Dendritic cell vaccination protects mice against lethality caused by genital herpes simplex virus type 2 infection.
We have evaluated the ability of antigen pulsed bone-marrow derived dendritic cells (bmDC), to induce protective immunity against a genital tract infection with herpes simplex virus type 2 (HSV-2) in mice. Intravenous but not vaginal administrations of bmDC pulsed in vitro with UV-inactivated HSV-2, or with purified HSV-2 envelope glycoproteins gave rise to complete protection against disease, as well as death caused by genital herpes infection. Protection was dependent on the antigens being presented by the bmDC as neither the antigens alone, nor the mock-pulsed bmDC prevented disease. Immunity was associated with HSV-2 specific IFN-gamma and antibody production, and was shown to be dependent on CD4(+) cells secreting IFN-gamma. Thus, ex vivo antigen-pulsed bmDC represents a powerful tool for the study of protective immunity to genital herpes infection, and for the identification of protective antigens. These findings might also have an impact on the design of vaccines against other sexually transmitted viral diseases.
Schön
E
E
Department of Medical Microbiology & Immunology, University of Göteborg, Guldhedsgatan 10A, 413 46, Göteborg, Sweden.
Harandi
A M
AM
Nordström
I
I
Holmgren
J
J
Eriksson
K
K
D000282:Administration, Intravaginal; D000818:Animals; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000008:administration & dosage / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016466:CHO Cells; D002465:Cell Movement; D002860:Chromium Radioisotopes; D006224:Cricetinae; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation*; D005260:Female; D006558:Herpes Genitalis / Q000276:immunology* / Q000517:prevention & control*; D018258:Herpesvirus 2, Human / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D007700:Kinetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014018:Tissue Distribution; D014185:Transplantation, Isogeneic; D014611:Vaccination
D000956:Antigens, Viral; D002860:Chromium Radioisotopes; D007371:Interferon-gamma