Neutralization of Human Cytomegalovirus Entry into Fibroblasts and Epithelial Cells
Human cytomegalovirus (HCMV) is a leading cause of permanent birth defects, highlighting the need to develop an HCMV vaccine candidate. However, HCMV vaccine development is complicated by the varying capacity of neutralizing antibodies (NAb) to interfere in vitro with the HCMV entry routes mediating...
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doaj-63bfeb3091b04cba9ac0bcd5b80199e12020-11-24T21:53:32ZengMDPI AGVaccines2076-393X2017-10-01543910.3390/vaccines5040039vaccines5040039Neutralization of Human Cytomegalovirus Entry into Fibroblasts and Epithelial CellsFelix Wussow0Flavia Chiuppesi1Heidi Contreras2Don J. Diamond3Department of Experimental Therapeutics, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USADepartment of Experimental Therapeutics, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USADepartment of Experimental Therapeutics, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USADepartment of Experimental Therapeutics, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USAHuman cytomegalovirus (HCMV) is a leading cause of permanent birth defects, highlighting the need to develop an HCMV vaccine candidate. However, HCMV vaccine development is complicated by the varying capacity of neutralizing antibodies (NAb) to interfere in vitro with the HCMV entry routes mediating infection of fibroblast (FB) and epithelial cells (EC). While HCMV infection of FB and EC requires glycoprotein complexes composed of gB and gH/gL/gO, EC infection depends additionally on the envelope pentamer complex (PC) composed of gH, gL, UL128, UL130 and UL131A. Unlike NAb to gB or gH epitopes that can interfere with both FB and EC infection, NAb targeting predominantly conformational epitopes of the UL128/130/131A subunits are unable to prevent FB entry, though they are highly potent in blocking EC infection. Despite the selective requirement of the PC for EC entry, the PC is exceptionally immunogenic as vaccine antigen to stimulate both EC- and FB-specific NAb responses due to its capacity to elicit NAb that target epitopes of the UL128/130/131A subunits and gH. These findings suggest that the PC could be sufficient in a subunit vaccine formulation to induce robust FB- and EC-specific NAb responses. In this short review, we discuss NAb responses induced through natural infection and vaccination that interfere in vitro with HCMV infection of FB and EC.https://www.mdpi.com/2076-393X/5/4/39cytomegalovirusneutralizing antibodyfibroblastsepithelial cellsvaccineglycoprotein complexpentamer |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Felix Wussow Flavia Chiuppesi Heidi Contreras Don J. Diamond |
spellingShingle |
Felix Wussow Flavia Chiuppesi Heidi Contreras Don J. Diamond Neutralization of Human Cytomegalovirus Entry into Fibroblasts and Epithelial Cells Vaccines cytomegalovirus neutralizing antibody fibroblasts epithelial cells vaccine glycoprotein complex pentamer |
author_facet |
Felix Wussow Flavia Chiuppesi Heidi Contreras Don J. Diamond |
author_sort |
Felix Wussow |
title |
Neutralization of Human Cytomegalovirus Entry into Fibroblasts and Epithelial Cells |
title_short |
Neutralization of Human Cytomegalovirus Entry into Fibroblasts and Epithelial Cells |
title_full |
Neutralization of Human Cytomegalovirus Entry into Fibroblasts and Epithelial Cells |
title_fullStr |
Neutralization of Human Cytomegalovirus Entry into Fibroblasts and Epithelial Cells |
title_full_unstemmed |
Neutralization of Human Cytomegalovirus Entry into Fibroblasts and Epithelial Cells |
title_sort |
neutralization of human cytomegalovirus entry into fibroblasts and epithelial cells |
publisher |
MDPI AG |
series |
Vaccines |
issn |
2076-393X |
publishDate |
2017-10-01 |
description |
Human cytomegalovirus (HCMV) is a leading cause of permanent birth defects, highlighting the need to develop an HCMV vaccine candidate. However, HCMV vaccine development is complicated by the varying capacity of neutralizing antibodies (NAb) to interfere in vitro with the HCMV entry routes mediating infection of fibroblast (FB) and epithelial cells (EC). While HCMV infection of FB and EC requires glycoprotein complexes composed of gB and gH/gL/gO, EC infection depends additionally on the envelope pentamer complex (PC) composed of gH, gL, UL128, UL130 and UL131A. Unlike NAb to gB or gH epitopes that can interfere with both FB and EC infection, NAb targeting predominantly conformational epitopes of the UL128/130/131A subunits are unable to prevent FB entry, though they are highly potent in blocking EC infection. Despite the selective requirement of the PC for EC entry, the PC is exceptionally immunogenic as vaccine antigen to stimulate both EC- and FB-specific NAb responses due to its capacity to elicit NAb that target epitopes of the UL128/130/131A subunits and gH. These findings suggest that the PC could be sufficient in a subunit vaccine formulation to induce robust FB- and EC-specific NAb responses. In this short review, we discuss NAb responses induced through natural infection and vaccination that interfere in vitro with HCMV infection of FB and EC. |
topic |
cytomegalovirus neutralizing antibody fibroblasts epithelial cells vaccine glycoprotein complex pentamer |
url |
https://www.mdpi.com/2076-393X/5/4/39 |
work_keys_str_mv |
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