First Multigene, Multiclade HIV-1 Vaccine Trial Opens

January 1, 2003

BETHESDA, Maryland-The first clinical trial of an HIV-1 vaccine based on multiple genes from three subtypes, or clades, of the virus began November 13, 2002, when researchers at the National Institute of Allergy and Infectious Diseases (NIAID) vaccinated three healthy volunteers. Researchers expect to enroll 50 participants in the 12-month phase I study. The DNA vaccine contains modified material from four genes from clades A, B, and C, which cause about 90% of HIV infections worldwide.

BETHESDA, Maryland—The first clinical trial of an HIV-1 vaccine based on multiple genes from three subtypes, or clades, of the virus began November 13, 2002, when researchers at the National Institute of Allergy and Infectious Diseases (NIAID) vaccinated three healthy volunteers. Researchers expect to enroll 50 participants in the 12-month phase I study. The DNA vaccine contains modified material from four genes from clades A, B, and C, which cause about 90% of HIV infections worldwide.

The new vaccine was developed at NIAID’s Dale and Betty Bumpers Vaccine Research Center (VRC), located on the grounds of the National Institutes of Health (NIH). The phase I trial will be conducted at NIH, with Barney S. Graham, MD, PhD, serving as the lead investigator.

"This trial begins a process that we hope will culminate in a globally effective HIV vaccine," said VRC head Gary Nabel, MD, PhD. "The first step is to develop a multiclade vaccine. If our candidate elicits an effective immune response and proves safe in clinical testing, we will include additional components in subsequent trials in hopes of boosting this response. Ultimately, we aim to build a potent vaccine designed to prevent HIV infection."

The vaccine, currently designated VRC-HIVDNA009-00-VP, contains parts of three HIV genes—gag, pol, and nef—from clade B, the HIV subtype that predominates in Europe and North America. The fourth component is derived from an HIV gene called env, which codes for a protein on the virus’s outer coat that enables the virus to recognize and attach to human cells.

The new vaccine is the first to combine a modified env from clades A and C, the most common cause of AIDS in Africa, with the env from clade B. Because the vaccine’s components have been modified, they cannot reconstitute into and infectious virus, but they can stimulate an immune response.

The new vaccine was tested in mice, guinea pigs, rabbits, and rhesus monkeys prior to its use in humans and produced good immune responses with no ill effects, Dr. Graham told ONI in an interview.

The development of an effective HIV vaccine has been stymied by both the existence of the various subtypes and by the virus’s ability to mutate rapidly and thus evade the body’s immune defenses. "Any HIV vaccine must hit a constantly moving target," Dr. Nabel said. "Essentially, we are trying to enlarge that target through a multiclade vaccine."

The first phase of the randomized, controlled, double-blinded trial is being conducted at NIH. Its primary objective is to evaluate the vaccine’s safety and tolerability in humans. Its secondary goals are to assess the vaccine’s immunogenicity and the social impact of participating in an HIV-1 vaccine trial. Participants in the study will receive either the HIV vaccine or a saline solution in increasing doses.

Assuming the success of the phase I trial, NIAID plans to expand testing of the vaccine through its vaccine trials network at several US sites, as well as testing it in Haiti, South Africa, and other international sites.

Researchers also want to determine whether a multiclade vaccine will prove more effective than one employing genes from a single clade. "That is one question we hope our vaccine trials will eventually answer," Dr. Nabel said.

The phase I trial is open to men and women between the ages of 18 and 40 who are not infected with HIV. Additional information about the trial is available toll-free at 1-866-833-5433 or online at www.clinicaltrials.gov.