New Antibody and Unique Binding Site Offer Possible Paths to Malaria Prevention

Scientists have discovered a human antibody that, when tested in mice, prevented malaria infection by binding a specific portion of a surface protein found in almost all strains of the malaria parasite worldwide. The human antibody was isolated from a protected subject who received an experimental vaccine containing whole, weakened malaria parasites (PfSPZ Vaccine-Sanaria).

The paired findings -- of both the antibody and the site it targets on the surface protein -- could open new pathways to malaria prevention. The research, published today in the journal Nature Medicine, was led by scientists at the National Institutes of Health and the Vaccine and Infectious Disease Division of Fred Hutchinson Cancer Research Center.

The study shows that the antibody, called CIS43, protects against malaria better than any antibody that has been described before, said Dr. Marie Pancera, a Fred Hutch structural biologist and co-senior author of the study with the NIH's Dr. Robert A. Seder. If shown to be effective in humans, the antibody could be given to people directly and potentially protect them from malaria for up to six months. Preventive malaria drugs available now must be taken daily.

What especially interests Pancera is whether researchers could use the unique binding site identified in the study, on the surface protein known as circumsporozoite protein, or CSP, to design a vaccine that could tickle the immune system to produce such antibodies.

Malaria kills about 445,000 people a year, mostly young children in sub-Saharan Africa, and sickens more than 200 million. It is caused by the Plasmodium parasite and spread to humans through the bite of an infected Anopheles mosquito. About half the world's population live in areas that put them at risk of infection and the huge social and economic burden that entails.

The parasite's complex life cycle and rapid mutations have long challenged vaccine developers. Only one experimental vaccine, known as RTS,S, has made it as far as a phase 3 clinical trial, which found it to protect only about one-third of young children who received it. Pilot introduction with continued evaluation is scheduled to begin this year in selected areas of Ghana, Kenya and Malawi.

RTS,S uses a fragment of CSP, the protein exposed at the surface of the malaria parasite, to elicit an immune response. Notably, however, it does not include this new site of vulnerability identified in Seder and Pancera's study. That gives scientists reason to believe that a vaccine that did so would provide broader protection.

Source: Fred Hutchinson Cancer Research Center