Tumor necrosis factor receptors on microorganisms

التفاصيل البيبلوغرافية
العنوان: Tumor necrosis factor receptors on microorganisms
Patent Number: 5,270,038
تاريخ النشر: December 14, 1993
Appl. No: 07/824,112
Application Filed: January 23, 1992
مستخلص: Cytokine receptors for tumor necrosis factor .alpha. which are found on microorganisms may, if bound with exogenous TNF.alpha., enhance the response of natural killer cells activated by the microorganisms, or increase TNF.alpha. production by peripheral blood lymphocytes treated with the microorganisms. Microorganisms with receptor-bound exogenous TNF.alpha. have enhanced cellular invasion ability which may change the immune response thereto. Clinical and pharmaceutical applications of these discoveries including vaccines with increased efficacy are provided.
Inventors: Klimpel, Gary R. (Santa Fe, TX); Niesel, David W. (League City, TX)
Assignees: Board of Regents, The University of Texas System (Austin, TX)
Claim: What is claimed is
Claim: 1. A composition consisting essentially of a Gram-negative bacterial or imperfect fungal microorganism having exogenous TNF.alpha. bound to a microorganism TNF.alpha. receptor.
Claim: 2. The composition of claim 1 wherein the microorganism is a Gram-negative bacteria.
Claim: 3. The composition of claim 1 wherein the microorganism is Salmonella typhimurium, Shigella flexneri, or Escherichia coli.
Claim: 4. The composition of claim 1 wherein the microorganism is Candida albicans.
Claim: 5. The composition of claim 1 wherein the microorganism is an imperfect fungi.
Claim: 6. The composition of claim 5 wherein the imperfect fungi is Candida albicans.
Claim: 7. A method of producing a vaccine of improved efficacy, the method comprising the steps of
Claim: identifying Gram-negative bacteria or imperfect fungi against which immunity is desired and which have TNF.alpha. receptors;
Claim: binding receptors of said bacteria or imperfect fungi with exogenous TNF.alpha.; and
Claim: preparing a pharmaceutically acceptable composition usable as a vaccine and consisting essentially of said Gram-negative bacteria or imperfect fungi having exogenous TNF.alpha. bound to said receptors, said bacteria or fungi being deactivated or fragmented to antigenic surface components and retaining bound TNF.alpha..
Claim: 8. The method of claim 7 wherein imperfect fungi are used.
Claim: 9. The method of claim 7 wherein Gram-negative bacteria are used.
Claim: 10. The method of claim 7 wherein the bacteria are Salmonella typhimurium, Shigella flexneri, or Escherichia coli.
Claim: 11. A vaccine for induction of immunity to a Gram-negative bacterial or imperfect fungal microorganism consisting essentially of a preparation with tumor necrosis factor .alpha. bound to an inactivated microorganism or a surface component thereof.
Claim: 12. A composition for the induction of immunity to a Gram-negative or imperfect fungal pathogen consisting essentially of a preparation with TNF.alpha. bound to an inactivated pathogen or pathogen component.
Current U.S. Class: 424/88; 424/92; 424/851; 4352/521; 4352/528; 435/879; 435/849; 435/922; 4352/554
Current International Class: A61K 3902; A61K 39112; A61K 39108; A61K 3900
Patent References Cited: 4764370 August 1988 Fields et al.
4820514 April 1989 Cummins
5100664 April 1992 Doyle et al.
Other References: Denis, M. et al., Interleukin-2 and Granulocyte-Marcophage Colony Stimulating Factor Stimulate Growth of a Virulent Strain of Escherichia coli, Infection and Immunity, 59(5): 1853-1856, 1991.
Le J. et al., Laboratory Investigation 56(3): 234-248, 1987.
Porat, R. et al., Enhancement of Growth of Virulent Strains of Escherichia coli by Interleukin-1, Science 254: 430-432, 1991.
Henney, C. S., Potential Therapeutical Applications of Interleukin-1, from a published transcript of the proceedings from the "International Conference on the Clinical Impact of Interleukins" at the Royal College of Physicians in London (Apr. 1989).
Primary Examiner: Nucker, Christine M.
Assistant Examiner: Krsek-Staples, Julie
Attorney, Agent or Firm: Arnold, White & Durkee
رقم الانضمام: edspgr.05270038
قاعدة البيانات: USPTO Patent Grants