Friday, April 26, 2024 4/26/2024

A nonhuman primate model to study the immunological effects of feminizing hormone therapy in transgender women

Award Number: R21AI157929
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By Issue Date FY or Funding FY:

View Award Abstract

HIV/AIDS thrives in the margins of society, where low education, unstable housing, and poverty heighten people's vulnerability to HIV. No population is more affected by these social injustices than transgender persons. A case in point is transgender women (TGW}-individuals who were assigned a male sex at birth but express their gender along a feminine spectrum. Sadly, TGW have some of the highest concentrated HIV epidemics in the world, with a pooled global prevalence of 19% and a 49-fold higher odds ratio of acquiring HIV than non-transgender adults. A key part of gender affirmation in TGW is feminizing hormone therapy (FHT), of which the main drug is the hormone estradiol. Although the physical female traits triggered by FHT are well established, less is known about the immunological effects of FHT in TGW. It is noteworthy that estradiol can modulate immune responses in many ways, including by upregulating CCR5 expression on CD4+ T-cells. Since activated CCR5+ CD4+ T-cells are highly permissive to HIV infection, a better understanding of how FHT impacts the male immune system may provide new insights into how to prevent HIV infection in TGW. In this regard, here we will model FHT in nonhuman primates to prospectively address two knowledge gaps about the impact of FHT on the male immune system. 1) Does FHT increase the availability of HIV-susceptible CD4+ T-cells in vivo? To answer this question, we will use flow cytometry to assess the frequency and phenotype of memory CD4+ Teens in blood and gut biopsies from male rhesus macaques receiving FHT (Group 1) or placebo (Group 2). By comparing the levels of activated CD4+ T-cells between animals in Groups 1 and 2, this analysis will reveal whether FHT modulates a crucial marker of HIV susceptibility in biological males. 2) Does FHT interfere with adeno-associated virus (AAV}-vectored immunoprophylaxis? Considering TGW's high risk of acquiring HIV, they stand to benefit greatly from AAV-mediated delivery of immunoglobulins as this approach can provide durable anti-HIV immunity after a one-time administration. Indeed, a single dose of an AAV vector encoding the potent and extremely broad HIV entry inhibitor eCD4-lg resulted in persistent expression of eCD4-lg and protection against stringent immunodeficiency virus challenges in rhesus macaques. However, given the immunoenhancing properties of estradiol, FHT may undermine AAV-driven eCD4-lg expression in TGW by amplifying host anti-drug antibodies (ADAs}-a major limiting factor for AAV delivery of biologics. To address this possibility, all animals in Groups 1 and 2 will be inoculated with AAV/eCD4-lg after 6 months of FHT or placebo therapy. We will then compare their serum levels of eCD4-lg and ADAs to determine the impact of FHT on AAV-mediated delivery of eCD4-lg in males. Ultimately, the experiments proposed here will begin to uncover how FHT can affect HIV susceptibility and the outcome of immune interventions in TGW.


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 = -$13,658 )
2024	2022	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Allergy and Infectious Diseases Research	000	3	10/23/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$13,658
														Subtotal = -$13,658

Issue Date FY: 2022 ( Subtotal = $204,495 )
2022	2022	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Allergy and Infectious Diseases Research	002	3	5/12/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$24,080
2022	2022	SCRIPPS RESEARCH INSTITUTE, THE	130 SCRIPPS WAY	JUPITER	FL	33458	PALM BEACH	USA	Allergy and Infectious Diseases Research	000	2	11/15/2021	NON-COMPETING CONTINUATION	$205,562
2022	2022	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Allergy and Infectious Diseases Research	005	3	8/29/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$208,991
2022	2022	SCRIPPS RESEARCH INSTITUTE, THE	130 SCRIPPS WAY	JUPITER	FL	33458	PALM BEACH	USA	Allergy and Infectious Diseases Research	001	2	5/12/2022	NON-COMPETING CONTINUATION	-$25,147
2022	2022	SCRIPPS RESEARCH INSTITUTE, THE	130 SCRIPPS WAY	JUPITER	FL	33458	PALM BEACH	USA	Allergy and Infectious Diseases Research	004	2	8/29/2022	NON-COMPETING CONTINUATION	-$180,415
2022	2022	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Allergy and Infectious Diseases Research	006	3	8/31/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2022	2021	SCRIPPS RESEARCH INSTITUTE, THE	130 SCRIPPS WAY	JUPITER	FL	33458	PALM BEACH	USA	Allergy and Infectious Diseases Research	003	1	8/29/2022	NEW	-$28,576
														Subtotal = $204,495

Issue Date FY: 2021 ( Subtotal = $272,626 )
2021	2021	SCRIPPS RESEARCH INSTITUTE, THE	130 SCRIPPS WAY	JUPITER	FL	33458	PALM BEACH	USA	Allergy and Infectious Diseases Research	000	1	11/24/2020	NEW	$272,626
														Subtotal = $272,626

Grand Total All Awards = $463,463

Top

All Categories

About

Search

Reports

Data Submission

Award Information

A nonhuman primate model to study the immunological effects of feminizing hormone therapy in transgender women

Award Number: R21AI157929

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer