BETHESDA, Maryland-Researchers at the National Institute of Allergy and Infectious Diseases (NIAID) have begun enrolling 21 volunteers in a phase I trial of a new plasmid DNA-based HIV vaccine (VRC4302). The randomized, controlled, double-blinded, dose-escalation study will examine the vaccine’s toxicity, dose, and immune response. It will be conducted on the National Institutes of Health campus.
BETHESDA, MarylandResearchers at the National Institute of Allergy and Infectious Diseases (NIAID) have begun enrolling 21 volunteers in a phase I trial of a new plasmid DNA-based HIV vaccine (VRC4302). The randomized, controlled, double-blinded, dose-escalation study will examine the vaccine’s toxicity, dose, and immune response. It will be conducted on the National Institutes of Health campus.
The 21 healthy men and women admitted to the study will be HIV negative and at low risk of becoming infected. They will be between 18 and 60 years old and randomized to receive either the experimental vaccine or a placebo.
The volunteers will be divided into three groups of seven members each; five volunteers in each group will receive the vaccine by intramuscular injection and two will get placebo.
The first group in the stepwise trial will receive 0.5 mg of the vaccine. The second group will receive 1.5 mg, and the third will get 4 mg. Each participant will receive three injections of either vaccine or placebo, each 28 days apart. Groups 2 and 3 will not receive their injections if the previous group suffered any significant toxicity.
The volunteers will be observed for at least 1 year after their first injection, and will be followed for another 3 years with once- or twice-a-year contacts by the study staff.
The HIV vaccine is one of several in the testing pipeline. It is meant to stimulate cellular immunity against the AIDS-causing virus.
The vaccine was developed in about a year’s effort at NIAID’s new Dale and Betty Bumpers Vaccine Research Center (VRC) by its director, Gary J. Nabel, MD, PhD, and co-workers Yue Huang, PhD, and Wing-Pui Kong, PhD. It is the first vaccine developed at the VRC, which has been described as a cross betwen a biotechnology company and an academic organization.
"To have taken this vaccine from concept to clinical-grade product in such a short time is an extraordinary accomplishment," said Anthony S. Fauci, MD, 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."
Dr. Nabel concurred: "The speed with which we reached this milestone demonstrates the dedication of the VRC staff to the goal of finding an effective AIDS vaccine."
Whereas traditional vaccines usually contain a weakened or killed form of a disease-causing agent or its proteins, DNA vaccines, as their name implies, instead contain only portions of the virus’ genetic material, the NIAID said in announcing the trial.
The new vaccine contains the DNA 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 to render them nonfunctional.
The vaccine’s DNA stimulates the production of small amounts of gag and pol, which should induce a protective immune response. The two virus segments remain fairly constant across the different strains of HIV and together account for about half of the virus’ total protein.
This is the first in a series of studies with different vaccine candidates aimed toward identifying those that have the best opportunity to protect against AIDS or HIV infection, Dr. Nabel said.
For More Information
The trial is being conducted at the NIH Clinical Center under the direction of Jorge Tavel, MD. More information can be found at the NIAID website www.niaid.nih.gov/vrc/clinstudies.htm or call toll-free 1-866-833-5433.