title: 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.
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.
authors.affiliation: 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.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Swanson
authors.affiliation: 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.
authors.forename: Pete
authors.initials: P
authors.lastname: Gillis
authors.affiliation: 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.
authors.forename: Nelmary
authors.initials: N
authors.lastname: Hernandez-Alvarado
authors.affiliation: 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.
authors.forename: Claudia
authors.initials: C
authors.lastname: Fernández-Alarcón
authors.affiliation: 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.
authors.forename: Megan
authors.initials: M
authors.lastname: Schmit
authors.affiliation: 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.
authors.forename: Jason C
authors.initials: JC
authors.lastname: Zabeli
authors.affiliation: Department of Virology, Beckman Research Institute of City of Hope, 1500 E. Duarte Rd, Duarte, CA 91010, United States.
authors.forename: Felix
authors.initials: F
authors.lastname: Wussow
authors.affiliation: Department of Virology, Beckman Research Institute of City of Hope, 1500 E. Duarte Rd, Duarte, CA 91010, United States.
authors.forename: Don J
authors.initials: DJ
authors.lastname: Diamond
authors.affiliation: 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.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Schleiss
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D003586:Cytomegalovirus Infections / Q000151:congenital* / Q000517:prevention & control* / Q000635:transmission; D022482:Cytomegalovirus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006168:Guinea Pigs; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control*; D009500:Neutralization Tests; D010750:Phosphoproteins / Q000276:immunology*; D011247:Pregnancy; D019211:Roseolovirus / Q000276:immunology*; D016019:Survival Analysis; D016896:Treatment Outcome; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology*; D019562:Viral Load; D014763:Viral Matrix Proteins / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D022482:Cytomegalovirus Vaccines; D010750:Phosphoproteins; D022223:Vaccines, Subunit; D014759:Viral Envelope Proteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa; C040495:glycoprotein B, Simplexvirus
keywords: CMV immune modulation; CMV pp65; CMV vaccine; Congenital CMV infection; Cytomegalovirus (CMV); Glycoprotein B; Guinea pig cytomegalovirus; Pentameric complex