STD Quarterly: HIV vaccines: New generation may reduce transmission of virus
October 1, 2002 4 minutes read
Prevention efforts must continue to stem spread of disease
Every day, the statistics mount in the AIDS epidemic. According to the Joint United Nations Programme on HIV/AIDS, an estimated 14,000 people worldwide become infected with HIV each day, with more than half of new infections occurring in young people younger than age 25. How will the epidemic be stemmed?
Look to progress on the HIV vaccine front. Two vaccines are in advanced clinical trials, and increased federal funding has expanded the research pipeline by allowing for more exploration of various vaccine strategies. According to the federal National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIH), six potential HIV vaccines were tested during the past five years in 12 small-scale clinical trials conducted in the United States and around the world. During the next two years, more than a dozen potential vaccines are expected to be ready for testing. They will require more than 20 clinical trials of various sizes.
Look to 2003 for results to be reported from the advanced clinical trials, says Jorge Flores, MD, chief of the Vaccine Clinical Research Branch of the NIH’s Division of AIDS. Both trials involve the AIDSVAX vaccine developed by Brisbane, CA-based VaxGen. The first trial involves 5,400 participants in North America, Puerto Rico, and the Netherlands, with the bivalent vaccine targeting two strains of HIV subtype B, found predominately in North America, Western Europe, Australia, New Zealand, and parts of South America. The study is scheduled to conclude at the end of 2002.
A second trial among 2,500 participants is taking place in Bangkok, Thailand, using a vaccine formulation designed to protect against the two predominant strains found in Southeast Asia and the Pacific Rim, subtypes B and E. Results of the Thailand study are expected to be available in the fourth quarter of 2003.
"In addition to these trials, we have multiple other studies going on, including Phase II trials," says Flores. "Four or five years from now, there will be five to six efficacy trials for different vaccines."
The vaccine formulations AIDSVAX B/B and AIDSVAX B/E are made from a synthetic clone of a protein found on the surface of HIV, gp120. Using recombinant DNA technology, the gene for gp120 is cloned and then duplicated by Chinese hamster ovary cells in commercial-scale fermenters. The gp120 then is purified and mixed with alum, an adjuvant that boosts the immune response, to create the vaccine.
When the trials are concluded, researchers will determine whether the immune system response induced by AIDSVAX reduces the amount of HIV to undetectable levels in vaccinated volunteers who became infected with HIV after receiving the vaccine, or lowers the amount of virus in the bloodstream to detectable but manageable levels. Either of these potential outcomes could represent a significant breakthrough by potentially helping HIV-infected people live longer and reduce their ability to infect others. It is not yet known whether either of these outcomes, known as secondary endpoints, would be considered for regulatory approval.
More vaccines on way
A new generation of T cell-based HIV vaccines also offers promise in delaying the onset of AIDS symptoms and reducing transmission of the virus. These vaccines have the potential to significantly impact the epidemic if they are shown to reduce the infectiousness of infected individuals for a prolonged period of time, says Lawrence Corey, MD, the principal investigator of the HIV Vaccine Trials Network, an international collaboration of scientists and institutions with headquarters at The Fred Hutchinson Cancer Research Center in Seattle.
T cell-based vaccines work differently from traditional vaccines as they work later and are aimed at controlling viremia and decreasing the viral load so that transmission can be reduced, explains Corey. These vaccines could significantly postpone development of HIV in infected individuals, he notes.
"It is also encouraging that cross-clade T cell responses to HIV are being achieved at high frequency with many of the T cell vaccines currently in clinical trials," says Corey. "Cross-clade responses to a potent vaccine may provide more efficacy than clade-specific responses to a weak vaccine, opening the door to economies of scale and global manufacture of a single vaccine."
Whether HIV vaccines prove to prevent infection or delay illness, researchers agree that a strong prevention message must continue to be emphasized in the battle against HIV/AIDS.
"People will still expose themselves to the risk of HIV infection, so we will have to continue fighting with whatever other measures that can protect people from that exposure, be it behavioral interventions, education, counseling, or other measures that prevent transmission," says Flores.
There is a natural tendency for people to think that once they are protected against disease to take risks, notes Flores. To prevent against this tendency, providers must help in changing behavior through education and counseling.
Eventually scientists will develop vaccines that are 100% effective, says Corey. However, it appears that the initial vaccines will not meet that goal, and mathematical modeling indicates a partially effective vaccine can be overwhelmed, he notes. An effective prevention and treatment program can aid in the fighting the battle, he notes.
"Vaccine deployment must take place within the context of a larger HIV prevention and treatment effort if we are to stem the tide of this pandemic," he states.
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content