First Aids Vaccine Made At NIAID Vaccine Research Center Enters Clinical Trial

Trial Begins Just One Year After Laboratories Open

National Institute of Allergy and Infectious Diseases (NIAID) researchers at the Dale and Betty Bumpers Vaccine Research Center (VRC) today announced the start of a clinical trial testing the first AIDS vaccine invented at the new facility. The VRC, described as a cross between a biotechnology company and an academic organization, is the first facility at the National Institutes of Health (NIH) dedicated solely to vaccine research and production. The vaccine was produced only one year after the building housing the new center opened in September 2000.

"To have taken this vaccine from concept to clinical-grade product in such a short time is an extraordinary accomplishment," comments Anthony S. Fauci, M.D., director of the NIAID. "The trial provides a tangible example, along with our outstanding group of scientists and their productive research programs, that the NIAID is moving at an unprecedented speed to try to make an AIDS vaccine a reality."

"The speed with which we reached this milestone demonstrates the VRC staff's dedication to the goal of finding an effective AIDS vaccine," comments VRC Director Gary J. Nabel, M.D., Ph.D. "We are absolutely committed to advancing AIDS vaccines from concept to the clinic, where we can begin the urgent task of evaluating their immune effects in people." Global statistics illustrate why their task is urgent: each day 7,000 people die from AIDS and another 15,000 become infected with the virus.

Dr. Nabel and two of his research fellows, Yue Huang, Ph.D., and Wing-Pui Kong, Ph.D., began developing the HIV DNA vaccine now being clinically tested a little more than a year ago.

Whereas traditional vaccines usually contain a weakened or killed form of a disease-causing agent or its proteins, as their name implies, DNA vaccines instead contain only portions of the genetic material for such.

The new vaccine contains the DNA blueprint for two pieces of HIV called "gag" and "pol." Gag is HIV's core protein. Pol includes three enzymes crucial for HIV replication, all of which have been modified for the vaccine to render them nonfunctional. Gag and pol remain relatively constant across different HIV strains, and together they make up about half of HIV's total protein.

Once inside the body, the DNA in the vaccine instructs certain cells to make small amounts of these HIV proteins. The purpose of this Phase I study is to determine if the vaccine is safe and if the body makes an immune response to these proteins. Because the vaccine does not contain genetic material for the whole virus, it is impossible for someone to become infected with HIV or to develop AIDS from the vaccine. Through a contract with Vical, Inc., of San Diego, the VRC had their laboratory product made into clinical grade DNA used in the vaccine.

The Phase 1 trial is recruiting 21 healthy men and women aged 18 to 60 who are not infected with HIV and who are at low risk for becoming so. Participants will be assigned at random to receive either the experimental vaccine or an inactive salt solution, known as a placebo.

Increasing doses of vaccine will be tested in a stepwise manner in three groups of seven volunteers. At each step, five people will receive vaccine while two other people receive placebo. The lowest study dose of vaccine (0.5 milligrams, or mg) tested in step one will be increased to 1.5 mg in step two, and to 4.0 mg in step three. The dose will be increased only if there are no significant adverse reactions in the previous group.

Participants will receive three injections in an upper-arm muscle-one injection per month for three months-with a needle-free device called a Biojector. The study will last about 12 months from the first injection.

There have been several DNA-based vaccines already tested in humans and none has caused serious adverse reactions, notes Barney Graham, M.D., Ph.D., chief of the Clinical Trials Core and Viral Pathogenesis Laboratory at the VRC. Persons interested in the study will be extensively educated and counseled, he adds, prior to signing an informed consent agreement to join the trial. The trial is being conducted at the NIH Clinical Center under the direction of Jorge Tavel, M.D.

Those interested in more information about the trial can call toll-free to 1-866-833-5433 or read a description of the trial at http://www.niaid.nih.gov/vrc/clinstudies.htm.

According to Dr. Nabel, their HIV DNA vaccine is intended to stimulate cellular immunity to the virus, which is thought to be important to protection against HIV. The vaccine will likely be combined in later studies with other DNA components that stimulate neutralizing antibody responses to the virus. This is the first in a series of studies, he adds, with different vaccine candidates aimed toward identifying those that have the best opportunity to protect against AIDS or HIV infection.

The development of vaccines and the prevention of disease have been part of the history of the NIH since it was founded in 1887. Vaccines against Rocky Mountain spotted fever, typhus, adenovirus, hemophilus influenzae B and hepatitis A are among the stellar accomplishments of NIH scientists.

With the opening of the VRC, however, the search for a vaccine against one of the world's most devastating diseases, AIDS, has taken on a new urgency. The VRC has ramped up quickly and currently has a roster of about 100 scientists and support staff. Most products evaluated in VRC clinical studies will be products conceived, developed and produced by VRC investigators.

NIAID is a component of the National Institutes of Health (NIH). NIAID supports basic and applied research to prevent, diagnose, and treat infectious and immune-mediated illnesses, including HIV/AIDS and other sexually transmitted diseases, tuberculosis, malaria, autoimmune disorders, asthma and allergies.

Press releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov. The VRC Web site can be accessed at http://www.vrc.nih.gov.