Vaccines：A new health food
GETTING two for the price of one is always a good bargain. And according to a paper in this week’s Proceedings of the National Academy of Sciences, that is what Tomonori Nochi of the University of Tokyo and his colleagues have done. Using genetic engineering, they have overcome two of the limitations of vaccines. One is that they are heat-sensitive and thus have to be transported along a “cold chain” of refrigerators to the clinics where they are used. The other is that, although they stimulate immune responses inside the body, they often fail to extend that protection to the outside, where it might prevent bacteria and viruses getting inside in the first place.In this context, the outside is not the skin: that is dry and hostile to germs. It is the damp and welcoming surface of places such as the lung and the gut that are at risk. Although these are casually called internal, technically they are not. Any nasties in the gut or lungs have to cross the walls of those organs before they can multiply inside the body.
Dr Nochi’s genetic engineering involved growing the vaccine in rice. To prove the principle, he chose cholera, but it should work with other vaccines as well. With cholera, the immune response is induced by what is known as the cholera toxin B-subunit. This is a protein, and Dr Nochi took the gene that encodes it and inserted that gene into the genome of rice. Next to the B-subunit gene itself, he inserted a second piece of DNA called a promoter. This, as its name suggests, promotes activity in an adjacent gene. Promoters themselves are activated by other molecules, and whether they are switched on or not depends on whether the cell they are in provides the necessary stimulation. In this case Dr Nochi picked a promoter that is active in the tissue of rice grains.
It was then just a question of growing the rice and feeding the resulting grains to some experimental mice to find out what would happen. The first thing that happened was that the grains protected the B-subunit from being broken down in the stomach, thus overcoming one of the regular bugbears of protein-based drugs: that they cannot be given by mouth, because they will be digested. This is a problem with today’s cholera vaccine which is indeed taken by mouth and therefore affords poor protection. When the B-subunits got to the intestines they did exactly what Dr Nochi hoped and induced the production of antibodies and the secretion of those antibodies into the mucous coating of the intestinal wall. Dr Nochi’s mice really were protected. When he fed them cholera toxin, they did not get sick.
On top of all this, he got as good a response with rice that had been stored at room temperature for 18 months as he did when he used fresh grains. For a vaccine against a disease that is found predominantly in poor countries—places that tend to lack refrigerators and have only intermittent power to run those that do exist—that is an enormous advance. If Dr Nochi’s finding can be translated into a product that is safe and effective for people, it will be a big boost to the health of the world’s poor.
