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Sci Transl Med. 2017 Jan 4;9(371). pii: eaad9099. doi: 10.1126/scitranslmed.aad9099.

Complete attenuation of genetically engineered Plasmodium falciparum sporozoites in human subjects.

Author information

1
Center for Infectious Disease Research, formerly Seattle Biomedical Research Institute, 307 Westlake Avenue North, Suite 500, Seattle, WA 98109, USA. stefan.kappe@cidresearch.org jkublin@fredhutch.org.
2
Department of Global Health, University of Washington, Seattle, WA 98195, USA.
3
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109-1024, USA.
4
Center for Infectious Disease Research, formerly Seattle Biomedical Research Institute, 307 Westlake Avenue North, Suite 500, Seattle, WA 98109, USA.
5
Department of Laboratory Medicine, University of Washington, 1959 Northeast Pacific Street, NW150, Seattle, WA 98195-7110, USA.
6
Center for Emerging and Re-emerging Infectious Diseases and Department of Microbiology, University of Washington, 750 Republican Street, E630, Seattle, WA 98109, USA.

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 volunteers. Pf GAP3KO sporozoites were delivered to 10 volunteers using infected mosquito bites with a single exposure consisting of 150 to 200 bites per subject. All subjects remained blood stage-negative and developed inhibitory antibodies to sporozoites. GAP3KO rodent malaria parasites engendered complete, protracted immunity against infectious sporozoite challenge in mice. The results warrant further clinical testing of Pf GAP3KO and its potential development into a vaccine strain.

PMID:
28053159
DOI:
10.1126/scitranslmed.aad9099
[Indexed for MEDLINE]

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