Preconceptual administration of an alphavirus replicon UL83 (pp65 homolog) vaccine induces humoral and cellular immunity and improves pregnancy outcome in the guinea pig model of congenital cytomegalovirus infection

Mark R Schleiss, Juan C. Lacayo, Yasmine Belkaid, Alistair McGregor, Greg Stroup, Jon Rayner, Kimberly Alterson, Jeffrey D. Chulay, Jonathan F. Smith

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

Abstract

Development of a vaccine against congenital cytomegalovirus (CMV) infection is a major public health priority. We report the use of a propagation- defective, single-cycle, RNA replicon vector system, derived from an attenuated strain of the alphavirus Venezuelan equine encephalitis virus, to produce virus-like replicon particles (VRPs) expressing GP83, the guinea pig CMV (GPCMV) homolog of the human CMV pp65 phosphoprotein. Vaccination with VRP-GP83 induced antibodies and CD4+ and CD8+ T cell responses in GPCMV-seronegative female guinea pigs. Guinea pigs immunized with VRP-GP83 vaccine or with a VRP vaccine expressing influenza hemagglutinin (VRP-HA) were bred for pregnancy and subsequent GPCMV challenge during the early third trimester. Dams vaccinated with VRP-GP83 had improved pregnancy outcomes, compared with dams vaccinated with the VRP-HA control. For VRP-GP83-vaccinated dams, there were 28 live pups and 4 dead pups (13% mortality) among 10 evaluable litters, compared with 9 live pups and 12 dead pups (57% mortality) among 8 evaluable litters in the VRP-HA-vaccinated group (P<.001, Fisher's exact test). Improved pregnancy outcome was accompanied by reductions in maternal blood viral load, measured by real-time polymerase chain reaction. These results indicate that cell-mediated immune responses directed against a CMV matrix protein can protect against congenital CMV infection and disease.

Original languageEnglish (US)
Pages (from-to)789-798
Number of pages10
JournalJournal of Infectious Diseases
Volume195
Issue number6
DOIs
StatePublished - Mar 15 2007

Bibliographical note

Funding Information:
Received 10 July 2006; accepted 21 September 2006; electronically published 6 February 2007. Potential conflicts of interest: J.R., K.A., J.D.C., and J.F.S. are employees of and/or own stock in AlphaVax. Other authors report no conflict of interest. Presented in part: 10th International CMV/Betaherpesvirus Workshop, Wil-liamsburg, VA, 24–28 April 2005 (abstract 10.05). Financial support: National Institutes of Health (grants HD38416-01 and HD44864-01); March of Dimes Birth Defects Foundations (grant FY01-22). Reprints or correspondence: Mark R. Schleiss, Div. of Pediatric Infectious Diseases, Center for Infectious Diseases and Microbiology Translational Research, 2001 6th St. SE, Minneapolis, MN 55455 (schleiss@umn.edu).

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