AUTHOR=Miyazaki Yukiko , Marin-Mogollon Catherin  , Imai Takashi , Mendes António M. , van der Laak Rianne , Sturm Angelika , Geurten Fiona J. A. , Miyazaki Shinya , Chevalley-Maurel Severine  , Ramesar Jai , Kolli Surendra K. , Kroeze Hans , van Schuijlenburg Roos , Salman Ahmed M. , Wilder Brandon K. , Reyes-Sandoval Arturo , Dechering Koen J. , Prudêncio Miguel , Janse Chris J. , Khan Shahid M. , Franke-Fayard Blandine 

TITLE=Generation of a Genetically Modified Chimeric Plasmodium falciparum Parasite Expressing Plasmodium vivax Circumsporozoite Protein for Malaria Vaccine Development

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2020.591046

DOI=10.3389/fcimb.2020.591046

ISSN=2235-2988

ABSTRACT=<p>Chimeric rodent malaria parasites with the endogenous circumsporozoite protein (<italic>csp</italic>) gene replaced with <italic>csp</italic> from the human parasites <italic>Plasmodium falciparum</italic> (<italic>Pf</italic>) and <italic>P. vivax</italic> (<italic>Pv</italic>) are used in preclinical evaluation of CSP vaccines. Chimeric rodent parasites expressing <italic>Pf</italic>CSP have also been assessed as whole sporozoite (WSP) vaccines. Comparable chimeric <italic>P. falciparum</italic> parasites expressing CSP of <italic>P. vivax</italic> could be used both for clinical evaluation of vaccines targeting <italic>Pv</italic>CSP in controlled human <italic>P. falciparum</italic> infections and in WSP vaccines targeting <italic>P. vivax</italic> and <italic>P. falciparum</italic>. We generated chimeric <italic>P. falciparum</italic> parasites expressing both <italic>Pf</italic>CSP and <italic>Pv</italic>CSP. These <italic>Pf</italic>-<italic>Pv</italic>CSP parasites produced sporozoite comparable to wild type <italic>P. falciparum</italic> parasites and expressed <italic>Pf</italic>CSP and <italic>Pv</italic>CSP on the sporozoite surface. <italic>Pf</italic>-<italic>Pv</italic>CSP sporozoites infected human hepatocytes and induced antibodies to the repeats of both <italic>Pf</italic>CSP and <italic>Pv</italic>CSP after immunization of mice. These results support the use of <italic>Pf</italic>-<italic>Pv</italic>CSP sporozoites in studies optimizing vaccines targeting <italic>Pv</italic>CSP.</p>