R01AI184623
Project Grant
Overview
Grant Description
Mechanisms of efficient control of Mycobacterium tuberculosis in the lungs prior to granuloma - Project summary/abstract.
Novel vaccination strategies are necessary to contain the TB pandemic, as the currently licensed anti-tubercular vaccine, Bacille Calmette-Guerin (BCG), has limited and variable efficacy.
Attenuated, live-replicating Mycobacterium tuberculosis (MTB) express the full complement of protective antigens not present in BCG.
As a result, these strains are most likely to induce long-lived immune responses and generate durable protection.
Rhesus macaques vaccinated with an isogenic MTB mutant in the allele encoding the stress-response master regular SIGH (DSIGH) were protected from TB after infection with a lethal dose of MTB, and characterized by the presence of inducible bronchus associated lymphoid tissue (iBALT) and robust T cell responses in the lungs.
Protection by DSIGH could be reversed by the depletion of CD20+ B cells which ablates iBALT.
Protection with DSIGH was validated in cynomolgus macaques, a second NHP species used as a model for TB vaccination.
Preliminary data presented in this proposal indicates that protection elicited by DSIGH is based on the generation of very early, potent, innate immune responses in the lung that drive rigorous immune dynamics and interactions.
We propose to use cutting-edge techniques that our group has optimized, such as single cell RNA sequencing in airways and lungs, PET/CT scans of whole animals and single cell imaging, to fully understand elite lung responses generated by DSIGH compared to MTB.
Our proposed work will not only provide in-depth knowledge of immune responses generated by a potential human intervention for TB, but also identify mechanisms by which MTB infection can be sterilized prior to the formation of the granuloma.
Novel vaccination strategies are necessary to contain the TB pandemic, as the currently licensed anti-tubercular vaccine, Bacille Calmette-Guerin (BCG), has limited and variable efficacy.
Attenuated, live-replicating Mycobacterium tuberculosis (MTB) express the full complement of protective antigens not present in BCG.
As a result, these strains are most likely to induce long-lived immune responses and generate durable protection.
Rhesus macaques vaccinated with an isogenic MTB mutant in the allele encoding the stress-response master regular SIGH (DSIGH) were protected from TB after infection with a lethal dose of MTB, and characterized by the presence of inducible bronchus associated lymphoid tissue (iBALT) and robust T cell responses in the lungs.
Protection by DSIGH could be reversed by the depletion of CD20+ B cells which ablates iBALT.
Protection with DSIGH was validated in cynomolgus macaques, a second NHP species used as a model for TB vaccination.
Preliminary data presented in this proposal indicates that protection elicited by DSIGH is based on the generation of very early, potent, innate immune responses in the lung that drive rigorous immune dynamics and interactions.
We propose to use cutting-edge techniques that our group has optimized, such as single cell RNA sequencing in airways and lungs, PET/CT scans of whole animals and single cell imaging, to fully understand elite lung responses generated by DSIGH compared to MTB.
Our proposed work will not only provide in-depth knowledge of immune responses generated by a potential human intervention for TB, but also identify mechanisms by which MTB infection can be sterilized prior to the formation of the granuloma.
Funding Goals
NOT APPLICABLE
Grant Program (CFDA)
Awarding / Funding Agency
Place of Performance
San Antonio,
Texas
782275302
United States
Geographic Scope
Single Zip Code
Related Opportunity
Analysis Notes
Amendment Since initial award the total obligations have increased 257% from $1,091,124 to $3,898,156.
Texas Biomedical Research Institute was awarded
Elite Lung Responses TB Control: Mechanisms Vaccination Strategies
Project Grant R01AI184623
worth $3,898,156
from the National Institute of Allergy and Infectious Diseases in July 2024 with work to be completed primarily in San Antonio Texas United States.
The grant
has a duration of 4 years 10 months and
was awarded through assistance program 93.855 Allergy and Infectious Diseases Research.
The Project Grant was awarded through grant opportunity Analyzing Early Events in TB and TB/HIV Infection for Interventional Targets (R01 Clinical Trial Not Allowed).
Status
(Ongoing)
Last Modified 7/6/26
Period of Performance
7/9/24
Start Date
5/31/29
End Date
Funding Split
$3.9M
Federal Obligation
$0.0
Non-Federal Obligation
$3.9M
Total Obligated
Activity Timeline
Subgrant Awards
Disclosed subgrants for R01AI184623
Transaction History
Modifications to R01AI184623
Additional Detail
Award ID FAIN
R01AI184623
SAI Number
R01AI184623-4110660516
Award ID URI
SAI UNAVAILABLE
Awardee Classifications
Nonprofit With 501(c)(3) IRS Status (Other Than An Institution Of Higher Education)
Awarding Office
75NM00 NIH National Institute of Allergy and Infectious Diseases
Funding Office
75NM00 NIH National Institute of Allergy and Infectious Diseases
Awardee UEI
J4EYPCJDQ1H6
Awardee CAGE
02MD3
Performance District
TX-20
Senators
John Cornyn
Ted Cruz
Ted Cruz
Modified: 7/6/26