Stage of Development

Proof of Concept – Animal Model

Vaccine Platform

Mycobacterial – Live Attenuated

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

Immune ResponseB-cell/Antibody
T-cell phenotypeCD4
T-cell functional profileCytolytic Capacity
B-cell/antibody characteristicsElicitation of B cell follicles, iBALT or GraLTiBALT
Preferential immune tissue localizationLung
Lymph node
Trained immunityYes

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.