Antibody dependent enhancement of Venezuelan Equine Encephalitis vector infection
View Patent ↗The present invention provides compositions and methods for delivering a nucleotide sequence to a cell using an alphavirus vector that is complexed with an enhancing antibody that specifically binds to the alphavirus vector. Venezuelan Equine Encephalitis vectors are preferred. The cell may be a cell in vitro or in vivo. Alternatively, the cell may be removed from a subject, administered the alphavirus vector ex vivo and then administered to a subject. Antigen-presenting cells are preferred, with dendritic cells being more preferred. Also provided are methods of producing an immune response in a subject, e.g., for producing an immune response against an antigen associated with a pathogen or for immunotherapy of cancer of tumors.
1. A method of administering a nucleotide sequence to a subject, comprising:
(a) administering a Venezuelan Equine Encephalitis (VEE) vector comprising a heterologous nucleotide sequence to a subject; and
(b) administering an antibody that specifically binds to the E1 glycoprotein and/or the E2 glycoprotein of the VEE vector to the subject;
wherein said administering steps of (a) and (b) are concurrent;
whereby the heterologous nucleotide sequence is introduced into and expressed in the subject.
2. The method of claim 1 , wherein there is no significant pathology in the subject as a result of said administering steps.
3. The method of claim 1 , wherein the subject is selected from the group consisting of primate, bovine, ovine, caprine, porcine, equine, feline, canine, lagomorph, and rodent subjects.
4. The method of claim 3 , wherein the subject is a human subject.
5. The method of claim 1 , wherein the VEE vector and the antibody are administered in a single formulation.
6. A method of administering a nucleotide sequence to a subject, comprising:
(a) administering a Venezuelan Equine Encephalitis (VEE) vector comprising a heterologous nucleotide sequence to a subject; and
(b) administering an antibody that specifically binds to the E1 glycoprotein and/or the E2 glycoprotein of the VEE vector to the subject;
wherein the antibody is administered prior to the VEE vector;
whereby the heterologous nucleotide sequence is introduced into and expressed in the subject.
7. The method of claim 6 , wherein there is no significant pathology in the subject as a result of said administering steps.
8. The method of claim 6 , wherein the subject is selected from the group consisting of primate, bovine, ovine, caprine, porcine, equine, feline, canine, lagomorph, and rodent subjects.
9. The method of claim 8 , wherein the subject is a human subject.