MtbDsigH
Candidate Overview
The parental candidate is an isogenic mutant in Mtb CDC1551 gene Rv3223c (sigH). We have now generated multiple Mtb double and triple knock-out (DKO, TKO) strains including:
1. DsigHDsecA2DsodA
2. DsigHDfbpADsapM
3. DsigHDleuCDpanCD
4. DsigHDmetA
5. DsigHDmce4EDmce4F
6. DsigHDfadD29
7. DsigHDhadC
8. DsigHDRv3683
9. DsigHDmce1A
10. DsigHDcobM
Sponsor / Lead Developer: Tulane University and Texas Biomedical Research Institute
Development partner(s): NIH, BMGF
Primary Indication: Prevention of Mtb infection or sustained infection
Other Indication(s): Prevention of TB disease
Target Population(s): Adolescents, Adults, Children, and Infants
Target Route of Administration: Aerosol
Immune tissue localization: Lung and Lymph node
Immunological responses: B-cell/Antibody and T-cell
Preclinical Animal Models: Nonhuman primate
Intended to elicit trained immunity: Yes
Additional Immunologic Response Information
HYPOTHESIZED | DEMONSTRATED |
|
| Immune Response | B-cell/Antibody T-cell |
|
| T-cell phenotype | CD4 CD8 |
|
| T-cell functional profile | Cytolytic Capacity Polycytotoxicity | IFN-γ TNF-α IL-17 |
| B-cell/antibody characteristics | Elicitation of B cell follicles, iBALT or GraLT | iBALT |
| Preferential immune tissue localization | Lung Lymph node |
|
| Trained immunity | Yes | |
Related Publications
- Nonpathologic Infection of Macaques by an Attenuated Mycobacterial Vaccine Is Not Reactivated in the Setting of HIV Co-Infection. (Am J Pathol., 2017)
- Mucosal vaccination with attenuated Mycobacterium tuberculosis induces strong central memory responses and protects against tuberculosis (Nat Commun., 2015)
Additional Information
We have previously demonstrated efficacy of mucosally delivered MtbDsigH in protecting rhesus macaques against lethal TB challenge. We now have data (in review) that mucosally delivered MtbDsigH also protects cynomolgus macaques against similar challenge. We have now generated 10 DKO/TKO strains derived from MtbDsigH for preclinical and clinical development.