Issue |
Vet. Res.
Volume 31, Number 1, January-February 2000
|
|
---|---|---|
Page(s) | 133 - 134 | |
DOI | https://doi.org/10.1051/vetres:2000030 | |
How to cite this article | Vet. Res. (2000) 133-134 |
Effects of cytokines upon the immune response of swine to Aujeszky's disease virus
S. Martina, P.F. Russella, P.M. Jaquaa, S. Grimma, D. Lowerya, D. Stromb and F.A. Zuckermannca Pharmacia & Upjohn Animal Health, 7923-190-353, 7000 Portage Rd, Kalamazoo, MI 49001, USA
b CSIRO, Division of Animal Health, Corner Flemington Road and Park Drive, Victoria 3052, Australia
c Department of Veterinary Pathobiology, University of Illinois, Urbana, Illinois, 61802, USA
Abstract -
Aujeszky's disease
is caused by suid herpesvirus 1 (SHV-1) a member of the alphaherpesvirinae.
This large and complex virus has been the subject of many studies designed to identify
successful vaccine formulations and many varied and efficacious vaccines have
been described in the literature. SHV-1 infection can manifest as a broad range of clinical
signs ranging from depression to death, and in many instances both the general
health and immune status of the animal upon challenge determine the outcome.
Interestingly,
challenge with virulent SHV-1 can have significant effects upon the growth
performance of pigs, apparent as a significant reduction in the accretion of body mass or
even cachexia and emaciation. The change in weight seven days after challenge
(
G7) has been shown to be a quantitative indicator of the magnitude of protection induced by
vaccination. Several investigators have used the
G7 weight change to define
a spectrum of vaccine ability to protect swine from infection. Many of the studies have
detailed that modified live virus vaccines (MLV) offer the best protection,
with some of the most successful ones preventing animals from showing any decrease in the
rate of gain during the first seven days of infection. In contrast, many of
the killed virus vaccines and sub-unit vaccines (live vectored or inactivated), while
engendering a protective immune response, fail to prevent the
G7 day weight
loss as effectively as some MLV. This model of weight loss due to infection offers a unique
model that is able to quantitatively differentiate the performance of vaccines
and their delivery vehicles (live vectors, adjuvants, etc). We have recently started to use
this model to investigate the role of cytokine therapy upon the types of
immune response generated during vaccination. Primarily using RT-PCR strategies we have
obtained cDNAs encoding the open reading frames of several porcine cytokines.
Experiments using genetic immunization approaches had identified this technology as a viable
delivery system for functional cDNAs. Consequently, we decided to investigate
this strategy for both vaccination and co-administration of a cytokine cDNA. The model system
we are using utilizes an immunization vector that expresses the envelope
glycoprotein gC of SHV-1. In addition several genetic immunization vectors have been
constructed to express the porcine cytokine cDNAs for IL-1b, IL-2, IL-4,
IL-5, IL-6, IFN-
or GM-CSF. Some of these vectors express the cytokine alone, while others
express them in a fusion with a truncated version of gC. All of these
construct are currently being evaluated in vaccination trials of swine, using both in vitro
analysis of immune responsiveness and challenge trials to determine the
effects of these cytokines upon the porcine immune system. Groups of SHV-1 free piglets were
immunized with purified plasmids encoding the cDNA for gC and/or a cDNA
for a porcine cytokine. The developing SHV-1 specific immune response was monitored by in
vitro assays measuring humoral response (ELISA and serum neutralization
assays) and cell mediated immunity (IFN-
ELISPOT and lymphoproliferation assays). Four to
six weeks after vaccination the animals were weighed and challenged
intranasally with virulent SHV-1. Surviving animals were weighed again seven days later. All
animals vaccinated with plasmids encoding the gC protein developed a specific
immune response against SHV-1 as measured with the in vitro assays. The magnitude of these
responses were not as great as those induced by commercial vaccines (killed or MLV)
and consequently the degree of protection against
G7 weight changes was not as great.
Co-administration of cytokines intended to bias the immune response towards a TH-1
(increase in IFN-
-secreting antigen-specific cells) or TH-2 (decrease in
IFN-
-secreting
antigen-specific cells) did not have the expected effect. While several studies
have shown that IFN-
can have small enhancing effects upon the
IFN-
secreting antigen
specific response, the inhibitory effect of IL-10 co-administration was not seen.
Surprisingly, despite the inhibitory effect of porcine IL-10 on in vitro mitogen stimulated
IFN-
secreting cells (unpublished data), co-administration of the plasmid encoding
IL-10 had enhancing effects upon the induction the IFN-
secreting SHV-1 specific cell
response in vivo. A precise interpretation of this effect after challenge was
further complicated by the modulating effect of the cytokine plasmids alone upon the
G7
weight change. These unexpected effects of cytokine co-administration are
being further evaluated using both genetic immunization and recombinant SHV-1 vectors. In
conclusion, the data collected to date has demonstrated that cytokines
delivered with genetic immunization can have an effect upon the developing immune response,
and that the characteristic TH-1 and TH-2 biases described in other species
may not function similarly in swine.
Corresponding author: S. Martin Tel.: (1) 616 833 3365;
e-mail: Stephen.Martin@am.pnu.com
© INRA, EDP Sciences 2000