Salmonella may be a key for a new vaccine

Gates Foundation-backed vaccine developers have found a way to send genetic text messages to the cells of the body to evoke immunity to pneumonia. It could save the lives of a million children a year, yet fluency in the language of the immune system will not come easily.
Crosscut archive image.

Color-enhanced scanning electron micrograph showing <i>Salmonella typhimurium</i> (red) invading cultured human cells. (National Institute of Allergy and Infectious Diseases)

Gates Foundation-backed vaccine developers have found a way to send genetic text messages to the cells of the body to evoke immunity to pneumonia. It could save the lives of a million children a year, yet fluency in the language of the immune system will not come easily.

Researchers at Arizona State University have genetically redesigned salmonella, bane of the salad bar, to deliver instructions for fending off pneumonia directly to cells. The modified salmonella actually destroy themselves in order to release their genetic payload. Affected cells pick up the instructions and blithely manufacture bits of pneumoccocus, prompting an immune response and — hopefully — immunity to pneumonia.

A pneumonia vaccine is already available in the United States. But many nations can't afford the cost, at upwards of $40 per dose. Also, dirt roads and rudimentary to non-existent medical systems further conspire against children getting the four required injections between the ages of one to six years. And if you're lucky enough to surmount those obstacles, you win protection, not from the strains of pneumonia common in your part of the world, but those prevalent in Europe and the United States.

In place of this perverse negligence, how about a single-dose vaccine that can be delivered orally soon after birth? This goal sits topmost among the Gates Foundation's Grand Challenges, the 14 most-needed breakthroughs in global health, and the team based at Arizona State is gunning for it. Lead researcher Roy Curtiss was among the 43 Grand Challenge grantees announced in 2005.

Gates has already enormously strengthened global means of vaccine delivery. The foundation made its first large grant for a vaccination program which, ten years on, has blended into the Global Alliance for Vaccines and Immunization (GAVI). Seeded with a further $1.5 billion from the foundation, GAVI has raised vaccination rates to historic highs.

How soon until this pipeline, branching and spreading over the poorest parts of the world, can be stuffed with new and better vaccines? For all its brilliance, the news from the Curtiss team represents welcome progress rather than breakthrough. An oral vaccine for pneumonia would be a humanitarian and scientific triumph, but Gates wants more than that. He seeks the ability to "program the immune system," making vaccine design a matter of engineering and enabling the systematic — and rapid — development of vaccines.

We aren't there yet. Curtiss has been working on his approach for more than two decades. In fooling the immune system into thinking it has seen a threat from pneumonia (without an actual infection), researchers face an enormous set of biological ruses to choose from, over 100 individual options plus all the possible combinations. However, we don't know enough about the immune system to know which sleight of hand will work without recourse to painstaking experiment.

Also, vaccine candidates first have to work in model animals, like mice, then in humans. Scientists can only cross their fingers and wait for the data. A researcher in tuberculosis guessed that a pool of 20 vaccine candidates will be needed in order to yield one that works in a process taking over nine years. One study showed that, across a decade, only 22 of 266 vaccine candidates succeeded.

Gates hopes to improve on this "costly process of trial and error" and its "uneven record of success," an aspiration figuring among his new Grand Challenges "Explorations." (See the Foundation's new approaches to vaccination.) Recently arrived from Microsoft and at a great remove from laboratory work, Gates hasn't been subjected to the brute force head banging endured by researchers. They would surely welcome an escape — and the many breakthroughs that would attend them — if Gates can find a way out that they themselves have not. Fingers crossed on the pneumonia vaccine.

  

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