Since the AIDS epidemic burst upon us in 1981, scientists have feverishly sought a vaccine to protect people from this deadly and incurable disease. But the path to a vaccine has not been easy. Over twenty years and nearly one million American AIDS cases later, an effective AIDS vaccine still eludes the best efforts of researchers.
One problem has thwarted all efforts: the HIV virus that causes AIDS has an unusually mistake-prone DNA copying
Making mistakes here and there as it produces offspring virus particles, HIV generates mutations at a prodigious rate. That is why few of those infected with HIV have exactly the same virus. A vaccine targeted against one version is ineffective against others.
Like a thief of many disguises, at least a few of the HIV particles in an infection are able to dodge any antibody a vaccine throws against it.
For twenty years this problem has seemed insurmountable, but recently researchers have devised a solution. They seized on a property of mutation so obvious it had been largely overlooked- mutations are accidents. A strain of HIV may produce numerous mutations as it proliferates, but each of these mutations occurs as a random mistake in a different virus particle.
No two particles undergo exactly the same mutation.
The key to an effective vaccine, then, is to use more than one HIV protein. In initial experiments, researchers used three. Any one virus might have mutated to be different from one of the three proteins, but the probability of all three proteins being mutated in the same virus particle is about the same as lightning striking the same person three times-real, but very very small.
Not content with this innovation, researchers set out to boost the power of the immune defenses. The human body has another line of immune defense, the cell-mediated response. Why not bring this to bear as well?
In a double-barreled attack on HIV, the researchers first infected 24 monkeys with a circular piece of naked DNA containing three HIV genes. Such naked DNA readily infects human cells. Once inside, it directs the production of the three HIV proteins. Passing to the cell surface, these proteins create a mock-HIV infection that kicks cell-mediated immunity into action. To the immune system, the cells look HIV-infected. Rushing to the body’s defense, the immune system produces killer cells that wait in ambush to attack and destroy any body cells displaying one of the three proteins.
A few weeks later, the researchers administered the same three HIV genes to the monkeys, but this time the HIV genes are stitched into a harmless virus. Introduced this way, they activate a monkey’s antibody defenses instead of its cell-mediated immunity. Within a few days, a burst of antibodies is produced directed against the three HIV proteins.
Seven months later, the 24 vaccinated animals were “challenged” by inoculating them with a laboratory version of HIV. Called SHIV, it is a genetically engineered version that is part HIV (to make it lethal) and part simian AIDS virus (to enable it to infect monkeys).
The vaccine worked! For more than a year, after the SHIV challenge, 23 of the infected monkeys continued to control the infection, and still had healthy immune systems. Four unvaccinated control animals, by contrast, all developed simian AIDS and died.
It was too soon to consider the vaccine a complete success, however. The monkeys remained HIV-infected, and after a year the HIV in the monkeys had accumulated mutations that allowed the infection to circumvent the immune defenses provided by the vaccine, and the monkeys began to die of simian AIDS. The vaccine had bought time, but not solved the basic problem of ridding the body of the virus.
Learning from this partial success, researchers have tweaked the approach in numerous ways. Although there were only two (unpromising) vaccines in clinical trials in the year 2000, now more than 2 dozen different AIDS vaccines have started clinical trials, employing this double-barreled, multigene approach in different ways.
It is difficult to avoid hope for these exciting developments. However, keep in mind that the initial studies were of an SHIV vaccine developed for monkeys.
There is no guarantee that it will work with humans. Many exciting discoveries fail to clear this last crucial hurdle. But in more than 20 years, no candidate AIDS vaccines have looked so promising.
