DNA immunization utilizing a herpes simplex virus type 2 myogenic DNA vaccine protects mice from mortality and prevents genital herpes.
A gene transfer vector for DNA immunization was developed in which the promoter was derived from the murine muscle creatine kinase (MCK) gene; a gene expressed only in differentiated skeletal muscle. In vitro, we observed high-level, but unrestricted, gene expression from the cytomegalovirus (CMV) promoter unlike expression from the MCK promoter which was weak but restricted to myofibers. A myogenic DNA vaccine (MDV) that encoded the glycoprotein D gene from herpes simplex virus type-2 (HSV-2) was used to DNA immunize mice. MDV immunization resulted in virus specific immunity that protected HSV-2 infected mice from mortality and prevented the development of genital herpes. Therefore, we conclude that high-level gene expression or the use of a strong transcription unit was not a prerequisite for an efficacious DNA vaccine and the use of a nonviral tissue specific promoter could suffice.
Gebhard
J R
JR
DNA Vaccines and Gene Transfer, Pharmadigm Inc, 2401 Foothill Drive, Salt Lake City, UT 84109, USA. jgebhard@pharmadigm.com
Zhu
J
J
Cao
X
X
Minnick
J
J
Araneo
B A
BA
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D003402:Creatine Kinase / Q000235:genetics; D005260:Female; D006558:Herpes Genitalis / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D018258:Herpesvirus 2, Human / Q000235:genetics / Q000276:immunology*; D007136:Immunoglobulins / Q000097:blood; D051379:Mice; D018482:Muscle, Skeletal / Q000378:metabolism; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D010957:Plasmids / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use; D011401:Promoter Regions, Genetic / Q000235:genetics; D015996:Survival Rate; D018417:Th1 Cells / Q000276:immunology; D014158:Transcription, Genetic / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology / Q000627:therapeutic use*; D014621:Vagina / Q000821:virology; D014759:Viral Envelope Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D017201:Virus Shedding / Q000187:drug effects / Q000276:immunology
D000914:Antibodies, Viral; D007136:Immunoglobulins; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; C040570:glycoprotein D-herpes simplex virus type 2; D003402:Creatine Kinase