Nerve growth factor as a vaccine adjuvant

Details Nerve growth factor as a vaccine adjuvant Nerve growth factor as a vaccine adjuvant

1999-06-01

2003-06-03

Kunz, Gary (Department: 1645)

Drug, bio-affecting and body treating compositions

Nonspecific immunoeffector, per se ; or nonspecific...

C424S184100, C424S198100, C514S002600, C514S012200

Reexamination Certificate

active

06572866

ABSTRACT:

FIELD OF THE INVENTION
The present invention relates to the field of vaccines.
DESCRIPTION OF THE BACKGROUND ART
Humans livestock and pets often are vaccinated to prevent disease, or reduce the severity of disease. Vaccination results in the production of antibodies, which are serum proteins capable of binding specifically to antigen substances used in the vaccine. This humoral response involves the selection of specific lines of B lymphocytes, and the proliferation and differentiation of the selected cells to yield clones of antibody-producing plasma cells.
Antibody production reaches a peak within several weeks after immunization, and then gradually declines. Because of a constant turnover of serum proteins, the decline in antibody production is accompanied by a corresponding decline in the circulating level of antibodies. However, if the patient is challenged again with the same antigen, a new response curve is initiated more rapidly and more intensely than the first one. This is called a secondary, booster, or anamnestic response, and in healthy patients results in much higher antibody levels with higher affinity to the antigen than the first exposure, or primary immunization. The increased rate of antibody synthesis is the result of an increased number of antibody producing plasma cells. These cells are scarce in the lymph nodes of the unimmunized patient, which contain mostly small lymphocytes. However, in healthy patients, plasma cells constitute up to 3% of the total lymph node cells after a primary immunization, and as much as 30% of the lymph node cells after a secondary immunization.
The secondary response is said to be due to immunological memory. That is, the healthy organism is able to “remember” its prior exposure to the antigen, and react more promptly and efficiently the second time it is exposed, even if the amount of specific antibodies in the serum has declined to a very low level in the meantime.
Certain conditions such as aging, malnutrition, drug addiction, alcoholism, and certain disease states such as diabetes and AIDS, lead to immunodeficiency, in which many immune responses are quenched and vaccination is of reduced effectiveness. There thus remains a need in the art for improved vaccination techniques, particularly among the elderly or otherwise immunodeficient.
SUMMARY OF THE INVENTION
In accordance with the present invention, a vaccination method utilizes a pharmaceutical combination for enhancing vaccine effectiveness. The pharmaceutical combination comprises an immune response-triggering vaccine capable of stimulating production in an immunodeficient animal of antibodies to a disease-causing agent foreign to said animal. The pharmaceutical combination further includes a vaccine effectiveness-enhancing amount of Nerve Growth Factor (NGF), which enhances production and affinity of said antibodies in said animal, in response to said vaccine. The vaccine and the NGF can be administered separately or together. In a preferred method, the vaccination method comprises administering to an immunodeficient animal a first dose of an immune response-triggering vaccine capable of stimulating production in an animal of antibodies to a disease-causing agent foreign to said animal; then, within a time period of between about 1 week and about 2 months after administration of said first dose, administering to said animal either 1) a vaccine effectiveness-enhancing amount of Nerve Growth Factor (NGF) which enhances production of said antibodies in said animal in response to said vaccine or 2) booster dose of said vaccine, along with a vaccine effectiveness-enhancing amount of said Nerve Growth Factor (NGF), so as to enhance effectiveness of said vaccine in said animal.


REFERENCES:
Paul, William E. “Fundamental Immunology”, 3rd ed., Raven Press, New York, pp. 1353-1369, 1993.*
Thorpe et al., “Mechanisms of lymphocyte activation by nerve growth factor”, Ann. N.Y. Acad. Of Sci., 1990, vol. 594, pp. 78-84.
Brodie et al., “Functional nerve growth factor receptors on human B lymphocytes. Interaction with IL-2”, Immunol., Jun. 1, 1992, vol. 148, No. 11, pp. 3492-3497.
Melamed et al., “Nerve growth factor signal transduction in human B lymphocytes is mediated by gp 140trk”, Eur. J. Immunol., Sep. 1996, vol. 26, pp. 1985-1992.
Richard J. Hodes, Aging and the immune system, Immunological Reviews, 160:5-8 (1997).
Maria Torcia et al., “Nerve Growth Factor Is an Autocrine Survival Factor for Memory B Lymphocytes”, Cell, vol. 85, May 3, 1996, pp. 345-356.
Eisen, Immunology An Introduction to Molecular and Cellular Principle of the Immune Responses, 2nd Ed., Harper & Row, Philadelphia, p. 447, 1980.
Kimball, Introduction to Immunology, 3rd Ed., Macmillan Publishing Company, New York, p. 453-457, 1990.

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