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HIV envelope polypeptides
| Details |
Inventors: Berman, Phillip W.; Nakamura, Gerald R.;
Assignee: Genentech, Inc. (South San Francisco, CA)
Primary Examiner: Stucker; Jeffrey
Assistant Examiner: Nelson; Brett
Attorney, Agent or Firm: McCutchen, Doyle, Brown & Enersen, LLP, Haliday; Emily M., Mack; Suzanne
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. |
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DETAILED DESCRIPTION The present invention provides a method for the rational design and preparation of vaccines based on HIV envelope polypeptides.
This invention is based on the discovery that there are neutralizing epitopes in the V2 and C4 domains of gp120, in addition to the neutralizing epitopes in the V3 domain.
In addition, the amount of variation of the neutralizing epitopes is highly constrained, facilitating the design of an HIV subunit vaccine that can induce antibodies that neutralize a plurality of HIV strains for a given geographic region.
In one embodiment, the present invention provides a method for making an HIV gp120 subunit vaccine for a geographic region in which a neutralizing epitope in the V2 and/or C4 domains of gp120 of HIV isolates from the geographic region is determined and an HIV strain having gp120 which has a neutralizing epitope in the V2 or C4 domain which is common among isolates in the geographic region is selected and used to make the vaccine.
In a preferred embodiment of the method, neutralizing epitopes for the V2, V3, and C4 domains of gp120 from HIV isolates from the geographic region 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 HIV gp120 subunit vaccine.
Preferably, each of the selected isolates have one of the most common neutralizing epitopes for the V2, V3, or C4 domains.
The invention also provides a multivalent HIV gp120 subunit vaccine.
The vaccine comprises gp120 from two isolates of HIV having at least one different neutralizing epitope.
Preferably, the isolates have the most common neutralizing epitopes in the geographic region for one of the domains.
A DNA sequence of less than 5 kilobases encoding gp120 from preferred vaccine strains of HIV, GNE.
sub.
8 and GNE.
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16, expression construct comprising the GNE.
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8 -gp120 and GNE.
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16 -gp120 encoding DNA under the transcriptional and translational control of a heterologous promoter, and isolated GNE
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Drugs 
