Superior antimalarial immunity after vaccination with late liver stage-arresting genetically attenuated parasites

Noah S Butler; Nathan W Schmidt; Ashley M Vaughan; Ahmed S Aly; Stefan H I Kappe; John T Harty

doi:10.1016/j.chom.2011.05.008

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Superior antimalarial immunity after vaccination with late liver stage-arresting genetically attenuated parasites

Journal article

Open access

Peer reviewed

Superior antimalarial immunity after vaccination with late liver stage-arresting genetically attenuated parasites

Noah S Butler, Nathan W Schmidt, Ashley M Vaughan, Ahmed S Aly, Stefan H I Kappe and John T Harty

Cell host & microbe, Vol.9(6), pp.451-462

06/16/2011

DOI: 10.1016/j.chom.2011.05.008

PMCID: PMC3117254

PMID: 21669394

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Abstract

While subunit vaccines have shown partial efficacy in clinical trials, radiation-attenuated sporozoites (RAS) remain the "gold standard" for sterilizing protection against Plasmodium infection in human vaccinees. The variability in immunogenicity and replication introduced by the extensive, random DNA damage necessary to generate RAS could be overcome by genetically attenuated parasites (GAP) designed via gene deletion to arrest at defined points during liver-stage development. Here, we demonstrate the principle that late liver stage-arresting GAP induce larger and broader CD8 T cell responses that provide superior protection in inbred and outbred mice compared to RAS or early-arresting GAP immunizations. Late liver stage-arresting GAP also engender high levels of cross-stage and cross-species protection and complete protection when administered by translationally relevant intradermal or subcutaneous routes. Collectively, our results underscore the potential utility of late liver stage-arresting GAP as broadly protective next-generation live-attenuated malaria vaccines and support their potential as a powerful model for identifying antigens to generate cross-stage protection.

Plasmodium berghei - immunology

Humans

Plasmodium berghei - genetics

Vaccination

CD8-Positive T-Lymphocytes - parasitology

Plasmodium yoelii - growth & development

Sporozoites - immunology

Sporozoites - growth & development

Liver - immunology

Gene Deletion

Vaccines, Attenuated - administration & dosage

Malaria Vaccines - immunology

Malaria - immunology

Mice, Inbred C57BL

Plasmodium yoelii - immunology

Plasmodium yoelii - genetics

Malaria - prevention & control

Vaccines, Attenuated - immunology

Animals

Malaria Vaccines - administration & dosage

Malaria - parasitology

Plasmodium berghei - growth & development

Mice

Mice, Inbred BALB C

Liver - parasitology

CD8-Positive T-Lymphocytes - immunology

Malaria Vaccines - genetics

Vaccines, Attenuated - genetics

Details

Title: Subtitle: Superior antimalarial immunity after vaccination with late liver stage-arresting genetically attenuated parasites
Creators: Noah S Butler - Department of Microbiology, University of Iowa, 3-512 Bowen Science Building, Iowa City, IA 52242, USA
Nathan W Schmidt
Ashley M Vaughan
Ahmed S Aly
Stefan H I Kappe
John T Harty
Resource Type: Journal article
Publication Details: Cell host & microbe, Vol.9(6), pp.451-462
Publisher: United States
DOI: 10.1016/j.chom.2011.05.008
PMID: 21669394
PMCID: PMC3117254
ISSN: 1931-3128
eISSN: 1934-6069
Grant note: F32 AI084329 / NIAID NIH HHS R01 AI085515-03 / NIAID NIH HHS F32-AI084329 / NIAID NIH HHS T32-AI0726024 / NIAID NIH HHS R01 AI095178 / NIAID NIH HHS R01 AI085515 / NIAID NIH HHS
Language: English
Date published: 06/16/2011
Academic Unit: Microbiology and Immunology; Pathology
Record Identifier: 9984001137002771

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