Vaccine and therapeutic delivery system
The present invention relates to a new vaccine delivery system. In particular, the present invention includes compositions and methods of integrally transformed non-pathogenic, commensal bacteria that can express a nucleic acid molecule of a foreign polypeptide, wherein the nucleic acid molecule that encodes the foreign polypeptide is stably integrated into genomic DNA of the bacteria. The foreign polypeptide includes a vaccine antigen that elicits an immunogenic response, an inhibitor of a pathogen, or an immune booster or modulator.
1. An integrally transformed non-pathogenic, commensal bacterium that expresses a synthetic nucleic acid molecule encoding a foreign fusion polypeptide comprising a C. difficile antigen and a signal polypeptide therein, wherein the synthetic nucleic acid molecule is stably integrated into genomic DNA of the bacterium, wherein the bacterium is Streptococcus mitis , and wherein the synthetic nucleic acid molecule comprises a TcdA/TcdB fusion construct having SEQ ID NO:81.
2. The integrally transformed non-pathogenic, commensal bacterium of claim 1 , wherein the foreign fusion polypeptide elicits an immunogenic response in an individual.
3. The integrally transformed non-pathogenic, commensal bacterium of claim 1 , wherein the foreign fusion polypeptide is expressed in the cytoplasm, in the cell membrane or cell wall, or exports to the cell surface of the bacterium.
4. The integrally transformed non-pathogenic, commensal bacterium of claim 3 , wherein the signal polypeptide is selected from the group consisting of: serine-rich GspB homologue and the pullulanase polypeptide.
5. The integrally transformed non-pathogenic, commensal bacterium of claim 1 , wherein the TcdA/TcdB fusion construct encodes an amino acid sequence comprising SEQ ID NO: 82.
6. The integrally transformed non-pathogenic, commensal bacterium of claim 5 , wherein the TcdA/TcdB fusion construct is inserted into a gene that encodes a pullulanase polypeptide.
7. The foreign fusion polypeptide expressed by the integrally transformed non-pathogenic, commensal bacterium of claim 1 .
8. A method of delivering a foreign fusion polypeptide to an individual comprising: contacting the integrally transformed non-pathogenic, commensal bacterium of claim 1 with tissue of the oral cavity or upper respiratory tract of the individual in an amount sufficient for colonization of said bacterium.