Live attenuated influenza b virus compositions methods of making and using thereof
AssigneeVersitech Limited
InventorsHonglin Chen, Pui Wang, Kowk-Yong Yuen
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AssigneeVersitech Limited
InventorsHonglin Chen, Pui Wang, Kowk-Yong Yuen
Estimating the term…
The NS1 protein of influenza virus is a key virulent element with multi-functional roles in virus replication and acts as a strong interferon (IFN) antagonist. A live attenuated virus (LAIV) is provided using a master backbone, which contains the influenza B (HK8038) virus and includes a deletion of the NSI coding region (DelNS1). The LAIV is based on novel adaptive mutations, which support DelNS1 influenza B live attenuated virus (LAIV) replication in vaccine producing cells. DelNS1 influenza B LAIV shows spontaneous cold adaption with preference to grow at 30-33° C. but restriction at 37-39° C. The LAIV can be used to protect a subject, against a lethal challenge of antigenic distant influenza B viruses. DelNS1 LAIV with adaptive mutations for growing in vaccine producing systems is an important strategy for making highly attenuated and immunogenic live attenuated influenza vaccines with the ability to induce broad cross protective immunity for seasonal influenza.
A live attenuated influenza virus (LAIV) B “LAIVB”) comprising a deletion in the coding region for NS1 (nonstructural protein 1), LAVIB/DelNS1 and one or more mutations selected from the group consisting of PA(T210C), NA T(1424C), NP(C182T) and M (A281G) (AM/LAVIB/DelNS1).
The virus of claim 6 wherein the vaccine producing system comprises MDCK cells culture.
A method for making LAIVB with a deletion of the viral virulence element, the NS1 protein (DelNS1) and an adaptive mutations which allows growth of the mutated strain in vaccine producing systems such as eggs and MDCK cells comprising (a) generating influenza B virus with deletion of the coding region of the NS1 coding region by transfecting the DelNS1 influenza B virus into one or more vaccine producing cells (b) rescuing LAVIB/DelNS1 and (c) passaging rescued virus culturing into one or more vaccine producing cells until viral titer is stabilized, to obtain AM/LAVIB/DelNS1.
A pharmaceutical composition comprising an effective amount of a virus to induce an immune response to an antigen encoded by virus's genome, the virus's genome comprising:
Dependencies are inferred from the claim text.