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J Virol. 2009 Oct;83(20):10664-76. doi: 10.1128/JVI.02584-08. Epub 2009 Aug 5.

Mucosal innate and adaptive immune responses against herpes simplex virus type 2 in a humanized mouse model.

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  • 1Michael G. DeGroote Institute for Infectious Disease Research, Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada L8N 3Z5.

Abstract

Genital herpes, caused by herpes simplex virus type 2 (HSV-2), is one of the most prevalent sexually transmitted diseases worldwide and a risk factor for acquiring human immunodeficiency virus. Although many vaccine candidates have shown promising results in animal models, they have failed to be effective in human trials. In this study, a humanized mouse strain was evaluated as a potential preclinical model for studying human immune responses to HSV-2 infection and vaccination. Immunodeficient mouse strains were examined for their abilities to develop human innate and adaptive immune cells after transplantation of human umbilical cord stem cells. A RAG2(-/-) gammac(-/-) mouse strain with a BALB/c background was chosen as the most appropriate model and was then examined for its ability to mount innate and adaptive immune responses to intravaginal HSV-2 infection and immunization. After primary infection, human cells in the lymph nodes were able to generate a protective innate immune response and produce gamma interferon (IFN-gamma). After intravaginal immunization and infection, human T cells and NK cells were found in the genital tract and iliac lymph nodes. In addition, human T cells in the spleen, lymph nodes, and vaginal tract were able to respond to stimulation with HSV-2 antigens by replicating and producing IFN-gamma. Human B cells were also able to produce HSV-2-specific immunoglobulin G. These adaptive responses were also shown to be protective and reduce local viral replication in the genital tract. This approach provides a means for studying human immune responses in vivo using a small-animal model and may become an important preclinical tool.

PMID:
19656896
[PubMed - indexed for MEDLINE]
PMCID:
PMC2753120
Free PMC Article
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