About: Quantification of Plasmodium knowlesi versus Plasmodium falciparum in the rhesus liver: implications for malaria vaccine studies in rhesus models

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About: Quantification of Plasmodium knowlesi versus Plasmodium falciparum in the rhesus liver: implications for malaria vaccine studies in rhesus models Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Quantification of Plasmodium knowlesi versus Plasmodium falciparum in the rhesus liver: implications for malaria vaccine studies in rhesus models
Creator	Murphy, Sean Hoffman, Stephen Kim Lee Sim, B. Seilie, Annette Shears, Melanie
Source	PMC
abstract	BACKGROUND: Rhesus macaques are valuable pre-clinical models for malaria vaccine development. The Plasmodium knowlesi/rhesus and Plasmodium falciparum/rhesus models are two established platforms for malaria vaccine testing, and both have previously been used to assess live-attenuated sporozoite vaccines. However, there is evidence that the susceptibility of the rhesus liver to P. knowlesi versus P. falciparum sporozoites likely differs, potentially complicating comparisons between these two platforms. METHODS: To quantify the differing susceptibility of rhesus to P. knowlesi and P. falciparum sporozoites, animals were infected by direct venous inoculation of purified, cryopreserved wild-type P. knowlesi sporozoites (PkSPZ) or P. falciparum sporozoites (PfSPZ). The entire liver was collected 5 days post-infection, and parasite burden in each liver lobe was quantified using an ultrasensitive Plasmodium 18S rRNA RT-PCR biomarker assay. The potential of using 18S rRNA copy number in the rhesus liver to directly measure the efficacy of vaccines targeting P. falciparum sporozoites and liver stages was also theoretically evaluated. RESULTS: Infection of rhesus with a high dose of PkSPZ led to consistently high burden liver stage infections (range 9.5–10.1 log(10) copies 18S rRNA/g of liver), with similar amounts of parasite 18S rRNA detected in every liver lobe. Inoculation of rhesus with high doses of PfSPZ led to more variable, lower liver burdens (range 4.9–6.6 log(10) copies 18S rRNA/g of liver in infected lobes), with parasite 18S rRNA below the limit of detection in some liver lobes. The low signal and heterogeneity of liver burden in the PfSPZ-infected animals indicates that even this extremely sensitive molecular assay cannot be used to assess reliably vaccine efficacy in the P. falciparum/rhesus platform. CONCLUSIONS: Detection of 18S rRNA in the liver following high dose intravenous PfSPZ confirmed that rhesus are modestly susceptible to wild-type P. falciparum sporozoites. However, comparison of 18S rRNA RT-PCR biomarker signal indicates that the P. falciparum liver burden was 3–5 logs lower than in PkSPZ-infected animals. Quantification of this difference in liver stage burden will help guide and interpret data from pre-clinical studies of live-attenuated sporozoite vaccines in rhesus models.
has issue date	2020-08-31(xsd:dateTime)
bibo:doi	10.1186/s12936-020-03385-4
has license	cc-by
schema:url	https://doi.org/10.1186/s12936-020-03385-4
resource representing a document's title	Quantification of Plasmodium knowlesi versus Plasmodium falciparum in the rhesus liver: implications for malaria vaccine studies in rhesus models
has PubMed Central identifier	PMC7457220
schema:publication	Malar J
resource representing a document's body	covid:PMC7457220#body_text
is schema:about of	named entity 'Plasmodium knowlesi' named entity 'liver' named entity 'parasites' named entity 'liver' named entity 'antigen' named entity 'sporozoites' named entity 'liver' named entity 'live-attenuated' named entity 'vaccine' named entity 'P. falciparum' named entity 'blood stage' named entity 'sporozoites' named entity 'liver' named entity 'induced immunity' named entity 'liver' named entity 'body weight' named entity 'malaria' named entity 'liver' named entity 'RNA' named entity 'parasites' named entity 'live-attenuated' named entity 'cryopreserved' named entity 'liver' named entity 'sporozoites' named entity 'liver' named entity 'parasite' named entity 'sporozoite' named entity 'treatment group' named entity 'infection' named entity 'virulent' named entity 'live-attenuated' named entity 'inoculation' named entity 'USP' named entity 'parasite' named entity '18S rRNA' named entity 'P. knowlesi' named entity 'liver' named entity 'liver' named entity 'correlation' named entity 'P. falciparum' named entity 'dynamic range' named entity 'confounding variables' named entity 'P. falciparum' named entity 'parasites' named entity 'aseptic' named entity 'parasite' named entity 'immunogenicity' named entity 'lysate' named entity 'liver' named entity 'live-attenuated' named entity 'sporozoite' named entity 'vaccine' named entity 'P. falciparum' named entity 'cryopreservation' named entity 'cryopreservation' named entity 'sporozoites' named entity 'human malaria' named entity '18S rRNA' named entity '18S rRNA' named entity 'vaccine studies' named entity 'sporozoite' named entity 'euthanasia' named entity 'liver' named entity 'vaccine efficacy' named entity 'sporozoite' named entity 'non-human primates' named entity 'sporozoites' named entity 'blood samples' named entity 'ketamine' named entity 'liver' named entity 'sporozoites' named entity 'clinical trials' named entity 'correlates of protection' named entity '18S rRNA' named entity 'parasite' named entity 'cryopreserved' named entity 'copy number' named entity 'sporozoites' named entity 'wild-type' named entity 'parasite'

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