The America’s SHIELD program application was submitted in response to a funding opportunity posted by the Advanced Research Projects Agency for Health (ARPA-H) in support of its Antigens Predicted for Broad Viral Efficacy through Computational Experimentation (APECx) Program. The primary awardee on the award is Erica Ollmann Saphire, PhD, Professor, President & CEO Center for Autoimmunity and Inflammation, Center for Cancer Immunotherapy, Center for Sex-based Differences in the Immune System, Center for Vaccine Innovation La Jolla Institute for Immunology (LJI). Co-PI is Jimmy Gollihar, PhD, Professor of Pathology and Genomic Medicine and Head of the Antibody Discovery & Accelerated Protein Therapeutics laboratory at Houston Methodist. Previous HHV vaccine efforts focused on one or more viral glycoproteins or complexes involved in entry, but HHVs have large DNA genomes encoding more than 10 surface glycoproteins and nearly 200 other genes for which we lack crucial information. The sheer number of possible vaccine antigens made traditional technologies untenable. In addition, it’s still unclear which conformations or combinations of these antigens are needed for robust immunity. The prior focus on neutralization of cell-free virus entry also ignores the needs of the >100 million Americans already latently infected who remain at risk of HHV-associated disease. Through the SHIELD program, researchers will develop an integrated sequence-, phylogeny-, structure-, and immunologically driven computational toolkit for antigen engineering with the potential to transform vaccine development against a myriad of pathogens with the potential to cause cancer. They will apply the toolkit to major public health and economic threats to Americans, the β- and γ-HHV.

“A critical and innovative aspect to our strategy is the targeting of antigens essential to multiple stages of the virus life cycle—beyond initial entry—to also include cell-to-cell spread, immune evasion and the latency and reactivation stages linked to cancer, autoimmune disease and other complications,” said Dr. Gollihar. By integrating advanced computational models, structural predictions, and immunological data, SHIELD will enable the rapid design and optimization of immunogens against a myriad of viruses, including those with high mutation rates or novel structures. This comprehensive approach will significantly impact immunogen design and facilitate rapid responses to known and emerging viral threats, potentially transforming vaccine development and therapeutic approaches targeting these dangerous pathogens.