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 journalArticlepeer-review

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

Bibliographical note

Funding Information:
The technical assistance of Amber Hickson and Keri Drake is acknowledged. We thank Ulrich Koszinowski and Wolfram Brune for sharing the pTsTm8 plasmid and for helpful discussions. This work was supported by National Institute of Health AI-65289 and HD38416-01, and March of Dimes Basic Research Grants FY98/99-0416 and FY01-226.

Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.

Keywords

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

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