Circumsporozoite protein explained

Circumsporozoite protein (CSP) is a secreted protein of the sporozoite stage of the malaria parasite (Plasmodium sp.) and is the antigenic target of RTS,S and other malaria vaccines.^[1] The amino-acid sequence of CSP consists of an immunodominant central repeat region flanked by conserved motifs at the N- and C- termini that are implicated in protein processing as the parasite travels from the mosquito to the mammalian vector.^[2] The amino acid sequence of CSP was determined in 1984.^{[3] [4]}

The structure and function of CSP is highly conserved across the various strains of malaria that infect humans, non-human primates and rodents. It can first be detected in large quantities as sporozoites are forming within oocysts residing in the midgut walls of infected mosquitoes. Upon egression from mature oocysts, sporozoites begin migrating to the salivary glands, and CSP is known to be an important mediator of this process. Additionally, CSP is involved in hepatocyte binding in the mammalian host. Here, the N-terminus and central repeat region initially facilitate parasite binding.^[5] On the hepatocyte surface proteolytic cleavage at region 1 of the N-terminus exposes the adhesive domain of the C-terminus, thereby priming the parasites for invasion of the liver.^[6]

CSP is an approximately 58 kD protein, anchored to the parasite's cell surface via a GPI-anchor.^[7]

Notes and References

1. Porter. Michael. Jennifer Nicki . Christopher Pool . Transgenic Parasites Stably Expressing Full-Length Plasmodium falciparum Circumsporozoite Protein as a Model for Vaccine Down-Selection in Mice Using Sterile Protection as an Endpoint. Clinical and Vaccine Immunology. June 2013. 20. 6. 803–810. 10.1128/cvi.00066-13. 3675977. 23536694.
2. Aldrich. Cassandra. Alessandro Magini . Carla Emiliani . Roles of the Amino Terminal Region and Repeat Region of the Plasmodium berghei Circumsporozoite Protein in Parasite Infectivity. PLOS ONE. February 2012. 7. 2. 10.1371/journal.pone.0032524. e32524. 22393411. 3290588. 2012PLoSO...732524A. free.
3. Dame . J. B. . Williams . J. L. . McCutchan . T. F. . Weber . J. L. . Wirtz . R. A. . Hockmeyer . W. T. . Maloy . W. L. . Haynes . J. D. . Schneider . I. . Roberts . D. . 1984-08-10 . Structure of the gene encoding the immunodominant surface antigen on the sporozoite of the human malaria parasite Plasmodium falciparum . Science . 225 . 4662 . 593–599 . 10.1126/science.6204383 . 0036-8075 . 6204383.
4. Enea . V. . Ellis . J. . Zavala . F. . Arnot . D. E. . Asavanich . A. . Masuda . A. . Quakyi . I. . Nussenzweig . R. S. . 1984-08-10 . DNA cloning of Plasmodium falciparum circumsporozoite gene: amino acid sequence of repetitive epitope . Science . 225 . 4662 . 628–630 . 10.1126/science.6204384 . 0036-8075 . 6204384.
5. Rathore. Dharmendar. John B. Sacci . Patricia de la Vega . Thomas F. McCutchan . Binding and Invasion of Liver Cells by Plasmodium falciparum Sporozoites. The Journal of Biological Chemistry. March 2002. 277. 9. 7092–7098. 10.1074/jbc.m106862200 . 11751898. free.
6. Coppi. Alida. Consuelo Pinzon-Ortiz . Christina Hunter . The Plasmodium circumsporozoite protein is proteolytically processed during cell invasion. The Journal of Experimental Medicine. January 2005. 201. 1. 27–33. 10.1084/jem.20040989. 1995445. 15630135.
7. Marques-da-Silva . Camila . Peissig . Kristen . Kurup . Samarchith P. . 2020-07-21 . Pre-Erythrocytic Vaccines against Malaria . Vaccines . 8 . 3 . E400 . 10.3390/vaccines8030400 . 2076-393X . 7565498 . 32708179. free .