Project Grant R01AI203609

The National Institute of Allergy and Infectious Diseases awarded the Trustees of Indiana University $370,835 on August 18, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to develop a computational framework for analyzing HIV immune escape across viral diversity.

The funded research addresses a critical gap in HIV immunology: the lack of a rigorous computational approach capable of distinguishing universal, robust escape mechanisms from noise caused by subtype-specific sampling and cohort bias. Current escape signatures often fail to generalize across HIV's genetic diversity, yielding fragmented, non-reproducible findings that resist translation into rational immunogen design or cure strategies. The project reframes HIV immune escape analysis as "generalization-first" science, treating robustness and uncertainty as primary scientific endpoints rather than post-hoc validation steps.

Work proceeds through three aims. Aim 1 constructs a foundational computational substrate delivering interpretable, epitope-level representations of immune escape explicitly annotated with calibrated uncertainty diagnostics and cross-clade generalization benchmarks. Aim 2 establishes an in silico evolutionary laboratory, treating immune pressure as a manipulable engineering variable to map the "virtual resistance landscape," identify evolutionary tipping points, and distinguish dead-end targets from accessible escape routes. Aim 3 bridges the gap between molecular virology and population-level dynamics. Performance occurs at Woodbridge, Indiana, with a period of performance through July 31, 2031.