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The<jats:italic>Plasmodium knowlesi<\/jats:italic>\/rhesus and<jats:italic>Plasmodium falciparum<\/jats:italic>\/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<jats:italic>P. knowlesi<\/jats:italic>versus<jats:italic>P. falciparum<\/jats:italic>sporozoites likely differs, potentially complicating comparisons between these two platforms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To quantify the differing susceptibility of rhesus to<jats:italic>P. knowlesi<\/jats:italic>and<jats:italic>P. falciparum<\/jats:italic>sporozoites, animals were infected by direct venous inoculation of purified, cryopreserved wild-type<jats:italic>P. knowlesi<\/jats:italic>sporozoites (PkSPZ) or<jats:italic>P. falciparum<\/jats:italic>sporozoites (PfSPZ). The entire liver was collected 5\u00a0days post-infection, and parasite burden in each liver lobe was quantified using an ultrasensitive<jats:italic>Plasmodium<\/jats:italic>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<jats:italic>P. falciparum<\/jats:italic>sporozoites and liver stages was also theoretically evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Infection of rhesus with a high dose of PkSPZ led to consistently high burden liver stage infections (range 9.5\u201310.1 log<jats:sub>10<\/jats:sub>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\u20136.6 log<jats:sub>10<\/jats:sub>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<jats:italic>P. falciparum<\/jats:italic>\/rhesus platform.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Detection of 18S rRNA in the liver following high dose intravenous PfSPZ confirmed that rhesus are modestly susceptible to wild-type<jats:italic>P. falciparum<\/jats:italic>sporozoites. However, comparison of 18S rRNA RT-PCR biomarker signal indicates that the<jats:italic>P. falciparum<\/jats:italic>liver burden was 3\u20135 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.<\/jats:p><\/jats:sec>","DOI":"10.1186\/s12936-020-03385-4","type":"journal-article","created":{"date-parts":[[2020,8,31]],"date-time":"2020-08-31T11:03:02Z","timestamp":1598871782000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Quantification of Plasmodium knowlesi versus Plasmodium falciparum in the rhesus liver: implications for malaria vaccine studies in rhesus models"],"prefix":"10.1186","volume":"19","author":[{"given":"Melanie J.","family":"Shears","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annette M.","family":"Seilie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B.","family":"Kim Lee Sim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen L.","family":"Hoffman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2048-0131","authenticated-orcid":false,"given":"Sean C.","family":"Murphy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,8,31]]},"reference":[{"key":"3385_CR1","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.chom.2018.06.008","volume":"24","author":"SJ Draper","year":"2018","unstructured":"Draper SJ, Sack BK, King CR, Nielsen CM, Rayner JC, Higgins MK, et al. 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All animals were cared for in accordance with the NIH Guide for the Care and Use of Laboratory Animals.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"MJS, AMS and SCM declare that they have no relevant competing interests. BKLS is an employee of Sanaria Inc. SLH is Chief Executive and Scientific Officer of Sanaria Inc.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"313"}}