Alphavirus vectors and virosomes with modified HIV genes for use in vaccines

A composition comprising a population of alphavirus replicon particles comprising two or more isolated nucleic acids selected from the group consisting of 1) an isolated nucleic acid encoding an env gene product, or a fragment containing an epitope thereof, of a human immunodeficiency virus, 2) an isolated nucleic acid encoding a gαg gene product, or a fragment containing an epitope thereof, of a human immunodeficiency virus, wherein the gαg gene product or said fragment thereof is modified to inhibit formation of virus-like particles containing the gαg gene product or said fragment thereof and their release from a cell, and 3) an isolated nucleic acid encoding a pol gene product, or a fragment containing an epitope thereof, of a human immunodeficiency virus, wherein the pal gene product or said fragment thereof is modified to inhibit reverse transcriptase activity.

A composition comprising a population of alphavirus replicon particles comprising two or more isolated nucleic acids selected from the group consisting of 1) an isolated nucleic acid encoding an env gene product or a fragment containing an epitope thereof, of a human immunodeficiency virus, 2) an isolated nucleic acid encoding a gag gene product, or a fragment containing an epitope thereof, of a human immunodeficiency virus, wherein the gag gene product or said fragment thereof is modified to inhibit formation of virus-like particles containing the gag gene product or said fragment thereof and their release from a cell, and 3) an isolated nucleic acid encoding a pol gene product, or a fragment containing an epitope thereof, of a human immunodeficiency virus, wherein the pol gene product or said fragment thereof is modified to inhibit reverse transcriptase activity, and wherein the alphavirus replicon particles comprise a replicon RNA or at least one structural protein which comprises one or more attenuating mutations.

A composition comprising two or more isolated nucleic acids selected from the group consisting of an isolated nucleic acid encoding an env gene product a fragment containing an epitope thereof of a human immunodeficiency virus, an isolated nucleic acid encoding a gag gene product a fragment containing an epitope thereof of a human immunodeficiency virus, wherein the gag gene product or said fragment thereof is modified to inhibit formation of virus-like particles containing the gag gene product or said fragment thereof and their release from a cell, and an isolated nucleic acid encoding a pol gene product or a fragment containing an epitope thereof of a human immunodeficiency virus, wherein the pol gene product or said fragment thereof comprises a modification resulting in deletion or inactivation of protease, integrase, RNase H and reverse transcriptase functions in the pol gene product or said fragment thereof.

A composition comprising a population of alphavirus replicon particles comprising two or more isolated nucleic acids selected from the group consisting of 1) an isolated nucleic acid encoding an env gene product, or a fragment containing an epitope thereof, of a human immunodeficiency virus, 2) an isolated nucleic acid encoding a gag gene product, or a fragment containing an epitope thereof, of a human immunodeficiency virus, wherein the gag gene product or said fragment thereof is modified to inhibit formation of virus-like particles containing the gag gene product or the said fragment thereof and their release from a cell, and 3) an isolated nucleic acid encoding a pol gene product, or a fragment containing an epitope thereof, of a human immunodeficiency virus, wherein the pol gene product or said fragment thereof comprises a modification resulting in deletion or inactivation of integrase, RNase H and reverse transcriptase functions in the pol gene product or said fragment thereof.

A composition comprising a population of alphavirus replicon particles comprising two or more isolated nucleic acids selected from the group consisting of 1) an isolated nucleic acid encoding an env gene product, or a fragment containing an epitope thereof, of a human immunodeficiency virus, 2) an isolated nucleic acid encoding a gag gene product, or a fragment containing an epitope thereof, of a human immunodeficiency virus, wherein the gag gene product or said fragment thereof is modified to inhibit formation of virus-like particles containing the gag gene product or said fragment thereof and their release from a cell, and 3) an isolated nucleic acid encoding a pol gene product, or a fragment containing an epitope thereof, of a human immunodeficiency virus, wherein the pol gene product or said fragment thereof comprises a modification resulting in deletion or inactivation of protease, integrase, RNase H and reverse transcriptase functions in the pol gene product or said fragment thereof, and wherein the alphavirus replicon particles comprise a replicon RNA or at least one structural protein which comprises one or more attenuating mutations.

An isolated nucleic acid encoding a pol gene product or a fragment containing an epitope thereof of a human immunodeficiency virus, wherein the pol gene product or said fragment thereof comprises a modification resulting in deletion or inactivation of integrase, RNase H and reverse transcriptase functions in the pol gene product or said fragment thereof.