| First Author | Kwant-Mitchell A | Year | 2009 |
| Journal | J Virol | Volume | 83 |
| Issue | 20 | Pages | 10664-76 |
| PubMed ID | 19656896 | Mgi Jnum | J:153773 |
| Mgi Id | MGI:4366216 | Doi | 10.1128/JVI.02584-08 |
| Citation | Kwant-Mitchell A, et al. (2009) Mucosal innate and adaptive immune responses against herpes simplex virus type 2 in a humanized mouse model. J Virol 83(20):10664-76 |
| abstractText | 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. |
