title: Immunogenicity evaluation of DNA vaccines that target guinea pig cytomegalovirus proteins glycoprotein B and UL83.
abstract: Vaccines are needed for control of congenital human cytomegalovirus (HCMV) infection. Although the species-specificity of cytomegaloviruses precludes preclinical evaluation of HCMV vaccines in animal models, the guinea pig cytomegalovirus (GPCMV), which causes disease in utero, is a relevant model for the study of vaccines against congenital infection. We investigated whether DNA vaccines that target two GPCMV proteins, glycoprotein B (gB) and UL83 (pp65), are capable of eliciting immune responses in vivo. After cloning each gene into an expression vector, DNA was delivered by intramuscular inoculation and by pneumatic epidermal delivery. In Swiss-Webster mice, anti-gB titers were significantly higher after epidermal delivery. After epidermal inoculation in guinea pigs, all gB-immunized animals (n = 6) had antibody responses comparable to those induced by natural infection. Viral neutralization titers ranged from 1:64 to greater than 1:128. A GPCMV UL83 DNA vaccine also elicited an antibody response in all immunized guinea pigs (n = 6) after epidermal administration. Immunoprecipitation and Western blot assays confirmed that immune sera were immunoreactive with virion-associated UL83 and gB proteins. We conclude that DNA vaccines against GPCMV structural proteins are immunogenic, and warrant further investigation in the guinea pig model of congenital CMV infection.
authors.affiliation: Division of Infectious Diseases, Children's Hospital Research Foundation, Cincinnati, Ohio 45229, USA. schlm0@chmcc.org
authors.forename: M R
authors.initials: MR
authors.lastname: Schleiss
authors.forename: N
authors.initials: N
authors.lastname: Bourne
authors.forename: N J
authors.initials: NJ
authors.lastname: Jensen
authors.forename: F
authors.initials: F
authors.lastname: Bravo
authors.forename: D I
authors.initials: DI
authors.lastname: Bernstein
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D015153:Blotting, Western; D003587:Cytomegalovirus / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000151:congenital / Q000517:prevention & control*; D022482:Cytomegalovirus Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D006168:Guinea Pigs; D006801:Humans; D051379:Mice; D009500:Neutralization Tests; D010750:Phosphoproteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D010957:Plasmids / Q000235:genetics; D011233:Precipitin Tests; D011994:Recombinant Proteins / Q000378:metabolism; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014771:Virion / Q000276:immunology / Q000378:metabolism
chemical_list: D000914:Antibodies, Viral; D022482:Cytomegalovirus Vaccines; D010750:Phosphoproteins; D011994:Recombinant Proteins; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa; C040495:glycoprotein B, Simplexvirus