Circumsporozoite protein (CSP) is a secreted
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
of the
sporozoite
Apicomplexans, a group of intracellular parasites, have life cycle stages that allow them to survive the wide variety of environments they are exposed to during their complex life cycle. Each stage in the life cycle of an apicomplexan organism i ...
stage of the
malaria
Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. S ...
parasite (''
Plasmodium
''Plasmodium'' is a genus of unicellular eukaryotes that are obligate parasites of vertebrates and insects. The life cycles of ''Plasmodium'' species involve development in a blood-feeding insect host which then injects parasites into a vert ...
'' sp.) and is the
antigen
In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...
ic target of
RTS,S
RTS,S/AS01 (trade name Mosquirix) is a recombinant protein-based malaria vaccine. In October 2021, the vaccine was endorsed by the World Health Organization (WHO) for "broad use" in children, making it the first malaria vaccine candidate, and fi ...
and other
malaria vaccine
A malaria vaccine is a vaccine that is used to prevent malaria. The only approved use of a vaccine outside the EU, as of 2022, is RTS,S, known by the brand name ''Mosquirix''. In October 2021, the WHO for the first time recommended the large-sc ...
s. 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. The amino acid sequence of CSP was determined in 1984.
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
oocyst
Apicomplexans, a group of intracellular parasites, have life cycle stages that allow them to survive the wide variety of environments they are exposed to during their complex life cycle. Each stage in the life cycle of an apicomplexan organism i ...
s 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
A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 80% of the liver's mass.
These cells are involved in:
* Protein synthesis
* Protein storage
* Transformation of carbohydrates
* Synthesis of cholesterol, ...
binding in the mammalian host. Here, the N-terminus and central repeat region initially facilitate parasite binding. On the hepatocyte surface
proteolytic cleavage
Proteolysis is the breakdown of proteins into smaller polypeptides or amino acids. Uncatalysed, the hydrolysis of peptide bonds is extremely slow, taking hundreds of years. Proteolysis is typically catalysed by cellular enzymes called proteases, ...
at region 1 of the N-terminus exposes the adhesive domain of the C-terminus, thereby priming the parasites for invasion of the
liver
The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
.
CSP is an approximately 58
kD soluble protein.
References
{{Reflist
Malaria
Apicomplexan proteins