New York University

Icahn School of Medicine at Mount Sinai

Molsoft LLC

Xiangpeng Kong

Susan Zolla-Pazner

Maxim Totrov

Timothy J Cardozo

Ruimin Pan

Xunqing Jiang

The present invention relates to isolated immunogenic polypeptides and their use. In one aspect, the isolated immunogenic polypeptide includes a scaffold polypeptide having a hairpin loop modified to include one or more epitopes heterologous to the scaffold polypeptide and from an amino acid loop linked by a disulfide bond. The scaffold polypeptide directs self-assembly with two other of the scaffold polypeptides to form a trimeric structure, which constrains the one or more epitopes to a conformation that is (i) substantially similar to one or more native pathogen epitopes in trimeric conformation and (ii) capable of binding an antibody reactive to the one or more native pathogen epitopes in trimeric conformation. Another aspect relates to an isolated immunogenic polypeptide that includes a scaffold polypeptide having a native loop modified to include one or more epitopes heterologous to the scaffold polypeptide and from an amino acid loop linked by a disulfide bond. The scaffold polypeptide directs self-assembly with four other of said scaffold polypeptides to form a pentameric structure, which constrains the one or more epitopes to a conformation capable of binding an antibody reactive to one or more native pathogen epitopes.

Immunogenic polypeptides

The present invention relates to an isolated immunogenic peptide comprising a V2 loop fragment from HIV surface envelope glycoprotein gp120. This peptide binds specifically with antibodies in blood of patients vaccinated with a vaccine that has shown protection from HIV-1 infection, does not react with blood of matched patients who did not receive the vaccine, and can, therefore, elicit anti-HIV-1 antibodies which protect against HIV-1 infection. Other aspects of the present invention relate to an isolated immunogenic polypeptide comprising the peptide inserted into an immunogenic scaffold protein, a vaccine composition comprised of the immunogenic peptide and an immunologically or pharmaceutically acceptable vehicle or excipient as well as methods of inducing an immune response against HIV-1 and methods of detecting HIV-1.

Peptides mimicking HIV-1 viral epitopes in the V2 loop for the GP120 surface envelope glycoprotein

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Xiangpeng Kong