Mark R Schleiss1. 1. Division of Infectious Diseases, Children's Hospital Research Foundation, Cincinnati, OH 45229, USA. schlm0@chmcc.org
Abstract
BACKGROUND: The strict species-specificity of cytomegalovirus (CMV) precludes preclinical evaluation of human CMV (HCMV) vaccines in animal models and necessitates the study of nonhuman CMVs. Among the CMVs of small mammals, the guinea pig cytomegalovirus (GPCMV) has unique advantages, due to its ability to cross the placenta, causing infection in utero. OBJECTIVE AND STUDY DESIGNS: Progress in GPCMV studies has been hampered by a lack of detailed molecular characterization of the viral genome. Therefore, recent efforts have been undertaken to characterize the GPCMV genome, and apply this information to in vivo subunit vaccine studies. RESULTS: Progress in the sequencing of the GPCMV genome has revealed the presence of both highly conserved as well as novel open reading frames (ORFs). Cloning of GPCMV vaccine candidates, such as the glycoprotein B (gB) and UL83 proteins, has facilitated subunit vaccine evaluation. Protein vaccines and DNA vaccines have shown evidence of protection in pregnancy/challenge experiments. In addition, the GPCMV genome has proved amenable to cloning as a bacterial artificial chromosome (BAC) in Escherichia coli, and BAC-derived recombinants retain the ability to replicate in vivo. CONCLUSIONS: Progress has been made in molecular characterization of GPCMV. Insights from these studies should prove germane to the understanding of the correlates of protective immunity for the fetus in vaccine studies, and should assist in prioritization of vaccine strategies in HCMV vaccine trials.
BACKGROUND: The strict species-specificity of cytomegalovirus (CMV) precludes preclinical evaluation of human CMV (HCMV) vaccines in animal models and necessitates the study of nonhuman CMVs. Among the CMVs of small mammals, the guinea pig cytomegalovirus (GPCMV) has unique advantages, due to its ability to cross the placenta, causing infection in utero. OBJECTIVE AND STUDY DESIGNS: Progress in GPCMV studies has been hampered by a lack of detailed molecular characterization of the viral genome. Therefore, recent efforts have been undertaken to characterize the GPCMV genome, and apply this information to in vivo subunit vaccine studies. RESULTS: Progress in the sequencing of the GPCMV genome has revealed the presence of both highly conserved as well as novel open reading frames (ORFs). Cloning of GPCMV vaccine candidates, such as the glycoprotein B (gB) and UL83 proteins, has facilitated subunit vaccine evaluation. Protein vaccines and DNA vaccines have shown evidence of protection in pregnancy/challenge experiments. In addition, the GPCMV genome has proved amenable to cloning as a bacterial artificial chromosome (BAC) in Escherichia coli, and BAC-derived recombinants retain the ability to replicate in vivo. CONCLUSIONS: Progress has been made in molecular characterization of GPCMV. Insights from these studies should prove germane to the understanding of the correlates of protective immunity for the fetus in vaccine studies, and should assist in prioritization of vaccine strategies in HCMV vaccine trials.