Protection against congenital cytomegalovirus (CMV) disease, conferred by a replication-disabled, bacterial artificial chromosome (BAC)-based DNA vaccine

Mark R Schleiss, Greg Stroup, Kelly Pogorzelski, Alistair McGregor

Research output: Contribution to journalArticle

29 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)6175-6186
Number of pages12
JournalVaccine
Volume24
Issue number37-39
DOIs
StatePublished - Sep 11 2006

    Fingerprint

Keywords

  • Animal models of CMV infection
  • Bacterial artificial chromsomes
  • Congenital CMV infection
  • Cytomegalovirus (CMV) vaccines
  • DNA cytomegalovirus (CMV) vaccines
  • DNA vaccines
  • Placenta
  • TORCH infection

Cite this