Development of a live-attenuated influenza B ΔNS1 intranasal vaccine candidate
| Autor: | Sabine Nakowitsch, Manfred Reiter, Nina Wressnigg, Johannes Humer, Tanja Ruthsatz, Alexander Morokutti, Ines Mayerhofer, Thorsten Wolff, Andrej Egorov, Christian Kittel, Daniel Voss, Julia Romanova, Thomas Muster |
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| Rok vydání: | 2009 |
| Předmět: |
Influenza vaccine
viruses M1 protein Viral Nonstructural Proteins Vaccines Attenuated Virus Replication Virus Cell Line Microbiology Orthomyxoviridae Infections Chlorocebus aethiops Animals Humans Administration Intranasal Attenuated vaccine Base Sequence General Veterinary General Immunology and Microbiology biology Ferrets Public Health Environmental and Occupational Health virus diseases Virology Vaccination Influenza B virus Infectious Diseases Immunization Viral replication Influenza Vaccines Mutation biology.protein Vero cell Molecular Medicine |
| Zdroj: | Vaccine. 27:2851-2857 |
| ISSN: | 0264-410X |
| Popis: | 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 (DeltaNS1-B virus) by reverse genetics, which was growing to titers of 8log(10)TCID(50)/ml in a Vero cell culture-based micro-carrier fermenter. The DeltaNS1-B vaccine candidate was attenuated in IFN-competent hosts such as human alveolar epithelial cells (A549) similar to influenza A DeltaNS1 viruses. In ferrets, the DeltaNS1-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 log(10)TCID(50)/animal induced a significant HAI response and provided protection against challenge with wild-type influenza B virus. So far, the lack of a DeltaNS1-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 DeltaNS1 intranasal influenza vaccine. |
| Databáze: | OpenAIRE |
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