| Successful modification | The parasite was generated by the genetic modification |
| The mutant contains the following genetic modification(s) |
Gene mutation
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| Reference (PubMed-PMID number) |
Reference 1 (PMID number) : 25092912
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| MR4 number |
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| Parent parasite used to introduce the genetic modification |
| Rodent Malaria Parasite | P. berghei |
| Parent strain/line | P. berghei ANKA |
| Name parent line/clone |
P. berghei ANKA 2.34
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| Other information parent line | P. berghei ANKA 2.34 is a cloned, gametocyte producer line of the ANKA strain (PubMed: PMID: 15137943). |
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| The mutant parasite was generated by |
| Name PI/Researcher | Mizutani M; Sinden RE; Yoshida S |
| Name Group/Department | Laboratory of Vaccinology and Applied Immunology |
| Name Institute | Kanazawa University School of Pharmacy |
| City | Kanazawa |
| Country | Japan |
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| Name of the mutant parasite |
| RMgm number | RMgm-1104 |
| Principal name | PvCSP(Sal)/Pb; PvCSP(VK210)/Pb |
| Alternative name | |
| Standardized name | |
| Is the mutant parasite cloned after genetic modification | Yes |
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| Phenotype |
| Asexual blood stage | Not different from wild type |
| Gametocyte/Gamete | Not different from wild type |
| Fertilization and ookinete | Not different from wild type |
| Oocyst | Not different from wild type |
| Sporozoite | Not different from wild type |
| Liver stage | Not different from wild type |
| Additional remarks phenotype | Mutant/mutation
In the mutant the endogenous P. berghei csp gene is replaced with (part of) the csp gene (210 allele) of P. vivax PVP01_0835600). See also 'Additional information genetic modification'.
Protein (function)
The CS protein is the major protein on the surface of sporozoites and is critical for development of sporozoites within the oocysts and is involved in motility and invasion of both the salivary gland of the mosquito and the liver cells. The protein is also found on the oocyst plasma membrane and on the inner surface of the oocyst capsule. Specific motifs in CS are involved in sporozoite binding to mosquito salivary glands and in sporozoite attachment to heparan sulfate proteoglycans in the liver of the mammalian host. During substrate-dependent locomotion of sporozoites, CS is secreted at the sporozoite anterior pole, translocated along the sporozoite axis and released on the substrate at the sporozoite posterior pole. Following sporozoite invasion of hepatocytes, the CS is released in the host cell cytoplasm.
Phenotype
The phenotype analyses indicate that the CS protein of P. vivax can complement the activity of the endogenous P. berghei CS protein.
Additional information
In the paper the development of a multistage Plasmodium vivax vaccine is described, which simultaneously expresses circumsporozoite protein (PvCSP) and P25 (Pvs25) protein of this species as a fusion protein, thereby acting as a pre-erythrocytic and TB vaccine, respectively. A new-concept vaccine platform based on the Baculovirus Dual Expression System (BDES) was evaluated. The BDES-Pvs25-PvCSP vaccine displayed correct folding of the Pvs25-PvCSP fusion protein on the viral envelope, and was highly expressed upon transduction of mammalian cells in vitro. This vaccine induced high levels of antibodies to Pvs25 and PvCSP, and elicited protective (43%) and TB efficacies (82%) against transgenic P. berghei parasites expressing the corresponding P. vivax antigens in mice.
Other mutants
RMgm-1443: In the mutant the endogenous P. berghei csp gene is replaced with (part of) the csp gene (247 allele) of P. vivax PVP01_0835600).
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*RMgm-1104
