Methods to increase transgene expression from bacterial-based delivery systems by co-expressing suppressors of the eukaryotic type I interferon response
Bacterial delivery systems with improved transgene expression are provided. The recombinant bacterial delivery systems deliver transgenes of interest and suppressors of the eukaryotic Type I interferon response to eukaryotic cells. Suppression of the eukaryotic Type I interferon response allows improved expression of the encoded transgene.
1. A recombinant bacterial vector, comprising:
a bacterium genetically transformed with one or more genetically engineered nucleic acid sequences coding for a host cell or tissue type 1 interferon (IFN) response suppressor factor, and
one or more genetically engineered nucleic acids coding for one or more antigens to which an immune response is desired,
wherein said one or more genetically engineered nucleic acids coding for said one or more antigens to which an immune response is desired are over expressed upon said bacterium invading said host cell or tissue.
2. The recombinant bacterial vector of claim 1 wherein said host cell or tissue type 1 IFN response suppressor factor is rotavirus NSP 1 or influenza virus NS1.
3. The recombinant bacterial vector of claim 1 wherein said one or more antigens to which an immune response is desired are selected from tuberculosis antigens and malaria antigens.
4. The recombinant bacterial vector of claim 1 wherein said one or more antigens to which an immune response is desired is one or more viral antigens.
5. The recombinant bacterial vector of claim 1 wherein said one or more antigens to which an immune response is desired are selected from hormone, enzymes, anticancer agents, and apoptotic factors.
6. The recombinant bacterial vector of claim 1 wherein said host cell or tissue type 1 IFN response suppressor factor is selected from the group consisting of rotavirus NSP1, influenza virus NS1, ectromelia virus C12R protein, hepatitis C virus NS3/4A protease, vaccinia virus vIFN-α/β Rc protein, adenovirus E1A protein, C proteins of paramyxoviruses, and human papillomavirus (HPV) E6 oncoprotein.
7. The recombinant bacterial vector of claim 4 wherein said one or more viral antigens is a rotavirus viral antigen, influenza virus viral antigen, ectromelia virus viral antigen, hepatitis virus viral antigen, vaccinia virus viral antigen, adenovirus viral antigen, paramyxovirus viral antigen, HPV viral antigen, HIV viral antigen, HTLV viral antigen, enterovirus viral antigen, herpesvirus viral antigen, EEE viral antigen, VEE viral antigen, West Nile virus viral antigen, Norwalk virus viral antigen, parvovirus viral antigen, dengue virus, viral antigen or hemorrhagic fever virus viral antigen.