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.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Vaccines Against Microbial Diseases Study Section (VMD)
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Salomon, Rachelle
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Icahn School of Medicine at Mount Sinai
Schools of Medicine
New York
United States
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Krammer, Florian; Fouchier, Ron A M; Eichelberger, Maryna C et al. (2018) NAction! How Can Neuraminidase-Based Immunity Contribute to Better Influenza Virus Vaccines? MBio 9:
Henry, Carole; Palm, Anna-Karin E; Krammer, Florian et al. (2018) From Original Antigenic Sin to the Universal Influenza Virus Vaccine. Trends Immunol 39:70-79
Tan, Jessica; Asthagiri Arunkumar, Guha; Krammer, Florian (2018) Universal influenza virus vaccines and therapeutics: where do we stand with influenza B virus? Curr Opin Immunol 53:45-50
Rajendran, Madhusudan; Nachbagauer, Raffael; Ermler, Megan E et al. (2017) Analysis of Anti-Influenza Virus Neuraminidase Antibodies in Children, Adults, and the Elderly by ELISA and Enzyme Inhibition: Evidence for Original Antigenic Sin. MBio 8:
Nachbagauer, R; Krammer, F (2017) Universal influenza virus vaccines and therapeutic antibodies. Clin Microbiol Infect 23:222-228
Krammer, F (2017) Strategies to induce broadly protective antibody responses to viral glycoproteins. Expert Rev Vaccines 16:503-513
Nachbagauer, Raffael; Choi, Angela; Hirsh, Ariana et al. (2017) Defining the antibody cross-reactome directed against the influenza virus surface glycoproteins. Nat Immunol 18:464-473
Wohlbold, Teddy John; Podolsky, Kira A; Chromikova, Veronika et al. (2017) Broadly protective murine monoclonal antibodies against influenza B virus target highly conserved neuraminidase epitopes. Nat Microbiol 2:1415-1424