Using Plasmodium knowlesi as a model for screening Plasmodium vivax blood-stage malaria vaccine targets reveals new candidates.

Autor: Ndegwa DN; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, United Kingdom.; Department of Biological Sciences, University of Embu, Embu, Kenya., Kundu P; Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Hills Road, Cambridge, United Kingdom., Hostetler JB; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, United Kingdom., Marin-Menendez A; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, United Kingdom., Sanderson T; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, United Kingdom., Mwikali K; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, United Kingdom., Verzier LH; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, United Kingdom., Coyle R; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, United Kingdom., Adjalley S; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, United Kingdom., Rayner JC; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, United Kingdom.; Cambridge Institute for Medical Research, University of Cambridge, Cambridge Biomedical Campus, Hills Road, Cambridge, United Kingdom.
Jazyk: angličtina
Zdroj: PLoS pathogens [PLoS Pathog] 2021 Jul 01; Vol. 17 (7), pp. e1008864. Date of Electronic Publication: 2021 Jul 01 (Print Publication: 2021).
DOI: 10.1371/journal.ppat.1008864
Abstrakt: Plasmodium vivax is responsible for the majority of malaria cases outside Africa. Unlike P. falciparum, the P. vivax life-cycle includes a dormant liver stage, the hypnozoite, which can cause infection in the absence of mosquito transmission. An effective vaccine against P. vivax 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 P. vivax, however, lags considerably behind P. falciparum, which has many identified targets with several having transitioned to Phase II testing. By contrast only one P. vivax blood-stage vaccine candidate based on the Duffy Binding Protein (PvDBP), has reached Phase Ia, in large part because the lack of a continuous in vitro culture system for P. vivax limits systematic screening of new candidates. We used the close phylogenetic relationship between P. vivax and P. knowlesi, for which an in vitro culture system in human erythrocytes exists, to test the scalability of systematic reverse vaccinology to identify and prioritise P. vivax blood-stage targets. A panel of P. vivax 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 P. knowlesi. These antibodies were then tested for inhibition of growth and invasion of both wild type P. knowlesi and chimeric P. knowlesi lines modified using CRISPR/Cas9 to exchange P. knowlesi genes with their P. vivax orthologues. Candidates that induced antibodies that inhibited invasion to a similar level as PvDBP were identified, confirming the utility of P. knowlesi as a model for P. vivax vaccine development and prioritizing antigens for further follow up.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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