Genetic Engineering and a New Vaccine for Malaria

Vaccines work by triggering the body's immune system to recognize and arm against a threat; the trick is to create a threat that is close enough to the dangerous microorganism to arm the immune system, but not so close as to make the patient seriously ill. So vaccines are built around dead or weakened organisms or just key parts of them. One version of the malaria vaccine now being tested uses parasites that have been irradiated to within an inch of death.

But we have the technology to weaken pathogens in much more clever ways, that is, by altering them at the genetic level. Case in point, a new, experimental vaccine for malaria:

The new approach disrupts the cycle of infection by knocking out three genes that P. falciparum needs to move into the blood stream. A team led by parasitologist Stefan Kappe at the Center for Infectious Disease Research in Seattle in Washington gave a rodent version of this “genetically attenuated parasite,” or GAP, to mice and showed that they were completely protected when later infected with an unmodified—or wild-type—version of the same Plasmodium strain. The researchers then infected mosquitoes with a GAP designed for P. falciparum and put 150 to 200 of these insects on the arms of 10 human volunteers. As the team reports today in Science Translational Medicine, no one developed malaria or suffered serious harm in this first phase of human tests, and the vaccine triggered antibodies against the sporozoites.

Malaria is a tough case because it enters the body in one form, which slips by our immune system because it is harmless. This harmless form, the sporozoite, migrates to the liver where each one makes thousands of copies of a dangerous form that travels through the blood to the rest of the body; the release of so many of the dangerous forms at once overwhelms the body's defenses, which is why malaria can be a recurrent disease, coming back in wave after wave. The body may defeat the aggressive parasites, but it never eliminates the harmless sporozoite. The disease-causing form also has some clever tricks to defeat immune defenses: it is produced in several different forms presenting different proteins to immune cells, and the prevalence of different surface types changes over time, keeping the immune system guessing. It reproduces very rapidly and also evolves very rapidly; if the body fully defeats one form, a new one may emerge over a matter of weeks.

So I doubt there will ever be a complete victory over malaria like the victory over smallpox. But genetically engineered vaccines may get us part of the way there.