Houston Methodist part of national consortium to develop vaccine against herpesviruses

Computational design expert Jimmy Gollihar Co-PI on ARPA-H award for developing America’s SHIELD

Houston Methodist

 

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Jimmy D. Gollihar, Ph.D. is the head of the Antibody Discovery & Accelerated Protein Therapeutics (ADAPT) laboratory at the Houston Methodist Research Institute. The ADAPT lab is a modern synthetic biology and protein engineering lab.

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Credit: Houston Methodist

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,” Gollihar said.

 

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.

 

For more information about Houston Methodist, visit our newsroom or our social media pages on X, Facebook, LinkedIn, Instagram and TikTok or our On Health and Leading Medicine blogs.

 

Houston Methodist prepares for next pandemic as part of national NIH-funded consortium

Houston Methodist

 

image: 

Jimmy D. Gollihar, Ph.D. is the head of the Antibody Discovery & Accelerated Protein Therapeutics (ADAPT) laboratory at the Houston Methodist Research Institute. The ADAPT lab is a modern synthetic biology and protein engineering lab. Gollihar will discover and engineer monoclonal antibodies to viruses in the Nairoviridae, Hantaviridae and Paramyxoviridae families, as well as contribute to the generation of gene sequences encoding stabilized viral antigens for potential mRNA vaccines through his ADAPT lab. 

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Credit: Houston Methodist

The question isn’t if, but when, the next pandemic will hit. Research and observation have identified strong potential for the next pandemic-causing virus to come from one or more of five different virus families. Houston Methodist scientists will focus on three of these as part of a national research consortium funded by the National Institutes of Health’s (NIH) National Institute of Allergy and Infectious Diseases (NIAID). The consortium is led by Albert Einstein College of Medicine in New York.

 

Scientists from the Houston Methodist Research Institute will work to develop efficacious vaccines and therapeutic antibodies for viruses in the Nairoviridae, Hantaviridae and Paramyxoviridae families. The potential exists for a virus member in one or all of these families to be the cause of the next major pandemic. The specific viruses in these families that will be looked at by Houston Methodist researchers include:

• Nairoviruses (primarily caused by ticks)
  • Crimean-Congo hemorrhagic fever
  • Hazara virus
  • Andes
• Hantaviruses (caused by exposure to urine, saliva or droppings of infected rodents)
  • Sin Nombre
  • Hantaan virus
• Paramyxoviruses (respiratory viruses that occur in animals and humans spread through respiratory droplets or direct contact) 
  • Menangle
  • Tioman
  • Sosuga
  • Nipah virus

 

“To prepare for potential outbreaks of these target viruses, we will investigate the antigenic determinants of these viruses, similar to what was done with the years of research into coronaviruses that led to vaccine developers being able to rapidly provide solutions to the SARS-CoV-2 virus,” said Jimmy D. Gollihar, Ph.D., one of PROVIDENT’s co-principal investigators and head of the Antibody Discovery & Accelerated Protein Therapeutics (ADAPT) laboratory at the Houston Methodist Research Institute. “We propose to target viruses within these families by manufacturing and testing monoclonal antibodies and RNA vaccines that can effectively treat and prevent disease caused by these viruses. Our work will provide the foundational knowledge to develop effective medical countermeasures in response to a potential outbreak and pandemic.”

 

Gollihar will discover and engineer monoclonal antibodies to these viruses, as well as contribute to the generation of gene sequences encoding stabilized viral antigens for potential mRNA vaccines through his ADAPT lab, which is a modern synthetic biology and protein engineering lab. His team will also collaborate with the RNA Core, led by John P. Cooke, M.D., Ph.D., medical director of the Center for RNA Therapeutics, to construct, encapsulate and validate them. Working with Cooke on this will be Francesca Taraballi, Ph.D., who is the director for the Center for Musculoskeletal Regeneration and works closely as a faculty member in the Center for RNA Therapeutics. She will provide a nanoscale drug delivery platform that will encapsulate the vaccines in lipid nanoparticles (LNPs) for testing and validation by the other investigators.

 

The use of mRNA encapsulated in LNPs was also something that greatly enhanced the ability of vaccine developers during the COVID-19 pandemic to rapidly provide the public with an effective vaccine against the SARS-CoV-2 virus.

 

Led by Kartik Chandran, Ph.D., at Albert Einstein College of Medicine under a five-year grant of $14 million per year (award number 1U19AI181977-01), the PROVIDENT (Prepositioning Optimized Strategies for Vaccines and Immunotherapeutics Against Diverse Emerging Infectious Threats) consortium is part of the Research and Development of Vaccines and Monoclonal Antibodies for Pandemic Preparedness (ReVAMPP) Network, focusing its research efforts on representative pathogens from virus families known to infect humans. By studying and developing solutions for these high-priority pathogens with the potential to cause deadly diseases, the scientists in the PROVIDENT consortium will build a knowledge base with the potential to be applied to other related viruses.

 

For more information about Houston Methodist, visit our newsroom or our social media pages on X, Facebook, LinkedIn, Instagram and TikTok or our On Health and Leading Medicine blogs.

 

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