New Orleans, Louisiana - Naval Medical Research Center (NMRC) scientists, in collaboration with Walter Reed Army Institute of Research (WRAIR), have developed a state-of-the-art method to analyze immune response to dengue vaccines by measuring antibody-dependent cellular cytotoxicity (ADCC).
The research was presented in New Orleans during the 2018 American Society of Tropical Medicine and Hygiene (ASTMH) Annual Meeting, Oct. 28-Nov. 1.
According to the Centers for Disease Control and Prevention (CDC) Aedes aegypti is the principal mosquito vector of dengue viruses, and responsible for infecting as many as 400 million people each year.
“Dengue virus poses a significant public health threat to U.S. military personnel deployed to tropical and subtropical regions of the world where the virus is endemic,” said Lt. Brian Morrison, immunology division officer, Infectious Diseases Directorate (IDD), NMRC, and a principal investigator on the study. “Development of an effective dengue vaccine is a priority for the Navy Medicine Research and Development enterprise.”
Morrison said the objective of the study was to evaluate cellular opsonization, the process by which a pathogen is marked for ingestion, and develop a test based on the level of natural killer (NK) cell degradation brought out by the use of dengue-infected CEM-NKR-DC-SIGN target cells. The opsonized target cells were co-incubated with peripheral blood mononuclear (PBMC) cells isolated from a healthy donor and then stained with an antibody cocktail. Afterward, the results of the assay were used to analyze vaccine-induced ADCC activity during the trial. The researchers then determined that opsonization and antibody-dependent NK cell degranulation increased following receipt of the vaccine for all four dengue serotypes.
With their results in hand, the scientists determined the study clearly demonstrated the value of CEM-NKR-DC-SIGN target cells to assess serum Ab activity capable of causing ADCC responses, which play an important role in the immune response to vaccination against dengue virus.
“Because of the historic and current military impact of dengue virus infections, the key focus of the Viral Diseases Division is the development of an FDA-approved vaccine to prevent dengue fever,” said Lt. Cmdr. Gabriel Defang, chief, Viral and Rickettsial Diseases Department (VRDD), NMRC. “A critical corollary to vaccine development efforts is the exploration of novel and improved measures for immunological protection against dengue infection.”
Because of the test’s positive results, researchers think CEM-NKR-DC-SIGN target cells can be used to predict patient clinical responses against specific dengue antigens, and reveal primary and secondary dengue infections by serving as a tool to assess ADCC activity against all four serotypes in patient sera and plasma globally.
As the largest scientific organization of experts dedicated to reducing the burden of infectious disease, the ASTMH Annual Meeting draws more than 4,000 attendees from around the world and provides an opportunity for tropical medicine and global health professionals, military personnel, researchers, industry leaders, and academics to exchange scientific knowledge and information.
About Naval Medical Research Center
NMRC's eight laboratories are engaged in a broad spectrum of activity from basic science in the laboratory to field studies at sites in austere and remote areas of the world to operational environments. In support of the Navy, Marine Corps, and joint U.S. warfighters, researchers study infectious diseases, biological warfare detection and defense, combat casualty care, environmental health concerns, aerospace and undersea medicine, medical modeling, simulation and operational mission support, and epidemiology and behavioral sciences.
NMRC and the laboratories deliver high-value, high-impact research products to support and protect today's deployed warfighters. At the same time researchers are focused on the readiness and well-being of future forces.