Beschreibung:
<jats:p><jats:italic>Plasmodium vivax</jats:italic>is responsible for the majority of malaria cases outside Africa. Unlike<jats:italic>P</jats:italic>.<jats:italic>falciparum</jats:italic>, the<jats:italic>P</jats:italic>.<jats:italic>vivax</jats:italic>life-cycle includes a dormant liver stage, the hypnozoite, which can cause infection in the absence of mosquito transmission. An effective vaccine against<jats:italic>P</jats:italic>.<jats:italic>vivax</jats:italic>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<jats:italic>P</jats:italic>.<jats:italic>vivax</jats:italic>, however, lags considerably behind<jats:italic>P</jats:italic>.<jats:italic>falciparum</jats:italic>, which has many identified targets with several having transitioned to Phase II testing. By contrast only one<jats:italic>P</jats:italic>.<jats:italic>vivax</jats:italic>blood-stage vaccine candidate based on the Duffy Binding Protein (PvDBP), has reached Phase Ia, in large part because the lack of a continuous<jats:italic>in vitro</jats:italic>culture system for<jats:italic>P</jats:italic>.<jats:italic>vivax</jats:italic>limits systematic screening of new candidates. We used the close phylogenetic relationship between<jats:italic>P</jats:italic>.<jats:italic>vivax</jats:italic>and<jats:italic>P</jats:italic>.<jats:italic>knowlesi</jats:italic>, for which an<jats:italic>in vitro</jats:italic>culture system in human erythrocytes exists, to test the scalability of systematic reverse vaccinology to identify and prioritise<jats:italic>P</jats:italic>.<jats:italic>vivax</jats:italic>blood-stage targets. A panel of<jats:italic>P</jats:italic>.<jats:italic>vivax</jats:italic>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<jats:italic>P</jats:italic>.<jats:italic>knowlesi</jats:italic>. These antibodies were then tested for inhibition of growth and invasion of both wild type<jats:italic>P</jats:italic>.<jats:italic>knowlesi</jats:italic>and chimeric<jats:italic>P</jats:italic>.<jats:italic>knowlesi</jats:italic>lines modified using CRISPR/Cas9 to exchange<jats:italic>P</jats:italic>.<jats:italic>knowlesi</jats:italic>genes with their<jats:italic>P</jats:italic>.<jats:italic>vivax</jats:italic>orthologues. Candidates that induced antibodies that inhibited invasion to a similar level as PvDBP were identified, confirming the utility of<jats:italic>P</jats:italic>.<jats:italic>knowlesi</jats:italic>as a model for<jats:italic>P</jats:italic>.<jats:italic>vivax</jats:italic>vaccine development and prioritizing antigens for further follow up.</jats:p>