An AIDS Vaccine: When?
It's been suggested that HIV has a mind of it's own. Unlike a simple bacterium, the virus changes, mutates, and "learns" in a matter of speaking how to get away with murder. This simple little viral pod sneaks in, injects its own genetic code into a cell and begins transcribing that information into cellular DNA, creating countless blueprints of itself. In the end, the cell doesn't belong to us anymore. It belongs to the virus.
Copies of the virus migrate out of the host, infect more cells and begin the process all over again.
The first attempts to create an HIV vaccine focused on identifying binding sites on the surfaces of both HIV and the host cell.
A multi-clustered molecule, glycoprotein 120 (gp120) on the surface of the virus was found to contain the CD4 or helper T-cell receptor. This receptor enables HIV to successfully attach itself to the body's first line of defense: a cell, which activates the immune response itself. Without it, the immune system's ability to communicate with the cytotoxic T-cells that destroy infection is irreparably damaged.
Scientists were confident that the presence of gp120 would elicit an immune response strong enough to attack gp120 on the surfaces of HIV.
Vaccines using gp120, like VaxGen's controversial AIDSVAX, are monomeric, meaning that there is only one molecule for every three present on the receptor. Moreover, research has shown that vaccines made up only of proteins tend to promote the creation of antibodies, but do little to activate cytotoxic T-cells.
Executives at VaxGen, have turned a deaf ear to their detractors, arguing that AIDSVAX successfully elicited antibody immune responses among nearly all who participated in phase I and II clinical trials and that even a partially effective vaccine would substantially affect HIV incidence rates around the world.
To this end, VaxGen has begun phase III trials of AIDSVAX B/B in the U.S., Canada, Puerto Rico and The Netherlands, to determine how well the vaccine prevents the sexual transmission of HIV, and AIDSVAX B/E in Thailand to test its efficacy against blood borne infections.
No one knows how successful or unsuccessful the trials will be, but executives at VaxGen are prepared to market AIDSVAX as a preventative vaccine if phase III trials show as little as a 30 percent reduction in the likelihood of HIV infection among participants.
Researchers at VaxGen are confident that the results of the trials, which will be released in the first and fourth quarters of 2003, will silence detractors and open the door to a multivalent vaccine designed to affect all five major subtypes of HIV. The problem, according to VaxGen Chief Executive Officer, Lance K. Gordon, Ph.D. is "how to move from those results to making products available."
Many researchers have theorized that vaccines using "logical molecules" like gp120 tend to be ineffective because gp120 blocks the binding site until the precise moment when CD4 is presented. At that moment, the docking site snaps open and closes around it almost immediately. This theory has made the idea of combining vaccines much more attractive to researchers.
Lawrence Corey, a principal investigator of the HIV Vaccine Trials Network says: "You'd like to have both [a cellular response and an antibody response], but the greatest progress has been in eliciting a cellular response."
Other researchers, like those at France's Advantis/Pasteur are currently working with a combination of AIDSVAX and a genetically engineered canarypox virus which will encode gp120 as well as a protein that makes up the HIV core and another which allows it to reproduce.
The benefit of the canarypox virus is that the presence of HIV in the cell will stimulate the creation of "killer" T-cells as well as an antibody response. Unfortunately, a duplicate trial of Advantis/Pasteur's vaccine performed by the National Institute of Allergy and Infectious Diseases showed that less than 30 percent of the participants generated "killer" T-cells against HIV.
Merck Pharmaceuticals, one of the leaders in the production of HIV medications, is also trying its hand at two possible HIV vaccines. Both are based on the use of the HIV gag gene, which encodes the virus' core protein.
In the first, the HIV gag gene is administered as raw DNA. The cell will bond with the HIV gag gene and use its DNA to create a viral protein which, in turn will promote the development of both helper and cytotoxic T-cells.
Dr. Emilio Emini, Merck's Senior Vice President for Vaccine Research, reported that cytotoxic T-cells increased markedly in 42 percent of volunteers who received the highest dose of the raw DNA vaccine.
In the second trial, the gene enters the cell via the crippled adenovirus and proceeds to reproduce, allowing the body to create antibodies specific to the HIV gag gene.
Emini reported that between 44 and 67 percent of the participants who received the adenovirus-based vaccine experienced a cellular response proportionate with size of and time between receiving the shots.
While this represents a great leap forward in the search for a vaccine, experts are still stumbling around in the dark. Scientists are no closer now to determining what immune responses against HIV are required to ensure safety from infection than they were 17 years ago. The existing candidates for a vaccine are still in the trial phase and, what's more, even if a vaccine is developed it is unknown whether or not a vaccine would work on different strains of HIV.
Experts like Lawrence Corey and Dr. Emilio Emini are confident that a viable HIV vaccine conferring at least partial immunity is within reach. The only question is: Will it take another 17 years?
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