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

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

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.

Related collections

Author and article information

Journal

Journal ID (iso-abbrev): Sci Transl Med

Title: Science translational medicine

Publisher: American Association for the Advancement of Science (AAAS)

ISSN (Electronic): 1946-6242

ISSN (Print): 1946-6234

Publication date (Electronic): Jan 04 2017

Volume: 9

Issue: 371

Affiliations

[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.

Article

Publisher Item ID: 9/371/eaad9099

DOI: 10.1126/scitranslmed.aad9099

PubMed ID: 28053159

SO-VID: 8f82a4ca-924d-49b6-8678-859cd73383f3

History

Data availability:

Comments

Camila França wrote:

Malaria vaccine development collection topic 3) Vaccines in development:

See https://www.scienceopen.com/collection/malariavaccine

Kublin and collaborators generated a genetically attenuated P. falciparum malaria parasite by deleting three genes expressed in the pre-erythrocytic stage (Pf p52(-)/p36(-)/sap1(-)). They show the results of safety and immunogenicity tests of the genetically engineered (Pf GAP3KO) sporozoites in human volunteers.

2018-10-08 21:48 UTC

Comment on this article

scite_

Cited by 50

See all cited by