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Influenza B mutant viruses with truncated NS1 proteins grow efficiently in Vero cells and are immunogenic in mice

¹ Avir Greenhills Biotechnology, Gersthoferstrasse 29–31, 1180 Vienna, Austria
² University of Vienna, Institute of Microbiology and Genetics, Dr Bohrgasse 9, 1030 Vienna, Austria
³ Influenza Research Institute, Russian Academy of Medical Sciences, Prof. Popov Str. 15/17, St Petersburg 197376, Russia
⁴ Robert Koch Institute, P15, Nordufer 20, 13353 Berlin, Germany
⁵ Clinical Institute for Virology, Medical University of Vienna, Kinderspitalgasse 15, 1090 Vienna, Austria
⁶ Department of Dermatology, Medical University of Vienna, Währinger Gurtel 18–20, 1090 Vienna, Austria

Correspondence
Andrej Egorov
a.egorov{at}greenhillsbiotech.com

Contemporary influenza B virus strains were generated encoding C-terminally truncated NS1 proteins. Viable viruses containing the N-terminal 14, 38, 57 or 80 aa of the NS1 protein were rescued in Vero cells. The influenza B virus NS1-truncated mutants were impaired in their ability to counteract interferon (IFN) production, induce antiviral pro-inflammatory cytokines early after infection and show attenuated or restricted growth in IFN-competent hosts. In Vero cells, all of the mutant viruses replicated to high titres comparable to the wild-type influenza B virus. Mice that received a single, intranasal immunization of the NS1-truncated mutants elicited an antibody response and protection against wild-type virus challenge. Therefore, these NS1-truncated mutants should prove useful as potential candidates for live-attenuated influenza virus vaccines.