Houston Methodist researchers will be part of a national consortium funded by an up to $49 million award from the U.S. Government's Advanced Research Projects Agency for Health (ARPA-H) to develop a vaccine against two of the most common and destructive strains of herpesviruses that latently infect a majority of Americans and can lead to acute infections, multiple forms of cancer, autoimmune disease and birth defects.
The award is part of ARPA-H's Antigens Predicted for Broad Viral Efficacy through Computational Experimentation (APECx) program and will fund the America's SHIELD project to develop prophylactic and therapeutic vaccines against the β- and γ- herpesviruses. Through the SHIELD (Strategic Herpesvirus Immune Evasion and Latency Defense) program, researchers will develop an integrated computational toolkit for antigen engineering with the potential to transform vaccine development against a myriad of pathogens.
These two herpesvirus subfamilies include human cytomegalovirus and Epstein-Barr virus, respectively, which clinically impact the largest proportion of the U.S. population, dormantly infecting Americans at an annual cost of at least $4 billion.
Epstein-Barr causes significant disease in adolescents and young adults as the cause of mono and also can later cause lymphomas, gastric and nasopharyngeal cancer, multiple sclerosis and diseases like non-Hodgkin's lymphoma and certain leukemias in transplant patients. The human cytomegalovirus is the leading cause of congenital birth defects, as in-utero infection can result in permanent hearing loss or more profound neurodevelopmental impairments that disproportionately impact socioeconomically disadvantaged children.
Jimmy D. Gollihar, Ph.D., who is a protein engineer, synthetic biologist and head of the Antibody Discovery & Accelerated Protein Therapeutics (ADAPT) laboratory at the Houston Methodist Research Institute, is a co-principal investigator with Erica Ollmann Saphire, Ph.D., M.B.A., president, CEO and a professor with the La Jolla Institute for Immunology and project leader of the consortium. They are among a team of leading scientists from 19 laboratories across the U.S. that are working on herpesviruses.
As one of the artificial intelligence and machine learning experts of this consortium, Gollihar will generate new gene sequences encoding viral antigens for these mRNA vaccines through the ADAPT lab, which is a modern synthetic biology and protein engineering lab. During the COVID-19 pandemic, Gollihar's group was directly involved in genomic surveillance, antigen production, serological testing and use of convalescent plasma, as well as monoclonal antibody discovery and engineering.
A critical and innovative aspect to our strategy is the targeting of antigens essential to distinct stages of viral infection – beyond initial entry – to also include cell-to-cell spread, immune evasion and the reactivation stages linked to cancer, autoimmune disease and other complications."
Jimmy D. Gollihar, Ph.D., Head, Antibody Discovery & Accelerated Protein Therapeutics (ADAPT) laboratory, Houston Methodist Research Institute
Joining Gollihar from Houston Methodist are co-investigators John P. Cooke, M.D., Ph.D., who is the medical director of the Center for RNA Therapeutics, and Francesca Taraballi, Ph.D., who is the director for the Center for Musculoskeletal Regeneration and also works closely with Cooke as a faculty member in the Center for RNA Therapeutics.
Led by Cooke, the Houston Methodist Research Institute's RNA Core, which has the capacity to synthesize molecular targeted drugs for first-in-human clinical trials under tightly controlled FDA regulations, will generate these mRNA herpesvirus vaccines. Taraballi, who also is an adjunct faculty member with the Department of Nanomedicine, will provide a nanoscale drug delivery platform with her group that will encapsulate the vaccines in lipid nanoparticles (LNPs) for testing and validation by the other investigators.
By integrating advanced computational models with immunological data, this comprehensive, multidisciplinary approach will not only accelerate herpesvirus vaccine development, but also will enable the rapid design and optimization of immunizing agents to trigger an immune response in the body against a myriad of other viruses. This will facilitate swifter responses to emerging viral threats, potentially transforming vaccine development and preparedness for future pandemics.
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