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Vaccines (Basel). 2019 Jun 14;7(2). pii: E51. doi: 10.3390/vaccines7020051.

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

Author information

1
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. ma.behzadi@mssm.edu.
2
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Kathryn.Stein@icahn.mssm.edu.
3
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. maria.bermudez-gonzalez@mssm.edu.
4
The Global Health Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. maria.bermudez-gonzalez@mssm.edu.
5
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. viviana.simon@mssm.edu.
6
The Global Health Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. viviana.simon@mssm.edu.
7
Division of Infectious Disease, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. viviana.simon@mssm.edu.
8
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. raffael.nachbagauer@mssm.edu.
9
Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. domenico.tortorella@mssm.edu.

Abstract

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.

KEYWORDS:

gH envelope protein; hemagglutinin; human cytomegalovirus; humoral immunity; influenza virus; neutralization; vaccine

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