Antigen presenting cell targeted anti-viral 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. A method of eliciting an immune response in a subject comprising administering to the subject an effective amount of a composition comprising a fusion protein with the formula:
Ab-(PL-Ag) x;
wherein Ab is an antibody or fragment thereof comprising the light chain hypervariable regions CDR1L having the amino acid sequence SASQGISNYLN (SEQ ID NO:41), CDR2L having the amino acid sequence YTSILHS (SEQ ID NO:42), and CDR3L having the amino acid sequence QQFNKLPPT (SEQ ID NO:43) and the heavy chain hypervariable regions CDR1H having the amino acid sequence GFTFSDYYMY (SEQ ID NO:44), CDR2H having the amino acid sequence YINSGGGSTYYPDTVKG (SEQ ID NO:45) and CDR3H having the amino acid sequence RGLPFHAMDY (SEQ ID NO:46);
PL is at least one peptide linker comprising at least one glycosylation site;
Ag comprises at least one of the following viral antigens:
Nef (66-97):
(SEQ ID NO: 1)
VGFPVTPQVPLRPMTYKAAVDLSHFLKEKGGL;
Nef (116-145):
(SEQ ID NO: 2)
HTQGYFPDWQNYTPGPGVRYPLTFGWLYKL;
Gag p17 (17-35):
(SEQ ID NO: 3)
EKIRLRPGGKKKYKLKHIV;
Gag p17-p24 (253-284):
(SEQ ID NO: 4)
NPPIPVGEIYKRWIILGLNKIVRMYSPTSILD;
or
Pol 325-355 (RT 158-188) is:
(SEQ ID NO: 5)
AIFQSSMTKILEPFRKQNPDIVIYQYMDDLY.
and
x is an integer from 1 to 20.
2. The method of claim 1 , wherein the Ab comprises SEQ ID NO: 37 and 38.
3. The method of claim 1 , wherein at least one of the viral antigens is a lipopeptide.
4. The method of claim 1 , wherein the Ag comprises a palmitoylation group.
5. The method of claim 1 , wherein the Ab is humanized.
6. The method of claim 1 , wherein the composition is administered intravenously, parenterally, intramuscularly or subcutaneously.
7. The method of claim 1 , wherein administering the composition elicits a humoral and cellular immune response.
8. The method of claim 1 , wherein administering the composition elicits an HIV-specific response.
9. The method of claim 1 , wherein the subject is infected with HIV or is suspected of having an HIV infection.