Disclosed herein are immunogenic compositions (e.g., vaccines) for use in the treatment of mycobacteria infections and biomarkers for monitoring of therapeutic responsiveness to the immunogenic compositions in a subject (e.g., a human). In a first aspect, the disclosure features a pharmaceutical composition containing between 1×10{circumflex over ( )}2 CPU and 1×10{circumflex over ( )}10 CPU of a Mycobacterium tuberculosis strain (Mtb) with one or more mutations that ablate or reduce expression of LprG and Rv1410 (ΔLprG Mtb) in a volume of between 0.05 mL and 3 mL.

Disclosed herein are immunogenic compositions (e.g., vaccines) for use in the treatment of mycobacteria infections and biomarkers for monitoring of therapeutic responsiveness to the immunogenic compositions in a subject (e.g., a human). In a first aspect, the disclosure features a pharmaceutical composition containing between 1×10{circumflex over ( )}2 CPU and 1×10{circumflex over ( )}10 CPU of a Mycobacterium tuberculosis strain (Mtb) with one or more mutations that ablate or reduce expression of LprG and Rv1410 (ΔLprG Mtb) in a volume of between 0.05 mL and 3 mL.

The present disclosure relates to compositions and therapeutic methods for activating an immune response in a patient in need thereof. In a preferred embodiment, the subject methods and compositions are able to antagonize the activity of VISTA, a naturally occurring “checkpoint” protein which contributes to immune tolerance, optionally in combination with an antagonist of a second checkpoint pathway such as PD-1. For example, such methods and compositions may be suitable for preventing and treating colon cancer or another cancer. An exemplary VISTA antagonist, specifically, an anti-VISTA antibody, is demonstrated herein to activate an immune response against cancer cells in vitro and in vivo, thereby conferring protective anti-tumor immunity which decreased tumor burden. Additionally, an additive benefit was observed when a VISTA antagonist was used in combination with a second checkpoint protein antagonist, specifically, an antibody against PD-1 ligand (PD-L1).

Provided herein are methods and compositions, including synergistic combinations, for the treatment of tuberculosis.

Provided herein are methods and compositions, including synergistic combinations, for the treatment of tuberculosis.

Anti-tubercular compounds include trisubstituted indolizines having the following structural formula: ##STR00001##
wherein R.sup.1 is selected from the group consisting of 4-OCH.sub.3, 4-Cl, 4-Br, 4-F, 2-NO.sub.2, 3,5-CF.sub.3, CN, CH.sub.3, R.sup.2 is COOCH.sub.3, COOC.sub.2H.sub.5, and R.sup.3 is H and COOCH.sub.3.

Anti-tubercular compounds include trisubstituted indolizines having the following structural formula: ##STR00001##
wherein R.sup.1 is selected from the group consisting of 4-OCH.sub.3, 4-Cl, 4-Br, 4-F, 2-NO.sub.2, 3,5-CF.sub.3, CN, CH.sub.3, R.sup.2 is COOCH.sub.3, COOC.sub.2H.sub.5, and R.sup.3 is H and COOCH.sub.3.

Provided herein are compounds of Formula (I) and Formula (II) as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of tuberculosis.

##STR00001##

Provided herein are compounds of Formula (I) and Formula (II) as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of tuberculosis.

##STR00001##

The present invention provides shortening TB Therapy and reducing relapse by co-administering Chloroquine with anti-TB drugs to drug-sensitive TB patients, multiple drug resistant (MDR) TB patients and TB patients co-infected with HIV-1. The present invention also provides shortening TB Therapy and reducing relapse by co-administering hydroxychloroquine with anti-TB drugs to drug-sensitive TB patients, multiple drug resistant (MDR) TB patients and TB patients co-infected with HIV-1.