DNA immunization confers protection against murine cytomegalovirus infection.
The murine cytomegalovirus (MCMV) immediate-early gene 1 (IE1) encodes an 89-kDa phosphoprotein (pp89) which plays a key role in protecting BALB/c mice against the lethal effects of the MCMV infection. In this report, we have addressed the question of whether "naked DNA" vaccination with a eukaryotic expression vector (pcDNA-89) that contains the MCMV IE1 gene driven by a strong enhancer/promoter can confer protection. BALB/c mice were immunized intradermally with pcDNA-89 or with the plasmid backbone pcDNAI/Amp (pcDNA) and then challenged 2 weeks later with either a lethal or a sublethal intraperitoneal dose of the K181 strain of MCMV. Variable results were obtained for the individual experiments in which mice received a lethal challenge. In four separate trials, an average of 63% of the mice immunized with pcDNA-89 survived, compared with 18% of the mice immunized with pcDNA. However, in two other trials there was no specific protection. The results of experiments in which mice were injected with a sublethal dose of MCMV were more consistent, and significant decreases in viral titer in the spleen and salivary glands of pcDNA-89-immunized mice were observed, relative to controls. At the time of peak viral replication, titers in the spleens of immunized mice were reduced 18- to >63-fold, while those in the salivary gland were reduced approximately 24- to 48-fold. Although DNA immunization elicited only a low level of seroconversion in these mice, by 7 weeks postimmunization the mice had generated a cytotoxic T-lymphocyte response against pp89. These results suggest that DNA vaccination with selected CMV genes may provide a safe and efficient means of immunizing against CMV disease.
González Armas
J C
JC
Department of Biology, University of California, San Diego, La Jolla, 92093-0357, USA.
Morello
C S
CS
Cranmer
L D
LD
Spector
D H
DH
D016475:3T3 Cells; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000235:genetics*; D019556:COS Cells; D004279:DNA, Viral / Q000276:immunology*; D005260:Female; D006566:Herpesviridae Infections / Q000517:prevention & control*; D017874:Immediate-Early Proteins / Q000235:genetics*; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D018146:Muromegalovirus / Q000276:immunology*; D012469:Salivary Glands / Q000276:immunology / Q000473:pathology / Q000821:virology; D013154:Spleen / Q000276:immunology / Q000473:pathology / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D015534:Trans-Activators / Q000235:genetics*; D019444:Vaccines, DNA / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*
D000914:Antibodies, Viral; D000956:Antigens, Viral; D004279:DNA, Viral; C094775:IE-1 protein, murine cytomegalovirus; D017874:Immediate-Early Proteins; D015534:Trans-Activators; D019444:Vaccines, DNA; D014765:Viral Vaccines; C052612:cytomegalovirus immediate early phosphoprotein pp89