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Identification, cloning, expression, and characterization of the gene for Plasmodium knowlesi surface protein
Babita Mahajan1, Dewal Jani, Rana Chattopadhyay
1Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, 1401 Rockville Pike, Rockville, MD 20852, USA.
Abstract:
Proteins present on the surface of malaria parasites that participate in the process of invasion and adhesion to host cells are considered attractive vaccine targets. Aided by the availability of the partially completed genome sequence of the simian malaria parasite Plasmodium knowlesi, we have identified a 786-bp DNA sequence that encodes a 262-amino-acid-long protein, containing an altered version of the thrombospondin type I repeat domain (SPATR). Thrombospondin type 1 repeat domains participate in biologically diverse functions, such as cell attachment, mobility, proliferation, and extracellular protease activities. The SPATR from P. knowlesi (PkSPATR) shares 61% and 58% sequence identity with its Plasmodium falciparum and Plasmodium yoelii orthologs, respectively. By immunofluorescence analysis, we determined that PkSPATR is a multistage antigen that is expressed on the surface of P. knowlesi sporozoite and erythrocytic stage parasites. Recombinant PkSPATR produced in Escherichia coli binds to a human hepatoma cell line, HepG2, suggesting that PkSPATR is a parasite ligand that could be involved in sporozoite invasion of liver cells. Furthermore, recombinant PkSPATR reacted with pooled sera from P. knowlesi-infected rhesus monkeys, indicating that native PkSPATR is immunogenic during infection. Further efficacy evaluation studies in the P. knowlesi-rhesus monkey sporozoite challenge model will help to decide whether the SPATR molecule should be developed as a vaccine against human malarias.
Insights
Researchers identified a novel malaria parasite protein, PkSPATR, on the surface of Plasmodium knowlesi. This protein is immunogenic and may be a potential vaccine target for malaria.
Area of Science:
- Malariology
- Parasitology
- Vaccinology
Background:
- Surface proteins of malaria parasites are crucial for host cell invasion and are attractive vaccine targets.
- The thrombospondin type 1 repeat domain (SPATR) is involved in various cellular functions, including attachment and mobility.
Purpose of the Study:
- To identify and characterize a novel SPATR protein from the simian malaria parasite Plasmodium knowlesi (PkSPATR).
- To investigate the expression, function, and immunogenicity of PkSPATR as a potential malaria vaccine candidate.
Main Methods:
- Genome sequence analysis to identify the PkSPATR gene.
- Recombinant protein expression in Escherichia coli.
- Immunofluorescence assays to determine protein localization.
- Binding assays with HepG2 cells.
- Serological assays using monkey sera.
Main Results:
- A 786-bp DNA sequence encoding a 262-amino-acid protein (PkSPATR) with an altered thrombospondin type 1 repeat domain was identified.
- PkSPATR shares significant sequence identity with orthologs from P. falciparum and P. yoelii.
- Immunofluorescence revealed PkSPATR is expressed on sporozoite and erythrocytic stages of P. knowlesi.
- Recombinant PkSPATR binds to HepG2 cells, suggesting a role in sporozoite invasion.
- Native PkSPATR is immunogenic in P. knowlesi-infected rhesus monkeys.
Conclusions:
- PkSPATR is a multistage malaria antigen expressed on the parasite surface.
- PkSPATR may function as a ligand involved in host cell invasion.
- Native PkSPATR elicits an immune response during infection, supporting its potential as a vaccine candidate.
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