Battling the bugs

A team of scientists has toiled for eight years to develop treatments for mosquito-borne viruses that have plagued people in developing nations – and crept into Northern Colorado.    

Scientists John Roehrig and Amanda Calvert at the Centers for Disease Control and Prevention’s vector-borne diseases lab in Fort Collins and Colorado State University scientist Carol Blair are.

The scientists and others are targeting West Nile, dengue fever and yellow fever, all of which can cause brain swelling and severe fever. The most widespread of these viruses is dengue fever, contracted by 400 million people annually worldwide. The disease is sometimes fatal, particularly in children.

The scientists’ work has important implications for developing countries in tropical regions and in the United States as mosquito-borne viruses proliferate. Mosquitoes that transmit illness can lay their eggs in small pools of water, such as in a potted plant, in people’s homes. Removing those kinds of breeding grounds can help, but they are difficult to eliminate in backyards where pools collect from frequent rainstorms, Blair said.

“The biggest way that dengue is controlled right now is mosquito control,” she said. “That’s easier said than done.”

This summer in Northern Colorado there was an outbreak of West Nile virus from hot weather and moist conditions that sickened nearly 100 people, according to Larimer County Public Health Department statistics. This year’s episode of West Nile pales in comparison with a 2003 epidemic in Larimer County that killed nine people and infected 546. The state saw 2,947 cases total and 63 deaths that year.

Yellow fever cases were first documented on the East Coast in the late 1600s, and 26,000 cases were documented annually in New Orleans during the mid-1800s. Mosquitoes infected with yellow fever still live in several U.S. states. Globally, yellow fever infects tens of thousands of people annually.

Although dengue fever largely has remained in the tropics, scientists have seen the virus move farther north and south because of climate change, Blair said.

Vaccines for mosquito-borne viruses are available only for yellow fever, although Fort Collins’ Inviragen Inc., acquired recently by Takeda Pharmaceutical Co. Ltd. in Japan, is developing a dengue vaccine. No drugs have been approved for treatment of any vector-borne diseases.

Aiming to develop those drugs, the CDC and CSU scientists are creating antibodies, or proteins made by the human body, to get rid of an infection. Humans cannot make the antibodies quickly enough to fight severe vector-borne viruses.

The researchers engage in a process known as immunotherapy by making monoclonal antibodies, or artificial cell systems developed using immunized mice. The scientists then grow the cells on their own and harvest the antibodies.

Roehrig started working with monoclonal antibodies in 1980, so he considers the immunotherapy his life’s work.

“The theory is then to supplement your own antibodies with these other antibodies in large quantities early in infection,” Roehrig said.

The scientists have developed many of the antibodies for dengue and yellow fevers, and have conducted preclinical trials on mice.

Their next step is to test the antibodies in primates. Other laboratories are developing antibodies to treat West Nile.

Developing drugs to treat mosquito-borne illnesses is important because some people cannot be vaccinated, including those with compromised immune systems. Drugs also can supplement vaccines when they’re not effective. New vaccines also can pose greater health risks than drugs.

“It’s not really known what kind of safety profile they’re going to have,” Roehrig said about vaccines in development. “It just depends on the type vaccine it is.”

Still, it will be some time before the drugs might hit store shelves: Roehrig estimates it will happen in another 10 years.