ArticleMalaria journal2018
Chimeric Plasmodium falciparum parasites expressing Plasmodium vivax circumsporozoite protein fail to produce salivary gland sporozoites.
Article in Malaria journal, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Generation of a TransgenicVaccines · 2025Article
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- A versatile Plasmodium falciparum reporter line expressing NanoLuc enables highly sensitive multi-stage drug assays.Communications biology · 2023Article
- Malaria therapeutics: are we close enough?Parasites & vectors · 2023Review
- Article
- Creation and preclinical evaluation of genetically attenuated malaria parasites arresting growth late in the liver.NPJ vaccines · 2022Article
- Malaria parasite evades mosquito immunity by glutaminyl cyclase-mediated posttranslational protein modification.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- A universal vaccine candidate against Plasmodium vivax malaria confers protective immunity against the three PvCSP alleles.Scientific reports · 2021Article
- Article
- Potential and Limitations of Cross-Protective Vaccine against Malaria by Blood-Stage Naturally Attenuated Parasite.Vaccines · 2020Article
- Generation of a Genetically Modified ChimericFrontiers in cellular and infection microbiology · 2020Article
- Cutting back malaria: CRISPR/Cas9 genome editing of Plasmodium.Briefings in functional genomics · 2019Review
- Investigating immune responses to parasites using transgenesis.Parasites & vectors · 2019Review
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Authors and funding
15 authors.
Funding
Abstract
backgroundRodent malaria parasites where the gene encoding circumsporozoite protein (CSP) has been replaced with csp genes from the human malaria parasites, Plasmodium falciparum or Plasmodium vivax, are used as pre-clinical tools to evaluate CSP vaccines in vivo. These chimeric rodent parasites produce sporozoites in Anopheles stephensi mosquitoes that are capable of infecting rodent and human hepatocytes. The availability of chimeric P. falciparum parasites where the pfcsp gene has been replaced by the pvcsp would open up possibilities to test P. vivax CSP vaccines in small scale clinical trials using controlled human malaria infection studies.
methodsUsing CRISPR/Cas9 gene editing two chimeric P. falciparum parasites, were generated, where the pfcsp gene has been replaced by either one of the two major pvcsp alleles, VK210 or VK247. In addition, a P. falciparum parasite line that lacks CSP expression was also generated. These parasite lines have been analysed for sporozoite production in An. stephensi mosquitoes.
resultsThe two chimeric Pf-PvCSP lines exhibit normal asexual and sexual blood stage development in vitro and produce sporozoite-containing oocysts in An. stephensi mosquitoes. Expression of the corresponding PvCSP was confirmed in oocyst-derived Pf-PvCSP sporozoites. However, most oocysts degenerate before sporozoite formation and sporozoites were not found in either the mosquito haemocoel or salivary glands. Unlike the chimeric Pf-PvCSP parasites, oocysts of P. falciparum parasites lacking CSP expression do not produce sporozoites.
conclusionsChimeric P. falciparum parasites expressing P. vivax circumsporozoite protein fail to produce salivary gland sporozoites. Combined, these studies show that while PvCSP can partially complement the function of PfCSP, species-specific features of CSP govern full sporozoite maturation and development in the two human malaria parasites.
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