Abstract: 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.

Abstract: Live attenuated viruses for protection against the novel coronavirus which emerged in Wuhan, Hubei Province of China, designated as Sars-CoV-2 by the World Health Organization (WHO) are provided. The live attenuated chimeric virus strains are based on a live attenuated influenza virus (LAIV), used a master backbone, which includes deletion of the viral virulence element, the NS1 (non-structural protein 1) (DeLNS1), engineered to express one or more antigens of the Sars-CoV-2 (herein, CoV2Ag). The chimeric virus strain is referred to generally herein, as DelNS1-Sars-CoV-2-CoV2Ag. The DelNS1-Sars-CoV-2-CoV2Ag strain preferably shows spontaneous cold adaption with preference to grow at 30-33° C. The DelNS1-Sars-CoV-2-CoV2Ag strain can be used to protect a subject in need thereof, against a challenge of Sars-CoV-2. DelNS1-Sars-CoV-2-CoV2Ag is an important strategy for making highly attenuated and immunogenic live attenuated vaccines with the ability to induce protective immunity against Sars-CoV-2.