Newly discovered antibodies 'nip' malaria in the bud

The new study describes antibodies able to directly neutralize the parasites injected by the mosquito and therefore to stop the infection in the bud. This work, published in the scientific journal Nature Medicine, was carried out in collaboration with researchers at the Scripps Research Institute in La Jolla and the Center for infectious disease research in Seattle and was partially funded by the Swiss National Science Foundation (SNSF), the European Research Council (ERC), Swiss Vaccine Research Institute and the Fondazione Aldo e Cele Daccò.

The most lethal form of malaria is caused by the protozoan parasite Plasmodium falciparum, which is responsible for approximately 400,000 deaths yearly. Only a small number of Plasmodium parasites (10-100) is delivered during each infectious mosquito bite. These Plasmodium parasites, also called sporozoites, quickly reach the liver where they expand and give rise to a massive infection of the red blood cells that causes a severe pathology. Antibodies can therefore protect at two levels: in the initial phase, by blocking sporozoites, and in the acute phase of the disease, by blocking the infected red blood cells. The same Swiss team had reported, in two papers published previously in the journal Nature, a new molecular mechanism that generates broad-spectrum antibodies able to bind red blood cells infected by the parasite and therefore to keep the infection under control.

A portion of the surface protein of sporozoites (CSP) is the basis of the current vaccine (RTS, S), which unfortunately has only a modest effectiveness in preventing the infection. For this reason, experimental vaccines based on attenuated whole parasites were tested. The Swiss team isolated a series of monoclonal antibodies from individuals who were protected from one of these experimental vaccines (Sanaria PfSPZ Vaccine) and found that the most effective antibodies recognized a distinct region within the surface protein of the sporozoites that has not been considered in malaria vaccines so far. Further testing performed in Seattle revealed that these antibodies were highly potent in reducing malaria infection. In summary, this study has identified a novel part of the parasite surface protein that is a key target of inhibitory antibodies and represents a candidate for a second generation malaria subunit vaccine.