Antibody vaccine conjugates and uses therefor
The present invention provides novel antibody vaccine conjugates and methods of using the same to induce a cytotoxic T cell (CTL) response. In a particular, embodiment, the vaccine conjugate includes a human chorionic gonadotropin beta subunit (βhCG) antigen linked to an anti-mannose receptor (MR) antibody.
1. A method of inducing or enhancing a cytotoxic T cell response against βhCG comprising:
contacting antigen presenting cells (APCs) either in vivo or ex vivo with a composition formulated without an adjuvant or immunostimulatory agent containing a conjugate of βhCG and a monoclonal antibody which binds to the human macrophage mannose receptor (MMR), such that βhCG is internalized, processed and presented to T cells in a manner which induces or enhances a cytotoxic T cell response mediated by both CD4 + and CD8 + T cells against βhCG.
2. The method of claim 1 , which further induces or enhances a helper T cell response against βhCG.
3. The method of claim 1 , wherein βhCG presenting cells are dendritic cells.
4. The method of claim 1 , wherein the T cell response is induced through both MHC Class I and MHC Class II pathways.
5. The method of claim 1 , wherein the antibody is selected from the group consisting of human, humanized and chimeric antibodies.
6. The method of claim 1 , wherein the antibody is selected from the group consisting of a whole antibody, an Fab fragment and a single chain antibody.
7. The method of claim 1 , wherein the conjugate is administered in vivo to a subject.
8. The method of claim 7 , wherein the subject is immunized against βhCG.
9. A method of inducing or enhancing a T cell-mediated immune response against βhCG, comprising contacting antigen presenting cells (APCs) with a composition formulated without an adjuvant or immunostimulatory agent containing a molecular conjugate of a monoclonal antibody that binds to the human macrophage mannose receptor (MMR) linked to βhCG, such that βhCG is processed and presented to T cells in a manner which induces or enhances a T cell-mediated response mediated by both CD4 + and CD8 + T cells against βhCG.
10. The method of claim 9 , wherein the T cell response is mediated by cytotoxic T cells and/or helper T cells.
11. The method of claim 9 , wherein the T cell response is induced by cross-presentation of βhCG to T cells through both MHC Class I and MHC Class II pathways.
12. The method of claim 9 , wherein the molecular conjugate is contacted with the dendritic cells in vivo.
13. The method of claim 9 , wherein the molecular conjugate is contacted with the dendritic cells ex vivo.
14. A method of immunizing a subject comprising administering a composition formulated without an adjuvant or immunostimulatory agent containing a molecular conjugate of a monoclonal antibody that binds to the human macrophage mannose receptor (MMR) linked to βhCG, such that the molecular conjugate induces or enhances a cytotoxic T cell response mediated by both CD4 + and CD8 + T cells against βhCG.
15. The method of claim 1 , 9 or 14 , wherein the antibody comprises a heavy chain variable region comprising FR1, CDR1, FR2, CDR2, FR3, CDR3 and FR4 sequences and a light chain variable region comprising FR1, CDR1, FR2, CDR2, FR3, CDR3 and FR4 sequences, wherein:
(a) the heavy chain variable region CDR3 sequence comprises SEQ ID NO: 15; and
(b) the light chain variable region CDR3 sequence comprises SEQ ID NO: 18;
(c) the heavy chain variable region CDR2 sequence comprises SEQ ID NO: 14;
(d) the light chain variable region CDR2 sequence comprises SEQ ID NO: 17;
(e) the heavy chain variable region CDR1 sequence comprises SEQ ID NO:13; and
(f) the light chain variable region CDR1 sequence comprises SEQ ID NO: 16.
16. The method of claim 15 , wherein the antibody comprises heavy chain and light chain variable regions comprising the amino acid sequences shown in SEQ ID NO:4 and SEQ ID NO:8, respectively.