Compositions and methods of enhancing immune responses
Provided herein are Salmonella enteritidis 13A strains and compositions comprising these strains. Also provided are methods of enhancing an immune response against Influenza A and methods of reducing morbidity associated with an Influenza A infection. Methods of enhancing an immune response to a vaccine vector by expressing a polypeptide of CD154 capable of binding CD40 are also disclosed. Methods of developing a bacterial vaccine vector are disclosed. Methods of generating scarless site-specific mutations in a bacterium are also disclosed.
1. A vaccine vector comprising a first polynucleotide sequence encoding an antigenic polypeptide and a CD154 polynucleotide sequence encoding a CD154 polypeptide capable of binding CD40, wherein the CD154 polypeptide is expressed on the surface of the vaccine vector.
2. The vaccine vector of claim 1 , wherein the antigenic polypeptide is expressed on the surface of the vaccine vector.
3. The vaccine vector of claim 2 , wherein the first polynucleotide and the CD154 polynucleotide are inserted into a third polynucleotide encoding an external portion of a transmembrane protein.
4. The vaccine vector of claim 1 , wherein the CD154 polypeptide has fewer than about 50 amino acids and comprises amino acids 140-149 of SEQ ID NO:26 or a homolog thereof.
5. The vaccine vector of claim 4 , wherein the CD154 polypeptide is selected from the group consisting of SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 27, SEQ ID NO: 28, and SEQ ID NO: 29.
6. The vaccine vector of claim 1 , wherein the vaccine vector is a bacterium.
7. The vaccine vector of claim 6 , wherein the bacterium is Salmonella enteritidis.
8. The vaccine vector of claim 6 , wherein the bacterium is a Salmonella strain of any of (a) Salmonella enteritidis having ATCC deposit number PTA-7871, (b) a Salmonella strain capable of colonizing a subject, (c) a Salmonella strain comprising a mutation in an aromatization pathway, (d) a Salmonella strain comprising a mutation within aroA, (e) a Salmonella strain comprising a mutation in a stress response pathway and (f) a Salmonella strain comprising a mutation in htrA.
9. A method of enhancing an immune response against the antigenic polypeptide in a subject comprising administering to the subject the vaccine vector of claim 1 in an amount effective to enhance the immune response of the subject to the antigenic polypeptide.
10. The method of claim 9 , wherein the subject is selected from the group consisting of human and chicken.
11. The method of claim 9 , wherein the antigenic polypeptide is expressed on the surface of the vaccine vector.
12. The method of claim 9 , wherein the first polynucleotide and the CD154 polynucleotide are inserted into a third polynucleotide encoding an external portion of a transmembrane protein.
13. The method of claim 9 , wherein the CD154 polypeptide has fewer than about 50 amino acids and comprises amino acids 140-149 of SEQ ID NO:26 or a homolog thereof.
14. The method of claim 13 , wherein the CD154 polypeptide is selected from the group consisting of SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 27, SEQ ID NO: 28, and SEQ ID NO: 29.
15. The method of claim 9 , wherein the vaccine vector is a bacterium.
16. The method of claim 15 , wherein the bacterium is Salmonella enteritidis.
17. The method of claim 15 , wherein the bacterium is a Salmonella strain of any of (a) Salmonella enteritidis having ATCC deposit number PTA-7871, (b) a Salmonella strain capable of colonizing a subject, (c) a Salmonella strain comprising a mutation in an aromatization pathway, (d) a Salmonella strain comprising a mutation within aroA, (e) a Salmonella strain comprising a mutation in a stress response pathway and (f) a Salmonella strain comprising a mutation in htrA.