Anti-cd40 antibodies and uses thereof

Abstract

The present invention includes compositions and methods for the expression, secretion and use of novel compositions for use as, e.g., vaccine and antigen delivery vectors, to delivery antigens to antigen presenting cells. In one embodiment, the vector is an anti-CD40 antibody, or fragments thereof, and one or more antigenic peptides linked to the anti-CD40 antibody or fragments thereof, including humanized antibodies.

What is claimed is: 
     
         1 - 56 . (canceled) 
     
     
         57 . A fusion protein comprising an anti-CD40 antibody comprising CDR1L, CDR2L, and CDR3L from SEQ ID NO:2 and CDR1H, CDR2H, and CDR3H from SEQ ID NO:1. and one or more antigens. 
     
     
         58 . The fusion protein of  claim 57 , wherein the one or more antigens comprise viral, bacterial, fungal, parasitic, or cancer antigens. 
     
     
         59 . The fusion protein of  claim 57 , wherein the one or more antigens comprise one or more viral antigens from human immunodeficiency virus, HCV, adenovirus, retrovirus, picornavirus, hepatitis A, hepatitis B, hepatits C, influenza, measles, polio, smallpox, rubella, rotavirus, cytomegalovirus, Epstein-Barr, respiratory syncytial virus, herpes simplex virus, varicella zoster virus, Japanese encephalitis, rabies, hantavirus, coronavirus, togavirus, flavirvirus, rhabdovirus, paramyxovirus, orthomyxovirus, bunyavirus, arenavirus, reovirus, papillomavirus, parvovirus, poxvirus, hepadnavirus, or spongiform virus. 
     
     
         60 . The fusion protein of  claim 57 , wherein the one or more antigens comprise one or more of Nef (66-97): VGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGL (SEQ ID NO.: 16), Nef (116-145): HTQGYFPDWQNYTPGPGVRYPLTFGWLYKL (SEQ ID NO.: 17), Gag p17 (17-35): EKIRLRPGGKKKYKLKHIV (SEQ ID NO.: 18), Gag p17-p24 (253-284): NPPIPVGEIYKRWIILGLNKIVRMYSPTSILD (SEQ ID NO.: 19), and Pol 325-355 (RT 158-188): AIFQSSMTKILEPFRKQNPDIVIYQYMDDLY (SEQ ID NO.: 20). 
     
     
         61 . The fusion protein of  claim 57 , wherein the one or more antigens comprise one or more bacterial antigens from pertussis, diptheria, tetanus, streptococcus, gram-negative bacilli, Mycobacterium tuberculosis, Helicobacter pylori, pneumococcus, haemophilus influenzae, anthrax, rickettsiae, chlamydia, mycoplasma, or mycobacteria. 
     
     
         62 . The fusion protein of  claim 57 , wherein the one or more antigens comprise one or more fungal antigens from candida, histoplasma, cryptococcus, coccidiodes, or tinea. 
     
     
         63 . The fusion protein of  claim 57 , wherein the one or more antigens comprise one or more cancer antigens from leukemia, lymphoma, astrocytoma, glioblastoma, melanoma, breast cancer, lung cancer, head and neck cancer, gastric cancer, colon cancer, liver cancer, pancreatic cancer, cervical cancer, uterine cancer, ovarian cancer, vaginal cancer, testicular cancer, prostate cancer, penile cancer, bone cancer, esophageal cancer, bladder cancer, kidney cancer, brain cancer, thyroid cancer, Hodgkin's disease, non-Hodgkin's lymphoma, or multiple myeloma. 
     
     
         64 . The fusion protein of  claim 57 , wherein the antigen comprises one or more of CEA, prostate specific antigen (PSA), HER-2/neu, BAGE, GAGE, MAGE 1-4, 6 and 12, MUC (Mucin), GM2 ganglioside, GD2 ganglioside, ras, myc, tyrosinase, MART (melanoma antigen), Pmel 17(gp100), GnT-V intron V sequence (N-acetylglucoaminyltransferase V intron V sequence), Prostate Ca psm, PRAME (melanoma antigen), β-catenin, MUM-1-B (melanoma ubiquitous mutated gene product), GAGE (melanoma antigen) 1, MAGE, BAGE (melanoma antigen) 2-10, c-ERB2 (Her2/neu), DAGE, EBNA (Epstein-Barr Virus nuclear antigen) 1-6, gp75, human papilloma virus (HPV) E6, HPV E7, p53, lung resistance protein (LRP), Bc1-2, Ki-67, Cyclin B 1, gp100, Survivin, and NYESO-1. [0127] 
     
     
         65 . The fusion protein of  claim 57 , wherein the fusion protein comprises one or more linkers. 
     
     
         66 . The fusion protein of  claim 65 , wherein the one or more linkers comprise one or more of SSVSPTTSVHPTPTSVPPTPTKSSP (SEQ ID NO.: 23);
 PTSTPADSSTITPTATPTATPTIKG (SEQ ID NO.: 24); TVTPTATATPSAIVTTITPTATTKP (SEQ ID NO.: 25); T NGS ITVAATAPTVTPTV NAT PSAA (SEQ ID NO.: 26); QTPTNTISVTPTNNSTPTNNSNPKPNP (residues 449 to 475 of SEQ ID NO:74).   
     
     
         67 . The fusion protein of  claim 57 , wherein CDR1L, CDR2L, and CDR3L comprise the amino acid sequences of SASQGISNYLN (SEQ ID NO.:41), YTSILHS (SEQ ID NO.:42), and QQFNKLPPT (SEQ ID NO.:43), respectively, and CDR1H, CDR2H, and CDR3H comprise the amino acid sequences of GFTFSDYYMY (SEQ ID NO.:44), YINSGGGSTYYPDTVKG (SEQ ID NO.:45), and RGLPFHAMDY (SEQ ID NO.:46), respectively. 
     
     
         68 . The fusion protein of  claim 57 , wherein the antibody is humanized. 
     
     
         69 . One or more isolated nucleic acid(s) encoding the fusion protein of  claim 57 . 
     
     
         70 . An expression vector comprising the nucleic acid(s) of  claim 69 , operably linked to control sequences recognized by a host cell transfected with the vector. 
     
     
         71 . A host cell comprising the vector of  claim 70 . 
     
     
         72 . The host cell of  claim 71 , wherein the cell is a bacterial, fungal, insect, or mammalian cell. 
     
     
         73 . A method of producing a polypeptide, comprising culturing the host cell of  claim 71  under conditions wherein the nucleic acid sequence is expressed, thereby producing the polypeptide, and recovering the polypeptide from the host cell. 
     
     
         74 . A method for eliciting an immune response in a subject, the method comprising administering the fusion protein of  claim 57  to the subject.