In one aspect, provided herein is a mosaic influenza virus hemagglutinin (HA) polypeptide comprising an influenza A virus HA ectodomain of an influenza A virus strain HA, wherein the HA ectodomain comprises an HA stem domain of the influenza A virus strain HA and an HA globular head domain of the influenza A virus strain HA, wherein the HA globular head domain of the influenza A virus strain HA has been engineered to comprise one or more amino acid substitutions in one, two, three, four or all of the antigenic sites. In another aspect, provided herein are immunogenic compositions comprising such a mosaic influenza virus HA polypeptide or an influenza A virus comprising such a mosaic influenza virus HA polypeptide. In yet another aspect, provided herein are methods for immunizing a subject against an influenza A vims in a subject comprising administering such an immunogenic composition to the subject.

The present invention relates to enveloped RNA viruses. The invention in particular relates to the generation of superior antigens for mounting an immune response by first identifying then mutating the immunosuppressive domains in fusion proteins of enveloped RNA viruses resulting in decreased immunosuppressive properties of viral envelope proteins from the viruses.

Provided is a recombinant H7N9 subtype avian influenza virus, a marked vaccine and a preparation method thereof. For the recombinant H7N9 subtype avian influenza virus, a strain JD/17 of H7N9 subtype avian influenza virus is used as parent virus and a peptide sequence in HA protein of the strain JD/17 is replaced with a peptide sequence in HA protein of H3 subtype; the strain JD/17 of H7N9 subtype avian influenza virus has a preservation number of CCTCC No. V201862. The results of HA titers, EID50, TCID50 show that the rescued virus maintains similar biological characteristics of parent virus, such as high HA titers and EID50, and chickens immunized with the marked inactivated and emulsified vaccine produce a high level of antibody, and this antibody can be distinguished from antibodies produced by chickens naturally infected with H7N9 subtype avian influenza virus.

Disclosed are delivery and expression systems of multiple antiviral therapeutic molecules. The therapeutic molecules include a novel class of dual-functional peptide and defective interfering genes of a virus. Also disclosed are compositions comprising the therapeutic molecules that are useful for the treatment and prevention of viral infections. Also disclosed herein are the method of making and using a vector that expresses the therapeutic molecules. Therapeutic molecules include cellular components such as RNA, DNA, peptide, proteins or combination thereof.

The present invention includes a live, self-attenuated therapeutic vaccine, virus and methods of making and using the same, comprising: an isolated virus comprising a viral genome that expresses one or more viral antigens; and an artificial microRNA 30 (amiR-30) expression cassette inserted into a viral neuraminidase (NA) or a viral non-structural (NS) gene segment that expresses an amiR-30 that specifically inhibits the expression of a host gene essential for influenza virus replication in host cells.

Mutation patterns of a virus (e.g., influenza virus) are identified and predicted based on identifying effective mutations in an amino acid sequence of the virus and an effective mutation period during which the mutation enables the virus to escape from human immunity. Based on analysis of existing virus composition and infection rates, a measure of genetic mutation activity (“g-measure”) is determined, and one or more associated parameters that further characterize virus genetic activity may also be optimized. The g-measure and/or associated parameters can be used to predict future genetic activity of the virus, which can aid in selection of strains for a future vaccine and/or predictions of infectious-disease outbreaks.

Provided herein are methods for generating a non-naturally occurring, broadly reactive, pan-epitopic antigen derived from H3 influenza virus that is capable of eliciting a broadly reactive immune response, such as a broadly reactive neutralizing antibody response, against H3 virus following administration to a subject. Also provided is a non-naturally occurring immunogen generated using the methods, and vaccines and compositions comprising the immunogen. Methods of generating an immune response in a subject by administering the immunogen, vaccine, or composition are provided. In particular, the immunogen comprises the hemagglutinin (HA) protein of H3 influenza vims strains.

Modified influenza virus neuraminidases are described herein that have stabilized NA tetramers which may improve vaccine production efficiency, thus improving the yield of vaccine viruses.

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.

The invention provides a composition useful to prepare influenza vaccine viruses, e.g., in the absence of helper virus, which includes internal viral segments from an influenza virus vaccine strain or isolate, e.g., one that is safe in humans, for instance, one that does not result in significant disease, and encodes a heterologous antigen.