Dendritic cell-specific antibody conjugate comprising anti-CD40 monoclonal antibodies conjugated to HIV-1 Gag/Nef
The present invention includes compositions and methods for making and using a vaccine that includes a DC-specific antibody or fragment thereof to which an engineered Gag antigen is attached to form an antibody-antigen complex, wherein the Gag antigen is less susceptible to proteolytic degradation by eliminating one or more proteolytic sites or a DC-specific antibody or fragment thereof to which an engineered Nef antigen is attached to form an antibody-antigen complex, wherein the Nef antigen comprises one or more codon usage optimization that increase antibody-antigen complex secretion, or both, wherein the vaccine is able to elicit an HIV-specific T cell immune response to Gag p17, Gag p24, Nef and/or Cyclin D1.
1. A composition comprising:
a dendritic cell (DC)-specific antibody or fragment thereof comprising a light chain sequence selected from the group consisting of SEQ ID NO: 24, 25, 26, 27 and 28 and a heavy chain sequence selected from the group consisting of SEQ ID NO: 29 and 30, to which one or more engineered Gag antigens are attached to form an antibody-antigen fusion protein wherein the engineered Gag antigens are less susceptible to proteolytic degradation by eliminating one or more proteolytic sites; and
a Nef antigen that is attached to the engineered Gag antigen wherein the composition is able to elicit a human immunodeficiency virus (HIV)-specific T cell immune response to Gag and Nef.
2. The composition of claim 1 , wherein the Gag and Nef antigens comprise a fusion protein separated by one or more flexible linkers.
3. The composition of claim 1 , wherein the protein comprises SEQ ID NO: 31.
4. The composition of claim 1 , wherein the Gag and Nef antigens comprise a fusion protein separated by one or more flexible linkers.
5. The composition of claim 4 , wherein the protein comprises SEQ ID NO: 31.