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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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5748606/ https://www.ncbi.nlm.nih.gov/pubmed/29088098 http://dx.doi.org/10.3390/vaccines5040039 |
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author | Wussow, Felix Chiuppesi, Flavia Contreras, Heidi Diamond, Don J. |
author_facet | Wussow, Felix Chiuppesi, Flavia Contreras, Heidi Diamond, Don J. |
author_sort | Wussow, Felix |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-5748606 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-57486062018-01-07 Neutralization of Human Cytomegalovirus Entry into Fibroblasts and Epithelial Cells Wussow, Felix Chiuppesi, Flavia Contreras, Heidi Diamond, Don J. Vaccines (Basel) Review 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. MDPI 2017-10-31 /pmc/articles/PMC5748606/ /pubmed/29088098 http://dx.doi.org/10.3390/vaccines5040039 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Wussow, Felix Chiuppesi, Flavia Contreras, Heidi Diamond, Don J. Neutralization of Human Cytomegalovirus Entry into Fibroblasts and Epithelial Cells |
title | 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_short | Neutralization of Human Cytomegalovirus Entry into Fibroblasts and Epithelial Cells |
title_sort | neutralization of human cytomegalovirus entry into fibroblasts and epithelial cells |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5748606/ https://www.ncbi.nlm.nih.gov/pubmed/29088098 http://dx.doi.org/10.3390/vaccines5040039 |
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