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The invention relates to chimeric HIV-1 gp120 glycoproteins, wherein at least a part of gp120 variable region V1 and/or V2 is replaced by a CD4-derived sequence to obtain the exposition of CD4 induced epitopes or CD4i capable of inducing a specific humoral immune response. Application for the preparation of vaccinal and pharmaceutical composition.

Titel:	Chimeric HIV-1 Glycoproteins and Their Biological Applications
Autor/in / Beteiligte Person:	Veas, Francisco ; Vita, Claudio ; Sauvage, Mireille C. ; Vita, Fabio ; Vita, Elena ; Martin, Loic ; Bray, Dorothy ; Benlhassan-Chahour, Kadija
Link:	View record in USPTO Patent Applications (Volltext)
Veröffentlichung:	2010
Medientyp:	Patent
Sonstiges:	Nachgewiesen in: USPTO Patent Applications Sprachen: English Document Number: 20100303858 Publication Date: December 2, 2010 Appl. No: 12/085632 Application Filed: November 28, 2006 Claim: 1. Chimeric HIV-1 gp120 glycoproteins, wherein at least a part of gp120 variable region V1 and/or V2 is replaced by a CD4-derived sequence to obtain the exposition of CD4 induced epitopes or CD4i capable of inducing a specific humoral immune response. Claim: 2. The chimeric HIV-1 gp120 glycoproteins of claim 1, wherein the CD4-derived sequence replaces V1 and a part of V2 gp120 variable regions. Claim: 3. The chimeric HIV-1 gp120 glycoproteins of claim 1, wherein the CD4-derived peptide mimics the CDR2-like loop of human CD4 receptor. Claim: 4. The chimeric HIV-1 gp120 glycoproteins of claim 1, which comprises 15 to 35 amino acids. Claim: 5. The chimeric HIV-1 gp120 glycoproteins of claim 4, which comprises 20 to 30 amino acids. Claim: 6. The chimeric HIV-1 gp120 glycoproteins of claim 1, wherein said peptide has 28 amino acids. Claim: 7. The chimeric HIV-1 gp120 glycoproteins of claim 6, having sequence SEQ ID NO 5 CNLEACQKRCQSLGLQGKCAGSFCAC. Claim: 8. The chimeric HIV-1 gp120 glycoproteins of claim 2, wherein the CD4-derived sequence replaces V1 and 10 to 20 amino acids from V2 loop, particularly 16 amino acids. Claim: 9. The chimeric HIV-1 gp120 glycoproteins of claim 1, which are recognized by anti-CD4i monoclonal antibodies, but are not recognized by anti-CD4 antibodies. Claim: 10. The chimeric HIV-1 gp120 glycoproteins of claim 1, characterized in that they bind CD4 receptor and CCR5 co-receptor. Claim: 11. The chimeric HIV-1 gp120 glycoproteins of FIGS. 1B and 1C. Claim: 12. The chimeric HIV-1 gp120 glycoproteins of claim 1 in combination with TLR ligands. Claim: 13. The chimeric HIV-1 gp120 glycoproteins of claim 1 in combination with IL22 and/or CCL28. Claim: 14. Antisera containing polyclonal antibodies directed to CD4i epitopes such as exposed in the chimeric HIV-1 gp120 glycoproteins of claim 1. Claim: 15. Polyclonal antibodies directed to CD4i epitopes such as exposed in the chimeric HIV-1 gp120 glycoproteins of claim 1. Claim: 16. Monoclonal antibodies directed to CD4i epitopes such as exposed in the chimeric HIV-1 gp120 glycoproteins of claim 1. Claim: 17. The DNA constructs encoding the chimeric HIV-1 gp120 glycoproteins of claim 1. Claim: 18. Expression vectors comprising a DNA construct according to claim 17. Claim: 19. Host cells transfected by the vectors of claim 18. Claim: 20. A vaccine composition specific to HIV-1 infections, comprising an effective amount of at least one antigenic chimeric HIV-1 constructs according to claim 1, with a carrier, or a combination thereof with TLR ligands. Claim: 21. The vaccine composition of claim 20 for preventing HIV-1 infections. Claim: 22. A pharmaceutical composition for alleviating and/or preventing and/or treating an HIV-1 infection comprising an effective amount of at least one chimeric HIV-1 gp120 glycoproteins according to claim 1, or a combination thereof with TLR ligands, IL22 and/or CCL28. Current U.S. Class: 4242/081 Current International Class: 61; 07; 07; 12; 12; 61; 61

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Chimeric HIV-1 Glycoproteins and Their Biological Applications