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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...

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Autores principales: Behzadi, Mohammad Amin, Stein, Kathryn R., Bermúdez-González, Maria Carolina, Simon, Viviana, Nachbagauer, Raffael, Tortorella, Domenico
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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.
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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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