Analysis of immune responses to varicella zoster viral proteins induced by DNA vaccination.
In this study we sought to examine the mechanism by which immune responses were induced following intramuscular injection of mice with DNA expression vectors encoding genes of varicella zoster virus (VZV). Both VZV-specific antibody and T cell proliferative responses were induced by immunization with DNA sequences for the immediate early 62 (IE62) and glycoprotein E (gE). The viral proteins were shown to be expressed in non-regenerating, rather than regenerating muscle cells. After primary immunization, muscle cells did not express major histocompatibility complex (MHC) class II transcripts and little inflammatory response was detected at the site of inoculation. Histochemical staining and non-isotopic in situ hybridization demonstrated that a second injection of IE62 plasmid DNA was again associated with protein synthesis in non-regenerating muscle cells but that a marked inflammatory infiltrate was induced in muscle tissue. These cells, but not muscle cells, expressed MHC class II transcripts. Significantly, PCR analyses demonstrated that IE62 DNA localized specifically to local draining lymph nodes following primary DNA immunization by intramuscular inoculation. These experiments indicate that transport of plasmid DNA to sites of antigen presentation in regional lymphoid tissue may play an important role in the initial generation of immune responses and that enhancement by secondary inoculation is mediated by immune cells that traffic to the site of viral protein synthesis in muscle cells.
Abendroth
A
A
Department of Pediatric Infectious Diseases, Stanford University School of Medicine, CA 94305-5208, USA.
Slobedman
B
B
Springer
M L
ML
Blau
H M
HM
Arvin
A M
AM
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D005260:Female; D005455:Fluorescent Antibody Technique; D014645:Herpesvirus 3, Human / Q000235:genetics / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D017874:Immediate-Early Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008198:Lymph Nodes / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D009132:Muscles / Q000276:immunology / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D016133:Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014765:Viral Vaccines / Q000276:immunology*
D000914:Antibodies, Viral; D000949:Histocompatibility Antigens Class II; C074221:IE62 protein, Human herpesvirus 3; D017874:Immediate-Early Proteins; D015534:Trans-Activators; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C056913:glycoprotein E, varicella-zoster virus