Twenty-one years after the discovery of HIV, researchers have developed treatments that dramatically extend the survival of people with HIV/AIDS (PHAs). However, none of these treatments, known as highly active antiretroviral therapy (HAART), can cure HIV infection. Moreover, HAART has short- and long-term side effects.
Researchers are also trying to develop a vaccine that could block the spread of HIV infection. But designing and testing an effective vaccine to prevent HIV is an undertaking that has been fraught with difficulty. Since 1987, at least 30 different potential HIV vaccines have been tested, all with disappointing results. The most recent failure was the VaxGen trial in North America and Thailand in 2003. Despite these setbacks, HIV vaccine development continues. Here are some of the key challenges researchers need to overcome as well as some possible vaccine strategies that are being investigated.
Some vaccines such as those used to prevent polio and smallpox use very weak viruses that cause infection but not disease. Using even a weakened form of HIV for a vaccine still carries enough risk that such a vaccine might cause AIDS. This has been the case in some experiments with monkeys vaccinated against SIV (simian immunodeficiency virus)—the virus that causes AIDS in those animals. And with current vaccine technology and knowledge, this risk of inadvertent infection from HIV cannot yet be eliminated in people.
Alternatively, researchers could use just pieces or proteins from HIV, such as gp120, gp41, p24 or p17. These cannot cause HIV infection. And by stimulating the immune system with these proteins, antibodies that attack HIV are made. However, this approach was tested in Thailand, North America and the European Union—and it failed.
To try to bridge these two approaches to a vaccine, researchers are using viruses other than HIV, such as weakened forms of pox viruses. Scientists take these viruses and place proteins from HIV inside them. The aim of these types of vaccines is to stimulate cells of the immune system, such as CD8+ cells, and get these cells to attack HIV-infected cells.
But some researchers are beginning to suspect that vaccines that rely on stimulating CD8+ cells are not likely to provide complete protection from HIV. This is because CD8+ cells only attack targets after they have been infected with HIV. Perhaps the best use for vaccines that stimulate CD8+ cells is to help HIV positive people suppress HIV production.
Vaccine designers also have to take into account the two strains of HIV that are known:
Not only are there two types of HIV, but HIV-1 has many subtypes (subtype B, C, D, and so on). Some of these subtypes have mixed or recombined in variations that have features of the parent subtypes.
This raises another issue: HIV is constantly changing or mutating, making it difficult to design a vaccine that will be able to attack every mutation.
Current approaches to HIV vaccine design rely on producing antibodies, stimulating CD8+ cells or both, in the hope that these immune responses will protect people from acquiring HIV infection. Antibodies and CD8+ cells play a role in an immune response called adaptive immunity. This type of response needs time, perhaps at least a week, to ramp up defenses against invading microbes. But in the parts of the body that will likely be the first to encounter HIV—the anus, penis and vagina—a much faster immune response, one that works in minutes or hours, is needed if HIV is to be contained.
The part of the immune system that responds quickly is called innate immunity and it is not well understood. Innate immunity can work against many different types of microbes and involves natural killer cells and many chemical signals and proteins (such as the complement system). The fast response associated with innate immunity has encouraged some scientists to begin studying it in the hope of harnessing this immune response against HIV.
Because of many challenges, it is not going to be easy to produce a vaccine that confers a high degree of protection from HIV. Such a vaccine is called a "sterilizing" vaccine. The good news: A much closer possibility is a "therapeutic" vaccine. This type of vaccine is designed to help the immune systems of PHAs cope better with HIV infection. Therapeutic vaccines may do this by stimulating improved antiviral defenses in general or enhancing specific responses to HIV in particular. One potential therapeutic vaccine is called Remune, and further details about its history appear in the next story.
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