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Open AccessArticle

An Influenza Virus Hemagglutinin-Based Vaccine Platform Enables the Generation of Epitope Specific Human Cytomegalovirus Antibodies

1
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
2
The Global Health Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
3
Division of Infectious Disease, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
*
Authors to whom correspondence should be addressed.
Equal contribution.
Vaccines 2019, 7(2), 51; https://doi.org/10.3390/vaccines7020051
Received: 6 May 2019 / Revised: 6 June 2019 / Accepted: 10 June 2019 / Published: 14 June 2019
(This article belongs to the Section Vaccines against Infectious Diseases)
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. View Full-Text
Keywords: influenza virus; human cytomegalovirus; vaccine; humoral immunity; neutralization; hemagglutinin; gH envelope protein influenza virus; human cytomegalovirus; vaccine; humoral immunity; neutralization; hemagglutinin; gH envelope protein
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Behzadi, M.A.; Stein, K.R.; Bermúdez-González, M.C.; Simon, V.; Nachbagauer, R.; Tortorella, D. An Influenza Virus Hemagglutinin-Based Vaccine Platform Enables the Generation of Epitope Specific Human Cytomegalovirus Antibodies. Vaccines 2019, 7, 51.

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