title: A Sporozoite- and Liver Stage-expressed Tryptophan-rich Protein Plays an Auxiliary Role in Plasmodium Liver Stage Development and Is a Potential Vaccine Candidate.
abstract: 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.
authors.affiliation: From the Infectious Diseases Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Dabbu Kumar
authors.initials: DK
authors.lastname: Jaijyan
authors.affiliation: From the Infectious Diseases Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Himanshu
authors.initials: H
authors.lastname: Singh
authors.affiliation: From the Infectious Diseases Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi 110067, India singhap@nii.res.in.
authors.forename: Agam Prasad
authors.initials: AP
authors.lastname: Singh
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000852:Anopheles / Q000469:parasitology; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D007111:Immunity, Cellular; D007114:Immunization; D007303:Insect Vectors / Q000469:parasitology; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D008288:Malaria / Q000276:immunology / Q000469:parasitology / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010962:Plasmodium berghei / Q000235:genetics / Q000276:immunology*; D015800:Protozoan Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D016415:Sequence Alignment; D034101:Sporozoites / Q000737:chemistry / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000469:parasitology
chemical_list: D017780:Malaria Vaccines; D015800:Protozoan Proteins; D011994:Recombinant Proteins
keywords: liver; malaria; parasitology; plasmodium; vaccine