Influenza B virus infections cause significant morbidity and mortality worldwide and pose a major public health problem, specifically in young children and infants. Influenza B viruses represent about 25% of circulating influenza viruses in an epidemic but cause up to 38% of influenza-related pediatric deaths. Currently licensed inactivated vaccines do not induce broad protection due to the fast antigenic drift of the viral hemagglutinin on which these vaccines focus. In this project we are aiming to investigate the cross-protection that influenza B virus neuraminidase-based antigens can confer and their effect on transmission in the guinea pig model. Furthermore, we will explore the epitope specificity of this broadly protective immunity. Preliminary data show that vaccination with B-neuraminidase can protect mice completely from morbidity and mortality when challenged with antigenically distinct influenza B viruses. More evidence comes from broadly protective antibodies that bind and inhibit antigenically distinct influenza B virus isolates spanning from 1940 to 2013. Influenza B viruses - in contrast to influenza A viruses - lack an animal reservoir and only circulate in humans. A broadly protective vaccine in combination with a high vaccination rate could theoretically be used to eradicate influenza B virus. This would result in an approximately 25% decrease in the global burden caused by influenza virus infections. A neuramindase-based immunogen given in combination with or as booster after regular trivalent influenza virus vaccine could be the golden bullet needed to achieve this goal.

Public Health Relevance

Influenza B virus infections cause approximately 25% of all influenza virus infections and up to 38% of all influenza-related pediatric deaths. Currently licensed inactivated vaccines do not provide broad protection due to antigenic drift of the viral hemagglutinin. Influenza B-neuraminidase based immunogens provide broad protection in the mouse model and could be developed into broadly protective influenza B virus vaccines.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI117287-04
Application #
9706000
Study Section
Vaccines Against Microbial Diseases Study Section (VMD)
Program Officer
Gordon, Jennifer L
Project Start
2016-06-20
Project End
2021-05-31
Budget Start
2019-06-01
Budget End
2020-05-31
Support Year
4
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Icahn School of Medicine at Mount Sinai
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
078861598
City
New York
State
NY
Country
United States
Zip Code
10029
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