Listeriolysin O-deficient Listeria monocytogenes as a vaccine delivery vehicle: antigen-specific CD8 T cell priming and protective immunity

Sara E Hamilton; Vladimir P Badovinac; Aaruni Khanolkar; John T Harty

doi:10.4049/jimmunol.177.6.4012

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Listeriolysin O-deficient Listeria monocytogenes as a vaccine delivery vehicle: antigen-specific CD8 T cell priming and protective immunity

Journal article

Open access

Peer reviewed

Listeriolysin O-deficient Listeria monocytogenes as a vaccine delivery vehicle: antigen-specific CD8 T cell priming and protective immunity

Sara E Hamilton, Vladimir P Badovinac, Aaruni Khanolkar and John T Harty

The Journal of immunology (1950), Vol.177(6), pp.4012-4020

09/15/2006

DOI: 10.4049/jimmunol.177.6.4012

PMID: 16951364

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Abstract

Strains of Listeria monocytogenes (LM) that are deficient in the virulence factor listeriolysin O (LLO) are highly attenuated and are thought not to elicit protective immunity. This failure has been attributed to the inability of the bacterium to enter the host cell cytosol and access MHC class I Ag processing machinery. We reexamined this issue using recombinant strains of LM that are deficient in LLO but express an additional CD8 T cell epitope derived from lymphocytic choriomeningitis virus. After infection with LLO-deficient strains, we find sizable priming of epitope-specific CD8 T cells and the development of a functional memory cell population. Mice primed with the LLO-deficient LM strain are equally resistant against high-dose challenge with virulent LM as mice primed with wild-type virulent bacteria and also resist heterologous challenge with lymphocytic choriomeningitis virus. Interestingly, priming with a low dose of LLO-deficient LM, which occurred in environment of reduced inflammation (IFN-gamma), allowed rapid amplification of Ag-specific CD8 T cells by booster immunization, despite an undetectable primary response. We conclude that the generation of protective immunity by LLO-deficient strains of LM does in fact occur and that this highly attenuated LM strain may be a useful platform for vaccine delivery.

Lymphocytic choriomeningitis virus - immunology

Hemolysin Proteins

Epitopes, T-Lymphocyte - administration & dosage

Listeria monocytogenes - immunology

Drug Delivery Systems

Heat-Shock Proteins - deficiency

Heat-Shock Proteins - genetics

Vaccines, Attenuated - immunology

Animals

Bacterial Vaccines - administration & dosage

Bacterial Vaccines - immunology

Vaccines, Attenuated - administration & dosage

CD8-Positive T-Lymphocytes - metabolism

Listeria monocytogenes - genetics

Lymphocytic choriomeningitis virus - genetics

Bacterial Toxins - genetics

Mice

Mice, Inbred BALB C

Epitopes, T-Lymphocyte - immunology

CD8-Positive T-Lymphocytes - immunology

Details

Title: Subtitle: Listeriolysin O-deficient Listeria monocytogenes as a vaccine delivery vehicle: antigen-specific CD8 T cell priming and protective immunity
Creators: Sara E Hamilton - Department of Microbiology and Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242, USA
Vladimir P Badovinac
Aaruni Khanolkar
John T Harty
Resource Type: Journal article
Publication Details: The Journal of immunology (1950), Vol.177(6), pp.4012-4020
Publisher: United States
DOI: 10.4049/jimmunol.177.6.4012
PMID: 16951364
ISSN: 0022-1767
eISSN: 1550-6606
Grant note: R01AI42767 / NIAID NIH HHS R01AI50073 / NIAID NIH HHS R01AI46653 / NIAID NIH HHS T32AI07511 / NIAID NIH HHS
Language: English
Date published: 09/15/2006
Academic Unit: Microbiology and Immunology; Pathology
Record Identifier: 9984047694602771

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