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

Elizabeth C Swanson, Pete Gillis, Nelmary Hernandez-Alvarado, Claudia L Fernandez Alarcon, Megan Schmit, Jason C. Zabeli, Felix Wussow, Don J. Diamond, Mark R Schleiss

Research output: Contribution to journalArticle

17 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4013-4018
Number of pages6
JournalVaccine
Volume33
Issue number32
DOIs
StatePublished - Jul 31 2015

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Keywords

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

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