Compositions and methods of enhancing immune responses to
Vaccine vectors and methods of using the vaccine vectors to enhance the immune response to an Apicomplexan parasite and reduce the morbidity or mortality associated with subsequent infection are provided herein. The vaccine vectors include a polynucleotide encoding a Rhomboid polypeptide and optionally include an immune-stimulatory polypeptide suitably expressed on the surface of the vaccine vector.
1. A vaccine vector comprising a first polynucleotide sequence encoding an Apicomplexan Rhomboid polypeptide expressed on the surface of the vaccine vector, wherein the Rhomboid polypeptide consists of a polypeptide having the amino acid sequence set forth in SEQ ID NO: 38 or an immunogenic fragment of SEQ ID NO: 38 comprising amino acids 1-11, 18-27, or 31-43 of SEQ ID NO: 38, and wherein the vaccine vector comprises a bacterial, yeast, viral or liposome-based vector.
2. The vaccine vector of claim 1 , further comprising a second polynucleotide sequence encoding an immunostimulatory polypeptide, wherein the immunostimulatory polypeptide is expressed on the surface of the vaccine vector, and wherein an immunostimulatory polypeptide comprises a polypeptide capable of stimulating an immune response.
3. The vaccine vector of claim 2 , wherein the immunostimulatory polypeptide comprises an HMGB1 polypeptide.
4. The vaccine vector of claim 3 , wherein the HMGB1 polypeptide comprises a polypeptide selected from the group consisting of SEQ ID NOs: 15-23, a polypeptide having at least 95% sequence identity to SEQ ID NO: 15-23 and combinations thereof.
5. The vaccine vector of claim 2 , wherein the immunostimulatory polypeptide comprises a CD154 polypeptide capable of binding CD40, the CD154 polypeptide having fewer than 50 amino acids and comprising amino acids 140-149 of a polypeptide selected from the group consisting of SEQ ID NO: 24, SEQ ID NO: 25, SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30 and polypeptides having at least 90% sequence identity to at least one of SEQ ID NOs: 24-30.
6. The vaccine vector of claim 2 , wherein the vector comprises more than one copy of the first polynucleotide or more than one copy of the second polynucleotide sequence.
7. The vaccine vector of claim 2 , wherein the first polynucleotide sequence is linked in the same reading frame to the second polynucleotide sequence.
8. The vaccine vector of claim 7 , wherein the first polynucleotide and the second polynucleotide are linked via a spacer nucleotide sequence.
9. The vaccine vector of claim 1 , wherein the vaccine vector is a Bacillus spp.
10. The vaccine vector of claim 2 , further comprising a third polynucleotide encoding a TRAP polypeptide selected from the group consisting of polypeptides having at least 95% sequence identity to SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, and SEQ ID NO: 40.
11. A pharmaceutical composition comprising the vaccine vector of claim 1 and a pharmaceutically acceptable carrier.
12. A method of enhancing the immune response against an Apicomplexan parasite 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 Apicomplexan parasite.
13. The method of claim 12 , wherein the enhanced immune response comprises an enhanced antibody response, an enhanced T cell response or both.
14. A method of reducing morbidity associated with infection with an Apicomplexan parasite in a subject comprising administering to the subject the vaccine vector of claim 1 in an amount effective to reduce the morbidity associated with subsequent infection of the subject with an Apicomplexan parasite as compared to a control subject not administered the vaccine vector.
15. The method of claim 12 , wherein the vaccine vector is administered by a route selected from the group consisting of oral, mucosal, parenteral, sub-cutaneous, intramuscular, intraocular and in ovo.
16. The method of claim 12 , wherein the subject is member of a poultry species or is a mammal.
17. The method of claim 12 , wherein about 10 4 to about 10 9 vector copies of the vaccine are administered to the subject.
18. The method of claim 12 , wherein the vaccine vector is killed prior to administration to the subject or is not capable of replicating in the subject.
19. The method of claim 12 , wherein the Apicomplexan parasite is selected from the group consisting of Eimeria, Plasmodium, Toxoplasma, Neospora and Cryptosporidium.