LT and CT in parenteral immunization methods against...

Details LT and CT in parenteral immunization methods against... LT and CT in parenteral immunization methods against...

1999-06-18

2003-06-10

Smith, Lynette R. F. (Department: 1645)

Drug, bio-affecting and body treating compositions

Antigen, epitope, or other immunospecific immunoeffector

Bacterium or component thereof or substance produced by said...

C424S236100, C424S184100, C424S094600, C514S012200, C530S350000, C530S403000

Reexamination Certificate

active

06576244

ABSTRACT:

BACKGROUND OF THE INVENTION
This invention relates to methods of immunizing against Helicobacter infection.
Cholera toxin (CT) and the heat-labile-enterotoxin of
E. coli
(LT) are commonly used as immunological adjuvants for mucosal immunization. The non-toxic B subunit of LT (LTB) has also been shown to have mucosal immunomodulating activity. When delivered mucosally with urease or other Helicobacter antigens, LT and CT each induce immune responses that protect mice against infection with
Helicobacter pylori.
Xu-Amano et al. (J. Exp. Med. 178:1309-1320, 1993) showed that mice develop specific serum IgM and IgG (but not IgA) responses following intraperitoneal immunization with tetanus toxin (TT) plus CT. TT alone gave low responses. Hornquist, et al. (Eur. J. Immunol. 23:2136-2143, 1993) showed that CT promotes priming of CD4+ T cells when delivered intravenously with Keyhole Limpet Hemocyanin (KLH). Marinaro et al. (J. Immunol. 155:4621-4629, 1995) showed that CT stimulates production of serum IgE to TT when the antigen and adjuvant are delivered subcutaneously.
SUMMARY OF THE INVENTION
We have discovered that parenterally delivered LT and LTB are effective adjuvants that enhance the immunoprotective effect of Helicobacter antigens, such as urease. We have also discovered that LT+LTB gives better results that LT alone.
Accordingly, the invention provides methods of inducing a protective or therapeutic immune response to Helicobacter infection in a mammal, in which (a) a Helicobacter antigen, and (b) an adjuvant including one or more of (i) LT, (ii) LTB, (iii) CT, and (iv) CTB (e.g., LT+LTB) is parenterally (e.g., subcutaneously, intradermally, intramuscularly, or intravenously) administered to a mammal.
The antigen and the adjuvant can be provided together in a solution, or separately. The antigen can be urease or a subunit, enzymatically inactivate derivative, or fragment thereof. The antigen can also be catalase, HspA, HspB, lactoferrin receptor, p76 (SEQ ID NOs:1-22), p32 (SEQ ID NOs:23 and 24), BabA, BabB, AlpA, AlpB, or an immunogenic fragment or derivative thereof. The methods of the invention also include the administration of more than one Helicobacter antigen.
The invention provides several advantages. For example, parenteral delivery of LT is advantageous in that the toxin does not contact the intestinal epithelial cells, and thus does not cause diarrhea. Also, the toxicity of parenterally administered LT we observed was limited to injection site swelling, and we observed no toxicity with LTB at high doses (see below), which matched the effectiveness of LT in augmenting protective immunity. Also, our observation of the heightened effect of parenterally administering LT (low dose)+LTB (high dose) minimizes the possibility of any potential side effects.
Other features and advantages of the invention are apparent from the following detailed description, the drawings, and the claims.


