With 34 million people currently living with HIV worldwide, developing a modality to induce an HIV functional cure is a top global health priority. We have recently discovered that 1) broadly neutralizing antibodies are able to potently eliminate the viral reservoir, and 2) that an IL-15 superagonist, ALT-803, is able to both reverse viral latency and activate natural killer cells in vivo. Therefore, we hypothesize that combining ALT-803 with broadly neutralizing antibodies under cover of cART can clear the latent reservoir. To investigate this intriguing idea, in specific aim 1 of the R21, we will establish the ability of ALT-803 to reactivate latent virus in the macaque model of HIV.
In specific aim 2, we will determine if ALT-803 activated NK cells can mediate antibody- dependent cell-mediated cytotoxicity on infected cells. If successful, we will combine ALT-803 with broadly neutralizing antibodies under cover of cART in the R33 phase. Successful completion of these studies could define an entirely new approach to clearing the latent reservoir.

Public Health Relevance

Although antiretroviral drugs can reduce peripheral HIV replication, these drugs are not curative and we currently have the most people ever in history infected. Therefore, an approach to induce a functional HIV cure is desperately needed. Here, we propose to test a novel combination of HIV-specific broadly neutralizing antibodies and an IL-15 superagonist to both reverse viral latency and activate NK cells in order to purge the latent reservoir.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants Phase II (R33)
Project #
5R33AI128970-04
Application #
10083693
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Poon, Betty
Project Start
2018-01-01
Project End
2022-12-31
Budget Start
2021-01-01
Budget End
2021-12-31
Support Year
4
Fiscal Year
2021
Total Cost
Indirect Cost
Name
Oregon Health and Science University
Department
Type
Overall Medical
DUNS #
096997515
City
Portland
State
OR
Country
United States
Zip Code
97239