Four species of the genus Plasmodium are human parasites. All of them cause malaria. And while malaria’s characteristic and recurrent waves of chills and fever are a thing of the past in industrialized and temperate countries like the United States, the disease still kills more than a million people each year, mostly children in Africa.
Plasmodium is a single-celled organism that cycles through two organisms: people and mosquitoes. Humans carry the parasite’s asexual phase. After it enters a new host, Plasmodium invades a liver cell and develops into a schizont – a structure that contains thousands of tiny clones of the parasite called merozoites. After a week or two, the schizont ruptures and releases the merozoites into the bloodstream. These new parasites find red blood cells, move inside, and repeat the process, munching on hemoglobin as they divide. Every week or two, the new schizonts rupture and release new merozoites, and the infected host gets sick again.
During these cycles, a few of the merozoites refrain from cloning themselves. Instead, they develop into sexual forms that hang around the bloodstream waiting for a mosquito to come along and bite their host. (They improve their chances by making their host smell more appetizing to mosquitoes.) When a mosquito bites an infected person, she sucks up male and female sexual forms of Plasmodium along with the blood. Inside the mosquito’s stomach, the sex cells mature, fuse, and develop into an oocyst filled with new infective parasites. When the oocyct ruptures, thousands of Plasmodium migrate to the mosquito’s salivary glands, ready to infect the next person she bites.
A lot of experimental vaccines have targeted Plasmodium in humans, with limited success. Vaccines prime the immune system to target the foreign proteins on the surface of a disease-causing cell. But the immune system can only target the cells it contacts in the bloodstream and interstitial fluids. Because the parasite spends most of its time on the inside of liver and red blood cells, it is usually invisible to the host’s immune system.
One research group from the National Institutes of Health is trying a different approach to the problem. They’ve developed a vaccine that targets a protein found on the reproductive forms of the parasite. So far, it’s only been tested in mice, but the results are promising. Here’s the idea: a person who gets the shot makes antibodies against the protein. The antibodies stay in the blood and get sucked up by biting mosquitoes along with the immature sexual forms of the parasite. As the sexual forms of Plasmodium mature inside the mosquito, the antibodies block their development, and the mosquito never becomes a malaria carrier.
So this vaccine doesn’t prime the human immune system to attack the merozoites directly – they’re hidden away inside cells most of the time anyway. Instead, it uses a human as an antibody-making machine to vaccinate the mosquitoes. It’s a shot for malaria that doesn’t prevent a person from getting malaria. But ideally, if enough people get the vaccine the area’s mosquito population will eventually lose the ability to transmit the parasite.
Kubler-Kielb, J., F. Majadly, Y. Wu, D. L. Narum, C. Guo, L. H. Miller, J. Shiloach, J. B. Robbins and R. Schneerson 2007. Long-lasting and transmission-blocking activity of antibodies to Plasmodium falciparum elicited in mice by protein conjugates of Pfs25 PNAS 104: 293-208. doi:10.1073/pnas.06098851
Malaria from the National Institutes of Health
Photo from the CDC.