<i>PLASMODIUM</i> PRE-ERYTHROCYTIC STAGES: BIOLOGY, WHOLE PARASITE VACCINES AND TRANSGENIC MODELS

Abstract

Malaria remains one of the world's worst health problems, which causes 216 million new cases and approximately 655,000 deaths every year WHO World Malaria Report, 2011. Malaria transmission to the mammalian host is initiated through a mosquito bite that delivers sporozoites into the vertebrate host. The injected sporozoites are selectively targeted to liver which is the first obligatory step in infection thus making this stage an attractive target for both drug and vaccine development. Research using rodent models of malaria has greatly facilitated the understanding of several aspects of pre-erythrocytic parasite biology and immunology. However, translation of this knowledge to combat Plasmodium falciparum infections still offers several challenges. We highlight in this review some of the recent advances in the field of Plasmodium sporozoite and liver stage biology and in the generation of whole organism attenuated vaccines. We also comment on the application of transgenic models central to Circumsporozoite Protein (CSP) in understanding the mechanism of pre-erythrocytic immunity.

Calcium-dependent Protein Kinases in Malaria Parasite Development and Infection

“…While migration within RBCs equips the sporozoites with a unique capacity to avoid detection by the host’s immune system, thereby avoiding destruction by phagocytic cells 47 , it also facilitates the contact of sporozoites with several other host factors that influence sporozoite infectivity to hepatocytes. CDPK6 regulates the sporozoite’s switch from migratory to invasive upon sensing high levels of hepatocyte-specific sulfate proteoglycans (HSPGs) once the RBCs reach the liver 48 . Therefore, inhibiting CDPK6 would likely halt the life cycle progression of the malaria parasite by preventing progression to schizonts in the liver, and is a potential therapeutic target.…”