title: Protection against congenital cytomegalovirus (CMV) disease, conferred by a replication-disabled, bacterial artificial chromosome (BAC)-based DNA vaccine.
abstract: It is unclear if protective immunity can be conferred by a cytomegalovirus (CMV) vaccine encoding a single protein subunit, or if multiple viral genes need to be targeted. Using the guinea pig model of congenital CMV infection, these studies examined the immunogenicity and efficacy of a DNA vaccine based on the guinea pig cytomegalovirus (GPCMV) genome cloned as a non-infectious BAC plasmid, modified by transposon insertion into the homolog of the HCMV tegument protein, UL48. Following vaccination of female Hartley guinea pigs with BAC DNA, adverse GPCMV-related pregnancy outcome were assessed after establishment of pregnancy, followed by GPCMV third-trimester challenge. Animals immunized with recombinant BACmid engendered anti-GPCMV antibodies by ELISA assay. Immunogenicity of BAC plasmid DNA was augmented by inclusion of the lipid adjuvant, DOTMA/DOPE, in the vaccine regimen. Among pups born to 12 control (sham-immunized) dams challenged with GPCMV in the third trimester, mortality was 23/35 (66%). In contrast, among evaluable pregnancy outcomes in pups born to 10 BAC-immunized pregnant dams, preconception immunization resulted in reduced pup mortality, to 10/34 pups (29%; p<0.005 versus control, Fisher's exact test). In addition, vaccinated dams had reduced viral load, compared to controls, as assessed by quantitative, real-time PCR.
authors.affiliation: Division of Infectious Diseases, University of Minnesota Medical School, Department of Pediatrics, Center for Infectious Diseases and Microbiology Translational Research, Minneapolis, MN 55455, United States. schleiss@umn.edu <schleiss@umn.edu>
authors.forename: Mark R
authors.initials: MR
authors.lastname: Schleiss
authors.forename: Greg
authors.initials: G
authors.lastname: Stroup
authors.forename: Kelly
authors.initials: K
authors.lastname: Pogorzelski
authors.forename: Alistair
authors.initials: A
authors.lastname: McGregor
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D003586:Cytomegalovirus Infections / Q000151:congenital* / Q000276:immunology / Q000517:prevention & control* / Q000635:transmission; D022482:Cytomegalovirus Vaccines / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D004251:DNA Transposable Elements / Q000235:genetics / Q000276:immunology; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D016679:Genome, Viral / Q000276:immunology; D006168:Guinea Pigs; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D051379:Mice; D008969:Molecular Sequence Data; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology* / Q000821:virology; D019211:Roseolovirus / Q000235:genetics / Q000276:immunology*; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology; D019562:Viral Load
chemical_list: D022482:Cytomegalovirus Vaccines; D004251:DNA Transposable Elements; D019444:Vaccines, DNA