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Searching For An AIDS Vaccine; Developing Women-Controlled Microbicides
Background Information for a Reporter’s Notebook, Part III of a Series
July 5 - This weekend, more than 15,000 participants will gather in Barcelona, Spain for the 14th International AIDS Conference, which runs July 7-12, 2002. Convened by the International AIDS Society (IAS), a professional society for scientists, health care, public health workers and other engaged in HIV/AIDS prevention, control and care, the meeting has emerged as one of the most important annual public health gatherings.
PLANetWIRE’s features are intended to inform reporters and others interested in focusing on some of the most profound issues shaping and/or surrounding the epidemic, some of which have received less than deserved attention in the media.
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The scope of the HIV/AIDS pandemic makes the search for a vaccine an urgent priority for the international public health community. But the disease has proven difficult to solve. 60 million people have been infected with HIV/AIDS: not one person has been cured.
The first trials of a prospective vaccine were launched in 1987 and some scientists predicted rapid development of a viable treatment. Fifteen years later, only one prospective vaccine has advanced the third and final stage of clinical testing, the disease has proven to be far more complicated than originally thought and researchers are far more humble about the timeframe for a widely available, affordable vaccine. In the mid-1990s, the United States began a patient, 10-year effort to develop a vaccine.
HIV/AIDS – AN ELUSIVE FOE
For a variety of reasons, the human immunodeficiency virus (HIV), which causes acquired immune deficiency syndrome (AIDS), has proven to be an elusive foe for researchers and scientists. Since it was first identified, three different groups and 30 different subtypes of the virus have been discovered – many of them unique to specific regions and/or countries of the globe. Each different subtype is as much as 30 percent different as its viral cousins. As a result, it is not clear whether one vaccine will be sufficient to prevent or treat all forms of the disease, or whether multiple vaccines will be needed.
In addition, HIV is able to infect an individuals entire system or individual cells, which complicates the search for a cure. And the virus is near diabolical in its ability to mutate, even after it has infected an individual.
HIV is unlike other viruses because it immobilizes the totality of the immune system. Typically, in treating other viral infections, the medical community has sought to stimulate a specific immune system response, such as encouraging development of certain antibodies to address the infection. With HIV, there is nothing to stimulate because the system is not working. Among other things, this makes testing of prospective vaccines especially difficult – safety and ethical considerations make researchers leery of testing prospective vaccines that have the potential to accidentally, and fatally infect humans.
The disease also poses different challenges for developed and developing nations, as subtypes of the virus, financial capabilities and other factors significantly effect the course of research. Paradoxically, although the vast majority of infections have occurred in developing countries, most research is on strains of the disease that infect people in industrialized nations.
Similar factors and considerations have served as a disincentive to more active engagement by pharmaceutical and other private sector interests in the search for an AIDS vaccine. Given that the majority of prospective users of a vaccine are in developing countries with little or no ability to pay for an antidote, and that the enormous costs associated with research and development (especially for one of the most complicated diseases ever encountered), companies are reluctant to invest in the search for a vaccine.
UNRAVELLING THE AIDS RIDDLE
More than one hundred years ago, Louis Pasteur almost accidentally discovered the potential of so-called attenuated, or weakened vaccines as a preventive approach to cholera. Much has been learned since and dozens of diseases are now prevented through the use of vaccinations. In the search for an AIDS vaccine, researchers are looking for a treatment that achieves one of several outcomes: 1) prevents infection altogether; 2) ensures brief, transient infection; 3) prevents significant effects after an individual is infected; and 4) whether it minimizes effects or not, prevents transmission to others.
To help inform ongoing efforts, researchers are looking both at empirical understandings of human immunology and at the surprising differences in individual responses to infection. Some individuals show a pronounced ability to avoid infection despite repeated high-risk behaviors. There also are individuals who have been infected with the virus but not evidence signs of continued progression of the disease. As a means of helping others, researchers would like to understand why certain individuals are so resilient to infection or effects of the disease. Similarly, researchers want to know why certain animals have a capacity to avoid infection from the virus altogether.
