA. Recombinant plasmids were generated from four encoding gene sequences and sub-cloned into pET3a prior to transformation, induction, and harvesting in E. coli Rosetta™ 2(DE3)pLysS (Vipond et al., 2006).
  • Virulence: Not virulent.
  • Description: Rv1806-1807 was one of three potential vaccines compared against gold-standard BCG vaccine and saline control. Rv1806-1807 induced protection in the guinea pig aerosol infection model 30 days post-challenge on the basis of reducing the bacterial burden of M tuberculosis in the lungs ( a reduction in log10 cfu of 0 . 52 and 0 . 83 in lungs and spleen , respectively , following DNA vaccination , compared with reductions of 0 . 3 and 0 . 57 , respectively , with a protein formulation) (Vipond et al., 2006).
  • Vaccine Ontology ID: VO_0000552
  • Type: Attenuated vaccine
  • Antigen: The antigen for this vaccine was an attenuated strain of M. bovis called WAg520, which cantains a deletion in a possible undecaprenol kinase gene (De et al., 1999).
  • Preparation: WAg520 was one of four nutritionally impaired strains of M. bovis selected from 440 M. bovis mutants produced by illegitimate recombination based upon their inability to grow in minimal medium (De et al., 1999).
  • Virulence: This strain, along with the other test M. bovis mutants, was shown to be avirulent for guinea pigs following the subcutaneous inoculation (De et al., 1999).
  • Description: WAg520, an attenuated strain of M. bovis, has only a 2-bp deletion in a possible undecaprenol kinase gene. It is one of two nutritionally impaired strains which produced significant protection in the lungs. The other one is strain WAg522 (De et al., 1999).
  • Vaccine Ontology ID: VO_0000557
  • Type: Attenuated vaccine
  • Antigen: The antigen for this vaccine was an attenuated strain of M. bovis called WAg522 (De et al., 1999).
  • Preparation: WAg522 is the second of four M. bovis mutants selected from 440 illegitimate recombinant M. bovis mutants via their inability to grow in minimal medium (De et al., 1999).
  • Virulence: This strain, along with the other tested M. bovis mutants in (De et al., 1999), was shown to be avirulent in guinea pigs following subcutaneous inoculation. Furthermore, the groups treated with WAg522 and WAg520 strains both showed significant differences in lung CFU versus nonvaccinated groups.
  • Vaccine Ontology ID: VO_0011478
  • Type: Other
  • Status: Research
  • Apa gene engineering:
    • Type: Recombinant vector construction
    • Detailed Gene Information: Click Here.
  • Vector: pUMVC3 and poxvirus (Kumar et al., 2003).
  • Immunization Route: Intradermal injection (i.d.)
  • 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).
  • 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_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: AS02 vaccine 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_0000565
  • Type: Live, attenuated vaccine
  • Antigen: BCG and Mycobacterium antigen Ag85A (Sugawara et al., 2007).
  • FbpA (Ag85A) gene engineering:
    • Type: Recombinant vector construction
    • Description: The Ag85A gene was amplified by PCR and subcloned into the pCR4 vector. The gene was inserted into the pBBN vector (Ag85A-HA) possessing a hemagglutinin (HA) tag at its 5′ end. The Ag85A-HA was expressed in Escherichia coli. The Ag85A-HA gene was then introduced into the downstream region of the pHPS integration vector. The vector was then electroporated into BCG Tokyo. The resulting recombinant was named (rBCG-Ag85A[Tokyo]) (Sugawara et al., 2007).
    • Detailed Gene Information: Click Here.
Host Response Host Response Host Response Host Response Host Response Host Response Host Response Host Response Host Response Host Response Host Response Host Response

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.

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 5x105 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 105 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 105 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 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

  • Host Strain: Balb/C mice
  • Vaccination Protocol: Groups of four Balb/C mice were vaccinated with either 2.5x103 CFUs of SO2 or 8x103 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 2.5x105 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 2x105, 2x104, or 2x103 viable BCG Pasteur, or 5.4x106, 5.4x105, or 5.4x104 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: 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 5x104BCG 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).

