Provided herein are influenza hemagglutinin stem domain polypeptides, compositions comprising the same, vaccines comprising the same and methods of their use.

The invention relates to transgene expressing Newcastle Disease Viruses (NDV), which have been demonstrated to possess significant oncolytic activity against mammalian cancers. The invention provides novel oncolytic viruses through the use of genetic engineering, including the transfer of foreign genes or parts thereof, such as genes encoding Ipilimumab, interleukin-12 or NS1. The present invention also provides nucleic acids encoding a reverse genetically engineered (rg-)NDV comprising one or more of these foreign genes and having a mutation in the HN gene, said mutation allowing replication of said rgNDV in a cancer cell to a higher level than replication of an otherwise identical rgNDV not having said mutation in the HN gene.

Recombinant strains of avian paramyxovirus (APMV), such as Newcastle disease virus (NDV), are provided. Also provided are compositions comprising them, and methods of using them to lyse tumor cells and to treat cancer. In certain aspects, genetically-engineered viral strains that incorporate therapeutic transgenes are also provided. The recombinant viruses may be used in accordance with methods of providing enhanced oncolytic efficacy and delivering an oncolytic virus to tumors present in a patient. Also provided are methods for identifying a recombinant virus as an oncolytically-effective agent.

A heat-resistant recombinant Newcastle Disease Virus vaccine strain rLS-tFib2-C capable of expressing truncated Fiber 2 protein of fowl adenovirus serotype 4 has been preserved at the China Center for Type Culture Collection, Wuhan University, Wuhan, China with the preservation number of CCTCC No. V202042.

The present application relates a composite multi-epitope expression cassette, a recombinant virus composed thereof and application thereof, and in particular to a chimeric recombinant Newcastle disease virus inserted with an IBV epitope cassette and a vaccine prepared by using the virus. The expression cassette comprises: (a) T cell epitopes derived from S1 proteins of avian infectious bronchitis virus Holte strain and avian infectious bronchitis virus QX-like strain; and (b) B cell epitopes derived from S1 protein of avian infectious bronchitis virus Australian T strain. In the present application, the multi-epitope chimeric ST/B gene of avian infectious bronchitis virus is inserted into the backbone of LaSota strain, so that the LaSota strain can express S1-T/B protein. Thus, the purpose of preventing both ND and IB diseases is achieved. In addition, the T cell epitopes and B cell epitopes act synergistically to produce an earlier and more comprehensive immune response against virus.

The present disclosure relates to a vaccine composition for preventing human infection SARS-CoV-2 (COVID-19) and alleviating infection symptoms, and the vaccine composition including a recombinant Newcastle disease virus on the surface of which the SARS-CoV-2 RBD protein of the present disclosure is expressed or antigen purified therefrom induces an immune response that can fight COVID-19 infection so that it can be useful as a vaccine for preventing and treating SARS-CoV-2 infection.

The present application relates a composite multi-epitope expression cassette, a recombinant virus composed thereof and application thereof, and in particular to a chimeric recombinant Newcastle disease virus inserted with an IBV epitope cassette and a vaccine prepared by using the virus. The expression cassette comprises: (a) T cell epitopes derived from S1 proteins of avian infectious bronchitis virus Holte strain and avian infectious bronchitis virus QX-like strain; and (b) B cell epitopes derived from S1 protein of avian infectious bronchitis virus Australian T strain. In the present application, the multi-epitope chimeric ST/B gene of avian infectious bronchitis virus is inserted into the backbone of LaSota strain, so that the LaSota strain can express S1-T/B protein. Thus, the purpose of preventing both ND and IB diseases is achieved. In addition, the T cell epitopes and B cell epitopes act synergistically to produce an earlier and more comprehensive immune response against virus.

Described herein are recombinant Newcastle disease viruses (“NDVs”) comprising a packaged genome, wherein the packaged genome comprises a transgene comprising a nucleotid sequence encoding a SARS-CoV-2 spike protein or nucleocapsid protein. Also described herein are recombinant NDVs comprising a packaged genome, wherein the packaged genome comprises a transgene encoding a chimeric F protein, wherein the chimeric F protein comprises a SARS-CoV-2 spike protein ectodomain and NDV F protein transmembrane and cytoplasmic domains. The recombinant NDVs and compositions thereof are useful for the immunizing against SARS-CoV-2 as well as the prevention of COVID-19.

Provided are an oncolytic virus for treating brain tumors using a recombinant Newcastle disease virus into which a Newcastle disease virus (NDV) vector-based PTEN (phosphatase and tensin homolog) gene is inserted and a composition for treating brain tumors using the same which can be used for a therapeutic viral agent that can induce reduction of clinical symptoms or partial or complete remission through brain tumor cell death or brain tumor tissue reduction by expressing normal PTEN protein after being infected with brain tumor cells, as a recombinant Newcastle disease virus containing a human PTEN protein gene.

In one aspect, provided herein are naturally occurring and recombinantly produced avian paramyxovirus (APMV) (e.g., an APMV-2, APMV-3, APMV-4, APMV-6, APMV-7, APMV-8, and APMV-9 strain) and uses of such APMV for the treatment of cancer. In particular, provided herein are methods for treating cancer comprising administering a naturally occurring or recombinantly produced APMV-4 strain to a subject in need thereof. In another aspect, provided herein are recombinant APMV comprising a packaged genome, wherein the packaged genome comprises a transgene. In particular, described herein are recombinant APMV (e g., APMV-2, APMV-3, APMV-4, APMV-6, APMV-7, APMV-8, and APMV-9). In another aspect, provided herein are methods for treating cancer comprising administering a recombinant APMV (e g., APMV-2, APMV-3, APMV-4, APMV-6, APMV-7, APMV-8, and APMV-9) to a subject in need thereof, wherein the recombinant APMV comprises a packaged genome comprising a transgene. In particular, provided herein are methods for treating cancer comprising administering a recombinant APMV-4 to a subject in need thereof, wherein the recombinant APMV-4 comprises a packaged genome comprising a transgene. In specific aspects, the use of APMV serotypes other than APMV-1 (such as described herein, in particular AMPV-4) to treat cancer is based, in part, on the similar or enhanced in vivo anti-tumor activities when compared to oncolytic NDV La Sota-L289A strain.