2017
DOI: 10.1126/scitranslmed.aad9099
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Complete attenuation of genetically engineered Plasmodium falciparum sporozoites in human subjects

Abstract: Immunization of humans with whole sporozoites confers complete, sterilizing immunity against malaria infection. However, achieving consistent safety while maintaining immunogenicity of whole parasite vaccines remains a formidable challenge. We generated a genetically attenuated Plasmodium falciparum (Pf) malaria parasite by deleting three genes expressed in the pre-erythrocytic stage (Pf p52/p36/sap1). We then tested the safety and immunogenicity of the genetically engineered (Pf GAP3KO) sporozoites in human v… Show more

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Cited by 92 publications
(113 citation statements)
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“…Importantly, the magnitude of the response of clinical samples in the SOPA did not always correlate with the titers of antibodies against PfCSP (Fig. 4D) (21), suggesting that sporozoite antigens other than CSP might be able to facilitate opsonic phagocytosis in this assay. Alternatively, the opsonic activity of CSP antibodies could differ between immunized volunteers.…”
Section: Resultsmentioning
confidence: 99%
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“…Importantly, the magnitude of the response of clinical samples in the SOPA did not always correlate with the titers of antibodies against PfCSP (Fig. 4D) (21), suggesting that sporozoite antigens other than CSP might be able to facilitate opsonic phagocytosis in this assay. Alternatively, the opsonic activity of CSP antibodies could differ between immunized volunteers.…”
Section: Resultsmentioning
confidence: 99%
“…Having demonstrated the proof-of-concept for the SOPA using a PfCSPspecific MAb, we next sought to determine the compatibility of the assay with serum from humans immunized with whole P. falciparum parasites (21).…”
Section: Resultsmentioning
confidence: 99%
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“…A recent clinical study showed a favorable safety profile with no breakthrough to blood stage infection when PfGAP3KO was administered to human subjects by the bites of approximately 200 PfGAP3KO-infected mosquitoes [16]. A further P. falciparum GAP was recently created that arrests early during hepatocyte infection [17] and will enter clinical trials in due course.…”
mentioning
confidence: 99%