Chemically Programmable Immunity

• US 20100285052A1
• Filed: 05/05/2010
• Published: 11/11/2010
• 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: US Department of The Air Force (U.S. Department Of Defense)
• Inventors: VIVEKANANDA, JEEVALATHA, MULLIS, KARY B., KIEL, JOHNATHAN LLOYD, COOK, RONALD M.
• Granted Patent: US 8,604,184 B2
• Time in Patent Office: Days
• US Class Current: 424/193.1
• 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 an immune system molecule and at least one second binding site that binds to a target,

wherein the second binding site is a thiolated aptamer.

2. The immunity linker molecule of claim 1 wherein the first site binds to an antibody.

3. The antibody of claim 2 wherein the antibody is from a human or animal that has been preimmunized against the first site.

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

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

6. The immunity linker molecule of claim 1, wherein the compound or molecule is a bacterial toxin.

7. The immunity linker molecule of claim 6, 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 heamorragic toxin.

13. The method of claim 1, wherein the immunity linker molecule is an aptamer.

8. A method of immunizing a human or animal against a molecule or compound comprising administering to the human or animal an immunity linker molecule, the immunity linker molecule containing at least one first site that binds to an immune system molecule, and a second site that binds to a target wherein the second binding site is a thiolated aptamer.

9. The method of claim 8, wherein the human or animal has been preimmunized against the first site on the immunity linker molecule.

10. The method of claim 8, wherein the immunity the desired compound or molecule is a microorganism.

11. The method of claim 10 wherein the microorganism is a bacteria, virus, or fungus.

12. The method of claim 8, wherein the compound or molecule is a drug.

14. A method of increasing an immune response to a target in an individual comprising,

administering to the individual an effective amount of a composition comprising one or more immunity linkers,

wherein the linker molecules comprise at least one first binding site and at least one second binding site,

wherein the individual has a pre-existing immune response to the first binding site, and

wherein the second binding site is a thiolated aptamer that binds to the target.

15. The method of claim 14, wherein the individual is a human and the first binding site comprises an alpha-galactosyl epitope.

16. The method of claim 14, wherein the individual is unable to mount an effective immune response to the target prior to administration of the immunity linker.

17. The method of claim 14, wherein the composition comprises a population of different immunity linkers wherein the first binding sites differ in a) their specificity for different epitopes on the immune response component, or b) their affinity for the same epitopes on the immune response component.

18. The method of claim 14, wherein the immune response component is an antibody.

19. The method of claim 14, wherein the composition comprises a population of different immunity linkers comprising second binding sites that differ in a) their specificity for different epitopes on the target, or b) their affinity for the same epitope on the target.