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

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...

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Bibliographic Details
Published in:The Journal of infectious diseases 2007-03, Vol.195 (6), p.789-798
Main Authors: Schleiss, Mark R., Lacayo, Juan C., Belkaid, Yasmine, McGregor, Alistair, Stroup, Greg, Rayner, Jon, Alterson, Kimberly, Chulay, Jeffrey D., Smith, Jonathan F.
Format: Article
Language:English
Subjects:
Alphavirus
Animals
Animals, Newborn
Base Sequence
Cytomegalovirus
Cytomegalovirus - immunology
Cytomegalovirus infections
Disease Models, Animal
DNA Primers
Female
Guinea Pigs
Humans
Immunity, Cellular
Immunization
Infant, Newborn
Infections
Molecular Sequence Data
Phosphoproteins - immunology
Plasmids
Polymerase chain reaction
Pregnancy
Pregnancy Outcome
Replicon
Replicon - immunology
Salivary Glands - virology
T lymphocytes
Vaccination
Venezuelan equine encephalitis virus
Viral Matrix Proteins - immunology
Viral Vaccines - therapeutic use
Virus Replication
Viruses
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Summary: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
ISSN:0022-1899
1537-6613
DOI:10.1086/511982