A Sporozoite and Liverstage Expressed Tryptophan Rich Protein Plays an Auxiliary Role in Plasmodium Liver Stage Development and is a Potential Vaccine Candidate [Molecular Bases of Disease]

May 10th, 2015 by Jaijyan, D. K., Singh, H., Singh, A. P.

The liver stages (LS) of malaria parasite are clinically silent and constitute ideal targets for causal prophylactic drugs and vaccines. Cellular and molecular events responsible for LS development are poorly characterized. Here, we show that SLTRiP forms large multimers. Mice immunized with a purified recombinant SLTRiP protein gave high antibody titers in both inbred and outbred mice. Immunized mice showed highly significant levels of protection upon challenge with sporozoites and exhibited 10,000-fold fewer parasite 18SrRNA copy numbers in their livers. The protection offered by immunization with SLTRiP came mainly from T cells, and antibodies had little role to play despite their high titers. Immunoflourescence assays showed that SLTRiP is expressed in the sporozoite and early to late liver stages of malaria parasites. SLTRiP protein is exported to the cytosol of infected host cells during the early hrs of parasite infection. Parasites deficient in SLTRiP were moderately defective in liver stage parasite development. A transcriptome profile of SLTRiP-deficient parasite infected hepatocytes highlighted that SLTRiP interferes with multiple pathways in the host cell. We have demonstrated a role for SLTRiP in sporozoites and the liver stage of malaria parasites.
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