Neutralizing antibodies that bind to the HIV-1 Env V2 critical neutralization domain
View Patent ↗This invention features polypeptides, variants thereof, and fragments thereof useful in eliciting an immune response (e.g., neutralizing antibodies) against a broad spectrum of HIV-1 isolates. The polypeptides, variants, and fragments include a portion of the gp120 V2 domain of HIV-1. The polypeptides, variants, and fragments display an epitope that is recognized by at least one antibody which neutralizes at least one HIV-1 primary isolate. This invention also features nucleic acid sequences encoding those polypeptides. In addition, the invention provides methods of screening for inhibitors of HIV-1 entry into cells, as well as methods of treatment using the inhibitors.
1. An antibody which binds a polypeptide comprising-an amino acid sequence EIKNC SFNXT TXXRD KXXXX YXLFY XLDXV (SEQ ID NO:1) or a fragment thereof
wherein the amino acid sequence includes KQKV (SEQ ID NO:3), KQKE (SEQ ID NO:4), KKKE (SEQ ID NO:26), KKKV (SEQ ID NO:27), KRQE (SEQ ID NO:28), KRKV (SEQ ID NO:29), KKQV (SEQ ID NO:30) or KKQE (SEQ ID NO:31) at amino acid positions 17-20, and
wherein the X at position 9 of SEQ ID NO:1 is M or I;
the X at position 12 of SEQ ID NO:1 is S, E, G, or N;
the X at position 13 of SEQ ID NO:1 is L, I, or M;
the X at position 22 of SEQ ID NO:1 is S or A;
the X at position 26 of SEQ ID NO:1 is K or R; and
the X at position 29 of SEQ ID NO:1 is I or V;
wherein said antibody neutralizes more than one HIV-1strain.
2. The antibody of claim 1 wherein the polypeptide is flanked at either end, or both ends, by a heterologous amino acid sequence.
3. The antibody of claim 1 , wherein the polypeptide is glycosylated.
4. A method of potently neutralizing the activity of multiple HIV-1 isolates, the method comprising contacting a cell or an HIV-1 virus with the antibody of claim 1 . The claim was amended to correct an obvious grammatical mistake.