Methods and compositions for immunizing against
View Patent ↗The present invention relates, in part, to methods and compositions for immunizing against infection by Chlamydia trachomatis . The methods and compositions rely, in part, on administering an immunogenic composition comprising one or more peptides derived from C. trachomatis major outer membrane protein (MOMP) to a subject to be immunized. In some embodiments, the compositions comprise a chimeric immunogens, expression vectors comprising the polynucleotides, and kits comprising the compositions are also provided.
1. A chimeric immunogen, comprising
a) a Pseudomonas exotoxin A (PE) receptor binding domain Ia;
b) a PE translocation domain II;
c) a Chlamydia trachomatis antigen comprising the amino acid sequence selected from the group consisting of: AGTEAA (SEQ ID NO: 4), AGTDAA (SEQ ID NO: 5), CTTLNPTIAGC (SEQ ID NO.: 17), CGAKPTATTGNATAPSTLTAREC (SEQ ID NO: 18), and CTTSDVAGLQNDPC (SEQ ID NO: 19) inserted into PE domain Ib; and
d) PE endoplasmic reticulum retention domain III, wherein the PE domain Ib is located between PE translocation domain II and PE endoplasmic reticulum retention domain III.
2. The chimeric immunogen of claim 1 , wherein said C. trachomatis antigen replaces all or a portion of said PE domain Ib.
3. The chimeric immunogen of claim 1 , wherein said PE endoplasmic reticulum retention domain III is an enzymatically inactive PE domain III.
4. The chimeric immunogen of claim 1 , wherein said enzymatically inactive PE domain III is inactivated by deleting a glutamate at position 553.
5. The chimeric immunogen of claim 1 , wherein said PE endoplasmic reticulum retention domain III comprises an amino acid sequence that is selected from the group of RDEL (SEQ ID NO.:20) or KDEL (SEQ ID NO.:21).
6. The chimeric immunogen of claim 1 , wherein said translocation domain II comprises amino acids 280 to 364 of domain II of Pseudomonas exotoxin A.
7. A composition comprising the chimeric immunogen of claim 1 .
8. The composition of claim 7 , wherein said composition further comprises a pharmaceutically acceptable diluent, excipient, vehicle, or carrier.
9. A kit, comprising an article of manufacture containing the composition claim 7 .
10. The chimeric immunogen of claim 1 , wherein said chimeric immunogen comprises more than one of said C. trachomatis antigens.
11. The chimeric immunogen of claim 10 , wherein said more than one C. trachomatis antigens are different C. trachomatis antigens.
12. A method for generating antibodies against Chlamydia trachomatis in a subject, the method comprising:
administering to said subject an immunogenic amount of a chimeric immunogen comprising:
a) a Pseudomonas exotoxin A (PE) receptor binding domain Ia,
b) a PE translocation domain II,
c) a Chlamydia trachomatis antigen comprising the amino acid sequence selected from the group consisting of: AGTEAA (SEQ ID NO: 4), AGTDAA (SEQ ID NO: 5), CTTLNPTIAGC (SEQ ID NO.: 17), CGAKPTATTGNATAPSTLTAREC (SEQ ID NO: 18), and CTTSDVAGLQNDPC (SEQ ID NO: 19) inserted into PE domain Ib, and
d) PE endoplasmic reticulum retention domain III, wherein the PE domain Ib is located between PE translocation domain II and PE endoplasmic reticulum retention domain III, thereby generating antibodies against C. trachomatis .
13. The method of claim 12 , wherein said subject is a mammal.
14. The method of claim 13 , wherein said subject is a rodent, lagomorph or primate.