{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T04:41:38Z","timestamp":1791434498672,"version":"4.3.3"},"update-to":[{"DOI":"10.1371\/journal.ppat.1008864","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T00:00:00Z","timestamp":1626220800000}}],"reference-count":99,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI137154"],"award-info":[{"award-number":["R01AI137154"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007601","name":"Horizon 2020","doi-asserted-by":"publisher","award":["MultiViVax 773073"],"award-info":[{"award-number":["MultiViVax 773073"]}],"id":[{"id":"10.13039\/501100007601","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["206194\/Z\/17\/Z"],"award-info":[{"award-number":["206194\/Z\/17\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    <jats:italic>Plasmodium vivax<\/jats:italic>\n                    is responsible for the majority of malaria cases outside Africa. Unlike\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>falciparum<\/jats:italic>\n                    , the\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>vivax<\/jats:italic>\n                    life-cycle includes a dormant liver stage, the hypnozoite, which can cause infection in the absence of mosquito transmission. An effective vaccine against\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>vivax<\/jats:italic>\n                    blood stages would limit symptoms and pathology from such recurrent infections, and therefore could play a critical role in the control of this species. Vaccine development in\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>vivax<\/jats:italic>\n                    , however, lags considerably behind\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>falciparum<\/jats:italic>\n                    , which has many identified targets with several having transitioned to Phase II testing. By contrast only one\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>vivax<\/jats:italic>\n                    blood-stage vaccine candidate based on the Duffy Binding Protein (PvDBP), has reached Phase Ia, in large part because the lack of a continuous\n                    <jats:italic>in vitro<\/jats:italic>\n                    culture system for\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>vivax<\/jats:italic>\n                    limits systematic screening of new candidates. We used the close phylogenetic relationship between\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>vivax<\/jats:italic>\n                    and\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>knowlesi<\/jats:italic>\n                    , for which an\n                    <jats:italic>in vitro<\/jats:italic>\n                    culture system in human erythrocytes exists, to test the scalability of systematic reverse vaccinology to identify and prioritise\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>vivax<\/jats:italic>\n                    blood-stage targets. A panel of\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>vivax<\/jats:italic>\n                    proteins predicted to function in erythrocyte invasion were expressed as full-length recombinant ectodomains in a mammalian expression system. Eight of these antigens were used to generate polyclonal antibodies, which were screened for their ability to recognize orthologous proteins in\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>knowlesi<\/jats:italic>\n                    . These antibodies were then tested for inhibition of growth and invasion of both wild type\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>knowlesi<\/jats:italic>\n                    and chimeric\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>knowlesi<\/jats:italic>\n                    lines modified using CRISPR\/Cas9 to exchange\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>knowlesi<\/jats:italic>\n                    genes with their\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>vivax<\/jats:italic>\n                    orthologues. Candidates that induced antibodies that inhibited invasion to a similar level as PvDBP were identified, confirming the utility of\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>knowlesi<\/jats:italic>\n                    as a model for\n                    <jats:italic>P<\/jats:italic>\n                    .\n                    <jats:italic>vivax<\/jats:italic>\n                    vaccine development and prioritizing antigens for further follow up.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1008864","type":"journal-article","created":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T14:48:27Z","timestamp":1625150907000},"page":"e1008864","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":34,"title":["Using Plasmodium knowlesi as a model for screening Plasmodium vivax blood-stage malaria vaccine targets reveals new candidates"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6980-9102","authenticated-orcid":true,"given":"Duncan N.","family":"Ndegwa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prasun","family":"Kundu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica B.","family":"Hostetler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4903-6392","authenticated-orcid":true,"given":"Alejandro","family":"Marin-Menendez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4177-2851","authenticated-orcid":true,"given":"Theo","family":"Sanderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4252-0744","authenticated-orcid":true,"given":"Kioko","family":"Mwikali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5518-8157","authenticated-orcid":true,"given":"Lisa H.","family":"Verzier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5838-1086","authenticated-orcid":true,"given":"Rachael","family":"Coyle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6658-1707","authenticated-orcid":true,"given":"Sophie","family":"Adjalley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9835-1014","authenticated-orcid":true,"given":"Julian C.","family":"Rayner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,7,1]]},"reference":[{"key":"ppat.1008864.ref001","unstructured":"WorldHealthOrganisation. 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