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Cytomegalovirus as a risk factor for exacerbation of Mycobacterium tuberculosis infection

Award Number: R21AI146442
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 11/01/2021
PERIOD OF PERFORMANCE END DATE: 03/31/2024

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Cytomegalovirus as a risk factor for exacerbation of Mycobacterium tuberculosis infection - SUMMARY Mycobacterium tuberculosis is a worldwide public health problem, and the need to develop new vaccines to prevent further deaths is critical. However, vaccine development is hindered by the difficulty of translating pre- clinical animal model data to human trials. There may be multiple factors associated with the difference in outcomes between pre-clinical and clinical settings. Of significant interest is the role that co-infections play in mediating immunity to M. tuberculosis infection and how these co-infections increase the risk of developing tuberculosis disease. Co-infections, such as with human Cytomegalovirus virus (HCMV), are important drivers of immune activation in HIV, particularly in sub-Saharan Africa. HCMV associated immune activation in the HIV exposed is known to drive CD4+ T cell decline, hasten immuno-senescence and lead to eventual immune exhaustion. There also emerging evidence to support the fact that HCMV plays a significant role in exacerbating tuberculosis disease in immunocompetent individuals, thus it is important to investigate the interaction between these pathogens and how they mediate the immunity. The current proposal is designed to develop an in vivo experimental co-infection in mice with M. tuberculosis and Cytomegalovirus and with M. tuberculosis. Thus the primary focus of this application is to develop a mouse model to investigate the role of co-infection in the immune mechanisms required to kill M. tuberculosis, and once these have been identified can we start to understand better how to make effective TB vaccines. We will focus on cytomegalovirus co-infection during M. tuberculosis infection to determine how it contributes to exacerbation of TB disease using a mouse model. We will develop the model to understand innate and adaptive immune responses during co-infection (Aim 1), test the hypothesis that excessive reactive species contribute to TB disease using a Type I interferon independent mechanism (Aim 2) and determine how infection with each pathogen interacts with neighboring cells and determine if CMV infection of macrophages and dendritic cells skews development of macrophages towards an M2 or suppressive phenotype resulting in poor adaptive immunity to M. tuberculosis in-vitro. (Aim 3). These studies will provide the basis for future model development to identify mechanisms that may interfere with the efficacy of new and existing anti-tuberculosis vaccines.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = -$48 )
2025	2021	UNIVERSITY OF SYDNEY	RESEARCH OFFICE MAIN QUADRANGLE A14	THE UNIVERSITY OF SYDNEY				AUS	Allergy and Infectious Diseases Research	000	3	10/29/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$48
														Subtotal = -$48

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2021	UNIVERSITY OF SYDNEY	LEVEL 3, ADMINISTRATION BUILDING F23	THE UNIVERSITY OF SYDNEY	NSW			AUS	Allergy and Infectious Diseases Research	000	3	4/17/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2021	COLORADO STATE UNIVERSITY	601 S HOWES ST	FORT COLLINS	CO	80521	LARIMER	USA	Allergy and Infectious Diseases Research	002	2	3/10/2022	NON-COMPETING CONTINUATION	$20,890
2022	2021	UNIVERSITY OF SYDNEY	LEVEL 3, ADMINISTRATION BUILDING F23	THE UNIVERSITY OF SYDNEY	NSW			AUS	Allergy and Infectious Diseases Research	007	3	3/22/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$116,597
2022	2021	UNIVERSITY OF SYDNEY	LEVEL 3, ADMINISTRATION BUILDING F23	THE UNIVERSITY OF SYDNEY	NSW			AUS	Allergy and Infectious Diseases Research	005	3	3/18/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$156,390
2022	2021	COLORADO STATE UNIVERSITY	601 S HOWES ST	FORT COLLINS	CO	80521	LARIMER	USA	Allergy and Infectious Diseases Research	004	2	3/18/2022	NON-COMPETING CONTINUATION	-$39,793
2022	2021	UNIVERSITY OF SYDNEY	LEVEL 3, ADMINISTRATION BUILDING F23	THE UNIVERSITY OF SYDNEY	NSW			AUS	Allergy and Infectious Diseases Research	006	3	3/21/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$116,597
2022	2021	COLORADO STATE UNIVERSITY	601 S HOWES ST	FORT COLLINS	CO	80521	LARIMER	USA	Allergy and Infectious Diseases Research	001	2	11/11/2021	NON-COMPETING CONTINUATION	-$116,597
2022	2021	UNIVERSITY OF SYDNEY	LEVEL 3, ADMINISTRATION BUILDING F23	THE UNIVERSITY OF SYDNEY	NSW			AUS	Allergy and Infectious Diseases Research	008	3	4/1/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2022	2021	UNIVERSITY OF SYDNEY	LEVEL 3, ADMINISTRATION BUILDING F23	THE UNIVERSITY OF SYDNEY	NSW			AUS	Allergy and Infectious Diseases Research	000	3	11/4/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$95,707
2022	2020	COLORADO STATE UNIVERSITY	601 S HOWES ST	FORT COLLINS	CO	80521	LARIMER	USA	Allergy and Infectious Diseases Research	003	1	3/18/2022	NEW	-$116,597
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $135,500 )
2021	2021	COLORADO STATE UNIVERSITY	601 S HOWES ST	FORT COLLINS	CO	80521	LARIMER	USA	Allergy and Infectious Diseases Research	000	2	3/15/2021	NON-COMPETING CONTINUATION	$135,500
														Subtotal = $135,500

Issue Date FY: 2020 ( Subtotal = $235,000 )
2020	2020	COLORADO STATE UNIVERSITY	601 S HOWES ST	FORT COLLINS	CO	80521	LARIMER	USA	Allergy and Infectious Diseases Research	000	1	4/1/2020	NEW	$235,000
														Subtotal = $235,000

Grand Total All Awards = $370,452

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Cytomegalovirus as a risk factor for exacerbation of Mycobacterium tuberculosis infection

Award Number: R21AI146442

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 11/01/2021

PERIOD OF PERFORMANCE END DATE: 03/31/2024

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