Compositions and methods for treating bacterial infections

Patent metadata

Field	Value
Publication number	US-11865168-B2
Application number	US-202017137481-A
Country	US
Kind code	B2
Filing date	Dec 30, 2020
Priority date	Dec 30, 2019
Publication date	Jan 9, 2024
Grant date	Jan 9, 2024

Abstract

Provided herein are compositions and methods for therapeutic and/or prophylactic treatment of an intracellular bacterial infection in a subject in need thereof, comprising one or more modulating agents, wherein the one or more modulating agents increase expression of IFNγ, IL-2, TNF, and/or IL-17 in systemic and/or lung T cells. In some embodiments, the increase of expression of IFNγ, IL-2, TNF, and/or IL-17 occurs in lung T cells. The lung T cells can be lung resident T cells or systemic T cells that are recruited to the lung. In some embodiments, the T cells are CD4+ and/or CD8+ T cells. In some embodiments, the intracellular bacterial infection is a Mycobacterium tuberculosis (MTB) infection.

First claim

What is claimed is:

1. A method of eliciting an enhanced immune response comprising administering intravenously (IV) to a subject in need of prophylactic treatment of Mycobacterium tuberculosis (MTB) a pharmaceutical formulation comprising one or more modulating agents and Bacille Calmette-Guerin (BCG), wherein the one or more modulating agents are selected from the group consisting of an RNA encoding one or more MTB antigens selected from Ag85A and Ag85B, a viral vector encoding one or more MTB antigens selected from Ag85A and Ag85B, and one or more MTB antigens selected from Ag85A and Ag85B, and wherein the one or more modulating agents increase expression of IFNγ, IL-2, TNF, and/or IL-17 in systemic and/or lung T cells; and
confirming an enhanced immune response was elicited in the subject, thereby providing an enhanced immune response for prophylactic treatment, by:
detecting an increased fractional or absolute number of Vγ9 + γδ T cells in a blood sample obtained from the subject; or
detecting an increased proportion of transitional (Ttm) memory cells compared to Central (Tcm) memory cells in a blood sample obtained from the subject.

2. The method of claim 1 , wherein the viral vector is an attenuated viral vector.

Assignees

• Massachusetts Inst Technology
• The Us Secretary Department Of Health & Human Services
• Univ Of Pittsburgh—Of The Commonwealth System Of Higher Education

Inventors

• Shalek Alexander K
• Hughes Travis
• Wadsworth Marc H
• Seder Robert
• Roederer Mario
• Flynn Joanne L
• Darrah Patricia

Classifications

• A61K39/04 Primary

  Mycobacterium, e.g. Mycobacterium tuberculosis · CPC title

• A61P31/06 Primary

  for tuberculosis · CPC title

• A61K2039/54

  characterised by the route of administration · CPC title

• A61K39/39

  characterised by the immunostimulating additives, e.g. chemical adjuvants · CPC title

• A61K2039/55594

  from bacteria · CPC title