Humanized DRAGA mice are a valuable model to study novel immunotherapies for HIV-1.

Abstract

Humanized (h) DRAGA mice are a promising in vivo model for investigating immunotherapies for treating HIV infections. These mice are not only susceptible to HIV infection, but they also develop functional human immune cells, including T cells and B cells, as well as follicular-like structures that mimic lymphoid B-cell follicles, where HIV-producing cells concentrate during infection in a manner similar to that found in humans. This study evaluated HIV-infected hDRAGA mice as a model for testing the safety, tissue targeting, and efficacy of HIV-specific CAR/CXCR5 T cells. We also evaluated whether HIV infection in hDRAGA mice can be suppressed by antiretroviral therapy. We produced functional HIV-specific CAR/CXCR5 T cells from disaggregated hDRAGA splenocytes and infused cell products into HIV-infected hDRAGA mice. CAR/CXCR5 T cells persisted in hDRAGA mice for the duration of the study, peaking 6 d postinfusion. Treatment with CAR/CXCR5 T cells appeared to be safe, with 100% survival rate and no noticeable changes in pathology. Six days after infusion, CAR/CXCR5 T cells had accumulated in the follicle-like structures in the spleen, with many in direct contact with HIV-producing cells. However, CAR/CXCR5 T-cell treatment did not reduce viral loads compared to controls, likely because CD4 T cells in the infused product became infected with and spread HIV infection. Despite this, all mice treated with antiretroviral therapy showed complete suppression of viral replication, indicating that HIV infection was treatment responsive in the DRAGA mice. These studies indicate that hDRAGA mice are a valuable model to study cellular immunotherapies for HIV.