Antibody-mediated protection against genital herpes simplex virus type 2 disease in mice by Fc gamma receptor-dependent and -independent mechanisms
| Autor: | Jane E. Strasser, Michael G. Meador, Chin-Fun Chu, Christal G. Young, Nigel Bourne, Gregg N. Milligan |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Male
Sexually transmitted disease medicine.drug_class Herpesvirus 2 Human Immunology Antibodies Viral Monoclonal antibody Article Epithelium Virus Immunoglobulin G Pathogenesis Mice Immune system medicine Animals Immunology and Allergy Mice Knockout Herpes Genitalis biology Receptors IgG Immunization Passive Herpes Simplex Virus Vaccines Obstetrics and Gynecology Viral Load Virology Gene Expression Regulation Reproductive Medicine Polyclonal antibodies Acute Disease Vagina biology.protein Female Receptors Chemokine Antibody |
| Zdroj: | Journal of Reproductive Immunology. 78:58-67 |
| ISSN: | 0165-0378 |
| DOI: | 10.1016/j.jri.2007.08.004 |
| Popis: | The ability of antibody (Ab) to modulate HSV pathogenesis is well recognized but the mechanisms by which HSV-specific IgG antibodies protect against genital HSV-2 disease are not well understood. The requirement for Ab interactions with Fcgamma receptors (FcgammaR) in protection was examined using a murine model of genital HSV-2 infection. IgG antibodies isolated from the serum of HSV-immune mice protected normal mice against HSV-2 disease when administered prior to genital HSV-2 inoculation. However, protection was significantly diminished in recipient mice lacking the gamma chain subunit utilized in FcgammaRI, FcgammaRIII, FcgammaRIV and FcepsilonRI receptors and in normal mice depleted of Gr-1(+) immune cell populations known to express FcgammaR, suggesting protection was largely mediated by an FcgammaR-dependent mechanism. To test whether neutralizing Ab might provide superior protection, a highly neutralizing HSV glycoprotein D (gD)-specific monoclonal antibody (mAb) was utilized. Similar to results with HSV-specific polyclonal IgG, administration of the gD-specific mAb did not prevent initial infection of the genital tract but resulted in lower virus loads in the vaginal epithelium and provided significant protection against disease and acute infection of the sensory ganglia; however, this protection was independent of host FcgammaR expression and was manifest in mice depleted of Gr-1(+) immune cells. Together, these data demonstrate that substantial Ab-mediated protection against genital HSV-2 disease could be achieved by either FcgammaR-dependent or -independent mechanisms. These studies suggest that HSV vaccines might need to elicit multiple, diverse antibody effector mechanisms to achieve optimal protection. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect