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Broadly inhibiting anti-neuraminidase monoclonal antibodies induced by trivalent influenza vaccine and H7N9 infection in humans

tetano

Editor, Senior Moderator
J Virol. 2019 Nov 20. pii: JVI.01182-19. doi: 10.1128/JVI.01182-19. [Epub ahead of print] [h=1]Broadly inhibiting anti-neuraminidase monoclonal antibodies induced by trivalent influenza vaccine and H7N9 infection in humans.[/h]
Rijal P[SUP]1,[/SUP][SUP]2[/SUP], Wang BB[SUP]3[/SUP], Tan TK[SUP]2[/SUP], Schimanski L[SUP]2[/SUP], Janesch P[SUP]2[/SUP], Dong T[SUP]4,[/SUP][SUP]2[/SUP], McCauley JW[SUP]5[/SUP], Daniels RS[SUP]5[/SUP], Townsend AR[SUP]4,[/SUP][SUP]2[/SUP], Huang KA[SUP]6,[/SUP][SUP]7[/SUP].
[h=3]Author information[/h] 1 Center for Translational Immunology, Chinese Academy of Medical Sciences Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 9DS, United Kingdom Pramila.rijal@rdm.ox.ac.uk arthur1726@cgmh.org.tw. 2 MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, OX3 9DS Oxford, United Kingdom. 3 Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China. 4 Center for Translational Immunology, Chinese Academy of Medical Sciences Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford OX3 9DS, United Kingdom. 5 Worldwide Influenza Centre, The Francis Crick Institute, London NW1 1AT, United Kingdom. 6 Division of Infectious Diseases, Department of Paediatrics, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan Pramila.rijal@rdm.ox.ac.uk arthur1726@cgmh.org.tw. 7 School of Medicine, Chang Gung University, Taoyuan 33302, Taiwan.

[h=3]Abstract[/h] The majority of antibodies induced by influenza neuraminidase (NA), like those against hemagglutinin (HA), are relatively specific to viruses isolated within a limited time-window as seen in serological studies and the analysis of many murine monoclonal antibodies (mAbs). We report three broadly reactive human mAbs targeting N1 NA. Two were isolated from a young adult vaccinated with trivalent influenza vaccine (TIV), which inhibited N1 NA from viruses isolated from humans over a period of a hundred years. The third antibody isolated from a child with acute mild H7N9 infection inhibited both group 1 N1 and group 2 N9 NAs. In addition, the antibodies cross-inhibited the N1 NAs of highly pathogenic avian H5N1 influenza viruses. These antibodies are protective in prophylaxis against seasonal H1N1 viruses in mice. This study demonstrates that human antibodies to N1 NA with exceptional cross-reactivity can be recalled by vaccination and highlights the importance of standardizing the NA antigen in seasonal vaccines to offer optimal protection.Importance Antibodies to the influenza NA can provide protection against influenza disease. Analysis of human antibodies to NA lags behind that for HA. We show that human monoclonal antibodies against NA induced by vaccination and infection can be very broadly reactive with the ability to inhibit a wide spectrum of N1 NAs on viruses isolated between 1918 and 2018. This suggests that antibodies to NA may be a useful therapy, and that efficacy of influenza vaccines could be enhanced by ensuring appropriate content of NA antigen.
Copyright ? 2019 Rijal et al.


PMID: 31748388 DOI: 10.1128/JVI.01182-19
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