Computer Models Aid Understanding of Antibody-Dependent Enhancement in Spread of Dengue Fever

Evolutionary Trade-Off Exists Between Advantage and Disadvantage

Some viruses’ ability to exploit the human body’s own defenses to increase their replication may be both a blessing and curse, according to the findings of a study conducted by researchers at the Johns Hopkins Bloomberg School of Public Health. The process is known as antibody-dependent enhancement. Scientists believe antibody-dependent enhancement may allow the dengue virus to grow more rapidly in people who were previously infected and have partial but incomplete immunity to the virus. Enhanced virus replication triggers a more deadly, hemorrhagic form of the disease. A study published in the online edition of Proceedings of the National Academy of Sciences suggests that antibody-dependent enhancement offers an evolutionary trade-off between advantage and disadvantage for the dengue virus. The findings could one day lead to new strategies for developing and deploying vaccines.

Using computational models based on epidemic theory, the researchers examined the dynamic role antibody-dependent enhancement plays in the spread of dengue viruses. They concluded that when antibody-dependent enhancement triggered small increases in transmission it gave viruses an edge over other co-circulating dengue viruses that did not experience enhancement. Counter-intuitively, larger increases in transmission resulted in more extinctions of the enhanced virus.

“Dengue dynamics are similar to predator-prey systems in ecology. Antibody-dependent enhancement makes a virus a better predator. But there comes a point where the predator gets so good it runs out of prey,” explained lead author Derek Cummings, a research associate in the Department of International Health at the Bloomberg School. “We found that antibody-dependent enhancement helps the dengue virus spread faster, but there are limits to how much the virus can exploit this strategy.”

According to the computer simulations, antibody-dependent enhancement creates oscillations, or “booms and busts” in the incidence of dengue virus infections. Enhancement results in larger booms, but also deeper troughs in incidence, which lead to extinction. Although the computer models were specifically developed for dengue, the researchers believe the results could apply to any disease in which partial immunity increases pathogen replication rates.

“Experimental dengue vaccines will soon be entering into large-scale clinical trials. We must understand the processes that affect transmission—such as antibody-dependent enhancement—to design optimal dengue vaccination strategies,” said Donald S. Burke, MD, senior author of the study and professor in the Department of International Health at the Bloomberg School.

“Dynamic effects of antibody-dependent enhancement on the fitness of viruses” was written by Derek A. T. Cummings, Ira B. Schwartz, Lora Billings, Leah B. Shaw and Donald S. Burke. Cummings and Burke are with the Johns Hopkins Bloomberg School of Public Health. Schwartz and Shaw are with the Naval Research Laboratory, Washington, D.C., and Billings is with Montclair State University.

Funding was provided by grants from the National Institute of General Medical Sciences of the National Institutes of Health, the National Oceanic and Atmospheric Administration, the Environmental Protection Agency, the National Aeronautics and Space Administration, the National Science Foundation, the Office of Naval Research and the Center for Army Analysis and the National Research Council.