The United States of America, As Represented by the Secretary, Department of Health and Human Services

The UAB Research Foundation (The University of Alabama at Birmingham)

The University of Alabama

The Administrators of the Tulane Educational Fund

Frederic Bibollet-Ruche

Beatrice H Hahn

George M Shaw

Peter D Kwong

James E Robinson

Julie Decker

Methods and compositions are provided which employ chimeric polypeptides having at least one heterologous epitope for a human immunodeficiency virus type 1 (HIV-1) neutralizing antibody. These chimeric polypeptides behave as molecular scaffolds which are capable of presenting the various heterologous HIV-1 epitopes. The invention demonstrates that a heterologous epitope recognized by the HIV-1 neutralizing antibody can be more fully exposed to neutralizing antibodies when presented within the backbone of the chimeric polypeptide than when the epitope is presented within the context of an HIV-1 backbone. Polynucleotides encoding these chimeric polypeptides are also provided. Immunogenic compositions are provided which comprise a chimeric polypeptide having at least one heterologous epitope that interacts with an HIV-1 neutralizing antibody. Immuno genie compositions comprising chimeric polynucleotides encoding the chimeric polypeptides of the invention are also provided. Vaccines comprising such immunogenic compositions are also provided. Further provided are methods which employ the immunogenic compositions of the invention. Such methods include, for example, methods for eliciting an immune response in a subject, methods for generating antibodies specific for the chimeric polypeptide or the chimeric polypeptide, and methods for inhibiting or preventing infection by HIV-1 in a subject.

Molecular scaffolds for HIV-1 immunogens

Methods and compositions are provided for the use of an envelope polypeptide or a functional variant thereof from a lentivirus that is not HIV-1 as a molecular scaffold for HIV-1 epitopes. The HIV-1 epitopes can be recognized by HIV-1 binding antibodies, HIV-1 neutralizing antibodies and/or CD4-induced antibodies. Thus, methods are provided for detecting HIV-1 binding antibodies in a subject infected with HTV-1. Further provided are methods to determine an epitope for an HIV-1 binding antibody; methods to assay for an HIV-1 binding antibody; methods to identify a soluble CD4 mimic; methods to neutralize an non-HIV-1 virus; diagnostic assays to monitor HIV disease in a subject or to monitor the subject's response to immunization by a HIV vaccine; and methods to alter the neutralization potential of an HIV-1 derived CD4-induced antibody. Chimeric polypeptides, chimeric polynucleotides, kits, cells and viruses are also provided.

Molecular scaffolds for HIV-1 epitopes

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Birmingham, AL, United States of America

Frederic Bibollet-Ruche