Clinical and Translational Science Institute-Children's National awards pilot grant to GW researchers

GW researchers in the School of Medicine, Jeffrey M. Bethony, Ph.D., Associate Professor of Microbiology, Immunology, and Tropical Medicine and David Diemert, M.D., FRCP(C), Associate Research Professor of Microbiology, Immunology, and Tropical Medicine and Director of Clinical Trials for the Sabin Vaccine Institute's Product Development Partnership (PDP), have been awarded a Pilot Grant from the Clinical and Translational Science Institute-Children's National (CTSI-CN) to investigate innovative methods for evaluating the immune response to vaccines with a novel Toll-like Receptor (TLR)-4 agonist adjuvant. The researchers will use several new antibody profiling techniques to determine if there is a qualitative change in the humoral immune response to an investigational hookworm vaccine when this novel adjuvant is used.

Hookworm is a parasitic infection that affects more than 500 million people throughout the world and leads to impaired growth and development in children. A joint effort between Children's National Medical Center and The George Washington University Medical Center, CTSI-CN is a Clinical and Translational Science Awards (CTSA) Institution, a consortium that is funded by the National Center for Advancing Translational Sciences, part of the National Institutes of Health.

"Novel adjuvants are seldom evaluated in early vaccine clinical development. Even fewer are evaluated using recent advances in antibody profiling technologies that can measure the quality of the immune response as well as its quantity," said Dr. Bethony. "Novel adjuvants are expected to do more than just increase the quantity of the immune response. They are expected to make better antibodies, not just more antibodies." Drs. Bethony and Diemert will conduct these novel antibody assessments as part of a Phase 1 clinical trial of an investigational hookworm vaccine that will take place at Children's National Medical Center (CNMC). Dr. Diemert will serve as the Principal Investigator of this trial.

In cooperation with Dr. Robert Hamilton, head of the Dermatology, Allergy and Clinical Immunology (DACI) Laboratory at the regional CTSA based at Johns Hopkins University, the researchers will first focus their research on a novel automatic antibody quantitation method using the ImmunoCAP system, which is currently used by allergists to measure IgE antibodies to allergens. Drs. Diemert and Bethony will test to see if this system can also be used in vaccine clinical trials as a rapid, precise, and quantifiable method for measuring antibody levels in response to vaccination with a recombinant protein. Also in collaboration with the DACI, they will use Surface Plasmon Resonance (Biacore) to determine if antibody affinity to a recombinant protein is enhanced by the use of a novel TLR-4 agonist adjuvant.

Finally, Drs. Diemert and Bethony will measure long-lived plasma cells and memory B cells, which are responsible for the long-term humoral immunity elicited by vaccines. The researchers will determine if these methods could be used to evaluate how well a new adjuvant maintains immunologic memory in humans in early clinical trials of an experimental vaccine.

"Through this research, we hope to determine if these new technologies can offer us rapid and effective methods for evaluating the role of novel adjuvants in the early stage of clinical development of recombinant protein vaccines," said Dr. Diemert. "This research will be critical in deciding on the optimal formulation of the first-ever hookworm vaccine that could benefit the hundreds of millions of people at risk of this parasitic infection around the world."

Drs. Bethony and Diemert will conduct this research in collaboration with the CNMC and the CTSA at the Johns Hopkins University. The hookworm vaccine that will be tested in the Phase 1 trial has been developed in partnership with the Sabin Vaccine Institute (Washington, DC).

Source: George Washington University Medical Center