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Development of a live-attenuated influenza B ΔNS1 intranasal vaccine candidate

2009; Elsevier BV; Volume: 27; Issue: 21 Linguagem: Inglês

10.1016/j.vaccine.2009.02.087

1873-2518

Nina Wressnigg, Daniel Voß, Thorsten Wolff, Julia Romanova, Tanja Ruthsatz, Ines Mayerhofer, Manfred Reiter, Sabine Nakowitsch, Johannes Humer, Alexander Morokutti, Thomas Muster, Andrej Egorov, Christian Kittel,

Respiratory viral infections research

We discovered a unique, single amino acid mutation in the influenza B M1 protein promoting viral growth of NS1 truncation mutants in Vero cells. Due to this mutation, we were able to generate an influenza B virus lacking the complete NS1 open reading frame (ΔNS1-B virus) by reverse genetics, which was growing to titers of 8 log10 TCID50/ml in a Vero cell culture-based micro-carrier fermenter. The ΔNS1-B vaccine candidate was attenuated in IFN-competent hosts such as human alveolar epithelial cells (A549) similar to influenza A ΔNS1 viruses. In ferrets, the ΔNS1-B virus was replication-deficient and did not provoke any clinical symptoms. Importantly, a single intranasal immunization of ferrets at a dose as low as 6 log10 TCID50/animal induced a significant HAI response and provided protection against challenge with wild-type influenza B virus. So far, the lack of a ΔNS1-B virus component growing to high titers in cell culture has been limiting the possibility to formulate a trivalent vaccine based on deletion of the NS1 gene. Our study closes this gap and paves the way for the clinical evaluation of a seasonal, trivalent, live replication-deficient ΔNS1 intranasal influenza vaccine.