"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, M.D., director of the NIAID.

WNV, initially isolated in Uganda in 1937, made its first U.S. 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.

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, M.D., Ph.D., 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.

Fifteen healthy volunteers between the ages of 18 and 50 will receive three injections of the DNA vaccine into the upper arm: one at the start of the trial, a second approximately four weeks later, and a third approximately four weeks after that. To help force the DNA plasmid into muscle cells, the vaccine will be administered by a needle-free injector rather than a conventional needle syringe. Volunteers will be monitored for possible symptoms or side effects as well as the body's ability to generate WNV-specific antibodies and T cells. The vaccine cannot cause West Nile virus infection or disease because it does not contain infectious material from the virus. For more information on the WNV vaccine trial, call the Vaccine Research Center's toll free number 1-866-833-LIFE, or visit the VRC Web site http://www.niaid.nih.gov/vrc/clintrials/clinstudies.htm.

The vaccine in this study builds upon an experimental vaccine developed by CDC researcher Jeff Chang, D.V.M., Ph.D., of Fort Collins, CO, that has been tested successfully in a variety of animals, including mice, horses and American crows.

Two other human WNV vaccines developed with NIAID support are currently in Phase I clinical trials. Called chimeric vaccines, these vaccines combine genes of the West Nile virus with genes of a closely related virus--yellow fever virus in the case of a vaccine developed by Acambis, Cambridge, MA, and dengue virus in the case of a vaccine developed by NIAID intramural researchers.

NIAID is a component of the National Institutes of Health, an agency of the U.S. Department of Health and Human Services. NIAID supports basic and applied research to prevent, diagnose and treat infectious diseases such as HIV/AIDS and other sexually transmitted infections, influenza, tuberculosis, malaria and illness from potential agents of bioterrorism. NIAID also supports research on transplantation and immune-related illnesses, including autoimmune disorders, asthma and allergies.

News releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.

Note: If no author is given, the source is cited instead.

• Infectious Diseases
• Vaccines
• Viruses

• Virology
• Bird Flu Research
• Pests and Parasites

• West Nile virus
• Flu vaccine
• Vector (biology)
• Rubella
• HPV vaccine
• Rotavirus