Fusion-Intermediate State of HIV-1 gP41 Targeted by Broadly Neutralizing Antibodies
AssigneeChildren's Medical Center Corporation
InventorsBing Chen, Gary H. Frey, Stephen C. Harrison
Life of this patent
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Abstract
Isolated, antigenic polypeptides including a prehairpin intermediate conformation of gp41 and vectors encoding such polypeptides are provided. Antibodies that bind to a prehairpin intermediate conformation of gp41 and methods of making antibodies a that bind to prehairpin intermediate conformation of gp41 are also provided. Vaccines against a prehairpin intermediate conformation of gp41, as well as methods of treating subjects infected with HIV, preventing HIV infection, and inhibiting HIV-mediated activities are also provided. Methods of screening compounds that bind to an isolated, prehairpin intermediate conformation of gp41 are further provided.
Claims28
An isolated, antigenic polypeptide comprising a prehairpin intermediate conformation of gp41 including:
- a first heptad repeat 2 motif;
- a second heptad repeat 2 motif;
- a heptad repeat 1 motif and
- a membrane-proximal external region,
- wherein the polypeptide elicits production of a broadly neutralizing antibody against HIV when injected into a subject.
An isolated, antigenic polypeptide comprising a prehairpin intermediate conformation of gp41 in the following order:
- a first heptad repeat 2 motif at the amino terminus of the polypeptide;
- a heptad repeat 1 motif;
- a C-C loop domain;
- a second heptad repeat 2 motif;
- and
- a membrane-proximal external region at the carboxy terminus of the polypeptide.
A vector expressing a polynucleotide encoding a polypeptide comprising a prehairpin intermediate conformation of gp41 in the following order:
- a first heptad repeat 2 motif at the amino terminus of the polypeptide;
- a heptad repeat 1 motif;
- a C-C loop domain;
- a second heptad repeat 2 motif;
- and
- a membrane-proximal external region at the carboxy terminus of the polypeptide.
A method of therapeutically treating a subject infected with HIV comprising:
- contacting a subject infected with HIV with an isolated polypeptide comprising a prehairpin intermediate conformation of gp41 including a first heptad repeat 2 motif, a second heptad repeat 2 motif, a heptad repeat 1 motif and a membrane-proximal external region,
- wherein the polypeptide elicits an immune response in the subject to therapeutically treat the subject.
A method of inhibiting an HIV-mediated activity in a subject in need thereof comprising:
- contacting an HIV-infected subject with an isolated polypeptide comprising a prehairpin intermediate conformation of an envelope glycoprotein including a first heptad repeat 2 motif, a second heptad repeat 2 motif, a heptad repeat 1 motif and a membrane-proximal external region,
- to inhibit the HIV-mediated activity.
A method of preventing HIV infection in a subject comprising:
- contacting a subject with an isolated polypeptide comprising a prehairpin intermediate conformation of gp41 including a first heptad repeat 2 motif, a second heptad repeat 2 motif, a heptad repeat 1 motif and a membrane-proximal external region, and
- eliciting an immune response against the polypeptide in the subject.
A method of screening a compound that binds to an isolated, prehairpin intermediate conformation of gp41 comprising:
- providing an isolated polypeptide including a prehairpin intermediate conformation of gp41 having a first heptad repeat 2 motif, a second heptad repeat 2 motif, a heptad repeat 1 motif and a membrane-proximal external region;
- contacting the polypeptide with the compound;
- and
- determining the ability of the compound to bind to the polypeptide.
A vaccine having an epitope comprising an isolated, prehairpin intermediate conformation of gp41 including a first heptad repeat 2 motif, a second heptad repeat 2 motif, a heptad repeat 1 motif and a membrane-proximal external region.
An anti-gp41 antibody specific against an epitope comprising an isolated, prehairpin intermediate conformation of gp41 including a first heptad repeat 2 motif, a second heptad repeat 2 motif, a heptad repeat 1 motif and a membrane-proximal external region.
A method of making an anti-gp41 antibody comprising the steps of:
- providing a host;
- contacting the host with an epitope comprising an isolated, prehairpin intermediate conformation of gp41 including a first heptad repeat 2 motif, a second heptad repeat 2 motif, a heptad repeat 1 motif and a membrane-proximal external region;
- and
- allowing production of an anti-gp41 antibody in the host.
Dependencies are inferred from the claim text.