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Vaccine. 2015 Jul 31;33(32):4013-8. doi: 10.1016/j.vaccine.2015.06.019. Epub 2015 Jun 13.

Comparison of monovalent glycoprotein B with bivalent gB/pp65 (GP83) vaccine for congenital cytomegalovirus infection in a guinea pig model: Inclusion of GP83 reduces gB antibody response but both vaccine approaches provide equivalent protection against pup mortality.

Author information

1
University of Minnesota Medical School, Department of Pediatrics, Center for Infectious Diseases and Microbiology Translational Research, 2001 6th Street SE, Minneapolis, MN 55455, United States.
2
Department of Virology, Beckman Research Institute of City of Hope, 1500 E. Duarte Rd, Duarte, CA 91010, United States.
3
University of Minnesota Medical School, Department of Pediatrics, Center for Infectious Diseases and Microbiology Translational Research, 2001 6th Street SE, Minneapolis, MN 55455, United States. Electronic address: schleiss@umn.edu.

Abstract

Cytomegalovirus (CMV) subunit vaccine candidates include glycoprotein B (gB), and phosphoprotein ppUL83 (pp65). Using a guinea pig cytomegalovirus (GPCMV) model, this study compared immunogenicity, pregnancy outcome, and congenital viral infection following pre-pregnancy immunization with a three-dose series of modified vaccinia virus Ankara (MVA)-vectored vaccines consisting either of gB administered alone, or simultaneously with a pp65 homolog (GP83)-expressing vaccine. Vaccinated and control dams were challenged at midgestation with salivary gland-adapted GPCMV. Comparisons included ELISA and neutralizing antibody responses, maternal viral load, pup mortality, and congenital infection rates. Strikingly, ELISA and neutralization titers were significantly lower in the gB/GP83 combined vaccine group than in the gB group. However, both vaccines protected against pup mortality (63.2% in controls vs. 11.4% and 13.9% in gB and gB/GP83 combination groups, respectively; p<0.0001). Reductions in pup viral load were noted for both vaccine groups compared to control, but preconception vaccination resulted in a significant reduction in GPCMV transmission only in the monovalent gB group (26/44, 59% v. 27/34, 79% in controls; p<0.05). We conclude that, using the MVA platform, the addition of GP83 to a gB subunit vaccine interferes with antibody responses and diminishes protection against congenital GPCMV infection, but does not decrease protection against pup mortality.

KEYWORDS:

CMV immune modulation; CMV pp65; CMV vaccine; Congenital CMV infection; Cytomegalovirus (CMV); Glycoprotein B; Guinea pig cytomegalovirus; Pentameric complex

PMID:
26079615
PMCID:
PMC4772145
DOI:
10.1016/j.vaccine.2015.06.019
[Indexed for MEDLINE]
Free PMC Article

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