Journal article

A Next-generation Genetically Attenuated Plasmodium falciparum Parasite Created by Triple Gene Deletion

Sebastian A Mikolajczak, Viswanathan Lakshmanan, Matthew Fishbaugher, Nelly Camargo, Anke Harupa, Alexis Kaushansky, Alyse N Douglass, Michael Baldwin, Julie Healer, Matthew O'Neill, Phuong Thuan, Alan Cowman, Stefan HI Kappe

MOLECULAR THERAPY | CELL PRESS | Published : 2014

Abstract

Immunization with live-attenuated Plasmodium sporozoites completely protects against malaria infection. Genetic engineering offers a versatile platform to create live-attenuated sporozoite vaccine candidates. We previously generated a genetically attenuated parasite (GAP) by deleting the P52 and P36 genes in the NF54 wild-type (WT) strain of Plasmodium falciparum (Pf p52(-)/p36(-) GAP). Preclinical assessment of p52(-)/p36(-) GAP in a humanized mouse model indicated an early and severe liver stage growth defect. However, human exposure to >200 Pf p52(-)/p36(-) GAP-infected mosquito bites in a safety trial resulted in peripheral parasitemia in one of six volunteers, revealing that this GAP wa..

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Grants

Awarded by Foundation for the National Institutes of Health through the Grand Challenges in Global Health Initiative


Awarded by Telemedicine & Advanced Technology Research Center at Fort Detrick, MD


Funding Acknowledgements

The research was partially funded by a Grant from the Foundation for the National Institutes of Health through the Grand Challenges in Global Health Initiative (Grant ID: 1481). This research and development program was also made possible by a cooperative agreement that was awarded and administered by the US Army Medical Research & Materiel Command and the Telemedicine & Advanced Technology Research Center, at Fort Detrick, MD, under contract number: W81XWH-11-2-0184. The authors declare no conflict of interest. S.H.I.K. is an inventor listed on US Patent No. 7,22,179, US Patent No. 7,261,884, and international patent application PCT/US2004/043023, each titled "Live Genetically Attenuated Malaria Vaccine."