Simple Idea to Improve Dengue Vaccinations

Eggs of the dengue fever mosquito
vector - Aedes aegypti; © PHIL

Dengue infection occurs from one of four closely related viruses. Previous exposure to one of the four – either by prior infection or by vaccination – makes people significantly more likely to develop a potentially lethal haemorrhagic infection if they are later infected by one of the other three viruses. Intrigued by these results, lead researcher Michael Deem, the John W. Cox Professor in Biochemical and Genetic Engineering and graduate student Hao Zhou developed a precise computer model of the immune system's biochemical scanning process to see if they could recreate the effect and find out what caused it. Their program conducts statistical calculations about the likelihood of specific interactions at the atomic level. They conducted trillions of calculations and gradually built up a bigger picture of what occurs in Dengue immunodominance.

"When faced with more than one version of the virus, the immune system may respond preferentially against the version for which it has T-cells with the strongest affinity, which is immunodominance," Deem said. He said polytopic vaccination – giving different vaccines simultaneously at different locations on the body – could help overcome immunodominance by taking advantage of the relative isolation of lymph nodes throughout the body. Each person has hundreds of lymph nodes. Deem believes vaccinations at four different sites, served by four different lymph nodes, could allow the body to simultaneously develop immune responses against all four versions of Dengue.

Deem concluded: "Ours is the first model that can predict immunodominance, and when we compare our results with experimental data from Dengue vaccination trials, they match quite closely. There may be other factors at work, but we appear to be explaining a significant portion of the effect that occurs in Dengue immunodominance."; Source: Rice University