Connaught Laboratories Limited

Aventis Pasteur Limited

Sanofi Pasteur Inc.

Fei-Long Yao

Benjamin Rovinski

Michel Henri Klein

Shi-Xian Cao

Roy Persson

Shi Xian Cao

James Tartaglia

Diane M Gajewczyk

Phillipe Moingeon

Non-infectious, retrovirus-like particles contain mutations to reduce gag-dependent RNA-packaging of the gag gene product, eliminate reverse transcriptase activity of the pol gene product, eliminate integrase activity of the pol gene product and eliminate RNase H activity of the pol gene product through genetic manipulation of the gag and pol genes. The corresponding nucleic acid molecules are described. The non-infectious, retrovirus-like particles have utility in in vivo administration including to humans and in diagnosis.

Retrovirus-like particles made non-infectious by a plurality of mutations

Non-infectious, non-replicating immunogenic HIV-like particles are produced by stable long-term constitutive expression in mammalian cells by eliminating elements toxic to the mammalian cells. An expression vector contains a nucleic acid molecule comprising a modified HIV genome devoid of long terminal repeats and wherein Tat and vpr sequences are functionally disabled and a constitutive promoter operatively connected to the modified HIV genome for constitutive expression of the modified genome to produce the HIV-like particles.

Constitutive expression of non-infectious HIV-like particles

Non-infectious, retrovirus-like particles comprise an assembly of an env gene product, a pol gene product and a gag gene product contain an antigenic marker which is non-retroviral or non-HIV retroviral. In one embodiment, the marker comprises an amino acid sequence containing an epitope inserted into the gag gene product at an antigenically-active insertion site. In another embodiment, the marker comprises an antigenic anchor sequence operatively connected to the env gene product replacing endogenous anchoring function. The corresponding nucleic acid molecules are described. The non-infectious, retrovirus-like particles have utility in in vivo administration including to humans and in diagnosis. The presence of the antigenic marker enables recognition that antiserum containing anti-retroviral antibodies has been generated by exposure to the non-infectious retrovirus-like particles by testing for antibodies specific to the antigenic marker.

Anigenically-marked non-infectious retrovirus-like particles

Non-infectious, immunogenic, human immunodeficiency virus-like particles devoid of long terminal repeats and a functional pol coding region

Antigentically-marked non-infectious retrovirus-like particles

Non-infectious, retrovirus-like particles contain mutations to reduce gag-dependent RNA-packaging of the gag gene product, eliminate reverse transcriptase activity of the pol gene product, eliminate integrase activity of the pol gene, product and eliminate RNase H activity of the pol gene product through genetic manipulation of the gag and pol genes. The corresponding nucleic acid molecules are described. The non-infectious, retrovirus-like particles have utility in in vivo administration including to humans and in diagnosis.

Retrovirus like particles made non infectious by a plurality of mutations

Diagnostic kits comprising genetically engineered human immunodeficiency virus-like particles containing heterologous antigenic markers

Non-infectious, retrovirus-like particles comprise an assembly of an,gene product, a,gene product and a,gene product contain an antigenic marker which is non-retroviral or non-HIV retroviral. In one embodiment, the marker comprises an amino acid sequence containing an epitope inserted into the,gene product at an antigenically-active insertion site. In another embodiment, the marker comprises an antigenic anchor sequence operatively connected to the,gene product replacing endogenous anchoring function. The corresponding nucleic acid molecules are described. The non-infectious, retrovirus-like particles have utility in in vivo administration including to humans and in diagnosis. The presence of the antigenic marker enables recognition that antiserum containing anti-retroviral antibodies has been generated by exposure to the non-infectious retrovirus-like particles by testing for antibodies specific to the antigenic marker.

Antigenically-marked non-infectious retrovirus-like particles

Vectors for DNA immunization against cervical cancer comprise a nucleic acid molecule encoding at least one non-toxic T-cell epitope of the E6 and/or E7 antigens of a strain of human papilloma virus (HPV) associated with cervical cancer, such as HPV-16, and a promoter operatively coupled to the nucleic acid molecule for expression of the nucleic acid molecule in a host to which the vector is administered.

Vectors for DNA immunization against cervical cancer

Non-infectious, non-replicating immunogenic HIV-like particles are produced by stable longn-term constitutive expression in mammalian cells by eliminating elements toxic to the mammalian cells. An expression vector contains a nucleic acid molecule comprising a modified HIV genome devoid of long terminal repeats and wherein Tat and vpr sequences are functionally disabled and a constitutive promoter operatively connected to the modified HIV genome for constitutive expression of the modified genome to produce the HIV-like particles.

Non-infectious, retrovirus-like particles contain mutations to reduce gag-dependent RNA-packaging of the gag gene product, eliminate reverse transcriptase activity of the pol gene product, eliminate integrase activity of the pol gene product and eliminate RNase H activity of the pol gene product through genetic manipulation of the gag and pol genes. The corresponding nucleic acid molecules are described. The non-infectious, retrovirus-like particles have utility in diagnosis.

Human immunodeficiency virus type 1 nucleic acids devoid of long

Methods for the detection of HIV-specific immune responses employing

The present invention is concerned with the ability to differentiate between infection by HIV and immunization with an immunogenic preparation. Accordingly, the present invention provides a non-infectious, non-replicating, HIV retrovirus-like particle containing a heterologous antigenic marker, comprising an assembly of (a) an env gene product; (b) a pol gene product; (c) a gag gene product; and, (d) at least one non-retroviral, non-mammalian antigenic marker. The antigenic marker may have between 5 and 100 amino acid residues. In one embodiment, the amino acid sequence contains a tobacco mosaic virus (TMV) epitope obtained from the coat protein. In another embodiment, the marker is inserted into the gag gene product at an antigenically-active insertion site. The presence of the antigenic marker enables recognition that antiserum containing anti-HIV antibodies has been generated by exposure to the non-infectious retrovirus-like particles, as opposed to wild-type HIV infection, by testing for antibodies specific to the antigenic marker.

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North York, Canada

Fei-Long Yao