scholarly journals B7 Costimulation Plays an Important Role in Protection from Herpes Simplex Virus Type 2-Mediated Pathology

2002 ◽  
Vol 76 (5) ◽  
pp. 2563-2566 ◽  
Author(s):  
Lydia G. Thebeau ◽  
Lynda A. Morrison
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Immune Responses ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Mortality Rates ◽  
Neurologic Disease ◽  
Wild Type ◽  
Simplex Virus

ABSTRACT We have used mice lacking both B7-1 and B7-2 costimulation molecules (B7KO) to investigate the effects of B7 costimulation on herpes simplex virus type 2 (HSV-2) pathogenesis. B7KO mice infected intravaginally with virulent HSV-2 showed more severe genital and neurologic disease and higher mortality rates than their wild-type counterparts. These results suggest that B7 costimulation molecules play an important role in the development of primary immune responses protective against HSV-2.

scholarly journals 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

1999 ◽  
Vol 73 (1) ◽  
pp. 501-509 ◽  
Author(s):  
Jeong-Im Sin ◽  
Jong J. Kim ◽  
Jean D. Boyer ◽  
Richard B. Ciccarelli ◽  
Terry J. Higgins ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Mouse Model ◽  
Immune Responses ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Model System ◽  
Cytokine Genes ◽  
Simplex Virus

ABSTRACT 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.

Optimized DNA Vaccine Enhanced by Adjuvant IL28B Induces Protective Immune Responses Against Herpes Simplex Virus Type 2 in Mice

2017 ◽  
Vol 30 (8) ◽  
pp. 601-614 ◽  
Author(s):  
Yan Zhou ◽  
Ziyan Wang ◽  
Yongqing Xu ◽  
Zeqiang Zhang ◽  
Rui Hua ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Immune Responses ◽  
Dna Vaccine ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Simplex Virus

Effect of the deletion of US2 and US3 from herpes simplex virus type 2 on immune responses in the murine vagina following intravaginal infection

Vaccine ◽  
2001 ◽  
Vol 20 (1-2) ◽  
pp. 98-104 ◽  
Author(s):  
Kyoko Inagaki-Ohara ◽  
Takuya Iwasaki ◽  
Daisuke Watanabe ◽  
Takeshi Kurata ◽  
Yukihiro Nishiyama
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Immune Responses ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Simplex Virus

scholarly journals Clearance of Herpes Simplex Virus Type 2 by CD8+ T Cells Requires Gamma Interferon and either Perforin- or Fas-Mediated Cytolytic Mechanisms

2005 ◽  
Vol 79 (23) ◽  
pp. 14546-14554 ◽  
Author(s):  
Melanie E. Dobbs ◽  
Jane E. Strasser ◽  
Chin-Fun Chu ◽  
Claudia Chalk ◽  
Gregg N. Milligan
Keyword(s):  
T Cells ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Gamma Interferon ◽  
Wild Type ◽  
Ifn Γ ◽  
Simplex Virus

ABSTRACT The T-cell-mediated resolution of herpes simplex virus type 2 (HSV-2) genital infections is not fully understood. In these studies, the mechanisms by which CD8+ T cells clear virus from the genital epithelium were examined. Ovalbumin (OVA)-specific CD8+ T cells from OT-I transgenic mice cleared a thymidine kinase-deficient, ovalbumin-expressing HSV-2 virus (HSV-2 tk− OVA) from the genital epithelium of recipient mice, and clearance was abrogated by in vivo neutralization of gamma interferon (IFN-γ). Further, CD8+ OT-I T cells deficient in IFN-γ were unable to clear HSV-2 tk− OVA from the vaginal epithelium. The requirement for cytolytic mechanisms in HSV-2 tk− OVA clearance was tested in radiation chimeras by adoptive transfer of wild-type or perforin-deficient OT-I T cells to irradiated Fas-defective or wild-type recipients. Although a dramatic decrease in viral load was observed early after challenge with HSV-2 tk− OVA, full resolution of the infection was not achieved in recipients lacking both perforin- and Fas-mediated cytolytic pathways. These results suggest that IFN-γ was responsible for an early rapid decrease in HSV-2 virus titer. However, either perforin- or Fas-mediated cytolytic mechanisms were required to achieve complete clearance of HSV-2 from the genital epithelium.

scholarly journals DNA Vaccines Encoding Interleukin-8 and RANTES Enhance Antigen-Specific Th1-Type CD4+ T-Cell-Mediated Protective Immunity against Herpes Simplex Virus Type 2 In Vivo

2000 ◽  
Vol 74 (23) ◽  
pp. 11173-11180 ◽  
Author(s):  
Jeong-Im Sin ◽  
Jong J. Kim ◽  
Catherine Pachuk ◽  
C. Satishchandran ◽  
David B. Weiner
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
T Cell ◽  
Immune Responses ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Interleukin 8 ◽  
Simplex Virus

ABSTRACT Chemokines are inflammatory molecules that act primarily as chemoattractants and as activators of leukocytes. Their role in antigen-specific immune responses is of importance, but their role in disease protection is unknown. Recently it has been suggested that chemokines modulate immunity along more classical Th1 and Th2 phenotypes. However, no data currently exist in an infectious challenge model system. We analyzed the modulatory effects of selected chemokines (interleukin-8 [IL-8], gamma interferon-inducible protein 10 [IP-10], RANTES, monocyte chemotactic protein 1 [MCP-1], and macrophage inflammatory protein 1α [MIP-1α]) on immune phenotype and protection against lethal challenge with herpes simplex virus type 2 (HSV-2). We observed that coinjection with IL-8 and RANTES plasmid DNAs dramatically enhanced antigen-specific Th1 type cellular immune responses and protection from lethal HSV-2 challenge. This enhanced protection appears to be mediated by CD4+ T cells, as determined by in vitro and in vivo T-cell subset deletion. Thus, IL-8 and RANTES cDNAs used as DNA vaccine adjuvants drive antigen-specific Th1 type CD4+ T-cell responses, which result in reduced HSV-2-derived morbidity, as well as reduced mortality. However, coinjection with DNAs expressing MCP-1, IP-10, and MIP-1α increased mortality in the challenged mice. Chemokine DNA coinjection also modulated its own production as well as the production of cytokines. These studies demonstrate that chemokines can dominate and drive immune responses with defined phenotypes, playing an important role in the generation of protective antigen-specific immunity.

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