Antibodies to liver stage associated with malaria resistance

November 12, 2001

High levels of antibodies against the liver stage of the malaria parasite appear to predict resistance to the disease say researchers from Brown University and the Seattle Biomedical Research Institute.

These findings, presented today at the 50th Annual Meeting of the American Society of Tropical Medicine and Hygiene, could eventually lead to new strategies for malaria vaccines or treatments.

"Malaria occurs in stages in the human body," says Jonathan Kurtis, Assistant Professor of Pathology and Laboratory Medicine at Brown University, and the lead author of the study. "In the first stage a low number of parasites invades the liver.

This liver stage is not harmful. It's the second stage, the blood stage, where the clinical disease we know as malaria occurs."

Proteins, known as antigens, that elicit immune responses are present in the material surrounding the parasite during the liver stage. These liver stage antigens (LSAs) are thought to stimulate resistance to develop against infection with the parasite.

The first LSA (LSA-1) to be identified was isolated using antibodies from a man who was immune to the liver stage but not the bloodstage of the parasite--a result of taking chloroquine for years while living in a malaria endemic area.

Kurtis and his colleagues at the Walter Reed Project in Kenya hypothesized that a strong antibody response to LSA-1 might be associated with high levels of resistance to malaria. To test this hypothesis they treated males in Kenya with antimalarial drugs to clear any existing infection and after 2 weeks tested their blood for the presence of antibodies. They then monitored the men for 20 weeks, testing their blood at regular intervals for malaria parasites. The data showed a relationship between antibody levels and infection.

"If you were one of the lucky few to have a high level of antibodies to LSA-1, you on average had a much lower reinfection density," says Patrick Duffy, Director of the Malaria Antigen Discovery Program at Seattle Biomedical Research Institute and an Infectious Disease Officer at the Walter Reed Army Institute of Research.

Duffy is also an author on the study. "When we repeated the study with a smaller group the following year we saw a similar trend."

Kurtis and Duffy are quick to point out that these results do not prove that high antibody levels to LSA-1 are the cause of disease resistance, only that they are correlated with it.

"We recognize this as a very useful marker for predicting who might have resistance," says Duffy. "The key question is, what is the immune response that is mediating protection? It seems unlikely that the antibody response to LSA-1 alone is enough to prevent infection."

"Other immune responses against LSA-1 are associated with infection as well. In our minds, targeting a vaccine against LSA might be an important component of a malaria vaccine strategy," says Kurtis.

One finding that caught the researchers' attention was that the antibodies that were associated with protection were not those that are typically associated with long-term immunity, the IgG antibodies, but instead were those most commonly seen during and just after an acute infection, the short-term or IgM antibodies.

"In future research we need to seek to better understand how the cells that make IgG and IgM, called B-cells, are stimulated and modulated during malaria infection," says Duffy. "Why don't people mount long-term responses to malaria antigens? Once we figure that out we can translate that information into developing new long-lasting vaccines and therapies."
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Additional releases and a tipsheet for the ASTMH meeting can be found in the online press kit at http://www.astmh.org/meetings/presskit/press.html

American Society for Microbiology

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