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

Abstract

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