Rat Response

  • Host Strain: Wistar rat
  • Vaccination Protocol: Wistar rats were vaccinated with 106 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 5X105 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 5x104 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 106 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
  • Vaccination Protocol: Groups of six guinea pigs were vaccinated with 105 CFU of one of the avirulent recombinant strains or BCG. Six animals were not vaccinated (control group) (Collins et al., 2005).
  • Challenge Protocol: Guinea pigs were challenged by aerosol with 2 to 10 CFU of wild-type M. bovis eight weeks post-vaccination (Collins et al., 2005).
  • Efficacy: Four mutants which did not induce any visible lesion were tested for vaccine efficacy. In the case of three mutants, animals were sacrificed 5 weeks post-challenge. The final mutant, WAg585 were sacrificed at 8 weeks post-challenge. Mutant WAg539 gave better, though not significantly different, protection than BCG vaccine, as well as the best vaccination of the four mutants (Collins et al., 2005).
  • Description: Animals were sacrificed and autopsied 5 weeks after challenge to enable the following analyses: weight, gross pathology, mycobacterial culturing and enumeration in splenic and lung tissues, and statistical analysis of macroscopic lesion count and other quantifiable measurements (Collins et al., 2005).

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: Hartley, 250-350g outbred male
  • Challenge Protocol: Animals were challenged nine weeks after first injection or skin testing via aerosol with 10-ml single-cell suspension containing 1x105 CFU (1st & 2nd experiment) or 2x105 CFU (3rd experiment) of M. tuberculosis Erdman, providing ~40 to 80 liver bacilli to lungs, respectively (Horwitz et al., 2000).
  • Efficacy: The highly susceptible guinea pig model of pulmonary TB, a model noteworthy for its close resemblance to human TB, was used for testing. Animals immunized with the recombinant BCG vaccine and challenged by aerosol with a highly virulent strain of M. tb. had 0.5 log fewer M. tb. bacilli in their lungs and 1 log fewer bacilli in their spleens on average than animals immunized with their parental conventional BCG vaccine counterparts. Statistically, the difference was highly significant. At necropsy, animals immunized with the recombinant BCG vaccine had fewer and smaller lesions in the lung, spleen, and liver and significantly less lung pathology than animals immunized with the parental BCG vaccine (Horwitz et al., 2000).

Guinea pig Response

  • Host Strain: Dunkin-Hartley guinea pig
  • Vaccination Protocol: Female Dunkin-Hartley guinea pigs were vaccinated by injecting 100 μg of protein intramuscularly into both hind quadriceps muscles per guinea pig in 100 μl of dioctadecylammonium (DDA) and trehalose dibehenate (TDB) (500 μg DDA plus 100 μg TDB) stable liposomes (SSI). Sub-cutaneous inoculation with 5×104 CFU BCG Pasteur was used as positive control. Saline was used as negative control. Ten guinea pigs were used for each group. Vaccinated animals were booster vaccinated with 200 μg protein in adjuvant after 3 and 6 weeks (Vipond et al., 2006).
  • Challenge Protocol: Six weeks after the final vaccination, six animals per group were aerosol challenged with approximately 50 CFU of M. tuberculosis H37Rv (NCTC 7416) each in a contained Henderson apparatus. Protection was assessed by CFU in the lungs and spleen at 30 days post-challenge (Vipond et al., 2006).
  • Efficacy: Level of protection by Rv1806-1807 at week 15 post challenge was significantly better than saline (p=.018) and comparable to related DNA vaccinations. However, the protection was significantly less than gold-standard BCG. An antigen dose of 10 μg/ml of Rv1806-1807 vaccine stimulated the better protection than for 1 μg/ml (Vipond et al., 2006).

