The Fifth International AIDS Vaccine Conference met in late August to discuss new developments in the search for both preventive and therapeutic HIV vaccines.
The conference represents the best snapshot of the latest research into HIV vaccines. Held over four days in the Netherlands, it unveiled the results of several early trials of potential therapeutic vaccines. Therapeutic vaccines, if they are determined to be safe and effective, are designed to boost the immune response of people living with HIV/AIDS (PLWHA) to help them fight the virus, and to reduce the need for antiretroviral treatment.
Therapeutic vaccines are chiefly designed to stimulate the immune system of PLWHA to create heightened T-cell defenses capable of destroying infected CD4 and other cells where the virus hides and replicates. Studies of experimental vaccines look at immunogencity, or the breadth and size of the vaccinated person’s T-cell response to the vaccine. A therapeutic vaccine would stimulate T-cells to recognize HIV-infected cells.
A number of safety and immunogencity studies of new therapeutic vaccines also use vectors being considered for preventive vaccines, such as pox virus vaccines. The current crop of therapeutic vaccines can include cytokine therapies to boost T-cell responses. The immune responses to the approaches presented at the conference are weaker than hoped for.
Nonetheless, these vaccines may be establishing important approaches that might control viral replication with the more effective immunization regimens. The potential of therapeutic vaccines will be to increase and expand the durability of HAART (highly active anti-retroviral therapy) regimens, to decrease viral load, and to avoid the need for patients to switch drugs.
Results were presented from a trial of ALVAC, a canarypox vector vaccine. The ALVAC vaccine is now being tested in a Phase III trial in Thailand among 16,000 HIV-negative men and women. The AACTG A5024 trial (Adult AIDS Clinical Trials Group) looked at the safety of adding the ALVAC vaccine and IL-2 (a cytokine found in the blood that helps boost the immune system) to HAART therapy.
This vaccine treatment was administered in volunteers who agreed to go off of HAART for the period of the study. The results found that the IL-2 made no difference in immunogencity, and was not well tolerated by some patients. Patients found some reduction in viral load during the trial, but their levels returned to previous levels after the trial was completed. The investigators are now considering ways to improve immune response.
Results of an AT-2 vaccine being tested in animal studies was also presented. The study design involved administering the vaccine to monkeys infected with SIV-239, an HIV-like virus, and then removing the animals from HAART. Although the vaccines were found to be safe, the vaccinated monkeys did not achieve the hoped for reduction in viral load.
Results were also presented from the European Union-funded TheraVac-01 program, which evaluated safety and immunogencity of the NYVAC-B vaccine in patients being successfully treated by HAART. The study tested a pox virus vaccine, based on technology also used for preventative vaccine trials, to induce a T-cell response. The NYVAC-B vaccine showed disappointing immunogencity, but there are plans to modify the vaccine or dosage to increase immunogencity.
Finally, there was also a Hungarian research team presenting on DermaVir, a patch to administer a DNA antigen as a therapeutic vaccine. The researchers found that the patch created potent T-cell responses, and there were no adverse events reported. Responses from the topical application of DermaVir appeared to provide a better response than injected DNA vaccines. Further studies of DermaVir are planned.
We were pleased to see that the conference included reports on a number of early stage therapeutic vaccines in development. This year, the program organizers for the first time developed an entire session devoted to therapeutic vaccines. In discussing T-cell vaccine development programs, Dr. Andrew McMichael of Oxford University urged that more sessions be devoted to this field in future conferences.
We hope that that the immunogencity of therapeutic vaccines can be improved and that they advance from these early trials to tests of efficacy in the future.
Steve Wakefield is Director of Community Education at the HIV Vaccine Trials Network, and Kevin Fisher is Senior Policy Associate with the AIDS Vaccine Advocacy Coalition.
Prevention vaccines
Researchers in Amsterdam presented reports on new developments in the prophylactic (prevention) vaccine field. Chief among these were the progress of the two Adenovirus vaccine candidates now being tested in clinical trials. These so-called Ad5 vaccines, with and without an HIV DNA prime, have shown the ability to induce high T-cell responses. The conference also featured discussions on the challenge of creating a vaccine that induces neutralizing antibody responses. Thus far, no vaccine candidate has been found that can produce antibodies which neutralize HIV and stop it from infecting CD4 and other cells. New research into the structure of HIV, however, holds the promise that new binding sites can be identified. Finally, researchers are renewing their focus on discovering why certain PLWHAs are able to naturally suppress viral loads. These so called elite controllers are currently being enrolled from all over the country in an observation study by The Partners AIDS Research Center and others. (If you are interested in seeing whether you are eligible to enroll, visit http://www.mgh.harvard.edu/aids/hiv_elite_controllers.asp)
It is hoped that the immune response of these individuals may yield a key to how an effective prophylactic, or perhaps a therapeutic, vaccine might be designed.—Steve Wakefield |
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