BCG w/MK-2206

Stage of Development

Proof of Concept – Animal Model

Vaccine Platform

Mycobacterial – Inactivated

Candidate Overview

Parental BCG efficacy is mainly hampered by its low induction of apoptosis along with high secretion of the immunosuppressive cytokine IL-10. We found that the host transcription factor FOXO3 mediates both, BCG-induced apoptosis and inhibition of IL-10 secretion. The novel vaccination procedure consists of induction of FOXO3 activity, during BCG vaccination, using an anti-cancer drug, the AKt inhibitor MK-2206.

Sponsor / Lead Developer: Institut Pasteur de Tunis (IPT)

Development partner(s): Translational Health Science and Technology Institute (THSTI)

Primary Indication: Prevention of Mtb infection or sustained infection

Other Indication(s): Prevention of TB disease

Target Population(s): Adolescents, Adults, Children, Infants, and To be determined

Target Route of Administration: Intradermal

Immune tissue localization: Lung and Lymph node

Immunological responses: Other and T-cell

Preclinical Animal Models: Guinea pig and Mouse

Intended to elicit trained immunity: Yes

Additional Immunologic Response Information

Immune ResponseMacrophagesT-cell
T-cell phenotypeCD4
Effector and Central Memory T Cells
T-cell functional profilePolycytotoxicity
Mycobacterial growth inhibition
Preferential immune tissue localizationLung
Lymph node
Trained immunityYes

Additional Information

Animals (mice and guinea pigs) were vaccinated with the parental BCG. Twenty four hours later, MK-2206 was administrated at the same site of BCG vaccination (intradermal). Animals receiving MK-2206 were more protected than the ones receiving BCG alone.