Vaccination with recombinant vaccinia viruses expressing ICP27 induces protective immunity against herpes simplex virus through CD4+ Th1+ T cells.
This study was designed to evaluate the efficacy and mechanisms of protection mediated by recombinant vaccinia viruses encoding immediate-early (IE) proteins of herpes simplex virus type 2 (HSV-2). Three mouse strains were immunized against the IE proteins ICP27, ICP0, and ICP4, and mice were challenged intracutaneously in the zosteriform model with HSV-2 strain MS. Protection was observed only following immunization with the ICP27 construct and then only in the BALB/c mouse strain. Protection in BALB/c mice was ablated by CD4+ T-cell suppression but remained intact in animals depleted of CD8+ T cells. Moreover, protection could be afforded to SCID nude recipients with CD4+ but not CD8+ T cells from ICP27-immunized mice. Only BALB/c mice developed a delayed-type hypersensitivity reaction to HSV-2, and in vitro measurements of humoral and cell-mediated immunity revealed response patterns to ICP27 and HSV that differed between protected BALB/c and unprotected mouse strains. Accordingly, BALB/c responses showed antigen-induced cytokine profiles dominated by type 1 cytokines, whereas C57BL/6 and C3H/HeN mice generated cytokine responses mainly of the type 2 variety. Our results may indicate that protection against zosterification is mainly mediated by CD4+ T cells that express a type 1 cytokine profile and that protective vaccines against HSV which effectively induce such T-cell responses should be chosen.
Manickan
E
E
Department of Microbiology, College of Veterinary Medicine, University of Tennessee, Knoxville 37996-0845, USA.
Francotte
M
M
Kuklin
N
N
Dewerchin
M
M
Molitor
C
C
Gheysen
D
D
Slaoui
M
M
Rouse
B T
BT
D000818:Animals; D005260:Female; D018258:Herpesvirus 2, Human / Q000235:genetics / Q000276:immunology*; D017874:Immediate-Early Proteins / Q000235:genetics / Q000276:immunology*; D007111:Immunity, Cellular; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D016513:Mice, SCID; D018417:Th1 Cells / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*
D017874:Immediate-Early Proteins; D014614:Vaccines, Synthetic; D014765:Viral Vaccines