Federal Grant Award Summary

Case Western Reserve University received a $282,757 Project Grant award from the National Institute of Allergy and Infectious Diseases under the Allergy and Infectious Diseases Research program (CFDA 93.855) effective April 1, 2026, through March 31, 2028. The award supports computational and experimental development of novel human monoclonal antibodies (MAbs) targeting Plasmodium vivax (PV), a parasitic pathogen responsible for malaria infections. The research leverages large language models and computational protein design tools (RFDiffusion, PyRosetta, and MPNN) to generate and optimize MAb scaffolds targeting PV invasion ligands and circumsporozoite protein variants (VK210 and VK247). The project encompasses three design approaches: enhancing existing MAbs based on HUMAB826827 and MAb864865, designing novel MAbs, and optimizing current candidates for improved production efficiency, binding specificity, conformational stability, and reduced immunogenicity.

The award's research deliverables include computational generation of approximately 1,000 MAb scaffolds per target epitope, in vitro testing of enhanced and novel MAb candidates using PV clinical isolates, and collaboration with a research network in Cambodia for experimental validation. This computational approach circumvents traditional bottlenecks associated with isolating peripheral blood mononuclear cells from PV-infected individuals, thereby accelerating MAb development for both liver-stage and blood-stage infection prevention. The project adapts methodologies previously employed in cancer therapeutics optimization to address the substantial global health burden of relapsing malaria parasites.