Generation of a Genetically Modified Chimeric Plasmodium falciparum ParasiteExpressing Plasmodium vivax Circumsporozoite Protein for Malaria Vaccine Development.

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

doi:10.3389/fcimb.2020.591046

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 PfCSP 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 PvCSP in controlled human P. falciparum infections and in WSP vaccines targeting P. vivax and P. falciparum. We generated chimeric P. falciparum parasites expressing both PfCSP and PvCSP. These Pf-PvCSP parasites produced sporozoite comparable to wild type P. falciparum parasites and expressed PfCSP and PvCSP on the sporozoite surface. Pf-PvCSP sporozoites infected human hepatocytes and induced antibodies to the repeats of both PfCSP and PvCSP after immunization of mice. These results support the use of Pf-PvCSP sporozoites in studies optimizing vaccines targeting PvCSP.

Highlights

Plasmodium falciparum (Pf) and P. vivax (Pv) are two major human malaria parasites that threaten public health, mainly in tropical areas
We have previously shown that chimeric P. falciparum parasites with the Pfcsp gene replaced by the two major Pvcsp alleles, VK210 and VK247, do not produce salivary gland sporozoites and most oocysts degenerate before formation of sporozoites (MarinMogollon et al, 2018)
In this study we describe a chimeric P. falciparum line, Pf-PvCSP, which expresses circumsporozoite protein (CSP) from both P. falciparum and P. vivax

Summary

Introduction

Plasmodium falciparum (Pf) and P. vivax (Pv) are two major human malaria parasites that threaten public health, mainly in tropical areas. RTS,S is based on the circumsporozoite protein (CSP), a major surface protein expressed by Plasmodium sporozoites and early liver stages which plays a critical role in sporozoite formation, invasion of mosquito salivary glands and invasion of host hepatocytes (Ménard, 2000; Sinnis and Coppi, 2007; Coppi et al, 2011). This protein contains a highly conserved central repeat region flanked by N- and C -terminal regions. Since P. vivax forms dormant hypnozoites in the liver, which can causing infection relapses, safe and effective means for clearance of hypnozoites are essential for P. vivax CHMI studies (Payne et al, 2017)

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Results

Conclusion