title: A genetically adjuvanted influenza B virus vector increases immunogenicity and protective efficacy in mice.
abstract: The existence of multiple antigenically distinct types and subtypes of influenza viruses allows the construction of a multivalent vector system for the mucosal delivery of foreign sequences. Influenza A viruses have been exploited successfully for the expression of extraneous antigens as well as immunostimulatory molecules. In this study, we describe the development of an influenza B virus vector whose functional part of the interferon antagonist NS1 was replaced by human interleukin 2 (IL2) as a genetic adjuvant. We demonstrate that IL2 expressed by this viral vector displays immune adjuvant activity in immunized mice. Animals vaccinated with the IL2 viral vector showed an increased hemagglutination inhibition antibody response and higher protective efficacy after challenge with a wild-type influenza B virus when compared to mice vaccinated with a control virus. Our results demonstrate that it is feasible to construct influenza B vaccine strains expressing immune-potentiating foreign sequences from the NS genomic segment. Based on these data, it is now hypothetically possible to create a trivalent (or quadrivalent) live attenuated influenza vaccine in which each component expresses a selected genetic adjuvant with tailored expression levels.
authors.affiliation: Avir Green Hills Biotechnology AG, Forsthausgasse 11, 1200, Vienna, Austria. dr.christian.kittel@gmail.com.
authors.forename: Christian
authors.initials: C
authors.lastname: Kittel
authors.affiliation: Avir Green Hills Biotechnology AG, Forsthausgasse 11, 1200, Vienna, Austria.
authors.forename: Nina
authors.initials: N
authors.lastname: Wressnigg
authors.affiliation: Avir Green Hills Biotechnology AG, Forsthausgasse 11, 1200, Vienna, Austria.|Influenza Research Institute, Russian Academy of Medical Sciences, Prof. Popov Str. 15/17, St. Petersburg, 197376, Russia.
authors.forename: Anna Polina
authors.initials: AP
authors.lastname: Shurygina
authors.affiliation: Avir Green Hills Biotechnology AG, Forsthausgasse 11, 1200, Vienna, Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Wolschek
authors.affiliation: Influenza Research Institute, Russian Academy of Medical Sciences, Prof. Popov Str. 15/17, St. Petersburg, 197376, Russia.
authors.forename: Marina
authors.initials: M
authors.lastname: Stukova
authors.affiliation: Influenza Research Institute, Russian Academy of Medical Sciences, Prof. Popov Str. 15/17, St. Petersburg, 197376, Russia.
authors.forename: Ekatherina
authors.initials: E
authors.lastname: Romanovskaya-Romanko
authors.affiliation: Avir Green Hills Biotechnology AG, Forsthausgasse 11, 1200, Vienna, Austria.
authors.forename: Julia
authors.initials: J
authors.lastname: Romanova
authors.affiliation: Influenza Research Institute, Russian Academy of Medical Sciences, Prof. Popov Str. 15/17, St. Petersburg, 197376, Russia.
authors.forename: Oleg
authors.initials: O
authors.lastname: Kiselev
authors.affiliation: Avir Green Hills Biotechnology AG, Forsthausgasse 11, 1200, Vienna, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Muster
authors.affiliation: Avir Green Hills Biotechnology AG, Forsthausgasse 11, 1200, Vienna, Austria.
authors.forename: Andrej
authors.initials: A
authors.lastname: Egorov
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007114:Immunization; D009981:Influenza B virus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D007376:Interleukin-2 / Q000235:genetics / Q000276:immunology; D051379:Mice
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007376:Interleukin-2