Wednesday, January 15, 2025 1/15/2025

A nonhuman primate model of stem cell transplantation to understand determinants of post-transplant SIV clearance

Award Number: R01AI129703
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY With the most people ever in history currently living with HIV, stopping the HIV epidemic remains imperative. Combination antiretroviral therapy (ART) limits viral replication, but is not curative. Thus, there is an urgent need to design a functional cure via elimination of the viral reservoir. Timothy Brown, aka the Berlin Patient, and Adam Castillejo, aka the London patient, were cured of HIV following leukemia-related, MHC-matched, allogeneic hematopoietic stem cell transplantation (HSCT) from a CCR5-deficient donor. Using our allogeneic HSCT model in Mauritian cynomolgus macaque (MCM), we have demonstrated that the allogeneic immune response can potently purge the latent reservoir, but is ultimately insufficient due to susceptibility to infection. This underscores the need for CCR5 deficient donors to fully eradicate HIV in the setting of HSCT. During the course of our previous studies we have demonstrated that the CCR5-specific antibody Leronlimab can mimic a CCR5 deficient donor by occupying all available CCR5 molecules. We are now proposing to utilize Leronlimab in the setting of allogeneic HSCT to definitely demonstrate the mechanism by which CCR5 deficiency achieves HIV cure. In specific aim 1, we will measure the effect and determine the mechanism of Leronlimab administration during the peri-transplant period in SHIV-infected, ART-suppressed MCM undergoing allogeneic HSCT. In specific aim 2, we will measure if Leronlimab administered during the peri-transplant period in an HIV+ patient undergoing allogenic HSCT for cancer treatment can replicate a CCR5-deficient donor and mediate an HIV cure. This work would expand our knowledge of the mechanism of HIV cure in the setting of allogeneic HSCT and establish a new therapeutic treatment for HIV cure.


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: 2024 ( Subtotal = $874,173 )
2024	2024	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Allergy and Infectious Diseases Research	000	8	6/14/2024	NON-COMPETING CONTINUATION	$874,173
														Subtotal = $874,173

Issue Date FY: 2023 ( Subtotal = $874,173 )
2023	2023	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Allergy and Infectious Diseases Research	003	7	6/21/2023	NON-COMPETING CONTINUATION	$874,173
2023	2022	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Allergy and Infectious Diseases Research	000	6	11/17/2022	COMPETING CONTINUATION	$0
2023	2022	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Allergy and Infectious Diseases Research	002	6	3/23/2023	COMPETING CONTINUATION	$85,713
2023	2021	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Allergy and Infectious Diseases Research	001	5	3/23/2023	NON-COMPETING CONTINUATION	-$85,713
														Subtotal = $874,173

Issue Date FY: 2022 ( Subtotal = $837,954 )
2022	2022	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Allergy and Infectious Diseases Research	001	6	7/12/2022	COMPETING CONTINUATION	$837,954
2022	2021	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Allergy and Infectious Diseases Research	000	5	6/29/2022	NON-COMPETING CONTINUATION	$0
														Subtotal = $837,954

Issue Date FY: 2021 ( Subtotal = $950,729 )
2021	2021	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Allergy and Infectious Diseases Research	000	5	11/20/2020	NON-COMPETING CONTINUATION	$950,729
														Subtotal = $950,729

Issue Date FY: 2020 ( Subtotal = $946,593 )
2020	2020	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Allergy and Infectious Diseases Research	000	4	11/21/2019	NON-COMPETING CONTINUATION	$785,596
2020	2020	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Allergy and Infectious Diseases Research	001	4	7/21/2020	NON-COMPETING CONTINUATION	$160,997
														Subtotal = $946,593

Issue Date FY: 2019 ( Subtotal = $796,277 )
2019	2019	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Allergy and Infectious Diseases Research	000	3	11/20/2018	NON-COMPETING CONTINUATION	$796,277
														Subtotal = $796,277

Issue Date FY: 2018 ( Subtotal = $825,078 )
2018	2018	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Allergy and Infectious Diseases Research	001	2	7/3/2018	NON-COMPETING CONTINUATION	-$38,706
2018	2018	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Allergy and Infectious Diseases Research	000	2	11/22/2017	NON-COMPETING CONTINUATION	$863,784
														Subtotal = $825,078

Issue Date FY: 2017 ( Subtotal = $851,904 )
2017	2017	OREGON HEALTH & SCIENCE UNIVERSITY	3181 SW SAM JACKSON PARK RD	PORTLAND	OR	97239	MULTNOMAH	USA	Allergy and Infectious Diseases Research	000	1	12/21/2016	NEW	$851,904
														Subtotal = $851,904

Grand Total All Awards = $6,956,881

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A nonhuman primate model of stem cell transplantation to understand determinants of post-transplant SIV clearance

Award Number: R01AI129703

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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