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Vaccine. 2009 Mar 11. [Epub ahead of print]
Development of a live-attenuated influenza B NS1 intranasal vaccine candidate.
Wressnigg N, Voss D, Wolff T, Romanova J, Ruthsatz T, Mayerhofer I, Reiter M, Nakowitsch S, Humer J, Morokutti A, Muster T, Egorov A, Kittel C. - Avir Green Hills Biotechnology, Gersthoferstrasse 29-31, 1180 Vienna, Austria; University of Vienna, Institute of Microbiology and Genetics, Dr. Bohrgasse 9, 1030 Vienna, Austria.
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 (?NS1-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 ?NS1-B vaccine candidate was attenuated in IFN-competent hosts such as human alveolar epithelial cells (A549) similar to influenza A ?NS1 viruses. In ferrets, the ?NS1-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 6log(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 ?NS1-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 ?NS1 intranasal influenza vaccine.
PMID: 19366569 [PubMed - as supplied by publisher]
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Development of a live-attenuated influenza B NS1 intranasal vaccine candidate.
Wressnigg N, Voss D, Wolff T, Romanova J, Ruthsatz T, Mayerhofer I, Reiter M, Nakowitsch S, Humer J, Morokutti A, Muster T, Egorov A, Kittel C. - Avir Green Hills Biotechnology, Gersthoferstrasse 29-31, 1180 Vienna, Austria; University of Vienna, Institute of Microbiology and Genetics, Dr. Bohrgasse 9, 1030 Vienna, Austria.
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 (?NS1-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 ?NS1-B vaccine candidate was attenuated in IFN-competent hosts such as human alveolar epithelial cells (A549) similar to influenza A ?NS1 viruses. In ferrets, the ?NS1-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 6log(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 ?NS1-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 ?NS1 intranasal influenza vaccine.
PMID: 19366569 [PubMed - as supplied by publisher]
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