Chemically programmable immunity

• US 8,604,184 B2
• Filed: 05/05/2010
• Issued: 12/10/2013
• Est. Priority Date: 05/05/2009
• Status: Active Grant

• Current Assignee: United States Of America As Represented By The Secretary Of The Air Force, US Department of The Air Force (U.S. Department Of Defense)
• Original Assignee: United States Of America As Represented By The Secretary Of The Air Force
• Inventors: Mullis, Kary B., Vivekananda, Jeevalatha, Cook, Ronald M., Kiel, Johnathan Lloyd
• Primary Examiner(s): Navarro, Albert
• Assistant Examiner(s): Portner, Ginny
• Application Number:
  US12/774,194
• Publication Number:
  US 20100285052A1
• Time in Patent Office: 1,315 Days
• Field of Search: None
• US Class Current: 536/24.5
• CPC Class Codes: A61K 31/7088 Compounds having three or more nucleosides or nucleotides
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/16 for influenza or rhinoviruses
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Methods and compositions for immediately immunizing an individual against any molecule or compound are provided. The present invention is directed to an immunity linker with at least two sites; (1) at least one first binding site that binds to an immune response component in an individual, and (2) at least one second binding site that binds specifically to a desired compound or molecule, the target. The second binding sites are preferably thiolated aptamers that have the benefit of increased stability, resistance to degradation and longer circulating half life. Methods of making and using pharmaceutical compositions including immunity linker molecules having a thiolated aptamer are also provided.

Claims

1. An immunity linker molecule comprising

at least one first binding site that binds to at least one first immune response component that binds to at least one immunogen corresponding to the at least one first binding site,

and at least one second binding site that binds to a target, wherein the at least one second binding site is a thiolated aptamer comprising SEQ ID NO:

2.

2. The immunity linker molecule of claim 1 wherein the at least one first immune response component is an antibody.

3. The immunity linker molecule of claim 1 wherein the target is a microorganism.

4. The immunity linker molecule of claim 3 wherein the microorganism is a bacteria, virus, or fungus.

5. The immunity linker molecule of claim 1 wherein the target is a bacterial toxin.

6. The immunity linker molecule of claim 5 wherein the bacterial toxin is selected from tetanus toxin, botulinum toxins, diptheria toxin, cholera toxin, Toxin B, Toxin A, fragilysin, B. anthracis lethal factor, B. anthracis oedema factor, B. anthracis protective antigen, E. coli heat-labile toxin, E. coli heat-stable toxin, C. sordelli lethal toxin, or C. sordelli haemorrhagic toxin.

7. The immunity linker molecule of claim 1, wherein the thiolated aptamer comprising SEQ ID NO:

2 is a monothiolated aptamer.

8. The immunity linker molecule of claim 1 wherein an amount of thiolation of a phosphate backbone of the thiolated aptamer is more than 80% and less than or equal to 99%.

9. The immunity linker molecule of claim 1 wherein the at least one first immune response component comprises at least one of an antibody, an antibody fragment, a lymphocyte, a macrophage, a granulocyte, and a receptor derived from at least one of a lymphocyte, a macrophage, and a granulocyte.

10. A method of immunizing a patient against a target comprising the steps of:

administering to the patient the immunity linker molecule of claim 1.

11. The method of claim 10 wherein the target is a microorganism.

12. The method of claim 11 wherein the microorganism is a bacteria, virus, or fungus.

13. The method of claim 10 wherein the target is a drug.

14. The method of claim 10 further comprising administering to the patient an effective amount of a composition comprising one or more immunity linker molecules.

15. The method of claim 14 wherein the first binding site comprises an alpha-galactosyl epitope.

16. The method of claim 14 wherein the patient is unable to mount an effective immune response to the target prior to administration of the one or more immunity linker molecules.

17. The method of claim 14 wherein the composition comprises a population of different immunity linker molecules, wherein at least one of the at least one first binding site differs in at least one of a specificity for different epitopes on the at least one first immune response component and an affinity for a same epitope on the at least one first immune response component.

18. The method of claim 10, wherein the patient has a preexisting immune response to the first binding site or an epitope thereof.

19. The method of claim 10, wherein the patient is unable to generate the at least one first immune response component, the method further comprising administering to the patient the at least one first immune response component.

20. The method of claim 19, wherein the at least one first immune response component is generated in an individual other than the patient.

21. The method of claim 10 wherein the at least one immunogen is a universal immunogen.