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An Influenza Virus Hemagglutinin-Based Vaccine Platform Enables the Generation of Epitope Specific Human Cytomegalovirus Antibodies
Human cytomegalovirus (CMV) is a highly prevalent pathogen with ~60%–90% seropositivity in adults. CMV can contribute to organ rejection in transplant recipients and is a major cause of birth defects in newborns. Currently, there are no approved vaccines against CMV. The epitope of a CMV neutralizin...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6630953/ https://www.ncbi.nlm.nih.gov/pubmed/31207917 http://dx.doi.org/10.3390/vaccines7020051 |
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author | Behzadi, Mohammad Amin Stein, Kathryn R. Bermúdez-González, Maria Carolina Simon, Viviana Nachbagauer, Raffael Tortorella, Domenico |
author_facet | Behzadi, Mohammad Amin Stein, Kathryn R. Bermúdez-González, Maria Carolina Simon, Viviana Nachbagauer, Raffael Tortorella, Domenico |
author_sort | Behzadi, Mohammad Amin |
collection | PubMed |
description | Human cytomegalovirus (CMV) is a highly prevalent pathogen with ~60%–90% seropositivity in adults. CMV can contribute to organ rejection in transplant recipients and is a major cause of birth defects in newborns. Currently, there are no approved vaccines against CMV. The epitope of a CMV neutralizing monoclonal antibody against a conserved region of the envelope protein gH provided the basis for a new CMV vaccine design. We exploited the influenza A virus as a vaccine platform due to the highly immunogenic head domain of its hemagglutinin envelope protein. Influenza A variants were engineered by reverse genetics to express the epitope of an anti-CMV gH neutralizing antibody that recognizes native gH into the hemagglutinin antigenic Sa site. We determined that the recombinant influenza variants expressing 7, 10, or 13 residues of the anti-gH neutralizing antibody epitope were recognized and neutralized by the anti-gH antibody 10C10. Mice vaccinated with the influenza/CMV chimeric viruses induced CMV-specific antibodies that recognized the native gH protein and inhibited virus infection. In fact, the influenza variants expressing 7–13 gH residues neutralized a CMV infection at ~60% following two immunizations with variants expressing the 13 residue gH peptide produced the highest levels of neutralization. Collectively, our study demonstrates that a variant influenza virus inserted with a gH peptide can generate a humoral response that limits a CMV infection. |
format | Online Article Text |
id | pubmed-6630953 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-66309532019-08-19 An Influenza Virus Hemagglutinin-Based Vaccine Platform Enables the Generation of Epitope Specific Human Cytomegalovirus Antibodies Behzadi, Mohammad Amin Stein, Kathryn R. Bermúdez-González, Maria Carolina Simon, Viviana Nachbagauer, Raffael Tortorella, Domenico Vaccines (Basel) Article Human cytomegalovirus (CMV) is a highly prevalent pathogen with ~60%–90% seropositivity in adults. CMV can contribute to organ rejection in transplant recipients and is a major cause of birth defects in newborns. Currently, there are no approved vaccines against CMV. The epitope of a CMV neutralizing monoclonal antibody against a conserved region of the envelope protein gH provided the basis for a new CMV vaccine design. We exploited the influenza A virus as a vaccine platform due to the highly immunogenic head domain of its hemagglutinin envelope protein. Influenza A variants were engineered by reverse genetics to express the epitope of an anti-CMV gH neutralizing antibody that recognizes native gH into the hemagglutinin antigenic Sa site. We determined that the recombinant influenza variants expressing 7, 10, or 13 residues of the anti-gH neutralizing antibody epitope were recognized and neutralized by the anti-gH antibody 10C10. Mice vaccinated with the influenza/CMV chimeric viruses induced CMV-specific antibodies that recognized the native gH protein and inhibited virus infection. In fact, the influenza variants expressing 7–13 gH residues neutralized a CMV infection at ~60% following two immunizations with variants expressing the 13 residue gH peptide produced the highest levels of neutralization. Collectively, our study demonstrates that a variant influenza virus inserted with a gH peptide can generate a humoral response that limits a CMV infection. MDPI 2019-06-14 /pmc/articles/PMC6630953/ /pubmed/31207917 http://dx.doi.org/10.3390/vaccines7020051 Text en © 2019 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 | Article Behzadi, Mohammad Amin Stein, Kathryn R. Bermúdez-González, Maria Carolina Simon, Viviana Nachbagauer, Raffael Tortorella, Domenico An Influenza Virus Hemagglutinin-Based Vaccine Platform Enables the Generation of Epitope Specific Human Cytomegalovirus Antibodies |
title | An Influenza Virus Hemagglutinin-Based Vaccine Platform Enables the Generation of Epitope Specific Human Cytomegalovirus Antibodies |
title_full | An Influenza Virus Hemagglutinin-Based Vaccine Platform Enables the Generation of Epitope Specific Human Cytomegalovirus Antibodies |
title_fullStr | An Influenza Virus Hemagglutinin-Based Vaccine Platform Enables the Generation of Epitope Specific Human Cytomegalovirus Antibodies |
title_full_unstemmed | An Influenza Virus Hemagglutinin-Based Vaccine Platform Enables the Generation of Epitope Specific Human Cytomegalovirus Antibodies |
title_short | An Influenza Virus Hemagglutinin-Based Vaccine Platform Enables the Generation of Epitope Specific Human Cytomegalovirus Antibodies |
title_sort | influenza virus hemagglutinin-based vaccine platform enables the generation of epitope specific human cytomegalovirus antibodies |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6630953/ https://www.ncbi.nlm.nih.gov/pubmed/31207917 http://dx.doi.org/10.3390/vaccines7020051 |
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