Flavivirus Research

Ongoing Research

Dengue Human Infection Model Study

University of Vermont vaccine researchers Sean Diehl, Ph.D., and Beth Kirkpatrick, M.D., of the UVM Vaccine Testing Center (VTC) and colleagues Jon Boyson, Ph.D., and Jason Botten, Ph.D., received a three-year $2.2 million grant from the Bill and Melinda Gates Foundation to study the immunological basis of protection from dengue fever.

Drs. Kirkpatrick and Diehl in VTC LabA reported 40 percent of the world’s population is at risk for dengue infection, with a rising number of home-grown cases occurring in the U.S. Dengue infection is caused by any of four related flaviviruses. Although some dengue infections are asymptomatic, severe infections of this flavivirus can cause hemorrhagic fever and dengue shock syndrome and have a higher risk of complications and death. Currently, no directed therapeutic options nor licensed vaccines.

In addition to UVM VTC investigators, the research team includes researchers from the Johns Hopkins Bloomberg School of Public Health, the National Institute of Allergy and Infectious Disease (NIAID), the La Jolla Institute for Allergy and Immunology, the University of North Carolina, and Atreca, Inc. A major focus of this study is the antibodies and T-cell responses produced in the blood in response to the dengue. The team is examining how the immune system recognizes dengue virus in an effort to confirm the protective effects of new vaccines in development. To date, the team’s research has shown that the antibodies produced by the vaccines can block infection of cells in a laboratory culture dish. However, other recent clinical trials of a different dengue vaccine candidate have revealed that vaccinated individuals can have a high level of antibodies in their bloodstream without being adequately protected from dengue infection.

Past Research

Live Attenuated Dengue Vaccine Study

Researchers at the University of Vermont (UVM) Vaccine Testing Center, along with collaborators at the National Institute of Allergy and Infectious Diseases (NIAID) at the National Institutes of Health and Johns Hopkins Bloomberg School of Public Health, have been working since 2008 to develop a dengue vaccine that will protect against all four dengue strains. The team’s latest research, published in Science Translational Medicine (March 2016), reported promising results from clinical trials on a new tetravalent vaccine (TV003) that is very effective at preventing dengue infection and is likely to require only a single dose.

Approximately 40 percent of the world’s population – 2.5 billion people – are at risk of contracting dengue, a viral infection spread by mosquitos in tropical and subtropical regions of the world. Dengue fever is best known for producing a high fever, rash and joint pain, but may also cause very serious disease, including hemorrhage and shock, as well as death. Development of vaccines for dengue has been complicated, since disease can be caused by any of four dengue virus serotypes and the vaccine must be tetravalent, providing equal protection against all four serotypes.

The NIH dengue vaccine was designed by Stephen Whitehead, Ph.D., a senior scientist and virologist at the Laboratory of Infectious Diseases at the NIAID. Clinical research was performed at both UVM and Johns Hopkins, where testing was led by Associate Professor Anna Durbin, M.D., corresponding author on the paper. In addition to Kirkpatrick and Pierce, UVM Vaccine Testing Center team members involved in this publication include Sean Diehl, Ph.D., assistant professor of medicine; Catherine Larsson, research specialist, and Marya Carmolli, senior research technician.

Read the Science Translational Medicine Article.