A Sporozoite and Liver Stage expressed Tryptophan rich Protein Plays an Auxiliary Role in Plasmodium Liver Stage Development and Is a Potential Vaccine Candidate*
Background: The liver stage is an obligatory step in the Plasmodium life cycle. Results: Liver stage tryptophan rich protein is exported to host cells and plays a role in the development of the exoerythrocytic form. Immunization with this protein protects mice against sporozoite challenge, primarily via T cells. Conclusion: Protein immunization provides T cell based protection. Significance: Tryptophan rich proteins have vaccine potential. The liver stages of the malaria parasite are clinically silent and constitute ideal targets for causal prophylactic drugs and vaccines. Cellular and molecular events responsible for liver stage development are poorly characterized. Here, we show that sporozoite, liver stage tryptophan rich protein (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 18S rRNA 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. Immunofluorescence 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 hours 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.
The Journal of Biological Chemistry