Analysis of immune responses to varicella tester viral proteins induced byDNA 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 tester virus (VZV). Both VZV-specific a ntibody and T cell proliferative responses were induced by immunization wit h DNA sequences for the immediate early 62 (IE62) and glycoprotein E (gE). The viral proteins were shown to be expressed in non-regenerating, rather t han regenerating muscle cells. After primary immunization, muscle cells did not express major histocompatibility complex (MHC) class II transcripts an d little inflammatory response was detected at the site of inoculation. His tochemical staining and non-isotopic in situ hybridization demonstrated tha t a second injection of IE62 plasmid DNA was again associated with protein synthesis in non-regenerating muscle cells but that a marked inflammatory i nfiltrate was induced in muscle tissue. These cells, but not muscle cells, expressed MHC class II transcripts. Significantly, PCR analyses demonstrate d that IE62 DNA localized specifically to local draining lymph nodes follow ing primary DNA immunization by intramuscular inoculation. These experiment s indicate that transport of plasmid DNA to sites of antigen presentation i n regional lymphoid tissue may play an important role in the initial genera tion of immune responses and that enhancement by secondary inoculation is m ediated by immune cells that traffic to the site of viral protein synthesis in muscle cells. (C) 1999 Elsevier Science B.V. All rights reserved.