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Journal of Virology, December 1999, p. 10214-10223, Vol. 73, No. 12
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Altering the Cellular Location of an Antigen
Expressed by a DNA-Based Vaccine Modulates the Immune
Response
P. J.
Lewis,
S.
van Drunen Littel-van den Hurk, and
L. A.
Babiuk*
Veterinary Infectious Disease Organization,
University of Saskatchewan, Saskatoon, Saskatchewan S7N 5E3, Canada
Received 9 June 1999/Accepted 9 September 1999
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.
*
Corresponding author. Mailing address: Veterinary
Infectious Disease Organization, University of Saskatchewan, 120 Veterinary Rd., Saskatoon, Saskatchewan S7N 5E3, Canada. Phone: (306)
966-7465. Fax: (306) 966-7478. E-mail:
babiuk{at}sask.usask.ca.

Present address: Department of Pathology and Microbiology, Atlantic
Veterinary College, University of Prince Edward Island,
Charlottetown,
Prince Edward Island C1A 4P3,
Canada.
Journal of Virology, December 1999, p. 10214-10223, Vol. 73, No. 12
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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