Vaccines Stage A Comeback

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One way that can happen is if a bacterial or viral illness gets out of control before the immune system can respond. That's where vaccines come in. "What a vaccine does," says Nabel, "is alert these specialized cells that an incoming agent could be a problem, and allow the immune system to respond more quickly and effectively than if it had never seen the bug before." In effect, he says, "you move up the immunologic-response chain of events so the final, acquired response kicks in faster."

That hasn't worked so far for deadly diseases like tuberculosis, malaria or AIDS, in part because no model for natural immunity exists for any of them. Thus scientists cannot crib from nature for vaccines, as Jenner did for smallpox. But that is changing as researchers get a sense of how many instruments in the immune-system orchestra they have at their disposal, and how to get the best performance from them. With HIV, for example, the virus mutates too rapidly. No sooner has the acquired immune system learned to identify and lock in on it than HIV develops new antigens on its surface and turns invisible again.

But a recent strategy, shown effective for the first time at NIAID, may be able to thwart this evasive action. Known as "prime-boost," it gives the immune system a whiff of the virus' scent before hitting it with the actual vaccine. In Nabel's lab, that whiff consists of a snippet of DNA from HIV's outer coating--not enough to trigger a full immune response but, as his work was the first to show in animals, enough to put the system on alert. In the past this strategy hasn't worked in humans because our immune system, unlike those of other mammals, doesn't respond robustly enough to DNA alone. To amplify DNA's poor signal strength, Nabel's group sends in the "boost"--a crippled common-cold virus packed with a payload of viral antigens--a few days after priming, and the immune system goes into high gear. That's the theory, anyway.

It's too early to know whether this strategy will work against HIV, but it is already working against another deadly virus. Ebola, though it has claimed far fewer victims than HIV, has enormous potential for devastation. There is no cure or vaccine for it--but in a recent trial, Nabel's group has shown that DNA priming can protect monkeys from Ebola.

A patient-ready AIDS vaccine may not be available for human trials for another decade, but once it is, Nabel and others plan to use every trick they have learned to boost its effectiveness. They may, for example, mix cytokines with the vaccine, counting on these chemicals to rally extra killer T cells against the virus. They may give a small jolt of electricity along with the priming dose of viral DNA; that shock seems to enhance the DNA's ability to trigger a response. And they are even experimenting with firing the DNA directly into immune-system cells at high pressure with so-called gene guns to make sure the nucleic acids have maximum impact.