Deletion of the beta 20-21 loop in HIV GP120 exposes the CD4 binding site for improved antibody binding and antibody induction

摘要

Disclosed herein are isolated immunogens including variant gp120 polypeptides. In an example, a variant gp120 polypeptide includes a deletion of at least 8 consecutive residues of the fourth conserved loop (C4) between residues 419 and 434 of gp120 according to HXB2 numbering. Also provided are isolated nucleic acid molecules encoding the disclosed isolated immunogens. In an example, an isolated nucleic acid molecule further includes a nucleic acid molecule encoding a hepatitis B surface antigen or a variant thereof. Compositions including the isolated immunogens including variant gp120 polypeptides are also disclosed. In some examples, a composition further includes a carrier protein, such as a hepatitis B surface antigen or a variant thereof (natural or recombinant). Viral-like particles are also provided including any of the disclosed isolated immunogens or compositions. Also disclosed are uses of these variant gp120 polypeptides and nucleic acids encoding variant polypeptides, such as to induce an immune response to HIV-1.

主权项

1. An isolated nucleic acid molecule encoding an isolated immunogen comprising a variant gp120 polypeptide, wherein the variant gp120 polypeptide has a deletion of at least 8 consecutive amino acid residues of the fourth conserved loop (C4) between residues 423 and 433, wherein said numbering scheme is based upon the prototypic HIV-1 isolate HXB2, wherein the deletion reveals a cryptic CD4 binding site in the variant gp120 and wherein the isolated nucleic acid molecule is operably linked to a promoter.