Lm::Mtb9Ag
Candidate Overview
This TB vaccine candidate comprises a live attenuated Listeria monocytogenes vector with two major virulence gene deletions and a T-cell immunity enhancing mutation (Lm ΔactA ΔinlB prfA*) that expresses nine M. tuberculosis immunoprotective proteins (Mpt64, TB10.4, ESAT-6, CFP10, Ag85B, EsxN, PPE68, EspA, and TB8.4 – four absent from BCG) from two chromosomal fusion protein expression cassettes.
Sponsor / Lead Developer: University of California, Los Angeles (UCLA)
Primary Indication: Prevention of TB disease
Other Indication(s): Immunotherapy/Improving TB Cure Rates, Immunotherapy/Shortening TB treatment, Prevention of Mtb infection or sustained infection, and Prevention of TB recurrence
Target Population(s): Adolescents, Adults, Elderly, People without Mtb infection, and To be determined
Target Route of Administration: Subcutaneous
Immune tissue localization: Lung, Skin, and Spleen
Immunological responses: T-cell
Preclinical Animal Models: Guinea pig, Mouse, and Nonhuman primate
Intended to elicit trained immunity: Yes
Additional Immunologic Response Information
HYPOTHESIZED | DEMONSTRATED |
|
| Immune Response | T-cell | |
| T-cell phenotype | Gamma-delta (γδ) | CD4 CD8 |
| T-cell functional profile | Polycytotoxicity Cytolytic Capacity Mycobacterial growth inhibition | IFN-γ TNF-α |
| Preferential immune tissue localization | Lung Skin Spleen |
|
| Trained immunity | Yes |
Related Publications
Additional Information
Vaccine has demonstrated efficacy against M. tuberculosis aerosol challenge in BALB/c mice, C57BL/6 mice, and guinea pigs.
Vaccine administered subcutaneously is cleared rapidly (1 week) from skin, lungs, and spleen of mice and guinea pigs.
Vaccine can be inexpensively grown overnight in simple broth culture without the need for extensive purification.
Parent vector (Lm ΔactA ΔinlB) has demonstrated safety in humans in multiple clinical studies.