Scientists using genetic engineering have produced a prototype malaria vaccine that works on mice and rabbits and that could be tested on humans as early as this summer if the Food and Drug Administration approves.
"If everything works, you could have a generally available vaccine in three to five years," said W. Ripley Ballou, of the Walter Reed Army Institute of Research here, one of the vaccine's 11 developers from five research centers.
Though eradicated from the United States, malaria remains the leading killer in the developing world. The World Health Organization estimates that there are 150 million new cases each year. In Africa, the hardest hit, more than 1 million children a year die from malaria and many millions of children and adults are disabled.
The experimental vaccine is one of several being developed at centers in the United States, Australia and Sweden to attack different stages of the malaria parasite's complex life cycle, which shuttles between humans and mosquitos. Researchers are reported moving rapidly to produce what are sometimes called synthetic vaccines.
Progress has been so rapid that world health experts are beginning to envision worldwide immunization campaigns. Although this first malaria vaccine might not be totally effective, others are nearing the testing stage. A combination of them may be best.
"Malaria vaccines are one of the hottest areas in science right now, and I'm very sanguine that we're going to get a useful vaccine in maybe five years," said Kenneth Warren, director for health sciences of the Rockefeller Foundation, which has supported parts of the research.
Conventional vaccines, which contain dead or crippled infectious agents such as bacteria and viruses, have proven impossible so far with malaria because the disease is caused by an organism -- a one-celled parasitic animal -- that no one has found a way to grow in the laboratory in large enough quantities. Synthetic vaccines, by contrast, contain laboratory-made replicas of portions of protein molecules that exist on the infectious agent's surface.
It is similar surface proteins on viruses and bacteria that stimulate the immune system to make antibodies, which are protein molecules tailored to bind to the foreign protein. Antibody attack can disable an invading germ and allow white blood cells to engulf and destroy it.
All the new approaches build on work started nearly 20 years ago by Ruth and Victor Nussenzweig of New York University. They identified the surface proteins of the malaria parasite and showed that if antibodies attacked the proteins, the parasite would lose its ability to infect.
A vaccine, the Nussenzweigs reasoned, did not have to contain the whole infectious agent, just the parts that stimulate antibody production. These parts, being portions of protein molecules, can be manufactured in the laboratory by installing into bacteria the genes that encode their structure. As in most recombinant deoxyribonucleic acid technology, the bacteria are grown in vats, each organism manufacturing quantities of the protein specified by the installed gene. This approach was used to make the prototype vaccine.
One possible problem with the vaccine is that its antibodies can act only during the few minutes between the time an infected mosquito bites, injecting thousands of the parasites into a person's bloodstream, and the parasites exit the stream and enter the liver, where antibodies cannot act, to undergo the next stage of their life cycle. If a single parasite makes it safely into the liver, it could produce thousands of progeny.
Some of the other vaccine approaches are aimed at stages in which the parasite enters red blood cells and then breaks out of those cells. One stratagem for a completely effective vaccine would be to combine several different kinds.
The joint report by the 11 scientists in collaboration was published in Science. The lead author was James F. Young of Smith Kline and French Laboratories in Philadelphia.