ANTIGEN PRESENTING CELL TARGETED VACCINES
The present invention includes compositions and methods for the expression, secretion and use of novel compositions for use as, e.g., vaccines 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.
1 .- 56 . (canceled)
57 . A fusion protein comprising:
an antibody or fragment thereof;
a peptide linker comprising at least one glycosylation site; and
a hepatitis C virus antigen;
wherein the fusion protein has more stability in solution than the same fusion protein without the glycosylation site.
58 . The fusion protein of claim 57 , wherein the hepatitis C virus antigen comprises a peptide from a hepatitis C virus.
59 . The fusion protein of claim 57 , wherein the hepatitis C virus antigen comprises a hepatitis C viral RNA.
60 . The fusion protein of claim 57 , wherein the hepatitis C virus antigen is comprised in a peptide concatemer.
61 . The fusion protein of claim 57 , wherein the antibody is an anti-CD40 antibody.
62 . The fusion protein of claim 61 , wherein the antibody comprises at least the variable region of the antibody anti-CD40 — 12E12.3F3 (ATCC Accession No. PTA-9854), anti-CD40 — 12B4.2C10 (ATCC Submission No. HS446, Accession No. PTA-10653), or of the antibody anti-CD40 — 11B6.1C3 (ATCC Submission No. HS440, Accession No. PTA-10652).
63 . The fusion protein of claim 57 , wherein the Ab comprises at least one variable domain having at least 90% sequence identity with a heavy chain variable domain of SEQ ID NOS: 148, 150, or 153 or with a light chain variable domain of SEQ ID NOS: 149, 151, 152, or 154, or both.
64 . The fusion protein of claim 57 , wherein the fusion protein comprises two or more peptides from hepatitis C virus separated by at least one peptide linker comprising at least one glycosylation site.
65 . The fusion protein of claim 64 , wherein the two or more peptides from hepatitis C virus are identical.
66 . The fusion protein of claim 57 , wherein the antibody fragment is selected from Fv, Fab, Fab′, F(ab′) 2 , Fc, or a ScFv.
67 . The fusion protein of claim 57 , wherein the Ab is an IgA, IgD, IgE, IgG, or IgM, or isotype thereof.
68 . The fusion protein of claim 57 , wherein the Ab is a human antibody or a humanized antibody.
69 . The fusion protein of claim 57 , wherein the peptide linker comprises an alanine and a serine.
70 . The fusion protein of claim 57 , wherein the peptide linker is selected from:
(SEQ ID NO.: 11)
SSVSPTTSVHPTPTSVPPTPTKSSP;
(SEQ ID NO.: 12)
PTSTPADSSTITPTATPTATPTIKG;
(SEQ ID NO.: 13)
TVTPTATATPSAIVTTITPTATTKP;
or
(SEQ ID NO.: 14)
TNGSITVAATAPTVTPTVNATPSAA.
71 . A pharmaceutical composition comprising the fusion protein of claim 57 .
72 . A method of eliciting an immune response in a subject comprising administering to the subject a composition comprising a fusion protein, wherein the fusion protein comprises:
an antibody or fragment thereof;
a peptide linker comprising at least one glycosylation site; and
a hepatitis C virus antigen;
wherein the fusion protein has more stability in solution than the same fusion protein without the glycosylation site.
73 . The method of claim 72 , wherein the hepatitis C virus antigen comprises a peptide from a hepatitis C virus.
74 . The method of claim 72 , wherein the hepatitis C virus antigen comprises a hepatitis C viral RNA.
75 . The method of claim 72 , wherein the antibody is an anti-CD40 antibody.
76 . The method of claim 75 , wherein the antibody comprises at least the variable region of the antibody anti-CD40 — 12E12.3F3 (ATCC Accession No. PTA-9854), anti-CD40 — 12B4.2C10 (ATCC Submission No. HS446, Accession No. PTA-10653), or of the antibody anti-CD40 — 11B6.1C3 (ATCC Submission No. HS440, Accession No. PTA-10652).