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Journal of Virology, January 1999, p. 501-509, Vol. 73, No. 1
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
In Vivo Modulation of Vaccine-Induced Immune
Responses toward a Th1 Phenotype Increases Potency and Vaccine
Effectiveness in a Herpes Simplex Virus Type 2 Mouse
Model
Jeong-Im
Sin,1
Jong J.
Kim,1
Jean D.
Boyer,1
Richard B.
Ciccarelli,2
Terry J.
Higgins,2 and
David B.
Weiner1,*
Department of Pathology and Laboratory
Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
19104,1 and
WLVP, Malvern, Pennsylvania
193552
Received 1 July 1998/Accepted 1 September 1998
Several vaccines have been investigated experimentally in the
herpes simplex virus type 2 (HSV-2) model system. While it is believed
that CD4+-T-cell responses are important for protection in
general, the correlates of protection from HSV-2 infection are still
under investigation. Recently, the use of molecular adjuvants to drive vaccine responses induced by DNA vaccines has been reported in a number
of experimental systems. We sought to take advantage of this
immunization model to gain insight into the correlates of immune
protection in the HSV-2 mouse model system and to further explore DNA
vaccine technology. To investigate whether the Th1- or Th2-type immune
responses are more important for protection from HSV-2 infection, we
codelivered the DNA expression construct encoding the HSV-2 gD protein
with the gene plasmids encoding the Th1-type (interleukin-2 [IL-2],
IL-12, IL-15, and IL-18) and Th2-type (IL-4 and IL-10) cytokines in an
effort to drive immunity induced by vaccination. We then analyzed the
modulatory effects of the vaccine on the resulting immune phenotype and
on the mortality and the morbidity of the immunized animals following a
lethal challenge with HSV-2. We observed that Th1 cytokine gene
coadministration not only enhanced the survival rate but also reduced
the frequency and severity of herpetic lesions following intravaginal
HSV challenge. On the other hand, coinjection with Th2 cytokine genes
increased the rate of mortality and morbidity of the challenged mice.
Moreover, of the Th1-type cytokine genes tested, IL-12 was a
particularly potent adjuvant for the gD DNA vaccination.
*
Corresponding author. Mailing address: Department of
Pathology and Laboratory Medicine, University of Pennsylvania, 505 Stellar-Chance Lab., 422 Curie Dr., Philadelphia, PA 19104. Phone:
(215) 662-2352. Fax: (215) 573-9436. E-mail:
dbweiner{at}mail.med.upenn.edu.
Journal of Virology, January 1999, p. 501-509, Vol. 73, No. 1
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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