Genentech, Inc.

Genetech, Inc.

Phillip W Berman

Laurence A Lasky

Gerald R Nakamura

Brian M Fendly

Timothy J Gregory

Daniel J Capon

Florian M Wurm

Avi J Ashkenazi

Tina M Etcheverry

David Brousseau

Elorian M Wurm

Disclosed is an invention related to the preparation and use of vaccines against pathogenic organisms, such as herpes virus. The vaccines hereof are based upon the use of truncated, membrane-free derivatives of a membrane-bound polypeptide from the pathogen. These polypeptides when incorporated into a vaccine composition afford protection against pathogenic challenge after administration.

Immunogenic composition based on a truncated derivative of a membrane bound protein and process for making it

Oligonucleotide sequences encoding gp120 polypeptides from breakthrough isolates of vaccine trials using MN-rgp120 and the encoded gp120 polypeptides are provided. Use of the gp120 polypeptides from one or more of the isolates in a subunit vaccine, usually together with MN-rgp120, can provide protection against HIV strains that are sufficiently different from the vaccine strain (e.g.; MN-rgp120) that the vaccine does not confer protection against those strains. Antibodies induced by the polypeptides are also provided.

HIV envelope polynucleotides and immunogenic composition

The invention provides antibodies specific for HIV env, including monoclonal antibodies and related hybridomas. The antibodies block CD4/g120 binding and reduce reverse transcriptase activity in vitro.

HIV env antibodies

A method for the rational design and preparation of vaccines based on HIV envelope polypeptides is described. In one embodiment, the method for making an HIV gp120 subunit vaccine for a geographic region comprises determining neutralizing epitopes in the V2 and/or C4 domains of gp120 of HIV isolates from the geographic region and selecting an HIV strain having gp120 a neutralizing epitope in the V2 or C4 domain which is common among isolates in the geographic region. In a preferred embodiment of the method, neutralizing epitopes for the V2, V3, and C4 domains of gp120 are determined. At least two HIV isolates having different neutralizing epitopes in the V2, V3, or C4 domain are selected and used.to make the vaccine. The invention also provides a multivalent HIV gp120 subunit vaccine. A DNA sequence encoding gp120 from preferred vaccine strains of HIV, GNE and GNE , expression constructs comprising the GNE -gp120 and GNE -gp120 encoding DNA under the transcriptional and translational control of a heterologous promoter, and isolated GNE -gp120 and GNE -gp120 are also described.

HIV envelopolype peptides

DNA constructs, host cells and production methods are disclosed for the expression and recovery of polypeptides, especially those altered to have one or more glycosylation sites added or deleted. The DNA constructs, host cells and methods provided herein employ a DNA segment corresponding to a mammalian tissue plasminogen activator signal and/or pro peptide.

Protein secretion

HIV envelope polypeptides and immunogenic composition

Diagnostic product and vaccine for Acquired Immuno-deficiency Syndrome (AIDS) and methods for making and using same, wherein viral polypeptide sequences from an AIDS associated retrovirus are expressed directly or as a fusion polypeptide in a prokaryotic or mammalian cell expression host to produce a diagnostic product which specifically binds complementary antibody produced by individuals afflicted with AIDS or a vaccine against AIDS which confers resistance to infection by AIDS associated retrovirus. The reverse transcriptase of an AIDS associated retrovirus is used separately or in a whole cell assay to identify compounds which selectively inhibit retroviral reverse transcriptase.

Molecularly cloned acquired immunodeficiency syndrome polypeptides and their methods of use

A method for the rational design and preparation of vaccines based on HIV envelope polypeptides is described. In one embodiment, the method for making an HIV gp120 subunit vaccine for a geographic region comprises determining neutralizing epitopes in the V2 and/or C4 domains of gp120 of HIV isolates from the geographic region and selecting an HIV strain having gp120 a neutralizing epitope in the V2 or C4-domain which is common among isolates in the geographic region. In a preferred embodiment of the method, neutralizing epitopes for the V2, V3, and C4 domains of gp120 are determined. At least two HIV isolates having different neutralizing epitopes in the V2, V3, or C4 domain are selected and used to make the vaccine. The invention also provides a multivalent HIV gp120 subunit vaccine. A DNA sequence encoding gp120 from preferred vaccine strains of HIV, GNE,and GNE,, expression constructs comprising the GNE,-gp120 and GNE,-gp120 encoding DNA under the transcriptional and translational control of a heterologous promoter, and isolated GNE,-gp120 and GNE,-gp120 are also described.

HIV envelope polypeptides

HIV envelope polypeptides and vaccine

A method for the rational design and preparation of vaccines based on HIV envelope polypeptides is described. In one embodiment, the method for making an HIV gp120 subunit vaccine for a geographic region comprises determining neutralizing epitopes in the V2 and/or C4 domains of gp120 of HIV isolates from the geographic region and selecting an HIV strain having gp120 a neutralizing epitope in the V2 or C4 domain which is common among isolates in the geographic region. In a preferred embodiment of the method, neutralizing epitopes for the V2, V3, and C4 domains of gp120 are determined. At least two HIV isolates having different neutralizing epitopes in the V2, V3, or C4 domain are selected and used to make the vaccine. The invention also provides a multivalent HIV gp120 subunit vaccine.

Molecularly cloned acquired immunodeficiency syndrome polypeptides and

Disclosed is an invention related to the preparation and use of vaccines against pathogenic organisms, such as herpes virus. The vaccines hereof are based upon the use of glycoproteins of the organism, that have been prepared via recombinant means, and preferably C-truncated versions thereof. These glycoproteins when incorporated into a vaccine composition afford protection against pathogenic challenge after administration.

Vaccine based on membrane bound proteins and process for making them

Methods for making unclipped HIV env proteins are provided. According to the methods, a genetically engineered cell line comprising an nucleic acid sequence encoding an HIV env protein is cultured to produce unclipped HIV env protein, which is recovered from the cell culture.

Method for making unclipped HIV envelope protein

Methods for producing and isolating unclipped HIV env proteins are provided. According to the methods, an antibody directed to an HIV epitope spanning the env clip site is used to selectively separate unclipped HIV env protein from clipped env protein.

Growing community of inventors

Portola Valley, CA, United States of America

Phillip W Berman