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 cocirculating dengue
viruses that did not experience enhancement.
Counterintuitively, 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," said 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,
senior author of the study and professor in the Department
of International Health at the Bloomberg School.
In addition to Cummings and Burke of Johns Hopkins,
the study was written by Ira B. Schwartz, Lora Billings and
Leah B. Shaw. 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.
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