A major challenge in developing an effective malaria vaccine has been the ability to produce a version that offers protection against the multiple forms of malaria parasites.

Researchers from the Center for Vaccine Development at the University of Maryland School of Medicine and the University of Bamako in Mali, West Africa, have generated information that may now lead to the creation of an effective vaccine.

Their findings, resulting from the largest study to date of genetic variation in malaria parasites, are published in the March 13, 2007, issue of the journal Public Library of Science Medicine.

"Malaria remains a major cause of disease and death worldwide, killing millions of people each year," says Shannon L. Takala, Ph.D., a post-doctoral fellow in the Center for Vaccine Development who is lead author on the study. "Researchers are trying to develop a vaccine based on proteins on the surface of the malaria parasite. The problem is that these proteins have many genetic variants, making it difficult to create one vaccine that works against all types of parasites. Our study provides data that will guide researchers as to which variants to include in future vaccine formulations, and will allow for a more accurate way to determine the effectiveness of current vaccines being tested in clinical trials."

For this study, 2,309 blood samples were taken from 100 volunteers enrolled in a field study conducted from 1999 to 2001 in Bandiagara, Mali, where the parasite Plasmodium falciparum accounts for 97 percent of malaria infections. The samples were collected monthly during each year’s malaria season and at every diagnosis of clinical malaria in the study population. Those samples underwent genetic tests to determine which forms of a malaria protein used to make malaria vaccines were present in people’s infections.

"We found that the majority of malaria parasites at this site have a different form of the protein than that contained in the leading vaccine candidate," says Takala. "If the vaccine protects only against infections with parasites from the same strain as the vaccine, then it may be less effective in this population. By looking at the relationship between specific genetic changes in the malaria parasite and the risk of malaria illness, we identified parts of the protein that may be important to consider in designing a vaccine that will be effective against multiple strains of the parasite."

"One way to think about this study is to compare it to the development of the polio vaccine" says Christopher V. Plowe, M.D., a professor of medicine at the University of Maryland School of Medicine, who served as Dr. Takala’s faculty advisor on the project. "A critical breakthrough in the development of that vaccine was the identification of the three strains of polio that needed to be included in the vaccine to protect all individuals from the multiple forms of polio," explains Dr. Plowe. "There are similar challenges in developing an effective malaria vaccine, because we don’t know if a vaccine based on a specific malaria strain would provide protection only against similar strains of the parasite. This study has identified genetic variations in malaria parasites in their natural environments, information that we hope can be used by vaccine developers to decide which strains should be included in a broadly protective malaria vaccine."

Funding for this study was provided by the National Institute of Allergy and Infectious Diseases and the United States Agency for International Development.