There are an estimated 200-300 million people infected with malaria annually, with a mortality rate of 1-3%, and 40% of the world’s population at risk of contracting the disease.  While the RTS,S (Mosquirix, GSK) recombinant protein-based vaccine is a breakthrough as the first vaccine candidate in pilot studies for countering parasites, the efficacy remains low (25-50% in infants and children).

Malaria infection begins when the Anopheles mosquito injects infective sporozoites into the mammalian host.  Sporozoites travel through different cells before settling into their final host hepatocyte. The sporozoite moves into a vacuole created by invagination of the hepatocyte plasma membrane.  Inside this compartment, the sporozoite transforms into a liver stage, which grows rapidly and undergoes multiple rounds of nuclear division.  The mature liver stage releases thousands of merozoites that will establish red blood cell infection in the host.

Liver stages are predicted to express many different proteins, some possibly unique to this stage, but only few of those unique molecules have been identified so far.  Identification of liver stage-specific molecules is important because the infected hepatocyte has been established as the primary target of the immune response in vaccine models for malaria.  In addition, liver stage molecules that can be detected in a human diagnostic sample may be useful for diagnosing early stage malaria.

Researchers in Drexel’s Department of Microbiology & Immunology, the Seattle Biomedical Research Institute, and the Walter Reed Army Institute of Research have isolated liver stage Plasmodium polypeptides.  These proteins are preferentially targeted by immune responses associated with protection from Plasmodium infection and could be used in developing a new malaria vaccine.