A small trial testing the safety of an experimental vaccine targeting West Nile virus (WNV) opened recently at the National Institutes of Health's (NIH) Clinical Centre in Bethesda, MD.

The vaccine, which will be tested first in 15 healthy adult volunteers, was developed for human clinical studies by researchers at the National Institute of Allergy and Infectious Diseases' (NIAID) Vaccine Research Centre (VRC), and Vical Inc., San Diego, based on an animal vaccine tested at the Centres for Disease Control and Prevention (CDC). Vical also manufactures the experimental vaccine.

"Although the prevalence of West Nile virus disease fluctuates seasonally and regionally, it continues to pose a serious public health threat, especially to older adults and people with weakened immune systems," says Anthony S. Fauci, director of the NIAID.

The experimental vaccine is composed of a small, circular piece of DNA-called a DNA plasmid-that contains genes that code for two key surface proteins of the West Nile virus. When the vaccine is injected into the muscle, the inner machinery of the muscle cells "reads" the DNA and converts it into two WNV proteins. Recognizing that the proteins are foreign, the muscle cells display them on their surface to alert the body's immune system-both helper T cells, which spur the production of antibodies to block the WNV from gaining entry into cells, and killer T cells, which kill WNV-infected cells outright.

"The DNA vaccine's exploitation of both cellular and antibody immunity offers a potentially potent defense against West Nile virus," says Barney Graham, chief of the VRC's Clinical Trials Core Laboratory. Adds Dr. Graham, "In our experience in clinical trials, DNA vaccines generally cause few side effects, making them a promising alternative to conventional vaccines."

Although no DNA vaccine has yet been licensed, other DNA vaccines developed by the VRC against HIV/AIDS, Ebola and SARS also are being tested in ongoing trials at NIH.

WNV, initially isolated in Uganda in 1937, made its first US appearance in New York City in 1999. The virus usually is transmitted to humans through the bite of a mosquito that has been infected after feeding on an infected bird or animal. The virus also can be spread through blood transfusions, organ transplants and breastfeeding, as well as from mother to child during pregnancy. Most people experience no symptoms or only mild symptoms, such as fever, headache and body aches; more serious cases can lead to infections of the brain and nervous system, such as encephalitis or meningitis. In 2004, 2,470 cases of WNV disease were reported in the United States, resulting in 88 deaths. Currently, no WNV vaccine is licensed for use in humans.