Guinea pig Response

  • Host Strain: Duncan-Hartley
  • Vaccination Protocol: Four to eight guinea pigs per group were vaccinated by subcutaneous injection with 105 CFU with one of the four impaired M. bovis strains or BCG. Ten animals were not vaccinated (control) (De et al., 1999).
  • Side Effects: No delayed-type hypersensitivity reactions observed prior to inoculation with mycobacteria (De et al., 1999). Authors were unable to determine if nutritionally-impaired mutants influenced the development of necrotizing lesions in the lungs (De et al., 1999).
  • Challenge Protocol: All animals were anesthetized eight weeks post-vaccination via intramuscular injection with 3 mg ketamine hydrochloride, followed by 10x2 CFU virulent M. bovis WAg201 introduced through mouth into the trachea via cannula. Three guinea pigs which were not challeged received 105 CFU of each of the four strains via subcutaneous innoculation (De et al., 1999).
  • Efficacy: Significant differences in lung CFU were observed between vaccinated groups and WAg520 & WAg522 strains (De et al., 1999). WAg520 elicited 0.92, 3.83, and 2.47 log10 increases in lung, splenic, and liver tissues, respectively (Table I, (De et al., 1999)). Macroscopic lesions were decreased in WAg520 recipients versus both non-vaccinated (significant different) and BCG-vaccinated (not significantly different) animals (Table 2, (De et al., 1999)).
  • Description: All animals were sacrificed 13 weeks post-vaccination.

Guinea pig Response

  • Host Strain: Duncan-Hartley
  • Vaccination Protocol: Four to eight guinea pigs per group were vaccinated by subcutaneous injection with 105 CFU with one of the four impaired M. bovis strains or BCG. Ten animals were not vaccinated (control) (De et al., 1999).
  • Side Effects: No delayed-type hypersensitivity reactions observed prior to inoculation with mycobacteria (De et al., 1999). Authors were unable to determine if nutritionally-impaired mutants influenced the development of necrotizing lesions in the lungs (De et al., 1999).
  • Challenge Protocol: All animals were anesthetized eight weeks post-vaccination via intramuscular injection with 3 mg ketamine hydrochloride, followed by 10x2 CFU virulent M. bovis WAg201 introduced through mouth into the trachea via cannula. Three guinea pigs which were not challeged received 105 CFU of each of the four strains via subcutaneous innoculation (De et al., 1999).
  • Efficacy: Significant differences in lung CFU were observed between vaccinated groups and WAg520 & WAg522 strains (De et al., 1999). WAg520 elicited 0.92, 3.83, and 2.47 log10 increases in lung, splenic, and liver tissues, respectively (see Table I, (De et al., 1999)). Macroscopic lesions were decreased in WAg520 recipients versus both non-vaccinated (significant different) and BCG-vaccinated (not significantly different) animals (see Table 2, (De et al., 1999)).

Guinea pig Response

  • Vaccination Protocol: Animals were immunized intradermally with APADNA, 200 μg, given three times, 4 weeks apart (at weeks 0, 4, and 8), followed by APAMVA, 107 PFU, given 4 weeks after the third DNA (at 12 weeks); or BCG Guindy, 106 CFU, given one time only (at week 0) or control DNA, 200 μg, given three times, 4 weeks apart (at weeks 0, 4, and 8), followed by MVA wild type, 107 PFU, given 4 weeks after the third DNA (at week 12) (Kumar et al., 2003).
  • Challenge Protocol: Animals were challenged intramuscularly in the thigh muscle at 4 weeks after the last immunization with 2 × 105 viable M. tuberculosis strain NTI64719. This challenge dose was sufficient to cause measurable clinical illness in all control animals within a relatively short time frame of 6 weeks (Kumar et al., 2003).
  • Efficacy: A poxvirus recombinant expressing the Apa protein conferred a significant level of protective immunity in guinea pigs against a challenge dose of virulent M. tuberculosis (Kumar et al., 2003).

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 × 105 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 5x104 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 2x106 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 5x107 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.

Guinea pig Response

  • Host Strain: Hartley female guinea pigs
  • Vaccination Protocol: Hartley female guinea pigs (group 2) were vaccinated with BCG Tokyo (Sugawara et al., 2007).

Cattle Response

  • Host Strain: Friesian Calves
  • Vaccination Protocol: Vaccinated subcutaneously in the neck with 2 mL of 2X105 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 2X103 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 105 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 ~8X103 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).
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