Genetic immunization against herpes simplex virus. Protection is mediated by CD4+ T lymphocytes.
Plasmid DNA encoding proteins represent a convenient novel approach to vaccination. We have investigated this "genetic immunization" approach as a means to protect against herpes simplex virus (HSV) infection using a mouse zosteriform model that mimics several aspects of reactivated HSV infection of humans. After i.m. immunization with plasmid DNA-encoding glycoprotein B (gB), (pc-gB), 80% of BALB/c mice were completely protected and lesions were delayed in the remaining animals. Upon pc-gB vaccination, the animals developed both gB- and HSV-specific IgG Ab response and the isotype examination revealed a predominance of IgG2a. These mice also have low levels (1/16) of HSV-neutralizing Abs. Immune splenocytes obtained from pc-gB-immunized mice, when restimulated in vitro with HSV resulted in production of type 1 cytokines. Evidence for CD(8+)-mediated cytotoxic T lymphocyte response was equivocal. Protection could be adoptively transferred to nude mice recipients by CD4+ T cells from pc-gB-immunized mice but not by CD8+ T cells. Our results demonstrate that genetic immunization is a potent means of inducing protection against HSV and that the mechanism of immunity responsible for clearing virus from cutaneous sites is principally by CD4+ T cells. It is likely that these cells are Th1 cells because type 1 cytokines were the major cytokines detected upon in vitro Ag stimulation.
Manickan
E
E
Department of Microbiology, College of Veterinary Medicine, University of Tennessee, Knoxville 37996, USA.
Rouse
R J
RJ
Yu
Z
Z
Wire
W S
WS
Rouse
B T
BT
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000032:analysis; D003601:Cytotoxicity Tests, Immunologic; D004247:DNA / Q000032:analysis; D004279:DNA, Viral / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology; D006561:Herpes Simplex / Q000517:prevention & control / Q000628:therapy; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000032:analysis; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D010957:Plasmids / Q000276:immunology*; D018139:Simplexvirus / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology; D014759:Viral Envelope Proteins / Q000494:pharmacology; D014765:Viral Vaccines / Q000276:immunology*
D000914:Antibodies, Viral; D016207:Cytokines; D004279:DNA, Viral; D006023:Glycoproteins; D007376:Interleukin-2; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C040495:glycoprotein B, Simplexvirus; D004247:DNA