REFERENCES:
patent: 4053584 (1977-10-01), Dobrescu et al.
patent: 4303638 (1981-12-01), Tayot et al.
patent: 4411888 (1983-10-01), Klipstein et al.
patent: 4808700 (1989-02-01), Anderson et al.
patent: 5079165 (1992-01-01), Clements et al.
patent: 5182109 (1993-01-01), Tamura et al.
patent: 5241053 (1993-08-01), Fujisawa et al.
patent: 5308835 (1994-05-01), Clements
patent: 5538729 (1996-07-01), Czinn et al.
patent: 5837240 (1998-11-01), Lee et al.
patent: 5837472 (1998-11-01), Labigne
patent: 5843460 (1998-12-01), Labigne et al.
patent: 5871749 (1999-02-01), Doidge et al.
patent: 5980898 (1999-11-01), Glenn et al.
patent: 6005090 (1999-12-01), Doidge et al.
patent: 6126938 (2000-10-01), Guy et al.
patent: 835928 (1998-04-01), None
patent: WO 92/19265 (1992-11-01), None
patent: WO 93/13202 (1993-07-01), None
patent: WO 93/20843 (1993-10-01), None
patent: WO 94/09823 (1994-05-01), None
patent: WO 95/17211 (1995-06-01), None
patent: WO 95/22987 (1995-08-01), None
patent: 96/31235 (1996-10-01), None
patent: WO 96/33732 (1996-10-01), None
patent: WO 98/28357 (1998-07-01), None
Atherton, JC et al, The Jordan Report, Accelerated Development of Vaccines, 1995, pp. 60-63.*
Blaser, Martin J., Trends in Microbiology, vol. 1(7), Oct. 1993, pp. 255-260.*
Chen, M et al, Gastroentrology, vol. 104(4), p. 681, Apr. 1993.*
Goodwin, C.S., Helicobacter pylori, Biology and Clinical Practice, Chapter 25, pp. 431-445, 1993.*
Guy, B et al, Vaccine Research, vol. 6(3), pp. 141-150, 1997.*
Haas, R et al, Biologicals, vol. 25, pp. 175-177, 1997.*
Lee, A et al, Infection Immunity, vol. 62(8), pp. 3594-3597, Aug. 1994.
Malfertheiner, P et al, Clinical Therapeutics, vol. 15(suppl. B), 1993.
Marchetti, M et al, Vaccine, vol. 16(1), pp. 33-37, 1998.
Radcliff, FJ et al, European Helicobacter pylori study group, Xth International Workshop on Gastroduodenal Pathology and Helicobacter pylori, Lisbon, Sep. 11-14, 1997, p. A60, abstract 06/213.
Telford, JL et al, Current Opinion, Drugs, Dec. 1996, vol. 52(6), pp. 799-804.
Varga Laszlo et al, Kazuisztika, pp. 359-361, issue 6, (english translation), 1992.*
Monath TP et al, Am. J. Gastroenterology, vol. 89(8), pp. 1383, 1994.*
Heap, K et al, Microb. Ecol. Health Dis, vol. 4, Oct. 7-10, 1991, p. S119, Vith International Workshop on Campylobacter, Helicobacter and Related Organisms.*
Bowen, JC et al, Immunology, Mar. 1994, vol. 81(3), pp. 338-342 (abstract).*
Hornquist, E et al, European J. Immunology, Sep. 1993, vol. 23(9), pp. 2136-2143.*
Bukanov et al, Molecular Biology, vol. 11(3), pp. 509-523, 1994.*
Tomb, J et al, Nature, vol. 388(7), pp. 539-547, Aug. 1997.*
Kaplan et al, South African Medical Journal, 1993, vol. 83(12), Dec. pp. 922-923*
Brzozowski, T et al, Gut, vol. 41(suppl 1, p. A30, 1997.*
Haines, DC et al, Vet. Pathology, May 1998, vol. 35(3), pp. 202-208.*
Chen et al., “Immunisation with Helicobacter. The First Evidence for Protection Against Gastric Infection,” Irish Journal of Medical Science 161:29 (1992).
Chen et al., “Immunisation Against Gastric Helicobacter Infection in a Mouse/Helicobacter felisModel,” The Lancet 339:1120-1121 (1992).
Clements et al., “Adjuvant Activity ofEscherichia coliHeat-Labile Enterotoxin and Effect on the Induction of Oral Tolerance in Mice to Unrelated Protein Antigens,” Vaccine 6:269-277 (1988).
Corthesy—Theulaz et al., “Helicobacter pyloriUrease Elicits Protection AgainstHelicobacter felisInfection in Mice,” VIIthInternational Workshop on Campylobacter, Helicobacter, and Related Organisms, Acta Gastro-Enterologica Belgica 56:64 (1993).
Czerkinsky et al., “Oral Administration of a Streptococcal Antigen Coupled to Cholera Toxin B Subunit Evokes Strong Antibody Responses in Salivary Glands and Extramucosal Tissues,” Infection and Immunity 57:1072-1077 (1989).
Czinn et al., “Oral Immunization AgainstHelicobacter pylori,” Infection and Immunity 59:2359-2363 (1991).
Czinn et al., “Oral Immunization Protects Germ-Free Mice Against Infection fromHelicobacter felis,” Gastroenterology 102:A611 (1992).
Czinn et al., “Protection of Germ-Free Mice from Infection byHelicobacter felisAfter Active Oral or Passive IgA Immunization,” Vaccine 11:637-642 (1993).
Davin et al., “H. pyloriUrease Elicits Protection AgainstH. felisInfection in Mice,” Gastroenterology 104:A1035 (1993).
Doidge et al., “Therapeutic Immunisation Against Helicobacter Infection,” The Lancet 343:914-915 (1994).
Elson et al., “Generalized Systemic and Mucosal Immunity in Mice After Mucosal Stimulation with Cholera Toxin,” The Journal of Immunology 132:2736-2741 (1984).
Elson et al., “Cholera Toxin Feeding Did Not Induce Oral Tolerance in Mice and Abrogated Oral Tolerance to an Unrelated Protein Antigen,” The Journal of Immunology 133:2892-2897 (1984).
Elson, “Cholera Toxin (CT) as a Mucosal Adjuvant—The Effect of H-2 Genes,” Fed. Proc., Abstract No. 1778 46:621 A (1987).
Elson, “Cholera Toxin and its Subunits as Potential Oral Adjuvants,” Current Topics in Microbiology and Immunology 146:29-33 (1989).
Ermak et al., “MHC Class-II but not MHC-Class I or B Cell Responses are Required for Vaccine-Induced Protection Against MurineHelicobacter pyloriInfection,

Affiliated with

Also associated with

Rating

LT and CT in parenteral immunization methods against... does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with LT and CT in parenteral immunization methods against..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and LT and CT in parenteral immunization methods against... will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3115912