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Volume 10
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10.3390/vaccines10071074
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Article

Neutralizing Antibodies to Human Cytomegalovirus Recombinant Proteins Reduce Infection in an Ex Vivo Model of Developing Human Placentas

by
Takako Tabata
1,
Matthew Petitt
1,
Julia Li
2,
Xiaoyuan Chi
2,
Wei Chen
2,
Irina Yurgelonis
2,
Sabine Wellnitz
2,3,
Simon Bredl
3,
Tiago Vicente
3,
Xinzhen Yang
2,
Philip R. Dormitzer
2 and
Lenore Pereira
1,*
1
Cell and Tissue Biology, School of Dentistry, University of California, San Francisco, CA 94143, USA
2
Vaccine Research and Development, Pfizer, Inc., New York, NY 10965, USA
3
RedVax Inc., a Wholly Owned Subsidiary of Pfizer, Inc., 8001 Zurich, Switzerland
*
Author to whom correspondence should be addressed.
Vaccines 2022, 10(7), 1074; https://doi.org/10.3390/vaccines10071074
Submission received: 19 April 2022 / Revised: 30 June 2022 / Accepted: 1 July 2022 / Published: 4 July 2022
(This article belongs to the Special Issue The Interaction of Cytomegalovirus with the Human Immune System)
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Abstract

Human cytomegalovirus (HCMV) is the leading viral cause of congenital disease and permanent birth defects worldwide. Although the development of an effective vaccine is a public health priority, no vaccines are approved. Among the major antigenic targets are glycoproteins in the virion envelope, including gB, which facilitates cellular entry, and the pentameric complex (gH/gL/pUL128-131), required for the infection of specialized cell types. In this study, sera from rabbits immunized with the recombinant pentameric complex were tested for their ability to neutralize infection of epithelial cells, fibroblasts, and primary placental cell types. Sera from rhesus macaques immunized with recombinant gB or gB plus pentameric complex were tested for HCMV neutralizing activity on both cultured cells and cell column cytotrophoblasts in first-trimester chorionic villus explants. Sera from rabbits immunized with the pentameric complex potently blocked infection by pathogenic viral strains in amniotic epithelial cells and cytotrophoblasts but were less effective in fibroblasts and trophoblast progenitor cells. Sera from rhesus macaques immunized with the pentameric complex and gB more strongly reduced infection in fibroblasts, epithelial cells, and chorionic villus explants than sera from immunization with gB alone. These results suggest that the pentameric complex and gB together elicit antibodies that could have potential as prophylactic vaccine antigens.
Keywords: cytomegalovirus; vaccine; congenital infection; placenta cytomegalovirus; vaccine; congenital infection; placenta

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MDPI and ACS Style

Tabata, T.; Petitt, M.; Li, J.; Chi, X.; Chen, W.; Yurgelonis, I.; Wellnitz, S.; Bredl, S.; Vicente, T.; Yang, X.; et al. Neutralizing Antibodies to Human Cytomegalovirus Recombinant Proteins Reduce Infection in an Ex Vivo Model of Developing Human Placentas. Vaccines 2022, 10, 1074. https://doi.org/10.3390/vaccines10071074

AMA Style

Tabata T, Petitt M, Li J, Chi X, Chen W, Yurgelonis I, Wellnitz S, Bredl S, Vicente T, Yang X, et al. Neutralizing Antibodies to Human Cytomegalovirus Recombinant Proteins Reduce Infection in an Ex Vivo Model of Developing Human Placentas. Vaccines. 2022; 10(7):1074. https://doi.org/10.3390/vaccines10071074

Chicago/Turabian Style

Tabata, Takako, Matthew Petitt, Julia Li, Xiaoyuan Chi, Wei Chen, Irina Yurgelonis, Sabine Wellnitz, Simon Bredl, Tiago Vicente, Xinzhen Yang, and et al. 2022. "Neutralizing Antibodies to Human Cytomegalovirus Recombinant Proteins Reduce Infection in an Ex Vivo Model of Developing Human Placentas" Vaccines 10, no. 7: 1074. https://doi.org/10.3390/vaccines10071074

APA Style

Tabata, T., Petitt, M., Li, J., Chi, X., Chen, W., Yurgelonis, I., Wellnitz, S., Bredl, S., Vicente, T., Yang, X., Dormitzer, P. R., & Pereira, L. (2022). Neutralizing Antibodies to Human Cytomegalovirus Recombinant Proteins Reduce Infection in an Ex Vivo Model of Developing Human Placentas. Vaccines, 10(7), 1074. https://doi.org/10.3390/vaccines10071074

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