Focus 1: Mechanistic Basis of Reservoir Targeting and Viral Persistence
We will seek to define signatures of viral persistence and rebound, and to define drivers of clonal expansion.
- Specific Aim 1: To define a virologic, immunologic, and transcriptomic signature of viral persistence and rebound and to determine how immunologic strategies target the viral reservoir in non-human primates and humans.
- Specific Aim 2: To define drivers of clonal expansion and persistence of the replication-competent viral reservoir in non-human primates and humans to enhance reservoir control and elimination.
Focus 2: Novel Strategies for Sustained Virus Remission
We will explore innovative immune engineering strategies to achieve sustained virus remission.
- Specific Aim 1: To evaluate innovative immune engineering strategies that provide long-term cellular or Env-directed immune control, including therapeutic vaccines, CAR-T cells, and engineered B cells.
- Specific Aim 2: To combine approaches that augment humoral and cellular immune responses to achieve sustained immunosurveillance and long-term ART-free virologic control.
Focus 3: Novel Strategies for Virus Eradication
We believe that combined immunologic strategies will likely be required to eliminate virally-infected cells.
- Specific Aim 1: To evaluate innovative strategies for rapid elimination of the majority of the viral reservoir, including improved LRAs combined with bNAbs, activated NK cells, and CAR-T cells.
- Specific Aim 2: To combine the most effective approach to rapidly eliminate the majority of the viral reservoir with sustained immunosurveillance to eliminate the residual viral reservoir.