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Vaccine Detail

MVA/IL-15/5Mtb vaccine
Vaccine Information
  • Vaccine Name: MVA/IL-15/5Mtb vaccine
  • Target Pathogen: Mycobacterium tuberculosis
  • Target Disease: Tuberculosis
  • 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
    • Description:
    • Detailed Gene Information: Click Here.
  • Ag85B from M. tuberculosis H37Rv gene engineering:
    • Type: Recombinant vector construction
    • Description:
    • Detailed Gene Information: Click Here.
  • EsxA (ESAT-6) gene engineering:
    • Type: Recombinant vector construction
    • Description:
    • Detailed Gene Information: Click Here.
  • Adjuvant:
  • Immunization Route: subcutaneous injection
Host Response

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.
  • Information about this animal model: Mouse Model for TB research
References
Kolibab et al., 2010: Kolibab K, Yang A, Derrick SC, Waldmann TA, Perera LP, Morris SL. Highly persistent and effective prime/boost regimens against tuberculosis that use a multivalent modified vaccine virus Ankara-based tuberculosis vaccine with interleukin-15 as a molecular adjuvant. Clinical and vaccine immunology : CVI. 2010; 17(5); 793-801. [PubMed: 20357059].