Vaccine for transcutaneous immunization

• US 7,527,802 B2
• Filed: 02/13/2002
• Issued: 05/05/2009
• Est. Priority Date: 02/13/2001
• Status: Expired due to Term

• Current Assignee: US Department of The Army (Government of the United States of America), The United States of America As Represented By The Secretary of Agriculture
• Original Assignee: The United States Of America As Represented By The Secretary Of The Army
• Inventors: Cassels, Frederick J., Glenn, Gregory M.
• Primary Examiner(s): MINNIFIELD, NITA M
• Application Number:
  US10/467,887
• Publication Number:
  US 20040146534A1
• Time in Patent Office: 2,638 Days
• Field of Search: 424/184.1, 424/242.1, 424/257.1, 424/234.1, 424/169.1, 424/190.1, 424/93.1, 424/241.1, 424/194.1, 424/449, 424/450, 514/2, 514/12
• US Class Current: 424/257.1
• CPC Class Codes: A61K 2039/521 inactivated (killed)
• CPC Class Codes: A61K 2039/54 characterised by the route of administration
• CPC Class Codes: A61K 2039/541 Mucosal route
• CPC Class Codes: A61K 2039/55544 Bacterial toxins
• CPC Class Codes: A61K 39/015 Hemosporidia antigens, e.g. Plasmodium antigens
• CPC Class Codes: A61K 39/0258 Escherichia
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/7023 Transdermal patches and similar drug-containing composite devices, e.g. cataplasms galenical aspects of iontophoretic devices A61K9/0009; microneedle arrays A61K9/0021; buccal patches A61K9/006
• CPC Class Codes: A61K 9/7061 Polyacrylates
• CPC Class Codes: A61P 1/12 Antidiarrhoeals
• CPC Class Codes: A61P 31/04 Antibacterial agents
• 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

A vaccine delivered by transcutaneous immunization provides an effective treatment against infections by pathogens such as, for example, enterotoxigenic Escherichia coli (ETEC) and/or for symptoms of diarrheal disease caused thereby. For example, one, two, three, four, five or more antigens derived from ETEC and capable of inducing an antigen-specific immune response (e.g., toxins, colonization or virulence factors) and one or more optional adjuvant (e.g., whole bacterial ADP-ribosylating exotoxins, B subunits or toxoids thereof, detoxified mutants and derivatives thereof) are used to manufacture vaccines or to induce systemic and/or mucosal immunity.

Claims

1. A method of preventing traveler'"'"'s diarrhea in a human that is to be subjected to exposure to pathogens causing traveler'"'"'s diarrhea comprising applying a vaccine transcutaneously to the skin of the human, prior to exposure to pathogens causing traveler'"'"'s diarrhea, wherein the vaccine comprises an effective amount of heat-labile enterotoxin of E. coli (LT) to prevent traveler'"'"'s diarrhea.

3. The method of claim 1 or 2, wherein the vaccine comprises LT and an adjuvant.

4. The method of claim 3, wherein the adjuvant is an ADP-ribosylating exotoxin or a derivative thereof having adjuvant activity.

5. The method of claim 1 or 2, wherein the vaccine comprises LT and an E. coli colonization factor antigen (CFA).

6. The method of claim 5, wherein the E. coli colonization factor antigen is selected from the group consisting of CFA/I, CS1, CS2, CS 4, CS5, CS6, CS17 and PCF 0166.

7. The method of claim 1, wherein the vaccine comprises LT and heat stable enterotoxin of E. coli (ST).

8. The method of claim 7, wherein the vaccine comprises a carrier or an excipient.

9. The method of claim 7, wherein LT is conjugated to ST.

10. The method of claim 1, wherein the method comprises pretreating the skin prior to administering the vaccine.

11. The method of claim 10, wherein pretreating comprises chemical penetration enhancement, physical penetration enhancement, or both.

12. The method of claim 1 or 2, wherein the vaccine is applied using a patch.

13. The method of claim 12 wherein the vaccine comprises a carrier or an excipient.

14. The method of claim 1, wherein LT is genetically detoxified.

15. The method of claim 1 or 2, wherein LT is a mutant form of the enterotoxin.

16. The method of claim 1 or 2, wherein LT is both an antigen and an adjuvant.

17. The method of claim 16, wherein LT is a mutant form of the enterotoxin.

2. A method of preventing traveler'"'"'s diarrhea in a human that is to be subjected to exposure to pathogens causing traveler'"'"'s diarrhea comprising applying a vaccine transcutaneously to the skin of the human, prior to exposure to pathogens causing traveler'"'"'s diarrhea, wherein the vaccine comprises an effective amount of heat-labile enterotoxin of E. coli (LT) to treat traveler'"'"'s diarrhea.