2020•Frontiers in Cellular and Infection MicrobiologyOpen access
Generation of a Genetically Modified Chimeric Plasmodium falciparum Parasite Expressing Plasmodium vivax Circumsporozoite Protein for Malaria Vaccine Development
Yukiko Miyazaki, Catherin Marin-Mogollon, Takashi Imai, António M. Mendes, Rianne van der Laak, Angelika Sturm, Fiona J. A. Geurten, Shinya Miyazaki, Severine C. Chevalley-Maurel, Jai Ramesar, Surendra Kumar Kolli, Hans Kroeze, Roos van Schuijlenburg, Ahmed M. Salman, Brandon Keith Wilder, Arturo Reyes‐Sandoval, Koen J. Dechering, Miguel Prudêncio, Chris J. Janse, Shahid M. Khan, Blandine M. D. Franke-Fayard
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Abstract
Chimeric rodent malaria parasites with the endogenous circumsporozoite protein ( csp ) gene replaced with csp from the human parasites Plasmodium falciparum ( Pf ) and P. vivax ( Pv ) are used in preclinical evaluation of CSP vaccines. Chimeric rodent parasites expressing Pf CSP have also been assessed as whole sporozoite (WSP) vaccines. Comparable chimeric P. falciparum parasites expressing CSP of P. vivax could be used both for clinical evaluation of vaccines targeting Pv CSP in controlled human P. falciparum infections and in WSP vaccines targeting P. vivax and P. falciparum . We generated chimeric P. falciparum parasites expressing both Pf CSP and Pv CSP. These Pf - Pv CSP parasites produced sporozoite comparable to wild type P. falciparum parasites and expressed Pf CSP and Pv CSP on the sporozoite surface. Pf - Pv CSP sporozoites infected human hepatocytes and induced antibodies to the repeats of both Pf CSP and Pv CSP after immunization of mice. These results support the use of Pf - Pv CSP sporozoites in studies optimizing vaccines targeting Pv CSP.
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