Immunogenic compositions containing a human immunodeficiency virus (HIV) gp140 protein, sorbitol, polysorbate 20, and histidine buffer are described. The described immunogenic compositions are advantageous in that they are stable at refrigerated temperature for extended periods of time, and are compatible with an adjuvant. Also described are methods of using the immunogenic compositions to induce an immune response against an HIV in a subject. The immunogenic compositions can be administered alone, or in combination with one or more additional HIV antigens, or one or more adenovirus vectors encoding the one or more additional HIV antigens.

Provided are methods of detecting replication competent virus, e.g., replication competent retrovirus such as gammaretrovirus or lentivirus, in a sample containing a cell transduced with a viral vector particle encoding a recombinant and/or heterologous molecule, e.g., heterologous gene product. The methods may include assessing transcription of one or more target genes, such as viral genes, that are expressed in a retrovirus but not expressed in the viral vector particle. Replication competent retrovirus may be determined to be present if the levels of RNA of the one or more target genes is higher than a reference value, which can be measured directly or indirectly, including from a positive control sample containing RNA from the respective target gene at a known level and/or at or above the limit of detection of the assay.

The present invention provides novel scaffolded HIV-1 vaccine immunogens. Some of the scaffolded immunogens contain a soluble gp140 trimer linked to the N-terminus of the nanoparticle subunit and a T-helper epitope that is fused via a short peptide spacer to the C-terminus of the nanoparticle subunit. Some other immunogens of the invention contain a soluble gp140 trimer protein that is linked to a stable nanoparticle via a short peptide spacer that is a T-helper epitope. Some of the scaffolded immunogens contain a gp140 trimer immunogen presented on a nanoparticle platform formed with I3-01 protein, E2p, or variants of protein 1VLW. Also provided in the invention are nucleic acids that encode the various vaccine immunogens described herein, and expression vectors and host cells harboring the nucleic acids. The invention further provides methods of using the scaffolded HIV-1 vaccine immunogens for preventing or treating HIV infections.

Provided are methods for identifying whether a compound inhibits entry of a virus into a cell. The method may include obtaining nucleic acid encoding a viral envelope protein from a patient infected by the virus and co-transfecting it into a first cell along with a viral expression vector which lacks a nucleic acid encoding the envelope protein. The method may further include contacting the viral particles produced by the first cell with a second cell to which the virus binds in the absence and presence of the compound and measuring the amount of signal produced by the second cell.

The present application relates to a lipopeptide for potently inhibiting HIV, a derivative thereof, or a pharmaceutical composition thereof, and use thereof. The lipopeptide is the following a) or b): a) a lipopeptide formed by linking a polypeptide having an antiviral activity to a lipophilic compound linked to the carboxyl-terminus of the polypeptide; or b) a lipopeptide formed by linking a polypeptide having an antiviral activity to a terminal protecting group and a lipophilic compound linked to the carboxyl-terminus of the polypeptide, wherein the terminal protecting group is an amino-terminal protecting group and/or a carboxyl-terminal protecting group, the polypeptide has a sequence of 28 amino acid residues, corresponding to amino acids at positions of 127-154 of the sequence of gp41 from HIV-1 strain HXB2. The anti-HIV activity of the lipopeptide of the present invention is higher than that of T-20 by several thousands of times or even tens of thousands of times, and is also significantly higher than that of the anti-HIV lipopeptides such as C34-Chol, LP-19 and the like.

The present invention provides methods for producing HIV-1 nanoparticle vaccines with enhanced immunogenicity. The methods entail (1) enzymatic digestion of glycan chain on the surface of a self-assembling nanoparticle vaccine displaying an HIV-1 Env derived trimer immunogen, or (2) expression of an HIV-1 nanoparticle construct in an expression system lacking normal glycosylation function for human proteins. Also provided in the invention are HIV-1 nanoparticle vaccines produced with the described methods. The invention further provides methods of using the HIV-1 nanoparticle vaccine compositions described herein in various therapeutic applications, e.g., for preventing or treating viral infections.

This disclosure relates to modified viruses, e.g., oncolytic vaccinia viruses, which have been modified to contain an exogenous nucleic acid that expresses a protein that modulates STAT3 activity. It is based, at least in part, on the discovery that vaccinia viruses modified to contain nucleic acid encoding PIAS3 and that express PIAS3 or a fragment thereof can inhibit STAT3 activity and enhance the anti-cancer activity of the vaccinia virus. Accordingly, this disclosure provides for oncolytic vaccinia viruses and methods of using them in the treatment of cancers.

This disclosure relates to modified viruses, e.g., oncolytic vaccinia viruses, which have been modified to contain an exogenous nucleic acid that expresses a protein that modulates STAT3 activity. It is based, at least in part, on the discovery that vaccinia viruses modified to contain nucleic acid encoding PIAS3 and that express PIAS3 or a fragment thereof can inhibit STAT3 activity and enhance the anti-cancer activity of the vaccinia virus. Accordingly, this disclosure provides for oncolytic vaccinia viruses and methods of using them in the treatment of cancers.

An experiment has shown that ranpirnase is a microbicide. It is believed that topical application of a topical pharmaceutical composition consisting essentially of a prophylactically effective concentration of an enzymatically-active ribonuclease (e.g. ranpirnase) and a viscous vehicle that does not unacceptably interfere with the enzymatic activity (e.g. K-Y® Brand Jelly) will prophylactically protect an individual from a sexually-transmitted viral infection, particularly HIV. It is also believed that e.g. ranpirnase can be delivered to tissues of an individual who is to be prophylactically protected against viral infections by transfecting ranpirnase DNA into human microbiota and exposing the individual to the thus-modified human microbiota. It is also believed that ranpirnase can be delivered to a woman who is to be prophylactically protected against a sexually-transmitted viral infection by use of an intravaginal ring that has been impregnated with ranpirnase.

An experiment has shown that ranpirnase is a microbicide. It is believed that topical application of a topical pharmaceutical composition consisting essentially of a prophylactically effective concentration of an enzymatically-active ribonuclease (e.g. ranpirnase) and a viscous vehicle that does not unacceptably interfere with the enzymatic activity (e.g. K-Y® Brand Jelly) will prophylactically protect an individual from a sexually-transmitted viral infection, particularly HIV. It is also believed that e.g. ranpirnase can be delivered to tissues of an individual who is to be prophylactically protected against viral infections by transfecting ranpirnase DNA into human microbiota and exposing the individual to the thus-modified human microbiota. It is also believed that ranpirnase can be delivered to a woman who is to be prophylactically protected against a sexually-transmitted viral infection by use of an intravaginal ring that has been impregnated with ranpirnase.