In order to be successful, an AIDS vaccine must exhibit a variety of characteristics. First and foremost, it will need to be affordable, especially given that the majority of infections are in developing countries. A vaccine will also need to be effective and flexible – able to address multiple strains of the virus. It must also be able to address two very different challenges unique to HIV: a vaccine must be able to guard against both “free virus” (by stimulating development of antibodies), and infected cells. It is likely, therefore, that a successful vaccine will in actuality be a “cocktail” vaccine, with the capability to address multiple strains and characteristics of this difficult virus.
The process of developing an HIV/AIDS vaccine involves extensive investment, time and commitment. At the outset, extensive basic research is needed, followed by research and development of candidate vaccines. Once a prospective vaccine has been developed and confidence gained in the laboratory, an elaborate system of clinical trials can commence. As noted above, the safety and ethical considerations related to development of AIDS vaccine make clinical testing a laborious procedure. In the first phase, researchers work with a group of 20-40 people to gauge the safety and efficacy of a candidate vaccine. Those prospective vaccines that show early success are advanced to phase II trials, which involve several hundred people. Finally, large-scale, phase III trials are begun involving thousands of individuals. Phase III trials can take up to four years to complete. Only two phase III trials have gotten underway to date (and only recently) in the United States and Thailand.
Researchers are taking a variety of different approaches to try and solve the HIV riddle. And advocacy groups and others are trying to encourage development as many prospective vaccine candidates as is possible. For example, efforts are underway to develop combination vaccines that enhance the responsiveness of the immune system; other researchers are working on DNA vaccines. Combination vaccines use several different vaccines to stimulate various effects by the immune system. Building off of Pasteur’s attenuated vaccines, researchers have been experimenting with antidotes for smallbox and other existing vaccines to generate certain antibodies, and then another vaccine to further advance their development. Combination vaccines have shown the greatest promise to date. DNA vaccines attempt to introduce specific proteins into the human body with the aim of inducing an immune system response. Despite initial optimism for this approach, its efficacy remains elusive.
PROGRESS TO DATE AND PRIORITIES FOR THE FUTURE
Despite the fact that no cure has been found and that only limited phase III trials have begun, there are several bright spots in the development of and AIDS vaccine. After initial optimism was tempered by disappointing results, government research has intensified and become more systematized. As a result, in the last several years, there has been a dramatic increase in the pace at which vaccines are being released for clinical trials.
Similarly, there has been an increase in the amount of resources allocated for vaccine research, including the mobilization of resources from the philanthropic sector. And through advocacy and development of creative incentives (such as guaranteed markets) for vaccines, the private sector has been encouraged to play more a role in vaccine research and development.
The development of an AIDS vaccine is years away from completion and the public needs to be prepared for a long-term, patient yet resolute – even urgent – effort to continue doing the necessary research and development. Moreover, the international community needs to brace itself for the prospect that a single vaccine is unlikely, as is a vaccine that is 100% reliable. And as has been learned with the introduction of anti-retroviral therapies, public health officials will need to launch comprehensive efforts to guard against complacency as vaccines are developed. Continued vigilance in traditional prevention efforts is likely to be crucial for the foreseeable future. That is why continued efforts on another research front – development of women-controlled microbicides is so important.
A microbicide is a compound that women can self-administer to protect themselves from infection by HIV or other sexually transmitted diseases. A microbicide could be produced as a gel, cream, suppository, film, or in the form of a sponge or vaginal ring that slowly releases the active ingredient over time. There is hope that successful microbicidess will also prevent unwanted pregnancy. There are several microbicides under development in laboratories and clinics around the world, but none are available yet because the research is complicated and under-funded. Microbicides will not cure AIDS, but they will stop transmission of the HIV-virus that causes AIDS.
To learn more about microbicides, visit: The Global Campaign for Microbicides
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