TY - JOUR
T1 - Comparison of monovalent glycoprotein B with bivalent gB/pp65 (GP83) vaccine for congenital cytomegalovirus infection in a guinea pig model
T2 - Inclusion of GP83 reduces gB antibody response but both vaccine approaches provide equivalent protection against pup mortality
AU - Swanson, Elizabeth C
AU - Gillis, Pete
AU - Hernandez-Alvarado, Nelmary
AU - Fernandez Alarcon, Claudia L
AU - Schmit, Megan
AU - Zabeli, Jason C.
AU - Wussow, Felix
AU - Diamond, Don J.
AU - Schleiss, Mark R
N1 - Funding Information:
This work was supported by National Institutes of Health grants AI-063356 and AI-103960 (DJD), HD-044864 , HD-082273 , and HD-038416 (MRS), and a City of Hope cancer center core services award ( P30CA033572 ). Appendix A
Publisher Copyright:
© 2015 Elsevier Ltd.
PY - 2015/7/31
Y1 - 2015/7/31
N2 - 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.
AB - 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.
KW - CMV immune modulation
KW - CMV pp65
KW - CMV vaccine
KW - Congenital CMV infection
KW - Cytomegalovirus (CMV)
KW - Glycoprotein B
KW - Guinea pig cytomegalovirus
KW - Pentameric complex
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U2 - 10.1016/j.vaccine.2015.06.019
DO - 10.1016/j.vaccine.2015.06.019
M3 - Article
C2 - 26079615
AN - SCOPUS:84937517235
SN - 0264-410X
VL - 33
SP - 4013
EP - 4018
JO - Vaccine
JF - Vaccine
IS - 32
ER -