Altering the cellular location of an antigen expressed by a DNA-based vaccine modulates the immune response.
The potential for DNA vaccines encoding mutated versions of the same antigen to modulate immune responses in C3H/HeN mice was investigated. We created expression plasmids that encoded several versions of glycoprotein D (gD) from bovine herpesvirus 1, including authentic membrane-anchored glycoprotein (pSLRSV.AgD), a secreted glycoprotein (pSLRSV.SgD), and an intracellular protein (pSLRSV.CgD). Immunization of an inbred strain of mice with these plasmids resulted in highly efficacious and long-lasting humoral and cell-mediated immunity. We also demonstrated that the cell compartment in which plasmid-encoded gD was expressed caused a deviation in the serum immunoglobulin (Ig) isotype profile as well as the predominant cytokines secreted from the draining lymph node. Immunization of C3H/HeN mice with DNA vaccines encoding cell-associated forms of gD resulted in a predominance of serum IgG2a and gamma interferon-secreting cells within the spleens and draining lymph nodes. In contrast, mice immunized with a secreted form of this same antigen displayed immune responses characterized by greater levels of interleukin 4 in the draining lymph node and IgG1 as the predominant serum isotype. We also showed evidence of compartmentalization of distinct immune responses within different lymphoid organs.
Lewis
P J
PJ
Veterinary Infectious Disease Organization, University of Saskatchewan, Saskatoon, Saskatchewan S7N 5E3, Canada.
van Drunen Littel-van den Hurk
Babiuk
L A
LA
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D019556:COS Cells; D002417:Cattle; D002460:Cell Line; D005260:Female; D015870:Gene Expression; D007242:Herpesvirus 1, Bovine / Q000235:genetics / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007132:Immunoglobulin Isotypes / Q000097:blood / Q000276:immunology; D016130:Immunophenotyping; D008198:Lymph Nodes; D051379:Mice; D008809:Mice, Inbred C3H; D009500:Neutralization Tests; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D014162:Transfection; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D000914:Antibodies, Viral; D000956:Antigens, Viral; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D019444:Vaccines, DNA; D014764:Viral Proteins; D014765:Viral Vaccines; C046998:bovine herpesvirus type-1 glycoproteins