An international team of scientists that includes a researcher from the U.S. Department of Energy's Brookhaven National Laboratory has determined the three-dimensional molecular structure of a promising malaria-vaccine component.
This research may help lead to a successful vaccine for the disease, which currently infects approximately 400 million people worldwide and kills about two million people each year -- mostly children. The study is described in the August 29, 2005, online edition of the Proceedings of the National Academy of Sciences.
"The high number of deaths from malaria is partly due to the malaria parasite's acquired resistance to traditional treatments," said the study's lead researcher, biologist Adrian Batchelor of the University of Maryland School of Pharmacy. "The parasite is a highly complex organism that develops through different life-cycle stages. This has allowed it to evade the immune system and makes creating a comprehensive vaccine a difficult task."
Malaria vaccines to date have not been entirely effective, only able to temporarily suppress the disease. A complete, fully protective malaria vaccine will likely consist of several components, each only partially successful at fighting malaria on its own. The potential "part" studied here is a protein known as "Apical Membrane Antigen 1" (AMA1), a protein found on the cell membrane of Plasmodium falciparum, the parasite that causes the most deadly form of malaria.
A vaccine based on AMA1 has a good chance for success because AMA1 is produced, or "expressed," in two critical parasite life-cycle stages. However, across different malaria strains, AMA1 can have many slight structure variations, called "polymorphisms." These variations are problematic for vaccine development. Locating the polymorphic sites on AMA1 by determining its structure is essential to understanding how those sites might impact the development of a vaccine.
The research team focused on a particular segment of AMA1. They studied it using x-rays at Brookhaven's National Synchrotron Light Source (NSLS), a facility that produces x-ray, ultraviolet, and infrared light for research. The x-ray analysis showed that the segment consists of two distinct regions, called domains, and further revealed unusual features: long molecular loops extending outward from the center of one domain. These loops form a "scaffold" for attached amino acids, which can mutate without affecting the function of AMA1. These mutations produce the different AMA1 polymorphisms.