The virus, spread mostly through mosquito bites, led to nearly 100 deaths in the United States last year, and over 2,200 cases.
The director of the National Institute of Allergy and Infectious Diseases, part of NIH, said West Nile Virus "has emerged as an important health threat" in the United States since first appearing in the country in 1999.
The clinical trial will test the safety of the experimental vaccine as well as its ability to produce an immune response. Fifty healthy men and women will participate, being randomly assigned to receive either a low dose of the vaccine, a higher dose, or a placebo.
NIH said the virus used to make the vaccine was inactivated and could not cause an infection of West Nile Virus. During studies on rats, the vaccine was effective at producing an antibody response which protected the rats against a lethal dose of the virus.
NIH said enrollment in the clinical trial was expected to be completed by December.
West Nile Virus is typically a seasonal epidemic in the United States that beings in late spring or early summer and continues into the fall. NIH said that since 1999, a total of 41,762 cases of the disease have been confirmed in the United States, including 1,765 deaths.
The majority of people infected with West Nile Virus will show no symptoms, while about 20 percent will display mild symptoms, such as fever, body aches and nausea. NIH said only about 1 in 150 people infected with the virus would develop a serious neurological illness, such as encephalitis or meningitis.
The World Health Organization says the disease was first discovered in 1937 in the West Nile District of Uganda.