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 HIV T20 polypeptide inhibitor 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 , wherein the signal polypeptide is pullulanase polypeptide, wherein said bacterium expresses or secretes the HIV T20 polypeptide inhibitor/pullulanase foreign fusion polypeptide, and wherein the HIV T20 polypeptide inhibitor/pullulanase foreign fusion polypeptide comprises the amino acid sequence set forth in SEQ ID NO: 80.
2. The integrally transformed non-pathogenic, commensal bacterium of claim 1 , wherein the nucleic acid molecule encoding 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.
3. The integrally transformed non-pathogenic, commensal bacterium of claim 1 , wherein the nucleic acid molecule encoding the HIV T20 polypeptide inhibitor/pullulanase foreign fusion polypeptide comprises SEQ ID NO: 79.
4. The foreign fusion polypeptide expressed by the integrally transformed non-pathogenic, commensal bacterium of claim 1 .
5. A method of delivering a foreign protein 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.