Development of a Plasmodium berghei transgenic parasite expressing the full-length Plasmodium vivax circumsporozoite VK247 protein for testing vaccine efficacy in a murine model

Mizutani, Masanori; Fukumoto, Shinya; Soubeiga, Adam Patrice; Soga, Akira; Iyori, Mitsuhiro; Yoshida, Shigeto

doi:10.1186/s12936-016-1297-3

Cited by 13 publications

(11 citation statements)

References 34 publications

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“…The role played by low complexity regions within Plasmodium species is debated. Evidence from previous studies have supported either a neutral or functional role of these regions based on experimental and computational analyses of regions primarily in Plasmodium falciparum and few other selected species and strains 10 , 20 , 23 , 41 – 43 . A more comprehensive evolutionary approach has the potential to clarify the role played by LCRs in relation to phenotypic variability by adding information on the history of these regions through time.…”

Section: Discussionmentioning

confidence: 98%

Comparative analysis of low complexity regions in Plasmodia

Chaudhry

Lwin

Phelan

et al. 2018

Sci Rep

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Low complexity regions (LCRs) are a common feature shared by many genomes, but their evolutionary and functional significance remains mostly unknown. At the core of the uncertainty is a poor understanding of the mechanisms that regulate their retention in genomes, whether driven by natural selection or neutral evolution. Applying a comparative approach of LCRs to multiple strains and species is a powerful approach to identify patterns of conservation in these regions. Using this method, we investigate the evolutionary history of LCRs in the genus Plasmodium based on orthologous protein coding genes shared by 11 species and strains from primate and rodent-infecting pathogens. We find multiple lines of evidence in support of natural selection as a major evolutionary force shaping the composition and conservation of LCRs through time and signatures that their evolutionary paths are species specific. Our findings add a comparative analysis perspective to the debate on the evolution of LCRs and harness the power of sequence comparisons to identify potential functionally important LCR candidates.

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Section: Discussionmentioning

confidence: 98%

Comparative analysis of low complexity regions in Plasmodia

Chaudhry

Lwin

Phelan

et al. 2018

Sci Rep

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“…b Salivary gland sporozoite no. b Reference; RMgmDB ID c Remarks (mutation, sporozoite phenotype) Chimeric CSP parasite lines P. berghei Py CSP WT WT [ 44 ]; 75 P. berghei Pf CSP WT Reduced (90%) [ 52 ]; 69 P. berghei Pf CSP WT Reduced (90%) 342 P. berghei Pf CSP WT WT [ 53 ]; 4110 P. berghei Pf CSP WT WT [ 54 ]; 4135 P. yoelii Pf CSP WT WT [ 55 ]; 1442 P. berghei Pv CSP-210 WT WT [ 27 ]; 4136 P. berghei Pv CSP-247 WT WT [ 28 ]; 1443 P. berghei Pv CSP-247 WT …”

Section: Resultsmentioning

confidence: 99%

“…The lack of complete functional complementation was unexpected, since chimeric rodent Plasmodium berghei parasites expressing Pv CSP-VK210 and Pv CSP-VK247 are able to produce salivary gland sporozoites in An. stephensi mosquitoes that are infective to mice [ 27 , 28 ]. The findings in this study and the species-specific features of CSP that may govern full maturation and development of sporozoites of the two human malaria-parasite species are discussed.…”

Section: Introductionmentioning

confidence: 99%

Chimeric Plasmodium falciparum parasites expressing Plasmodium vivax circumsporozoite protein fail to produce salivary gland sporozoites

Marin-Mogollon

Pul

Miyazaki

et al. 2018

Malar J

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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.Electronic supplementary materialThe online version of this article (10.1186/s12936-018-2431-1) contains supplementary material, which is available to authorized users.

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“…While previous studies using intravenously inoculated sporozoites demonstrated that P. yoelii sporozoites develop better in the liver compared to P. berghei (16)(17)(18)(19), our results suggest that the higher infectivity of P. yoelii sporozoites is also due to their behavior in the skin, further supporting the notion that sporozoite motility in the dermis is a valid correlate for infectivity of the parasite. Recently a number of transgenic rodent parasite lines expressing P. falciparum or P. vivax CSP have been developed for pre-clinical vaccine testing in the rodent model (27)(28)(29). The different biology of the two rodent malaria species could impact the interpretation of antibody-based interventions performed in the rodent model and should be considered when evaluating vaccine candidates targeting sporozoites.…”

Section: Discussionmentioning

confidence: 99%

Quantitative intravital imaging ofPlasmodium falciparumsporozoites: A novel platform to test malaria intervention strategies

Hopp

Kanatani

Archer³

et al. 2019

Preprint

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Malaria infection starts with the injection of motile Plasmodium sporozoites into the host's skin during a mosquito bite. Previous studies using the rodent malaria model indicate that the dermal inoculation site may be where sporozoites are most vulnerable to antibodies, yet, functional in vivo assays with human malaria parasites are lacking. Here, we present the first characterization of P. falciparum sporozoites in the skin, comparing their motility to two rodent malaria species and investigating whether the environment of its natural host influences P. falciparum sporozoite motility using a human skin xenograft model. The combined data suggest that in contrast to the liver and blood stages, the skin is not a species-specific barrier for Plasmodium. We observe that P. falciparum sporozoites inoculated into mouse skin move with similar speed, displacement and duration, and enter blood vessels in similar numbers as the rodent parasites. Thus, interventions targeting P. falciparum sporozoite migration can be tested in the murine dermis. Importantly, to streamline quantification of sporozoite motility, we developed a toolbox allowing for automated detection and tracking of sporozoites in intravital microscopy videos. This establishes a platform to test vaccine candidates, immunization protocols, monoclonal antibodies and drug candidates for their impact on human malaria sporozoites in vivo. Screening of intervention strategies for in vivo efficacy against Pf sporozoites using this new platform will have the potential to validate targets prior to expensive clinical trials.

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Development of a Plasmodium berghei transgenic parasite expressing the full-length Plasmodium vivax circumsporozoite VK247 protein for testing vaccine efficacy in a murine model

Cited by 13 publications

References 34 publications

Comparative analysis of low complexity regions in Plasmodia

Comparative analysis of low complexity regions in Plasmodia

Chimeric Plasmodium falciparum parasites expressing Plasmodium vivax circumsporozoite protein fail to produce salivary gland sporozoites

Quantitative intravital imaging ofPlasmodium falciparumsporozoites: A novel platform to test malaria intervention strategies

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