Researchers are using weakened strains of the dengue virus to investigate why a second infection can cause more severe disease. In a human challenge study involving 45 people, scientists exposed participants to a modified mild strain of dengue virus and compared their immune responses with blood and lymph-node samples.
Dengue fever is transmitted by the bite of an infected female Aedes mosquito. The viral disease infects as many as 400 million people and kills approximately 40,000 people each year. Bangladesh and Kenya are among the countries battling serious outbreaks.
Most adults survive their first dengue infection, but they can develop more severe symptoms when later infected with a different strain. This unusual feature has complicated efforts to develop dengue vaccines. The study, published in Science Translational Medicine on October 281, is beginning to clarify the immune mechanisms underlying severe disease during a subsequent infection.
Understanding the biology behind dengue transmission patterns could help researchers develop better vaccines, says study co-author Leah Katzelnick, an epidemiologist at the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland.
“Dengue fever is still considered a neglected tropical disease,” she says. “But it’s now a problem for almost everyone.”
Existing vaccines have also raised concerns because immunization can affect the risk associated with later infections. In the Philippines, those concerns intensified after a large-scale public immunization campaign began in 2016 and some children developed severe dengue infections.
A dangerous immune memory
Scientists do not yet know why secondary infections can be more severe. One theory is that, when the immune system encounters a different dengue strain, it deploys antibodies produced during an earlier infection. Those antibodies might bind to the new strain without neutralizing it effectively, potentially worsening symptoms. Later infections with other dengue variants do not appear to trigger the same immune response.
To investigate dengue immunity, Katzelnick and her colleagues recruited 45 healthy people and divided them into three groups. The participants had different histories of infection with dengue strains, including infection with a particular strain and infection with several strains. The researchers then exposed all of them to a weakened version of DENV-3, one of the virus’s four strains, and compared their immune responses using blood and lymph-node samples.
Source: www.nature.com
